NaCl intake and preference threshold of spontaneously hypertensive rats.

PubMed

Fregly, M J

1975-09-01

Both male and female spontaneously hypertensive (SH) rats have an appetite for NaCl solution. The appetite is present when a choice is offered between distilled water and either isotonic or hypertonic (0.25 M) NaCl solution to drink. Total fluid intake (water plus NaCl solution) was greater for SH rats than for controls while food intakes (g/100 g body wt/day) of SH rats were not different from controls. Mean body weight of SH rats was always less than that of controls. The appetite for NaCl solution was accompanied by a significant reduction in preference (detection) threshold. SH rats could detect the difference between distilled water and NaCl solution when the concentration of the latter was 12 mEq/liter compared to a control threshold of 30 mEq/liter. The NaCl appetite and reduced NaCl preference threshold induced by spontaneous hypertension is in marked contrast to the NaCl aversion induced by other types of experimentally induced hypertension in rats. The mechanism or mechanisms responsible for these differences remain for further study.

Lipid emulsion enhances cardiac performance after ischemia-reperfusion in isolated hearts from summer-active arctic ground squirrels.

PubMed

Salzman, Michele M; Cheng, Qunli; Deklotz, Richard J; Dulai, Gurpreet K; Douglas, Hunter F; Dikalova, Anna E; Weihrauch, Dorothee; Barnes, Brian M; Riess, Matthias L

2017-07-01

Hibernating mammals, like the arctic ground squirrel (AGS), exhibit robust resistance to myocardial ischemia/reperfusion (IR) injury. Regulated preference for lipid over glucose to fuel metabolism may play an important role. We tested whether providing lipid in an emulsion protects hearts from summer-active AGS better than hearts from Brown Norway (BN) rats against normothermic IR injury. Langendorff-prepared AGS and BN rat hearts were perfused with Krebs solution containing 7.5 mM glucose with or without 1% Intralipid™. After stabilization and cardioplegia, hearts underwent 45-min global ischemia and 60-min reperfusion. Coronary flow, isovolumetric left ventricular pressure, and mitochondrial redox state were measured continuously; infarct size was measured at the end of the experiment. Glucose-only AGS hearts functioned significantly better on reperfusion than BN rat hearts. Intralipid™ administration resulted in additional functional improvement in AGS compared to glucose-only and BN rat hearts. Infarct size was not different among groups. Even under non-hibernating conditions, AGS hearts performed better after IR than the best-protected rat strain. This, however, appears to strongly depend on metabolic fuel: Intralipid™ led to a significant improvement in return of function in AGS, but not in BN rat hearts, suggesting that year-round endogenous mechanisms are involved in myocardial lipid utilization that contributes to improved cardiac performance, independent of the metabolic rate decrease during hibernation. Comparative lipid analysis revealed four candidates as possible cardioprotective lipid groups. The improved function in Intralipid™-perfused AGS hearts also challenges the current paradigm that increased glucose and decreased lipid metabolism are favorable during myocardial IR.

[Analysis of parameters of serum concentration and pharmacokinetic of liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats].

PubMed

Zha, Lin; Zhao, Yan; Zhu, Hong-Yan; Cai, En-Bo; Liu, Shuang-Li; Yang, He; Zhao, Ying; Gao, Yu-Gang; Zhang, Lian-Xue

2017-05-01

The experiment was aimed to investigate the difference of plasma concentration and pharmacokinetic parameters between liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats, such as ginsenosides Rg₁, Re, Rf, Rb₁, Rg₂, Rc, Rb₂, Rb₃, Rd. After intravenous injection of liposome and aqueous solution in rats, the blood was taken from the femoral vein to detect the plasma concentration of the above 9 ginsenoside monomers in different time points by using HPLC. The concentration-time curve was obtained and 3p97 pharmacokinetic software was used to get the pharmacokinetic parameters. After the intravenous injection of ginsenosides to rats, nine ginsenosides were detected in plasma. In general, among these ginsenosides, the peak time of the aqueous solution was between 0.05 to 0.083 3 h, and the serum concentration peak of liposome usually appeared after 0.5 h. After software fitting, the aqueous solution of ginsenoside monomers Rg₁, Re, Rf, Rg₂, Rc, Rd, Rb₃ was two-compartment model, and the liposomes were one-compartment model; aqueous solution and liposome of ginsenoside monomers Rb₁ were three-compartment model; aqueous solution of ginsenoside monomers Rb₂ was three-compartment model, and its liposome was one-compartment model. Area under the drug time curve (AUC) of these 9 kinds of saponin liposomes was larger than that of aqueous solution, and the retention time of the liposomes was longer than that of the aqueous solution; the removal rate was slower than that of the aqueous solution, and the half-life was longer than that of the water solution. The results from the experiment showed that by intravenous administration, the pharmacokinetic parameters of two formulations were significantly different from each other; the liposomes could not only remain the drug for a longer time in vivo, but also reduce the elimination rate and increase the treatment efficacy. As compared with the traditional dosage forms, the total ginsenoside of ginseng stems and leaves can improve the sustained release of the drug, which is of great significance for the research and development of new dosage forms of ginsenosides in the future. Copyright© by the Chinese Pharmaceutical Association.

Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats

PubMed Central

Zhou, Feng; Hui, Yu; Xin, Hua; Xu, Yong-De; Lei, Hong-En; Yang, Bi-Cheng; Guan, Rui-Li; Li, Meng; Hou, Jian-Quan; Xin, Zhong-Cheng

2017-01-01

This study aimed to explore the therapeutic effects of adipose-derived stem cells (ADSCs)-based microtissues (MTs) on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg kg−1), and 8 weeks later, the determined diabetic rats randomly received intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and tumor necrosis factor-stimulated gene-6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors. PMID:27345005

[Effect of hypertonic saline solution on the viscoelasticities of erythrocyte membrane in rats subjected to hemorrhagic shock].

PubMed

Zhou, X; Hu, D; Liu, L; Wu, Z; Qin, J; Cai, S

2001-12-01

We have studied the effect of hypertonic saline solution on the viscoelasticities of erythrocyte membrane in hemorrhage-shocked rats using micropippette aspiration technique. Wistar rats were randomly divided into three groups of 0.9% NaCl(NS), 7.5% NaCl (HS) and 5% NaCl-3.5% NaAc (HSA), respectively. The animals were bled to reach a mean arterial pressure of 5.3 kPa in 10 minutes and maintained in shock for 90 minutes. 4 ml/kg NS, HS and HSA was given intravenously and respectively in 5 minutes following hemorrhagic shock. The blood was collected to determine the viscoelasticities of erythrocyte membrane at baseline, shock and after treatment. The results showed that the elastic moduli and viscous coefficients of erythrocyte membrane were increased obviously following hemorrhagic shock. HS raised elastic moduli and reduced viscous coefficients significantly compared with NS after treatment. The elastic moduli and viscous coefficients of erythrocyte membrane were decreased remarkably in HSA group than in NS and HS group. These data suggested that HSA could improve the viscoelasticities of erythrocyte membrane significantly in rats subjected to hemorrhagic shock.

The selective cyclooxygenase-2 inhibitor parecoxib markedly improves the ability of the duodenum to regulate luminal hypertonicity in anaesthetized rats.

PubMed

Sedin, J; Sjöblom, M; Nylander, O

2012-07-01

To examine whether the prevention of post-operative duodenal ileus by treatment with parecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, affects the ability of the duodenum to respond to luminal hypertonicity. The proximal duodenums of anaesthetized rats were perfused with hypertonic NaCl solutions with osmolalities of 400, 500, 600 or 700 mOsm kg(-1) , and the effects on mucosal permeability, motility, transepithelial net fluid flux and effluent osmolality were assessed in the absence (control) and presence of parecoxib. Parecoxib-treated, but not control animals, exhibited duodenal contractions, which were reduced by the nicotinic receptor antagonists mecamylamine and hexamethonium and by perfusion with 700 mOsm kg(-1) . All animals responded to luminal hypertonicity with induction of net fluid secretion, which peaked at an osmolality of 500 mOsm kg(-1) . The hypertonicity-induced increases in fluid secretion were twofold greater in parecoxib-treated than in control rats and attenuated by nicotinic receptor blockade. The decrease in luminal osmolality correlated with the osmolality of the perfusion solution in both control and parecoxib-treated animals but the osmolality-adjusting capability was markedly better in the latter group. Rats exposed to duodenal luminal distension responded to hypertonicity with a greater fluid secretion and a larger decrease in luminal osmolality than control rats. Perfusion with 700 mOsm kg(-1) increased mucosal permeability in parecoxib-treated animals only, an effect abolished by nicotinic receptor blockade. Parecoxib markedly improved the ability of the duodenum to sense and to decrease luminal hypertonicity by a mechanism most probably involving inhibition of COX-2 and stimulation of nicotinic acetylcholine receptors. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

Fasting ameliorates metabolism, immunity, and oxidative stress in carbon tetrachloride-intoxicated rats.

PubMed

Sadek, Km; Saleh, Ea

2014-12-01

Fasting has been recently discovered to improve overall health, but its beneficial effects in the presence of hepatic insufficiency have not been proven. The influence of fasting on the metabolism, immunological aspects, and oxidative stress of 40 male carbon tetrachloride (CCl4)-intoxicated Wistar rats was investigated in the present study. The rats were divided into four groups, including a placebo group, CCl4-intoxicated rats, which were injected subcutaneously with 1.0 ml/kg of CCl4 solution, a fasting group, which was fasted 12 h/day for 30 days, and a fourth group, which was injected with CCl4 and fasted. The metabolism, immunity, and oxidative stress improved in CCl4-intoxicated rats fasted for 12 h/day for 30 days, as evidenced in significant increase (p < 0.05) in total protein, globulin, immunoglobulin M (IgM) and IgG levels, and total antioxidant capacity. In contrast, significant decrease (p < 0.05) in blood glucose, total cholesterol, low-density lipoprotein-cholesterol, alanine aminotransferase, C-reactive protein, and malondialdehyde levels were observed. Compared with CCl4-intoxicated rats, significant differences in the albumin, triacylglycerol, high-density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol, cardiovascular risk factor, calcium and magnesium levels were not detected. The results of the present study showed that fasting improved metabolism, immunity, and oxidative stress in CCl4-intoxicated rats. Thus, fasting during Ramadan is safe for patients with hepatic disorders, as the prophet Mohammed (S) said "Keep the fast, keep your health". © The Author(s) 2014.

Gaseous signalling molecule SO2 via Hippo-MST pathway to improve myocardial fibrosis of diabetic rats

PubMed Central

Liu, Maojun; Liu, Shengquan; Tan, Wenting; Tang, Fen; Long, Junrong; Li, Zining; Liang, Biao; Chu, Chun; Yang, Jun

2017-01-01

Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)-generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo-MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague-Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L-Aspartic acid β-hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra-peritoneal injection of STZ (40 mg/kg) Following model establishment, intra-peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo-MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis-associated protein B-cell lymphoma associated protein X, caspase-3 and caspase-9 were upregulated, and Bcl-2 expression was downregulated. The expression of ERS and Hippo-MST pathway-associated proteins, including CHOP, GRP94, MST1 and MST2, were significantly upregulated. By contrast, these above-mentioned changes were reversed by SO2 treatment. Compared with STZ group, the HDX group had a further increase of myocardial fibrosis and apoptosis, while there were no statistically significant differences in the expression of Bax/Bcl-2, caspase-3, caspase-9 and ERS and Hippo-MST pathway-associated proteins. The results of the present study demonstrated that the gaseous signal molecule SO2 can effectively improve the myocardial fibrosis of diabetic rats, and its mechanism may be associated with reduced apoptosis and ERS by downregulated Hippo-MST pathway. PMID:28990064

Gaseous signalling molecule SO2 via Hippo‑MST pathway to improve myocardial fibrosis of diabetic rats.

PubMed

Liu, Maojun; Liu, Shengquan; Tan, Wenting; Tang, Fen; Long, Junrong; Li, Zining; Liang, Biao; Chu, Chun; Yang, Jun

2017-12-01

Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)‑generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo‑MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague‑Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L‑Aspartic acid β‑hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra‑peritoneal injection of STZ (40 mg/kg) Following model establishment, intra‑peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo‑MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis‑associated protein B‑cell lymphoma associated protein X, caspase‑3 and caspase‑9 were upregulated, and Bcl‑2 expression was downregulated. The expression of ERS and Hippo‑MST pathway‑associated proteins, including CHOP, GRP94, MST1 and MST2, were significantly upregulated. By contrast, these above‑mentioned changes were reversed by SO2 treatment. Compared with STZ group, the HDX group had a further increase of myocardial fibrosis and apoptosis, while there were no statistically significant differences in the expression of Bax/Bcl‑2, caspase‑3, caspase‑9 and ERS and Hippo‑MST pathway‑associated proteins. The results of the present study demonstrated that the gaseous signal molecule SO2 can effectively improve the myocardial fibrosis of diabetic rats, and its mechanism may be associated with reduced apoptosis and ERS by downregulated Hippo‑MST pathway.

Combined Treatment with Interlukin-1 and Tumor Necrosis Factor-Alpha Antagonists Improve Type 2 Diabetes in Rats.

PubMed

DiK, Burak; Bahcivan, Emre; Eser Faki, Hatice; Uney, Kamil

2018-03-20

In the present study, combined treatment with etanercept and anakinra were tested in the streptozotocin-induced diabetic rats. Forty male Wistar albino rats were divided into 5 groups; healthy control (HC), diabetic control (DC), diabetic+anakinra (DAT), diabetic+etanercept (DET), and diabetic+etanercept+anakinra (DEAT). HC and DC groups received subcutaneous (sc.) injection with a saline solution, while DAT and DET groups received anakinra (10 mg/kg/day, sc.) or etanercept (10 mg/kg, twice a week, sc.), and DEAT rats received both anakinra and etanercept treatments for 21 days after diabetes has developed. Anakinra and etanercept treatments significantly increased insulin and homeostatic model assessment-β cell function levels and decreased glucose levels compared to the DC group as single (DAT and DET) and combined treatments (DEAT). The thiobarbituric acid reactive substances level was significantly decreased in DAT group. The combine use of etanercept and anakinra can improve insulin and blood glucose in type 2 diabetic rats. The combined treatment of anakinra and etanercept together was more effective than single treatment and might have a potential new treatment strategy and to reduce the mortality and morbidity resulting from diabetes.

Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats.

PubMed

Bopda, Orelien Sylvain Mtopi; Longo, Frida; Bella, Thierry Ndzana; Edzah, Protais Marcellin Ohandja; Taïwe, Germain Sotoing; Bilanda, Danielle Claude; Tom, Esther Ngo Lemba; Kamtchouing, Pierre; Dimo, Theophile

2014-04-28

The leaves of Kalanchoe pinnata (Crassulaceae) are used in Cameroon folk medicine to manage many diseases such as cardiovascular dysfunctions. In this work, we aimed to evaluate the activities of aqueous leaf extract of Kalanchoe pinnata on the blood pressure of normotensive rat (NTR) and salt hypertensive rats (SHR), as well as its antioxidant properties. Hypertension was induced in rats by oral administration of 18% NaCl for 4 weeks. For the preventive study, three groups of rats received 18% NaCl solution and the plant extract at 25 mg/kg/day, 50 mg/kg/day or 100 mg/kg/day by gavage. Two positive control groups received 18% NaCl solution and either spironolactone (0.71 mg/kg/day) or eupressyl (0.86 mg/kg/day) by gavage for 4 weeks. At the end of this experimental period, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR) were measured by the invasive method. Some oxidative stress biomarkers (reduced glutathione (GSH), superoxide dismutase (SOD), nitric monoxide (NO) were evaluated in heart, aorta, liver and kidney. NO level was indirectly evaluated by measuring nitrite concentration. Kalanchoe pinnata extract prevented significantly the increase of systolic and diastolic arterial pressures in high salt-loaded rats (SHR). In SHR, concomitant administration of Kalanchoe pinnata at 25, 50 and 100 mg/kg/day significantly prevented the increase in blood pressure by 32%, 24% and 47% (for SAP); 35%, 33% and 56% (for DAP), respectively. No significant change was recorded in heart rate of those rats. The plant extract improved antioxidant status in various organs, but more potently in aorta. Thus, antioxidant and modulatory effects of Kalanchoe pinnata at the vasculature might be of preponderant contribution to its overall antihypertensive activity. The work demonstrated that the concomitant administration of high-salt and the aqueous extract of Kalanchoe pinnata elicits prevention of salt-induced hypertension in rat. This antihypertensive activity is associated with an improvement of antioxidant status. Overall, results justify and support the use of Kalanchoe pinnata as antihypertensive medicine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Semen Cassiae Extract Improves Glucose Metabolism by Promoting GlUT4 Translocation in the Skeletal Muscle of Diabetic Rats

PubMed Central

Zhang, Meiling; Li, Xin; Liang, Hangfei; Cai, Huqiang; Hu, Xueling; Bian, Yu; Dong, Lei; Ding, Lili; Wang, Libo; Yu, Bo; Zhang, Yan; Zhang, Yao

2018-01-01

Diabetes mellitus is a clinical syndrome characterised by hyperglycaemia; its complications lead to disability and even death. Semen Cassiae is a traditional Chinese medicine, which has anti-hypertensive, anti-hyperlipidaemia, anti-oxidation, and anti-ageing properties. Our study was designed to evaluate the action of total anthraquinones of Semen Cassiae extract (SCE) on the improvement of glucose metabolism in diabetic rats and to elucidate the underlying mechanism. First, we evaluated the effect of SCE on normal rats. Next, we observed the effect of SCE using a rat model of diabetes, which was established by feeding rats with high-energy diet for 4 weeks and a single intraperitoneal injection of streptozotocin (STZ; 30 mg/kg) 3 weeks after starting the high-energy diet. Rats in different SCE groups (administered 54, 108, and 324 mg/kg/day of SCE) and metformin group (162 mg/kg/day, positive control drug) were treated with the corresponding drugs 1 week before starting high-energy diet and treatment continued for 5 weeks; meanwhile, rats in the control group were administered the same volume of sodium carboxymethyl cellulose solution (vehicle solution). One week after STZ injection, fasting blood glucose (FBG), oral glucose tolerance (OGT), fasting serum insulin (FSI) and serum lipids were quantified. Finally, the expression of proteins in the phosphatidylinositol-3-kinase (PI3K)–Akt–AS160–glucose transporter isoform 4 (GLUT4) signalling pathway was detected by western blotting. The data indicated that the levels of FBG and serum lipids were significantly lowered, and OGT and FSI were markedly increased in diabetic rats treated with SCE (108 mg/kg/day); however, SCE did not cause hypoglycaemia in normal rats. The molecular mechanisms were explored in the skeletal muscle. SCE markedly restored the decreased translocation of GLUT4 in diabetic rats. Moreover, the protein expressions of phosphorylated-AS160 (Thr642), phosphorylated-Akt (Ser473) and PI3K were significantly increased after SCE treatment in the skeletal muscle. These results indicate that SCE exerts an anti-hyperglycaemic effect by promoting GLUT4 translocation through the activation of the PI3K–Akt–AS160 signalling pathway. Our findings suggest that treatment with SCE, containing anthraquinones, could be an effective approach to enhance diabetes therapy. PMID:29670524

Swimming-Induced Taste Aversion and Its Prevention by a Prior History of Swimming

ERIC Educational Resources Information Center

Masaki, Takahisa; Nakajima, Sadahiko

2004-01-01

In two experiments, the evidence showed that 20 min of forced swimming by rats caused aversion to a taste solution consumed before swimming. When one of two taste solutions (sodium saccharin or sodium chloride, counterbalanced across rats) was paired with swimming and the other was not, the rats' intakes of these two solutions showed less…

The Mitochondria-Targeted Antioxidant Mitoquinone Protects against Cold Storage Injury of Renal Tubular Cells and Rat Kidneys

PubMed Central

Mitchell, Tanecia; Rotaru, Dumitru; Saba, Hamida; Smith, Robin A. J.; Murphy, Michael P.

2011-01-01

The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ∼2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation. PMID:21159749

The mitochondria-targeted antioxidant mitoquinone protects against cold storage injury of renal tubular cells and rat kidneys.

PubMed

Mitchell, Tanecia; Rotaru, Dumitru; Saba, Hamida; Smith, Robin A J; Murphy, Michael P; MacMillan-Crow, Lee Ann

2011-03-01

The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ~2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation.

The febrile responses in rabbits and rats to leucocyte pyrogens of different species.

PubMed Central

Borsook, D; Laburn, H; Mitchell, D

1978-01-01

1. We have investigated the effects on body temperature of rats and rabbits of leucocyte pyrogen derived from the blood of rat, rabbit, ox, pig and baboon. 2. In the rabbit intravenous injections (3.5 ml.) of solutions containing leucocyte pyrogen derived from ox, pig and rabbit blood produced fevers with short latencies; no fevers resulted from injections of similar solutions derived from rat or baboon blood. 3. In the rat intraperitoneal injections (2.0 ml.) of solutions containing leucocyte pyrogen derived from ox blood caused a fever, while pig leucocyte pyrogen produced a marked hypothermia. Neither rabbit, baboon, nor rat leucocyte pyrogen had any significant effect on rectal temperature of the rats. 4. Our results show that there is a variability of response in the rat and the rabbit to injection of leucocyte pyrogen of different species; leucocyte pyrogen may be species specific. PMID:671345

[Protective effect of emodin pretreatment in young rats with intrahepatic cholestasis].

PubMed

Xiong, Xiao-Li; Yan, Su-Qi; Qin, Huan; Zhou, Li-Shan; Zhang, Ling-Ling; Jiang, Zhi-Xia; Ding, Yan

2016-02-01

To investigate the protective effect of emodin in young rats with intrahepatic cholestasis. A total of 120 young Sprague-Dawley rats were randomly divided into control, model, and high-, medium-, and low-dose emodin groups, with 24 rats in each group. The rats in the control and model groups were given sodium carboxymethyl cellulose solution by gavage, while the other groups were given different doses of emodin solution by gavage. On the 5th day of experiment, alpha-naphthylisothiocyanate (ANIT, 50 mg/kg) was applied by gavage to establish the model of intrahepatic cholestasis in all groups except the control group. At 24, 48, and 72 hours after gavage, 8 rats in each group were sacrificed. Colorimetry was used to measure the serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in each group, and hematoxylin-eosin staining was applied to observe the morphological changes of the liver under a light microscope at different time points. Compared with the control group, the model group had significantly increased serum levels of TBIL, DBIL, TBA, ALP, GGT, ALT, and AST at the 24-hour, 48-hour, and 72-hour time points (P<0.01). In the model group, the serum levels of TBIL, DBIL, TBA, ALT, and AST showed varying degrees of increase at 48 hours after establishment of model, compared with the values at 24 and 72 hours (P<0.05). At 24, 48, and 72 hours, the high-, medium-, and low-dose emodin groups had varying degrees of reductions in the serum levels of TBIL and TBA compared with the model group (P<0.05); the high- and low-dose emodin groups had significantly increased serum levels of TBA compared with the medium-dose emodin group (P<0.05). The model group had the most severe pathological changes at 48 hours. Compared with the model group, the high-, medium-, and low-dose emodin groups showed certain improvement in pathological changes of the liver at each time point, and the medium-dose emodin group had better improvement compared with the high- and low-dose emodin groups. Emodin can effectively improve ANIT-induced intrahepatic cholestasis in young rats, and medium-dose emodin shows the best effect.

Investigation of the Blood Glucose Lowering Potential of the Jamaican Momordica charantia (Cerasee) Fruit in Sprague-Dawley Rats

PubMed Central

Burnett, A; McKoy, M-L; Singh, P

2015-01-01

ABSTRACT The Momordica charantia (MC) fruit has been documented to possess antidiabetic properties. However, these studies were not without controversy surrounding the blood glucose-lowering ability and the mechanism of action in diabetes therapy. In an effort to evaluate such claims in the Jamaican MC species known as cerasee, aqueous extracts of the unripe fruit were studied in normal and diabetic rats. Normal male Sprague-Dawley rats were divided into groups (n = 6) orally administered distilled water, 10% dimethyl sulfoxide (DMSO) solution, the aqueous extract (400 mg/kg body weight) and glibenclamide (15 mg/kg body weight), respectively prior to assessment of fasting blood glucose (FBG) concentration. The oral glucose tolerance test (OGTT) was conducted in normoglycaemic rats orally administered distilled water, 10% DMSO solution, glibenclamide (15 mg/kg body weight) or aqueous extracts of the fruit (200 and 400 mg/kg body weight). Blood glucose concentration was also monitored in streptozotocin-induced diabetic rats administered the aqueous extract (250 mg/kg body weight) or water vehicle after an overnight fast. The aqueous extracts showed no hypoglycaemic or antidiabetic activity. However, the administration of the aqueous extracts (200 and 400 mg/kg body weight) resulted in significant improvement in glucose tolerance of glucose-primed normoglycaemic rats during the OGTT. These data suggest that the glucose-lowering mechanism of the Jamaican MC fruit species likely involves altered glucose absorption across the gastrointestinal tract. PMID:26624580

Long-term dietary supplementation with cystathionine improves tissue glutathione in ageing rats.

PubMed

Pouget, Mélanie; Perrot, Marie; Denis, Philippe; Vuichoud, Jacques; Dardevet, Dominique; Vidal, Karine; Breuillé, Denis; Papet, Isabelle

2016-08-01

Ageing is associated with decrease in tissue glutathione that can be reduced by food fortification with the amino acid cysteine. However, cysteine is not stable in solution and generates bad taste. Cystathionine, the direct precursor of cysteine, could be a valuable alternative. This study aimed to determine whether long-term dietary supplementation with cystathionine induces an increase in glutathione pools. Aged rats (20.5-month-old) were fed ad libitum during 29 weeks with either a cystathionine-supplemented diet (7.3 g/kg, n = 90 rats) or a control iso-nitrogenous alanine-supplemented diet (2.9 g/kg, n = 90 rats). Cystathionine was detected in the plasma of the cystathionine-supplemented rats but not in the control alanine-supplemented rats. Cystathionine increased glutathione concentrations in liver, small intestine and gastrocnemius muscle (P < 0.03). No adverse effect was observed. Cystathionine supplementation being able to increase moderately glutathione in healthy old rats could be considered as a candidate for nutritional supports aiming to revert the stronger glutathione depletions occurring in unhealthy elderly.

A lecithin-based microemulsion of rh-insulin with aprotinin for oral administration: Investigation of hypoglycemic effects in non-diabetic and STZ-induced diabetic rats.

PubMed

Cilek, A; Celebi, N; Tirnaksiz, F; Tay, A

2005-07-14

The aim of this study was to develop a microemulsion formulation providing an improved efficacy of orally administered insulin. The microemulsions were prepared using Labrafil M 1944 CS, Phospholipon 90 G (lecithin), absolute alcohol and bi-distilled water. The microemulsions of recombinant human (rh)-insulin and aqueous solution (200 IU/kg) were administered intragastrically by a canulla to diabetic and non-diabetic rats. Aprotinin (2500 KIU/g) was added as the enzyme inhibitor to the formulation. Upon the administration of intragastric rh-insulin solution (IS) to non-diabetic rats, the plasma glucose and insulin levels were not changed significantly. Therefore, the hypoglycemic effect caused by subcutaneous rh-insulin solution (SC), microemulsion containing rh-insulin (IME) and microemulsion containing rh-insulin and aprotinin (IMEA) were analyzed in diabetic rats. The area above the plasma glucose levels time curves (AAC), minimum glucose concentration (Cmin) and time to Cmin (tmin) were derived from the plasma glucose profiles. IME and IMEA caused approximately 30% decrease in plasma glucose levels. The decrease in the plasma glucose levels continued after the 90th min. The highest AAC value was obtained when IMEA was administered to rats. The maximum plasma insulin concentration (Cmax), time to reach Cmax (tmax), terminal half-life (t(1/2)), area under the plasma concentration-time curve (AUC), mean residence time (MRT) and elimination rate constant (k(el)) values were also calculated. It was observed that t(1/2) values varied between 0.53 and 1.31h. No significant difference could be found between the pharmacokinetic parameters of the IME and IMEA administered groups. Addition of aprotinin to the microemulsion containing rh-insulin increased bioavailability when compared to those not containing it, although the difference is not significant.

Effect of lawsonia innermis (linn) leaves ethanolic extract on blood glucose and malondialdehyde level in alloxan-induced diabetic rats

NASA Astrophysics Data System (ADS)

Indah Sari, Mutiara; Ilyas, Syafruddin; Widyawati, Tri; Anjelir Antika, Maya

2018-03-01

The case of diabetes mellitus (DM) tends to increase worldwide. DM triggers the oxidative stress condition that caused by the increasing of free radical. The present study was conducted to evaluate the effect of giving ethanolic extract of Lawsonia inermis (Linn) leaves to the glucose and malondialdehyde (MDA) level in alloxan-induced diabetic Wistar male rats. The powder of dry leaves of L.inermis was macerated in ethanol 96% to obtain ethanolic extract (LLEE).Thirty five of rats were divided into five groups, ie. K (normal and given 0.9% NaCl solution ), P1-P4 were induced using alloxan (120 mg/kg) intraperitoneally to get diabetic condition. Diabetic rats then were treated as follows: P1 (given 0.9% NaCl solution) P2 (LLEE (200 mg/kg BW), P3 (LLEE (400 mg/kg BW)), P4 ( LLEE (600 mg/kg BW)). All groups were treated for 28 days. The fasting blood glucose levels were measured at day 1, 7, 14, 21, 28 whereas MDA levels were measured at the end of treatment. The result showed that LLEE improved blood glucose level (BGLs) of alloxan-induced diabetic rats significantly (p< 0.001) at 29th day. However, LLEE could not affect the MDA level (p > 0.5). The study concluded that LLEE have antihyperglycemic properties.

Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats.

PubMed

Zhao, Ying-Zheng; Jin, Rong-Rong; Yang, Wei; Xiang, Qi; Yu, Wen-Ze; Lin, Qian; Tian, Fu-Rong; Mao, Kai-Li; Lv, Chuan-Zhu; Wáng, Yi-Xiáng J; Lu, Cui-Tao

2016-01-01

Intranasal administration of phospholipid-based gelatin nanoparticles (GNP) was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP) on hemiparkinsonian rats. The SP-loaded gelatin nanoparticles (SP-GNP) were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM). The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA) induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH), phosphorylated c-Jun protein (p-c-Jun) and Caspase-3 (Cas-3) expressed in substantia nigra (SN) region of hemiparkinsonian rats. PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration. With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis.

Japanese traditional miso soup attenuates salt-induced hypertension and its organ damage in Dahl salt-sensitive rats.

PubMed

Yoshinaga, Mariko; Toda, Natsuko; Tamura, Yuki; Terakado, Shouko; Ueno, Mai; Otsuka, Kie; Numabe, Atsushi; Kawabata, Yukari; Uehara, Yoshio

2012-09-01

We investigated the effects of long-term miso soup drinking on salt-induced hypertension in Dahl salt-sensitive (Dahl S) rats. Dahl S rats were divided into four groups that consumed 1) water, 2) a 0.9% NaCl solution, 3) a 1.3% sodium NaCl solution, or 4) miso soup containing 1.3% NaCl. They were followed for 8 wk. Systolic blood pressure and hypertensive organ damage were determined. Systolic blood pressure increased in an age- and dose-dependent manner in Dahl S rats drinking salt solutions. The systolic blood pressure increase was significantly less in the Dahl S rats that drank miso soup, although the ultimate cumulative salt loading was greater than that in the Dahl S rats given the 1.3% NaCl solution. This blood pressure decrease was associated with a morphologic attenuation of glomerular sclerosis in the kidney and collagen infiltration in the heart. Urinary protein excretions were less in the miso group than in the rats given the 1.3% NaCl solution. The fractional excretion of sodium was increased and that of potassium was decreased in Dahl S rats given the 1.3% NaCl solution, and these effects were reversed in rats given miso soup toward the values of the control. We found that long-term miso soup drinking attenuates the blood pressure increase in salt-induced hypertension with organ damage. This may be caused by a possible retardation of sodium absorption in the gastrointestinal tract or by the direct effects of nutrients in the miso soup from soybeans. The decrease was associated with decreases in cardiovascular and renal damage. Copyright © 2012 Elsevier Inc. All rights reserved.

A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats.

PubMed

Wen, Jiaming; Wang, Bohan; Du, Chuanjun; Xu, Gang; Zhang, Zhewei; Li, Yi; Zhang, Nan

2015-10-01

Diabetes is an important risk factor for erectile dysfunction (ED). Recent studies have indicated that A2B adenosine receptor (ADORA2B) signaling is essential for penile erection. Thus, we hypothesize that diabetic ED may be attributed to impaired A2B adenosine signaling. To test this hypothesis, we generated diabetic rats by injecting streptozocin as animal model. After 12 weeks, immunohistochemistry staining was used to localize the expression of ADORA2B. Western Blot and quantitative PCR were employed to determine ADORA2B expression level. Intracavernosal pressure (ICP) measurement was used to evaluate erectile function. Diabetic rats received a single intravenous injection of BAY 60-6583, an ADORA2B agonist, or vehicle solution, at 60 min before the ICP measurement. The results showed that ADORA2B expressed in the nerve bundle, smooth muscle, and endothelium in penile tissue of control mice. Western Blot and quantitative PCR results indicated that the expression levels of ADORA2B protein and mRNA were significantly reduced in penile tissues of diabetic rats. Functional studies showed that the erectile response induced by electrical stimulation was remarkably decreased in diabetic rats, compared with age-matched control rats. However, at 60 min after BAY 60-6583 treatment, the erectile function was improved in diabetic rats, suggesting that enhancement of ADORA2B signaling may improve erectile function in diabetic ED. This preclinical study has revealed a previously unrecognized therapeutic possibility of BAY 60-6583 as an effective and mechanism-based drug to treat diabetic ED. In conclusion, we propose that impaired A2B adenosine signaling is one of the pathological mechanisms of diabetic ED.

Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats

PubMed Central

2014-01-01

Background WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc’s anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. Methods Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation. Results Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p < 0.05), with improved jejunum histology (p < 0.0001). Zinc supplementation diminished bacterial translocation only in lactose-challenged undernourished rats (p = 0.03) compared with the untreated challenged controls and reduced intestinal IL-1β and TNF-α cytokines to control levels. Conclusion Altogether our findings provide novel mechanisms of zinc action in the setting of diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea. PMID:25095704

Anti-fibrosis effects of Huisheng oral solution in CCl4-induced hepatic fibrosis in rat.

PubMed

Li, Wenting; Wu, Yuanbo; Zhu, Chuanlong; Wang, Zheng; Gao, Rentao; Wu, Quan

2014-01-01

Some gradient of Huisheng oral solution (HOS) has been reported to have anti-fibrosis activity. This study was designed to investigate whether HOS could inhibit liver fibrosis and to elucidate its molecular mechanism of action. Hepatic fibrosis model in rat was induced by subcutaneous injection of CCl4. Rats in the treatment group were administrated with HOS intragastrically. Hematoxylin and eosin (H and E) staining and Masson's trichrome staining were used to examine the changes in liver pathology. Levels of ALT, AST, LDH, hyaluronic acid (HA) and laminin (LN) in serum and hydroxyproline (Hyp) in liver were detected by biochemical examination and radioimmunoassay, respectively. The expression and distribution of Smad3, TGF-β1, α-SMA and TIMP-1 were observed and the active TGF-β1 was tested. Our data demonstrated that HOS alleviated CCl4-induced collagen deposition in liver tissue, improved liver condition and liver function in rats. HOS also significantly reduced the expression and distribution of Smad3, TGF-β1, α-SMA and TIMP-1 as well as decreased active TGF-β1. This study revealed that HOS attenuates the development of liver fibrosis through suppressing the TGF-β1 pathway. It provides us a new approach to treatment of liver fibrosis.

Pyruvate-enriched oral rehydration solution improved intestinal absorption of water and sodium during enteral resuscitation in burns.

PubMed

Hu, Sen; Liu, Wei-wei; Zhao, Ying; Lin, Zhi-long; Luo, Hong-min; Bai, Xiao-dong; Sheng, Zhi-yong; Zhou, Fang-qiang

2014-06-01

To investigate alteration in intestinal absorption during enteral resuscitation with pyruvate-enriched oral rehydration solution (Pyr-ORS) in scalded rats. To compare pyruvate-enriched oral rehydration solution (Pyr-ORS) with World Health Organisation oral rehydration solution (WHO-ORS), 120 rats were randomly divided into 6 groups and 2 subgroups. At 1.5 and 4.5 h after a 35% TBSA scald, the intestinal absorption rate, mucosal blood flow (IMBF), Na(+)-K(+)-ATPase activity and aquaporin-1 (AQP-1) expression were determined (n = 10), respectively. The intestinal Na(+)-K(+)-ATPase activity, AQP-1 expression and IMBF were markedly decreased in scald groups, but they were profoundly preserved by enteral resuscitation with WHO-ORS and further improved significantly with Pyr-ORS at both time points. Na(+)-K+-ATPase activities remained higher in enteral resuscitation with Pyr-ORS (Group SP) than those with WHO-ORS (Group SW) at 4.5 h. AQP-1 and IMBF were significantly greater in Group SP than in Group SW at both time points. Intestinal absorption rates of water and sodium were obviously inhibited in scald groups; however, rates were also significantly preserved in Group SP than in Group SW with an over 20% increment at both time points. The Pyr-ORS may be superior to the standard WHO-ORS in the promotion of intestinal absorption of water and sodium during enteral resuscitation. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Hydrogen Supplementation of Preservation Solution Improves Viability of Osteochondral Grafts

PubMed Central

Yamada, Takuya; Onuma, Kenji; Kuzuno, Jun; Ujihira, Masanobu; Kurokawa, Ryosuke; Sakai, Rina; Takaso, Masashi

2014-01-01

Allogenic osteochondral tissue (OCT) is used for the treatment of large cartilage defects. Typically, OCTs collected during the disease-screening period are preserved at 4°C; however, the gradual reduction in cell viability during cold preservation adversely affects transplantation outcomes. Therefore, improved storage methods that maintain the cell viability of OCTs are needed to increase the availability of high-quality OCTs and improve treatment outcomes. Here, we evaluated whether long-term hydrogen delivery to preservation solution improved the viability of rat OCTs during cold preservation. Hydrogen-supplemented Dulbecco's Modified Eagles Medium (DMEM) and University of Wisconsin (UW) solution both significantly improved the cell viability of OCTs during preservation at 4°C for 21 days compared to nonsupplemented media. However, the long-term cold preservation of OCTs in DMEM containing hydrogen was associated with the most optimal maintenance of chondrocytes with respect to viability and morphology. Our findings demonstrate that OCTs preserved in DMEM supplemented with hydrogen are a promising material for the repair of large cartilage defects in the clinical setting. PMID:25506061

Development of Intra-knee Joint Sustained-Release Gel Formulation and Evaluation of Its Pharmacological Efficiency in Rats.

PubMed

Noda, Takehiro; Okuda, Tomoyuki; Ban, Kousuke; Mizuno, Ryota; Tagami, Tatsuaki; Ozeki, Tetsuya; Okamoto, Hirokazu

2017-06-01

In the development of a drug for intra-articular administration, a sustained-release formulation is desirable since it is difficult to sustain the effects of conventional injections due to fast drug leakage from the joint cavity. In this study, we prepared sustained release gel formulations for intra-articular administration containing indocyanine green (ICG) as a model drug to follow its fate after intra-articular administration in rats with in-vivo imaging system (IVIS). ICG administered as an aqueous solution leaked from the joint cavity in a short time and was excreted out of the body within a day. On the other hand, ICG in the sustained-release formulations was retained and released in the joint cavity for a week. Next, we prepared a sustained-release formulation with hyaluronic acid (HA) as the gel base containing a pain-relief drug (Drug A). We had administered it and other formulations into the rat knee where we injected bradykinin to evaluate their walking distance after 1 and 3 d. The effect of an aqueous solution of Drug A disappeared on day 3. The HA gel formulation without Drug A was more effective than the aqueous solution. The HA gel formulation with Drug A was the most effective; the walking distance was about 85% of the baseline on day 3. This study showed that the gel formulations were effective to sustain the release of a drug in the knee joint, and that the combination of a pain-relief drug with HA gel was effective to improve the mobility of the acute pain model rats.

Beer improves copper metabolism and increases longevity in Cu-deficient rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, R.J.; Klevay, L.M.

Moderate consumption of alcoholic beverages decreases risk of death from ischemic heart disease (IHD). Evidence suggests that Cu-deficiency is important in the etiology and pathophysiology of IHD. The effect of beer (25 ng Cu/ml) drinking on the severity of Cu-deficiency was examined in weanling, male Sprague-Dawley rats fed a low Cu diet (0.84 {mu}g Cu/g). Beer drinking increased median longevity to 204 or 299 d from 62 or 42 d respectively in rats drinking water in two experiments (15 rats/group). In experiment 3, a single dose of {sup 67}Cu (3.3 {mu}Ci as chloride) was added to 1 g of feedmore » and given to 12-h fasted rats 30 d after the start of the experiment. Whole body counting over 13 d showed apparent Cu absorption and t{sub {1/2}} (biological) were greater in Cu-deficient rats drinking beer than in similar rats drinking water. Plasma cholesterol was lower but hematocrit and liver Cu were higher in surviving rats drinking beer than in rats drinking water. Body weight was not affected by beer in any experiment. In experiment 4, a 4% aqueous ethanol solution had no effect on longevity of copper deficient rats. A non-alcohol component of beer alters Cu metabolism and mitigates the severity of nutritional Cu-deficiency in rats.« less

Characterization of blood drawn rapidly for use in blood volume expansion studies: An animal model for simulated weightlessness

NASA Technical Reports Server (NTRS)

Chenault, V. Michelle; Lynch, Colleen D.; Morris, Mariana; Clodfelter, Jill; Hutchins, Phillip M.

1990-01-01

It was demonstrated that up to 8ml of blood can be drawn from donar rats without significantly increasing volume and stress sensitive hormones, and thus can be used for volume expansion studies. Infusion of whole blood allows more physiological changes that can be seen with volume expansion by saline or other ionic solutions. The infusion of whole blood to induce hypervolemia may provide an improved model to study the fluid balance and control mechanisms operative in weightlessness. Blood samples were drawn as quickly as possible from femoral artery catheters chronically implanted in Sprague Dawley rats and analyzed for hematocrit, plasma sodium, potassium, osmolality, corticosterone, epinepherine, norepinephrine, and vasopressin. The levels were found to be comparable to those of normal rats.

Prevention of duodenal ileus reveals functional differences in the duodenal response to luminal hypertonicity in Sprague-Dawley and Dark Agouti rats.

PubMed

Sedin, J; Sjöblom, M; Nylander, O

2014-03-01

The mechanism by which the duodenum adjusts the luminal osmolality remains unclear. The aim was to compare the duodenal osmoregulation in response to different hyperosmolar solutions in Sprague-Dawley and Dark Agouti rats and to elucidate whether cyclooxygenase-2 inhibition affects these responses. The duodenum was perfused in situ with a 700-milliosmolar solution (NaCl alone, D-glucose ± NaCl, D-mannitol ± NaCl or orange juice), and the effects on the duodenal motility, mucosal permeability, luminal alkalinization, fluid flux and osmoregulation were assessed in anaesthetized rats. The change in net fluid flux and luminal osmolality, in response to a given hyperosmolar solution, was almost identical in control rats of both strains. In control rats, hypertonic D-glucose-NaCl induced fluid secretion only in the presence of phlorizin, an inhibitor of SGLT1. Cyclooxygenase-2 inhibition potentiated the hypertonicity-induced fluid secretion and increased the osmolality-adjusting capability in both strains, but the responses were greater in Dark Agouti rats. While cyclooxygenase-2-inhibited Dark Agouti rats responded to the hyperosmolar solutions with depression of motility and increased mucosal permeability, these effects were absent or smaller in the Sprague-Dawley strain. In contrast, orange juice induced the same duodenal responses in cyclooxygenase-2-inhibited Dark Agouti and Sprague-Dawley rats. The duodenum possesses the ability to absorb fluid despite a very high luminal osmolality. Inhibition of cyclooxygenase-2 markedly enhanced the capability of the duodenum to secrete fluid and to decrease luminal osmolality, irrespective of the hyperosmolar solution or the rat strain used, and revealed notable differences between the two strains with regard to their osmolality-adjusting capability. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration.

PubMed

Din, Fakhar Ud; Choi, Ju Yeon; Kim, Dong Wuk; Mustapha, Omer; Kim, Dong Shik; Thapa, Raj Kumar; Ku, Sae Kwang; Youn, Yu Seok; Oh, Kyung Taek; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

2017-11-01

Intravenously administered for the treatment of rectum cancer, irinotecan produces severe side effects due to very high plasma concentrations. A novel irinotecan-encapsulated double reverse thermosensitive nanocarrier system (DRTN) for rectal administration was developed as an alternative. The DRTN was fabricated by dispersing the thermosensitive irinotecan-encapsulated solid lipid nanoparticles (SLN) in the thermosensitive poloxamer solution. Its gel properties, pharmacokinetics, morphology, anticancer activity and immunohistopathology were assessed after its rectal administration to rats and tumor-bearing mice. In the DRTN, the solid form of the SLN and the liquid form of the poloxamer solution persisted at 25 °C; the former melted to liquid, and the latter altered to gel at 36.5 °C. The DRTN was easily administered to the anus, gelling rapidly and strongly after rectal administration. Compared to the conventional hydrogel and intravenously administered solution, it retarded dissolution and initial plasma concentration. The DRTN gave sustained release and nearly constant plasma concentrations of irinotecan at 1-3 h in rats, resulting in improved anticancer activity. It induced no damage to the rat rectum and no body weight loss in tumor-bearing mice. Thus, this irinotecan-encapsulated DRTN associated with a reduced burst effect, lack of toxicity and excellent antitumor efficacy would be strongly recommended as a rectal pharmaceutical product alternative to commercial intravenous injection in the treatment of rectum and colon cancer.

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

PubMed

Okumura, Shinya; Uemura, Tadahiro; Zhao, Xiangdong; Masano, Yuki; Tsuruyama, Tatsuaki; Fujimoto, Yasuhiro; Iida, Taku; Yagi, Shintaro; Bezinover, Dmitri; Spiess, Bruce; Kaido, Toshimi; Uemoto, Shinji

2017-09-01

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

In vivo application of chitosan to improve bioavailability of cyanocobalamin, a form of vitamin B12, following intraintestinal administration in rats.

PubMed

Goto, Yuko; Masuda, Ayumi; Aiba, Tetsuya

2015-04-10

The effect of chitosan on the intestinal absorption of cyanocobalamin (VB12), a stable form of vitamin B12, was investigated in vivo in rats, with the aim of improving the oral bioavailability of VB12 for anemia treatment in patients with gastrectomy. The bioavailability was evaluated based on the plasma concentration profile of VB12 following intraintestinal administration of the VB12 solution containing chitosan at various concentrations. The bioavailability of VB12 was 0.6±0.2% when the chitosan-free VB12 solution was administered, while it increased to 10.5±3.3% when chitosan was dissolved in the VB12 solution at a concentration of 1%. The bioavailability of VB12 increases with the chitosan concentration, in which chitosan seems to augment the amount of VB12 absorbed without affecting the absorption rate constant of VB12. It was also shown that the bioavailability of VB12 does not increase further when the degree of chitosan deacetylation is increased from 83 to 100% by substitutively employing the fully deacetylated chitosan. These findings suggest that the oral administration of VB12 with readily available chitosan may be a practical approach for anemia treatment in patients with gastrectomy. Copyright © 2015 Elsevier B.V. All rights reserved.

Flow distribution during infusion of UW and HTK solution in anaesthetised rats.

PubMed

Jansson, Leif; Carlsson, Per-Ola; Bodin, Birgitta; Källskog, Orjan

2011-06-01

Organ transplantation necessitates the use of preservation solutions to maintain the integrity of the organs during retrieval. The aim of this study was to investigate the flow distribution in abdominal organs in rats during acute infusion of preservation solution. Microspheres were used to estimate the distribution of flow in the pancreas, duodenum, ileum, colon, liver, kidneys and lungs in untreated Wistar-Furth rats and in animals with an opened abdominal cavity and catheterised aorta. Some animals were infused by free flow of 5 ml of UW, HTK or Ringer solution containing microspheres at a pressure of 100 cm H(2)O through an intra-aortic catheter. Opening of the abdominal cavity did not affect any of the organ blood flow values. However, the fraction of total pancreatic blood flow diverted through the islets increased. During infusion of microsphere-containing UW, HTK or Ringer solution, splanchnic and renal organ flow values, represented by microsphere contents, were similar. The fraction of microspheres found in the islets was lower in UW-infused rats. The number of microspheres present in the lungs or liver was very low, suggesting that shunting was negligible. Infusion of HTK and UW solution into anaesthetised rats results in a flow distribution which is similar to that in normal animals in most abdominal organs, but there is a reduction in islet blood perfusion by UW but not HTK solution.

Comparative efficacy of Belzer or Euro-Collins solutions for pancreatic preservation during cold ischemic storage in rats.

PubMed

Perez, Rogério Renato; Goldenberg, Alberto; Netto, Alcides Augusto Salzedas; Gonzalez, Adriano Miziara

2014-03-01

To compare the efficacy of different types of solutions (Belzer or Euro-Collins) for the preservation of rat pancreas during cold ischemia. Thirty Wistar rats were divided into three groups according to the perfusion or storage solution: Group E (perfusion and storage in Euro-Collins solution); Group B (perfusion and storage in Belzer solution) and Group BE (Perfusion in Belzer solution and storage in Euro-Collins solution). After perfusion, the pancreas was excised and stored at 4˚C for 18 hours. Amylase was measured at 6, 12 and 18h, and histological analysis of the pancreas was performed after 18h of cold storage. Amylase was elevated and comparable in Groups E and BE after 12 and 18 hours of ischemia (p<0.05). In the exocrine pancreas, histological differences in the amount of necrosis (p=0.049), lymphocytic infiltrate (p<0.001) and neutrophilic infiltrate (p=0.004) were observed, with more favorable features present in Group B. In the endocrine pancreas, Group B showed less edema (p<0.001), but other parameters were similar among all groups. The Euro-Collins solution is inferior to the Belzer solution for the preservation of rat pancreas during cold ischemia.

Effects of topical oxiconazole and boric acid in alcohol solutions to rat inner ears.

PubMed

Özdemir, Süleyman; Tuncer, Ülkü; Tarkan, Özgür; Akar, Funda; Sürmelioğlu, Özgür

2013-06-01

The aim of this study is to evaluate the ototoxicity of topical oxiconazole and boric acid in alcohol solutions. Prospective controlled animal study. Research laboratory. Fifty adult Wistar albino rats were divided into 5 groups consisting of 10 animals each. The right tympanic membranes were perforated, and baseline and posttreatment distortion product otoacoustic emission (DPOAE) measurements were performed. The solutions were applied through the external ear canal to the middle ear twice a day for 14 days. The rats in group I and group II received 0.1 mL of oxiconazole-containing solution drops and 4% boric acid in alcohol solution drops, respectively. Group III received gentamicin solution (40 mg/mL) (ototoxic control), group IV received saline solution, and group V was followed without any medication. The baseline DPOAE results of the right ears of all animals tested were normal. Animals in groups I, II, IV, and V showed no statistically significant change in the DPOAE amplitudes. The rats in the gentamicin group showed a significant decrease. This study demonstrates that topically used oxiconazole and boric acid in alcohol solutions to the middle ear appear to be safe on the inner ear of rats. The safety of these drugs has not yet been confirmed in humans. Caution should be taken when prescribing these drugs, especially to patients who had tympanic membrane perforation. Ear drops should be chosen more carefully in an external ear infection for patients with tympanic membrane perforation to avoid ototoxicity.

Calcium deprivation increases the palatability of calcium solutions in rats.

PubMed

McCaughey, Stuart A; Forestell, Catherine A; Tordoff, Michael G

2005-02-15

Calcium-deprived rats have elevated intakes of CaCl2, other calcium salts, and some non-calcium compounds. We used taste reactivity to examine the effects of calcium deprivation on the palatability of CaCl2 and other solutions. Nine male Sprague-Dawley rats were calcium-deprived by maintenance on a low-calcium diet, and eight replete rats were used as controls. All rats were videotaped during intraoral infusion of the following solutions: 30 and 300 mM CaCl2, 30 mM calcium lactate, 100 and 600 mM NaCl, 30 mM MgCl2, 1 mM quinine.HCl, 2.5 mM sodium saccharin, and deionized water. We counted individual orofacial and somatic movements elicited by the infusions and used them to calculate total ingestive and aversive scores. Relative to controls, calcium-deprived rats gave a significantly larger number of tongue protrusions and had higher total ingestive scores for CaCl2, calcium lactate, NaCl, and MgCl2. Our results suggest that CaCl2, calcium lactate, NaCl, and MgCl2 taste more palatable to rats when they are calcium-deprived than replete, and this may be responsible for the increased intake of these solutions following calcium deprivation.

Development of ionic-complex-based nanostructured lipid carriers to improve the pharmacokinetic profiles of breviscapine.

PubMed

Li, Mei; Zheng, Yong; Shan, Feng-ying; Zhou, Jing; Gong, Tao; Zhang, Zhi-rong

2013-08-01

Breviscapine isolated from the Chinese herb Erigeron breviscapus (Vant) Hand-Mazz is widely used to treat cardiovascular and cerebrovascular diseases. The aim of this study was to improve the pharmacokinetic profiles of breviscapine using nanostructured lipid carrier based on an ionic complex formation. Breviscapine nanostructured lipid carrier (Bre-NLC) was prepared using the thin film homogenization method. The morphology of Bre-NLCs was determined using transmission electron microscopy. The mean particle size, polydispersity index, zeta-potential analysis and entrapment efficiency were analized. In vitro release was studied using the dialysis method. In vitro stability was studied in fresh plasma and liver slurry of rats. In vivo pharmacokinetics was analyzed in rats after intravenous injection of a dose equivalent to breviscapine (10 mg/kg). The Bre-NLCs were spherical with a mean particle size of ~170 nm, a zeta potential of ∼20 mV and a high entrapment efficiency of ~89%. Compared with a commercially available solution, a substantial decrease in the cumulative release of breviscapine was found for the Bre-NLCs. The NLC has a significantly protective effect against the liver enzyme degradation of breviscapine. After intravenous administration in rats, the Bre-NLCs exhibited a 32 times increase in the AUC0-t and a 12 times increase in T1/2 as compared to the commercially available breviscapine solution. The results demonstrate that the NLC has great potential to use as a novel sustained release system for breviscapine.

Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats

PubMed Central

Kieffer, Dorothy A.; Piccolo, Brian D.; Vaziri, Nosratola D.; Liu, Shuman; Lau, Wei L.; Khazaeli, Mahyar; Nazertehrani, Sohrab; Moore, Mary E.; Marco, Maria L.; Martin, Roy J.

2016-01-01

Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function. PMID:26841824

Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats.

PubMed

Kieffer, Dorothy A; Piccolo, Brian D; Vaziri, Nosratola D; Liu, Shuman; Lau, Wei L; Khazaeli, Mahyar; Nazertehrani, Sohrab; Moore, Mary E; Marco, Maria L; Martin, Roy J; Adams, Sean H

2016-05-01

Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function. Copyright © 2016 the American Physiological Society.

Alanyl-glutamine and glutamine plus alanine supplements improve skeletal redox status in trained rats: involvement of heat shock protein pathways.

PubMed

Petry, Eder Ricardo; Cruzat, Vinicius Fernandes; Heck, Thiago Gomes; Leite, Jaqueline Santos Moreira; Homem de Bittencourt, Paulo Ivo; Tirapegui, Julio

2014-01-17

We hypothesized that oral l-glutamine supplementations could attenuate muscle damage and oxidative stress, mediated by glutathione (GSH) in high-intensity aerobic exercise by increasing the 70-kDa heat shock proteins (HSP70) and heat shock factor 1 (HSF1). Adult male Wistar rats were 8-week trained (60-min/day, 5 days/week) on a treadmill. During the last 21 days, the animals were supplemented with either l-alanyl-l-glutamine dipeptide (1.5 g/kg, DIP) or a solution containing the amino acids l-glutamine (1g/kg) and l-alanine (0.67 g/kg) in their free form (GLN+ALA) or water (controls). Plasma from both DIP- and GLN+ALA-treated animals showed higher l-glutamine concentrations and reduced ammonium, malondialdehyde, myoglobin and creatine kinase activity. In the soleus and gastrocnemius muscle of both supplemented groups, l-glutamine and GSH contents were increased and GSH disulfide (GSSG) to GSH ratio was attenuated (p<0.001). In the soleus muscle, cytosolic and nuclear HSP70 and HSF1 were increased by DIP supplementation. GLN+ALA group exhibited higher HSP70 (only in the nucleus) and HSF1 (cytosol and nucleus). In the gastrocnemius muscle, both supplementations were able to increase cytosolic HSP70 and cytosolic and nuclear HSF1. In trained rats, oral supplementation with DIP or GLN+ALA solution increased the expression of muscle HSP70, favored muscle l-glutamine/GSH status and improved redox defenses, which attenuate markers of muscle damage, thus improving the beneficial effects of high-intensity exercise training. Copyright © 2013 Elsevier Inc. All rights reserved.

Neuromotor Activity, Anxiety and Cognitive Function in the In Vivo Model of Alimentary Hyperlipidemia and Obesity.

PubMed

Apryatin, S A; Sidorova, Yu S; Shipelin, V A; Balakina, A; Trusov, N V; Mazo, V K

2017-05-01

Behavioral indicators characterizing specific features of the pathological process of alimentary-dependent diseases were studied using in vivo model of alimentary hyperlipidemia in rats and mice. Rats and mice of the control groups received balanced semisynthetic diet for 63 days; animals of the experimental groups received a diet with high fat content (30% dry weight), balanced or high-fat diet with fructose solution instead of water, balanced cholesterol-enriched diet (0.5% dry weight), or balanced cholesterol-enriched diet with fructose solution. During the experiment, the mass of food, consumed by the animals, was monitored daily. Muscle tone was assessed by the front paw grip strength on days 33 and 54 of the experiment. Anxiety was tested in the elevated plus maze on days 36 and 57. Behavior and memory were assessed by conditioned passive avoidance reflex on days 39, 40, and 61. A significant increase in muscle tone was revealed on day 54 in rats fed with a balanced diet with fructose, and in mice, that received a similar diet, supplemented with fructose and cholesterol. Anxiety in the second test (day 57) was significantly decreased in rats fed high-fat diet and increased in mice fed high fat diet and high fat diet with fructose. In the second test, additional amount of cholesterol in the diet was the factor that significantly improved both short-term and long-term memory in both species. In mice, in contrast to rats, addition of fructose, including combination with high-fat diet, significantly worsened short-term and long-term memory. Thus, dietary factors, contributing to alimentary dyslipidemia development in rats and mice, can significantly affect the indices of neuromotor activity, anxiety level and cognitive functions, and the nature and direction of these changes are largely species-specific.

The Influence of Manganese and Glutamine Intake on Antioxidants and Neurotransmitter Amino Acids Levels in Rats' Brain.

PubMed

Szpetnar, Maria; Luchowska-Kocot, Dorota; Boguszewska-Czubara, Anna; Kurzepa, Jacek

2016-08-01

Depending on the concentration, Mn can exert protective or toxic effect. Potential mechanism for manganese neurotoxicity is manganese-induced oxidative stress. Glutamine supplementation could reduce manganese-induced neurotoxicity and is able to influence the neurotransmission processes. The aim of this study was to investigate whether the long term administration of manganese (alone or in combination with glutamine) in dose and time dependent manner could affect the selected parameters of oxidative-antioxidative status (superoxide dismutase and glutathione peroxidase activities, concentrations of vitamin C and malonic dialdehyde) and concentrations of excitatory (Asp, Glu) and inhibitory amino acids (GABA, Gly) in the brain of rats. The experiments were carried out on 2-months-old albino male rats randomly divided into 6 group: Mn300 and Mn500-received solution of MnCl2 to drink (dose 300 and 500 mg/L, respectively), Gln group-solution of glutamine (4 g/L), Mn300-Gln and Mn500-Gln groups-solution of Mn at 300 and 500 mg/L and Gln at 4 g/L dose. The control group (C) received deionized water. Half of the animals were euthanized after three and the other half-after 6 weeks of experiment. The exposure of rats to Mn in drinking water contributes to diminishing of the antioxidant enzymes activity and the increase in level of lipid peroxidation. Glutamine in the diet admittedly increases SOD and GPx activity, but it is unable to restore the intracellular redox balance. The most significant differences in the examined amino acids levels in comparison to both control and Gln group were observed in the group of rats receiving Mn at 500 mg/L dose alone or with Gln. It seems that Gln is amino acid which could improve antioxidant status and affect the concentrations of the neurotransmitters.

Hydrophilic solute transport across the rat blood-brain barrier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucchesi, K.J.

1987-01-01

Brain capillary permeability-surface area products (PS) of hydrophilic solutes ranging in size from 180 to 5,500 Daltons were measured in rats according to the method of Ohno, Pettigrew and Rapoport. The distribution volume of 70 KD dextran at 10 minutes after i.v. injection was also measured to determine the residual volume of blood in brain tissue at the time of sacrifice. Small test solutes were injected in pairs in order to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. This issue was examined in rats whose blood-brain barrier (BBB)more » was presumed to be intact (untreated) and in rats that received intracarotid infusions to open the BBB (isosmotic salt (ISS) and hyperosmolar arabinose). Ohno PS values of {sup 3}H-inulin and {sup 14}C-L-glucose in untreated rats were found to decrease as the labelling time was lengthened. This was evidence that a rapidly equilibrating compartment exists between blood and brain that renders the Ohno two-compartment model inadequate for computing true transfer rate constants. When the data were reanalyzed using a multi-compartment graphical analysis, solutes with different molecular radii were found to enter the brain at approximately equal rates. Furthermore, unidirectional transport is likely to be initiated by solute adsorption to a glycocalyx coat on the luminal surface of brain capillary endothelium. Apparently, more inulin than L-glucose was adsorbed, which may account for its slightly faster transfer across the BBB. After rats were treated with intracarotid infusions of ISS or hyperosmolar arabinose, solute PS values were significantly increased, but the ratio of PS for each of the solute pairs approached that of their free-diffusion coefficients.« less

The dopamine β-hydroxylase inhibitor, nepicastat, suppresses chocolate self-administration and reinstatement of chocolate seeking in rats.

PubMed

Zaru, Alessandro; Maccioni, Paola; Colombo, Giancarlo; Gessa, Gian Luigi

2013-10-01

Craving for chocolate is a common phenomenon, which may evolve to an addictive-like behaviour and contribute to obesity. Nepicastat is a selective dopamine β-hydroxylase (DBH) inhibitor that suppresses cocaine-primed reinstatement of cocaine seeking in rats. We verified whether nepicastat was able to modify the reinforcing and motivational properties of a chocolate solution and to prevent the reinstatement of chocolate seeking in rats. Nepicastat (25, 50 and 100 mg/kg, intraperitoneal) produced a dose-related inhibition of operant self-administration of the chocolate solution in rats under fixed-ratio 10 (FR10) and progressive-ratio schedules of reinforcement, measures of the reinforcing and motivational properties of the chocolate solution, respectively. The effect of nepicastat on the reinstatement of chocolate seeking was studied in rats in which lever-responding had been extinguished by removing the chocolate solution for approximately 8 d. Nepicastat dose-dependently suppressed the reinstatement of lever-responding triggered by a 'priming' of the chocolate solution together with cues previously associated with the availability of the reward. In a separate group of food-restricted rats trained to lever-respond for regular food pellets, nepicastat reduced FR10 lever-responding with the same potency as for the chocolate solution. Spontaneous locomotor activity was not modified by nepicastat doses that reduced self-administration of the chocolate solution and regular food pellets and suppressed the reinstatement of chocolate seeking. The results indicate that nepicastat reduces motivation to food consumption sustained by appetite or palatability. Moreover, the results suggest that DBH inhibitors may be a new class of pharmacological agents potentially useful in the prevention of relapse to food seeking in human dieters.

Successive Negative Contrast after Partial Reinforcement in the Consummatory Behavior of Rats

ERIC Educational Resources Information Center

Pellegrini, Santiago; Muzio, Ruben N.; Mustaca, Alba E.; Papini, Mauricio R.

2004-01-01

Rats given access to a 32% sucrose solution later reject a 4% solution significantly more than controls that have only received the 4% solution. In Experiment 1, this consummatory successive negative contrast (cSNC) effect was attenuated by previous exposure to 50% partial reinforcement. Furthermore, recovery from cSNC was also facilitated by…

The application of polymerized porcine hemoglobin (pPolyHb) in the rat small bowel preservation.

PubMed

Huang, He; Ma, Jun; Zhu, Wenjin; Sun, Jinghui; Yan, Kunping; Song, Bo; Xue, Yuejin; Xin, Jianguo; Pan, Wencan; Zhu, Hongli; Chen, Chao

2014-10-01

Small bowel transplantation (SBTx) has become a standard clinical treatment for short bowel syndrome or irreversible intestinal function failure. Optimum preservation of the organ is essential for the success of transplantation. In this study, pPolyHb was used as an additive to hypertonic citrate adenine solution (HCA) to provide oxygen for rat small bowel transplant. Rat small bowels were preserved in HCA, HCA with pPolyHb, and University of Wisconsin solution (UW) for 12, 24, and 36 h, respectively. The results suggested that the preservation effect of HCA with pPolyHb was comparable with the UW solution, and more effective than the HCA solution.

Increased bioavailability of tacrolimus after rectal administration in rats.

PubMed

Sakai, Masayuki; Hobara, Norio; Hokama, Nobuo; Kameya, Hiromasa; Ohshiro, Susumu; Sakanashi, Matao; Saitoh, Hiroshi

2004-09-01

The oral bioavailability of tacrolimus is low and varies considerably in humans due to first-pass metabolism by cytochrome P450 (CYP) 3A4 and the active efflux mediated by P-glycoprotein. This study was undertaken to elucidate the usefulness of rectal administration of tacrolimus as an alternative route to improve its bioavailability. Tacrolimus powder was suspended in a suppository base (witepsol H-15) and the tacrolimus suppository was inserted into the anus of the rats. For comparison, tacrolimus was suspended in 0.5% sodium methylcellulose solution and administered orally to rats. The dose of tacrolimus was fixed to 2 mg/kg. Blood samples were collected periodically up to 24 h after dosing, and tacrolimus concentrations were assayed by microparticle enzyme immunoassay. The whole blood concentrations of tacrolimus after rectal administration were much greater than those after oral administration. The C(max) and AUC(0-24 h) values after rectal administration were 3.9- and 6.9-fold greater than those after oral administration, respectively. These results clearly suggest a possibility that rectal administration of tacrolimus is capable of improving its bioavailability and cutting the costs of tacrolimus treatment.

Montmorillonite ameliorates hyperthyroidism of rats and mice attributed to its adsorptive effect.

PubMed

Cai, Yan; Meng, Xin-fang; Cao, Yong-xiao; Lu, Hua; Zhu, Shao-fei; Zhou, Liang-zhen

2006-12-03

The present study aims to evaluate the adsorbing effect of montmorillonite on thyroid hormone in the entero-hepatic circulation. The concentration of thyroid hormone in the serum of hyperthyroidism model rats and in solution was measured by radioimmunoassay and ultraviolet spectrometry, respectively. The body weight, temperature, and consumption of food and water were observed in hyperthyroidism model rats. Furthermore, hypoxia tolerance, sodium-pentobarbital-induced sleep time, spontaneous activities were measured on hyperthyroidism model mice after being treated with montmorillonite. Results showed that montmorillonite adsorbed thyroxin (T(4)) and triiodothyronine (T(3)) in vitro. Montmorillonite at dosage of 1.0 g/kg and 0.3 g/kg decreased thyroid hormone levels on hyperthyroidism model rats; Montmorillonite (2.0 g/kg and 0.6 g/kg) prolonged the sleep time, improved the hypoxia tolerant capacity and reduced the spontaneous activities of the hyperthyroidism model mice. These results suggest montmorillonite has anti-hyperthyroidism effect attributed to its adsorptive effect.

Evaluation of chronic alcohol self-administration by a 3-bottle choice paradigm in adult male rats. Effects on behavioural reactivity, spatial learning and reference memory.

PubMed

Cacace, Silvana; Plescia, Fulvio; La Barbera, Marco; Cannizzaro, Carla

2011-06-01

Chronic ethanol consumption is able to modify emotional behaviour and cognition in humans. In particular, the effects exerted by alcohol may depend on doses, time and modalities of administration. In this study we investigated, in adult male rats, ethanol self-administration and preference patterns using a 3-bottle choice paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on novelty-induced explorative behaviour in the open field, and on spatial learning and reference memory in the Morris water maze was also evaluated. Our results indicate that: (i) rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; (ii) at the fourth week of the free-access paradigm rats show a high explorative behaviour in the central squares of the open field and an improvement in spatial information processing in the new-place learning task of the Morris water maze. In conclusion our data suggest that, interestingly, rats exposed to the free-access paradigm were able to self-regulate their alcoholic intake, and indicated that a moderate alcohol consumption was able to induce an increase in behavioural reactivity and an enhancement in spatial learning flexibility. Copyright © 2011 Elsevier B.V. All rights reserved.

Enhanced consumption of salient solutions following pedunculopontine tegmental lesions.

PubMed

MacLaren, D A A; Markovic, T; Daniels, D; Clark, S D

2015-01-22

Rats with lesions of the pedunculopontine tegmental nucleus (PPTg) reliably overconsume high concentration sucrose solution. This effect is thought to be indicative of response-perseveration or loss of behavioral control in conditions of high excitement. While these theories have anatomical and behavioral support, they have never been explicitly tested. Here, we used a contact lickometer to examine the microstructure of drinking behavior to gain insight into the behavioral changes during overconsumption. Rats received either excitotoxic (ibotenic acid) damage to all PPTg neuronal subpopulations or selective depletion of the cholinergic neuronal sub-population (diphtheria toxin-urotensin II (Dtx-UII) lesions). We offered rats a variety of pleasant, neutral and aversive tastants to assess the generalizability and specificity of the overconsumption effect. Ibotenic-lesioned rats consumed significantly more 20% sucrose than sham controls, and did so through licking significantly more times. However, the behavioral microstructure during overconsumption was unaffected by the lesion and showed no indications of response-perseveration. Furthermore, the overconsumption effect did not generalize to highly consumed saccharin. In contrast, while only consuming small amounts of quinine solution, ibotenic-lesioned rats had significantly more licks and bursts for this tastant. Selective depletion of cholinergic PPTg neurons had no effect on consumption of any tastant. We then assessed whether it is the salience of the solution which determines overconsumption by ibotenic-lesioned rats. While maintained on free-food, ibotenic-lesioned rats had normal consumption of sucrose and hypertonic saline. After mild food deprivation ibotenic PPTg-lesioned rats overconsumed 20% sucrose. Subsequently, after dietary-induced sodium deficiency, lesioned rats consumed significantly more saline than controls. These results establish that it is the salience of the solution which is the determining factor leading to overconsumption following excitotoxic PPTg lesion. They also find no support for response-perseveration contributing to this effect. Results are discussed in terms of altered dopamine (DA) and salience signaling. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines.

PubMed

Camargo, A; Ferreira, S H

1971-06-01

BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF.

Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines

PubMed Central

Camargo, A.; Ferreira, S. H.

1971-01-01

BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF. PMID:5091164

Phosphodiesterase type 1 inhibition improves learning in rats exposed to alcohol during the third trimester equivalent of human gestation

PubMed Central

Filgueiras, Claudio C.; Krahe, Thomas E.; Medina, Alexandre E.

2010-01-01

Deficits in learning and memory have been extensively observed in animal models of fetal alcohol spectrum disorders (FASD). Here we use the Morris Maze to test whether Vinpocetine, a Phosphodiesterase type 1 inhibitor, restores learning performance in rats exposed to alcohol during the third trimester equivalent of human gestation. Long Evans rats received ethanol (5 g/Kg ip) or saline on alternate days from postnatal day (P) 4 to P10. Two weeks later (P25), the latency to find a hidden platform was evaluated (2 trials per day spaced at 40-min inter-trial intervals) during 4 consecutive days. Vinpocetine treatment started on the first day of behavioral testing: animals received vinpocetine (20 mg/kg ip) or vehicle solution every other day until the end of behavioral procedures. Early alcohol exposure significantly affected the performance to find the hidden platform. The average latency of ethanol exposed animals was significantly higher than that observed for the control group. Treatment of alcohol-exposed animals with vinpocetine restored their performance to control levels. Our results show that inhibition of PDE1 improves learning and memory deficits in rats early exposed to alcohol and provide evidence for the potential therapeutic use of vinpocetine in FASD. PMID:20219634

Skeletal muscle microvascular oxygenation dynamics in heart failure: exercise training and nitric oxide-mediated function.

PubMed

Hirai, Daniel M; Copp, Steven W; Holdsworth, Clark T; Ferguson, Scott K; McCullough, Danielle J; Behnke, Bradley J; Musch, Timothy I; Poole, David C

2014-03-01

Chronic heart failure (CHF) impairs nitric oxide (NO)-mediated regulation of skeletal muscle O2 delivery-utilization matching such that microvascular oxygenation falls faster (i.e., speeds PO2mv kinetics) during increases in metabolic demand. Conversely, exercise training improves (slows) muscle PO2mv kinetics following contractions onset in healthy young individuals via NO-dependent mechanisms. We tested the hypothesis that exercise training would improve contracting muscle microvascular oxygenation in CHF rats partly via improved NO-mediated function. CHF rats (left ventricular end-diastolic pressure = 17 ± 2 mmHg) were assigned to sedentary (n = 11) or progressive treadmill exercise training (n = 11; 5 days/wk, 6-8 wk, final workload of 60 min/day at 35 m/min; -14% grade downhill running) groups. PO2mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP; NO donor; 300 μM), and N(G)-nitro-l-arginine methyl ester (L-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained CHF rats had greater peak oxygen uptake and spinotrapezius muscle citrate synthase activity than their sedentary counterparts (p < 0.05 for both). The overall speed of the PO2mv fall during contractions (mean response time; MRT) was slowed markedly in trained compared with sedentary CHF rats (sedentary: 20.8 ± 1.4, trained: 32.3 ± 3.0 s; p < 0.05), and the effect was not abolished by L-NAME (sedentary: 16.8 ± 1.5, trained: 31.0 ± 3.4 s; p > 0.05). Relative to control, SNP increased MRT in both groups such that trained CHF rats had slower kinetics (sedentary: 43.0 ± 6.8, trained: 55.5 ± 7.8 s; p < 0.05). Improved NO-mediated function is not obligatory for training-induced improvements in skeletal muscle microvascular oxygenation (slowed PO2mv kinetics) following contractions onset in rats with CHF.

Skeletal muscle microvascular oxygenation dynamics in heart failure: exercise training and nitric oxide-mediated function

PubMed Central

Copp, Steven W.; Holdsworth, Clark T.; Ferguson, Scott K.; McCullough, Danielle J.; Behnke, Bradley J.; Musch, Timothy I.; Poole, David C.

2014-01-01

Chronic heart failure (CHF) impairs nitric oxide (NO)-mediated regulation of skeletal muscle O2 delivery-utilization matching such that microvascular oxygenation falls faster (i.e., speeds PO2mv kinetics) during increases in metabolic demand. Conversely, exercise training improves (slows) muscle PO2mv kinetics following contractions onset in healthy young individuals via NO-dependent mechanisms. We tested the hypothesis that exercise training would improve contracting muscle microvascular oxygenation in CHF rats partly via improved NO-mediated function. CHF rats (left ventricular end-diastolic pressure = 17 ± 2 mmHg) were assigned to sedentary (n = 11) or progressive treadmill exercise training (n = 11; 5 days/wk, 6–8 wk, final workload of 60 min/day at 35 m/min; −14% grade downhill running) groups. PO2mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP; NO donor; 300 μM), and NG-nitro-l-arginine methyl ester (L-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained CHF rats had greater peak oxygen uptake and spinotrapezius muscle citrate synthase activity than their sedentary counterparts (p < 0.05 for both). The overall speed of the PO2mv fall during contractions (mean response time; MRT) was slowed markedly in trained compared with sedentary CHF rats (sedentary: 20.8 ± 1.4, trained: 32.3 ± 3.0 s; p < 0.05), and the effect was not abolished by L-NAME (sedentary: 16.8 ± 1.5, trained: 31.0 ± 3.4 s; p > 0.05). Relative to control, SNP increased MRT in both groups such that trained CHF rats had slower kinetics (sedentary: 43.0 ± 6.8, trained: 55.5 ± 7.8 s; p < 0.05). Improved NO-mediated function is not obligatory for training-induced improvements in skeletal muscle microvascular oxygenation (slowed PO2mv kinetics) following contractions onset in rats with CHF. PMID:24414070

Propentofylline treatment on open field behavior in rats with focal ethidium bromide-induced demyelination in the ventral surface of the brainstem.

PubMed

Martins-Júnior, J L; Bernardi, M M; Bondan, E F

2016-03-01

Propentofylline (PPF) is a xanthine derivative with pharmacological effects that are distinct from those of classic methylxanthines. It depresses the activation of microglial cells and astrocytes, which is associated with neuronal damage during neural inflammation and hypoxia. Our previous studies showed that PPF improved remyelination following gliotoxic lesions that were induced by ethidium bromide (EB). In the present study, the long-term effects of PPF on open field behavior in rats with EB-induced focal demyelination were examined. The effects of PPF were first evaluated in naive rats that were not subjected to EB lesions. Behavior in the beam walking test was also evaluated during chronic PPF treatment because impairments in motor coordination can interfere with behavior in the open field. The results showed that PPF treatment in unlesioned rats decreased general activity and caused motor impairment in the beam walking test. Gliotoxic EB injections increased general activity in rats that were treated with PPF compared with rats that received saline solution. Motor incoordination was also attenuated in PPF-treated rats. These results indicate that PPF reversed the effects of EB lesions on behavior in the open field and beam walking test. Copyright © 2016 Elsevier Inc. All rights reserved.

In vivo evaluation of anionic thiolated polymers as oral delivery systems for efflux pump inhibition.

PubMed

Palmberger, Thomas F; Laffleur, Flavia; Greindl, Melanie; Bernkop-Schnürch, Andreas

2015-08-01

Recently, the cationic polymer thiolated chitosan has been reported to modulate drug absorption by inhibition of intestinal efflux pumps. The objective of this study was to evaluate in vitro and in vivo whether thiolated anionic biopolymers also show an efflux pump inhibitory effect in order to improve intestinal transcellular drug uptake. Therefore, three thiomers have been synthesized due covalent attachment of cysteine to various polymer backbones: pectin-cysteine (pect-cys), carboxymethylcellulose-cysteine (CMC-cys) and alginate-cysteine (alg-cys). In vitro, the permeation enhancing properties of these thiomers and their corresponding unmodified polymers have been evaluated on rat small intestine in Ussing-type chambers, using sulforhodamine 101 (SR-101) as MRP2 model substrate. In comparison to buffer only, SR-101 transport in presence of pect-cys, CMC-cys and alg-cys was improved 1.5-fold, 1.8-fold and 3.0-fold, respectively. Due to the comparatively best in vitro performance of thiolated alginate, it has been chosen for in vivo studies: a SR-101 solution containing 4% (w/v) alg-cys led to an AUC0 ≥ 12 of SR-101 of 109 ng ml(-1)h in rats representing a 3.8-fold improvement in comparison to a SR-101 buffer solution. Unmodified alginate improved the AUC0 ≥ 12 of SR-101 by a factor of 1.9. These findings suggest thiolated alginate as promising auxiliary agent for drugs being anionic efflux pump substrates, since the oral bioavailability of a MRP2 substrate could be significantly improved. Copyright © 2015 Elsevier B.V. All rights reserved.

The efficacy of an antioxidant cocktail on lipid peroxide level and superoxide dismutase activity in aged rat brain and DNA damage in iron-induced epileptogenic foci.

PubMed

Komatsu, M; Hiramatsu, M

2000-08-07

Mixed natural antioxidants can be combined in a prophylactic food against age related disease involving reactive oxygen species. beta-Catechin is an antioxidant drink, having free radical scavenging activities. It contains green tea extract as a main component as well as ascorbic acid, sunflower seed extract, dunaliella carotene and natural vitamin E. In the present study, we examined the effect of beta-catechin on lipid peroxide formation and superoxide dismutase (SOD) activity in aged rat brain and the effect on 8-hydroxy-2'-deoxyguanosine (8-OHdG) in ipsilateral cortex, 30 min after ferric chloride solution was injected into the left cortex of rats. beta-Catechin solution was orally administered to aged rats and normal rats for 1 month. One-month administration of beta-catechin solution increased SOD activity in the mitochondria fraction of striatum and midbrain and decreased thiobarbiturate reactive substance formation in the cortex and cerebellum of aged rats. It also inhibited 8-OHdG formation in the ipsilateral cortex 30 min after injection of ferric chloride solution. These results suggest that beta-catechin is a suitable prophylactic beverage against age-related neurological diseases associated with reactive oxygen species.

Polysorbate 80-coated PLGA nanoparticles improve the permeability of acetylpuerarin and enhance its brain-protective effects in rats.

PubMed

Sun, Deqing; Xue, Aiying; Zhang, Bin; Lou, Haiyan; Shi, Huanying; Zhang, Xiumei

2015-12-01

Acetylpuerarin (AP) is an acetylated derivative of puerarin (PUE). The study aimed to prepare polysorbate 80-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles to improve the permeability of AP across the blood-brain barrier (BBB) and enhance its brain-protective effects. AP-loaded PLGA nanoparticles (AP-PLGA-NPs) were prepared using a solvent diffusion methodology. The NPs were characterized. The pharmacokinetics, tissue distributions and brain-protective effects of AP-PLGA-NPs were evaluated in animals. AP-PLGA-NPs were successfully prepared with a mean particle size of 145.0 nm and a zeta potential of -14.81 mV. The in-vitro release of AP from the PLGA-NPs showed a biphasic release profile. AP was metabolized into PUE in rats. The AUC0-∞ values of AP and PUE for AP-PLGA-NPs were 2.90- and 2.29-fold as great as those for AP solution, respectively. The values of the relative targeting efficiency in the brain were 2.40 and 2.58 for AP and PUE, and the ratios of peak concentration were 1.91 and 1.89 for AP and PUE, respectively. Compared with the crude drug, AP-PLGA-NPs showed better brain-protective effects in rats. Polysorbate 80-coated PLGA-NPs can improve the permeability of AP cross the BBB and enhance its brain-protective effects in rats. © 2015 Royal Pharmaceutical Society.

Development and validation of an LC-MS/MS method for simultaneous quantification of levodopa and MD01 in rat plasma and its application to a pharmacokinetic study of mucuna pruriens extract.

PubMed

Yang, Guangjie; Zhang, Fangrong; Deng, Linfang; Chen, Chang; Cheng, Zhongzhe; Huang, Jiangeng; Liu, Jiangyun; Jiang, Hongliang

2016-09-01

Mucuna pruriens, an ancient Indian herbal medicine containing levodopa, is widely used for Parkinson's disease. In order to simultaneously determine levodopa and 1,1-dimethyl-3-carboxy-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (MD01) in rat plasma, an improved LC-MS/MS method was developed and validated for a pharmacokinetic study in rats orally administered levodopa or Mucuna pruriens extract (MPE). Elimination of matrix effect and improvement of extraction recovery were achieved through systematic optimization of reversed-phase and hydrophilic interaction chromatographic conditions together with sample clean-up procedures. A satisfactory chromatographic performance was obtained with a Thermo Aquasil C18 column (50 × 2.1 mm, 3 µm) using acetonitrile and water containing 0.2% formic acid as mobile phases. Futhermore, sodium metabisulfite and formic acid were used as stabilizers in neat solutions as well as rat plasma. The method was validated in a dynamic range of 20.0-10,000 ng/mL for levodopa and MD01; the intra- and inter-day precision and accuracy were acceptable. The method was successfully utilized to determine the levodopa level in plasma samples of rats administered levodopa or MPE. Pharmacokinetic results showed that an increase in the AUC of levodopa was observed in rats following oral administration of multiple doses of MPE. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Pepsin egg white hydrolysate ameliorates metabolic syndrome in high-fat/high-dextrose fed rats.

PubMed

Moreno-Fernández, S; Garcés-Rimón, M; González, C; Uranga, J A; López-Miranda, V; Vera, G; Miguel, M

2018-01-24

The aim of this study was to examine the effect of a pepsin egg white hydrolysate (EWH) on metabolic complications using a high-fat/high-dextrose diet-induced Metabolic Syndrome (MetS) experimental model. Male Wistar rats were divided into 4 groups which received: standard diet and water (C), standard diet and a solution with 1 g kg -1 day -1 of EWH (CH), high-fat/high-dextrose diet and water (MS), and high-fat/high-dextrose diet and a solution with 1 g kg -1 day -1 of EWH (MSH). EWH consumption normalized body weight gain; abdominal obesity and peripheral neuropathy developed in MetS animals, and adipose tissue and liver weight, as well as plasma glucose were reduced. Oxidative stress and inflammation biomarkers were normalized in MSH animals. In conclusion, the oral administration of EWH could be used as a functional food ingredient to improve some complications associated with MetS induced by unhealthy diets.

Peritoneal and Systemic Responses of Obese Type II Diabetic Rats to Chronic Exposure to a Hyperbranched Polyglycerol-based Dialysis Solution.

PubMed

Han, Bo La; Guan, Qiunong; Chafeeva, Irina; Mendelson, Asher A; Roza, Gerald da; Liggins, Richard; Kizhakkedathu, Jayachandran N; Du, Caigan

2018-05-12

Metabolic syndrome (MetS) is commonly observed among peritoneal dialysis (PD) patients, and hyperbranched polyglycerol (HPG) is a promising glucose-sparing osmotic agent for PD. However, the biocompatibility of a HPG-based PD solution (HPG) in subjects with MetS has not been investigated. This study compared the local and systemic effects of a HPG solution with conventional Physioneal (PYS) and Icodextrin (ICO) PD solutions in rats with MetS. Obese type 2 diabetic ZSF1 rats received a daily intraperitoneal injection of PD solutions (10 mL) for 3 months. The peritoneal membrane (PM) function was determined by ultrafiltration, and the systemic responses were determined by profiling blood metabolic substances, cytokines and oxidative status. Tissue damage was assessed by histology. At the end of the 3-month treatment with PD solutions, PM damage and ultrafiltration loss in both the PYS and ICO groups were greater than those in the HPG group. Blood analyses showed that compared to the baseline control, the rats in the HPG group exhibited a significant decrease only in serum albumin and IL-6 and a minor glomerular injury, whereas in both the PYS and ICO groups, there were more significant decreases in serum albumin, antioxidant activity, IL-6, KC/GRO (CXCL1) and TNF-α (in ICO only) as well as a mores substantial glomerular injury compared to the HPG group. Furthermore, PYS increased serum creatinine, serum glucose and urine production. In conclusion, compared to PYS or ICO solutions, the HPG solution had less adverse effects locally on the PM and systemically on distant organs (e.g., kidneys) and the plasma oxidative status in rats with MetS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Effects of warm needling moxibustion on knee cartilage and morphology in rats with knee osteoarthritis].

PubMed

Zhang, Yongliang; Mi, Yiqun; Gang, Jiahong; Wang, Huamin

2016-02-01

To observe the effects of warm needling moxibustion on body mass, knee cartilage andmorphology in rats with knee osteoarthritis (KOA). Forty SD rats were randomly divided into a normalgroup, a model group, a medication group and a warm needling group, 10 rats in each one. Except the normalgroup, the rats in the remaining three groups were injected with papain to establish the model of KOA. After themodeling, rats in the model group did not receive any treatment; rats in the warm needling group were treated withwarm needling moxibustion at bilateral "Xiqian"; rats in the medication group were treated with intragastric administration of meloxicam; rats in the normal group were treated with 0. 9% NaCl solution (identical dose as medication group) and immobilized as the warm needling group. The treatment was given once a day for consecutive20 days. The body mass, scale of knee cartilage and morphological changes were observed in each group after'treatment. The increasing of body mass in the medication group and warm needling group was faster than!that in the model group, but slower than that in the normal group (all P<0. 05); the difference between medication group and warm needling group was not statistically significant (P>0. 05). The scale of knee cartilage in thewarm needling group and medication group was significantly lower than that in the model group (both P<0. 05),while the scale in the warm needling group was lower than that in the medication group (P<. 05). Regarding theknee morphology under micro-CT, the relief of knee degeneration and improvement of knee recovery in the warm needlinggroup were superior to those in the medication group. The warm needling moxibustion could effectively reduce the knee pain, improve the recovery of knee cartilage, which is a safe and effective treatment.

Pretreatment with intravenous lipid emulsion reduces mortality from cocaine toxicity in a rat model.

PubMed

Carreiro, Stephanie; Blum, Jared; Hack, Jason B

2014-07-01

We compare the effects of intravenous lipid emulsion and normal saline solution pretreatment on mortality and hemodynamic changes in a rat model of cocaine toxicity. We hypothesize that intravenous lipid emulsion will decrease mortality and hemodynamic changes caused by cocaine administration compared with saline solution. Twenty male Sprague-Dawley rats were sedated and randomized to receive intravenous lipid emulsion or normal saline solution, followed by a 10 mg/kg bolus of intravenous cocaine. Continuous monitoring included intra-arterial blood pressure, pulse rate and ECG tracing. Endpoints included a sustained undetectable mean arterial pressure (MAP) or return to baseline MAP for 5 minutes. The log-rank test was used to compare mortality. A mixed-effect repeated-measures ANOVA was used to estimate the effects of group (intravenous lipid emulsion versus saline solution), time, and survival on change in MAP, pulse rate, or pulse pressure. In the normal saline solution group, 7 of 10 animals died compared with 2 of 10 in the intravenous lipid emulsion group. The survival rate of 80% (95% confidence interval 55% to 100%) for the intravenous lipid emulsion rats and 30% (95% confidence interval 0.2% to 58%) for the normal saline solution group was statistically significant (P=.045). Intravenous lipid emulsion pretreatment decreased cocaine-induced cardiovascular collapse and blunted hypotensive effects compared with normal saline solution in this rat model of acute lethal cocaine intoxication. Intravenous lipid emulsion should be investigated further as a potential adjunct in the treatment of severe cocaine toxicity. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Hypophosphatemia occurs with insulin administration during refeeding by total parenteral nutrition in rats.

PubMed

Kawamura, Hiromi; Tanaka, Sarasa; Uenami, Yuri; Tani, Mariko; Ishitani, Midori; Morii, Saeko; Sakaue, Motoyoshi; Ito, Mikiko

2018-01-01

Refeeding syndrome (RFS) is characterized by the metabolic and clinical changes that occur following aggressive nutritional supplementation in malnourished patients. Hypophosphatemia is the hallmark of RFS and is key to its prevention and treatment in clinical practice. However, the mechanism of hypophosphatemia during RFS is unclear because of the lack of an animal model. In this study, we developed a rat RFS model as a first step to clarifying the molecular mechanism. After establishing the parenteral route, rats were fasted for 5 days and refeeding was started using total parenteral nutrition. The animals were infused with a high calorie solution with or without insulin administration. Results showed that plasma phosphate levels did not decrease in rats infused with the high calorie solution alone;in contrast, a 20% reduction compared to baseline was observed in rats administered insulin. In addition, rats infused with the high calorie solution containing added phosphate did not present with hypophosphatemia. Thus, we developed a rat RFS model with hypophosphatemia by tube feeding and insulin administration, and demonstrated the importance of phosphate in preventing refeeding hypophosphatemia. J. Med. Invest. 65:50-55, February, 2018.

Tunable Biodegradable Nanocomposite Hydrogel for Improved Cisplatin Efficacy on HCT-116 Colorectal Cancer Cells and Decreased Toxicity in Rats.

PubMed

Abdel-Bar, Hend Mohamed; Osman, Rihab; Abdel-Reheem, Amal Youssef; Mortada, Nahed; Awad, Gehanne A S

2016-02-08

This work describes the development of a modified nanocomposite thermosensitive hydrogel for controlled cisplatin release and improved cytotoxicity with decreased side effects. The system was characterized in terms of physical properties, morphological architecture and in vitro cisplatin release. Cytotoxicity was tested against human colorectal carcinoma HCT-116. In vivo studies were conducted to evaluate the acute toxicity in terms of rats' survival rate and body weight loss. Nephro and hepatotoxicities were evaluated followed by histopathological alterations of various tissue organs. Nanocomposite thermosensitive hydrogel containing nanosized carrier conferred density and stiffness allowing a zero order drug release for 14 days. Enhanced cytotoxicity with 2-fold decrease in cisplatin IC50 was accomplished. A linear in vivo-in vitro correlation was proved for the system degradation. Higher animal survival rate and lower tissue toxicities proved the decreased toxicity of cisplatin nanocomposite compared to its solution.

A comparison of the biocompatibility of phosphate-buffered saline and dianeal 3.86% in the rat model of peritoneal dialysis.

PubMed

Wieczorowska-Tobis, K; Polubinska, A; Breborowicz, A; Oreopoulos, D G

2001-01-01

Phosphate-buffered saline (PBS), an isotonic solution with a physiologic pH can be considered an example of a biocompatible dialysis fluid. This study compared the biocompatibility of PBS with that of Dianeal 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.), using a model of peritoneal dialysis in the rat. In an acute experiment, after catheter implantation, rats were infused on day 1 with PBS, on day 5 with standard dialysis solution (Dianeal 3.86%), and on day 7 again with PBS. When rats were injected with Dianeal 3.86%, the inflammatory reaction was suppressed as compared with PBS. The cell count was lower with Dianeal (-85%, p < 0.001), the neutrophil:macrophage ratio in dialysate was 80% lower (p < 0.01), total protein concentration in the Dianeal dialysate was 73% lower (p < 0.01), and the dialysate nitrite level was 45% lower (p < 0.01). In a chronic experiment, after catheter implantation, rats were dialyzed for four weeks with PBS or with Dianeal 3.86%. At the end of the study, a 1-hour peritoneal equilibration test (PET) was performed. As evaluated on a semiquantitative scale, macroscopic changes in the peritoneum were more severe in rats exposed to PBS than in those exposed to Dianeal 3.86% (8.6 +/- 3.2 vs 5.2 +/- 2.6, p < 0.05). The thickness of the visceral peritoneum was comparable in both groups; but, in PBS-treated rats, the peritoneal interstitium contained more inflammatory cells and more new vessels. During the 1-hour PET, peritoneal permeability to water and solutes was comparable in the two groups. Despite a more physiologic composition, PBS is a less biocompatible peritoneal dialysis solutions than is standard, acidic, hypertonic dialysis solution.

High-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulation.

PubMed

Mock, Kaitlin; Lateef, Sundus; Benedito, Vagner A; Tou, Janet C

2017-01-01

High-fructose corn syrup-55 (HFCS-55) has been suggested to be more lipogenic than sucrose, which increases the risk for nonalcoholic fatty liver disease (NAFLD) and dyslipidemia. The study objectives were to determine the effects of drinking different sugar-sweetened solutions on hepatic gene expression in relation to liver fatty acid composition and risk of NAFLD. Female rats were randomly assigned (n=7 rats/group) to drink water or water sweetened with 13% (w/v) HFCS-55, sucrose or fructose for 8 weeks. Rats drinking HFCS-55 solution had the highest (P=.03) hepatic total lipid and triglyceride content and histological evidence of fat infiltration. Rats drinking HFCS-55 solution had the highest hepatic de novo lipogenesis indicated by the up-regulation of stearoyl-CoA desaturase-1 and the highest (P<.001) oleic acid (18:1n-9) content. This was accompanied by reduced β-oxidation indicated by down-regulation of hepatic peroxisome proliferator-activated receptor α. Disposal of excess lipids by export of triglyceride-rich lipoprotein from the liver was increased as shown by up-regulation of gene expression of microsomal triglyceride transfer protein in rats drinking sucrose, but not HFCS-55 solution. The observed lipogenic effects were attributed to the slightly higher fructose content of HFCS-55 solution in the absence of differences in macronutrient and total caloric intake between rats drinking HFCS-55 and sucrose solution. Results from gene expression and fatty acid composition analysis showed that, in a hypercaloric state, some types of sugars are more detrimental to the liver. Based on these preclinical study results, excess consumption of caloric sweetened beverage, particularly HFCS-sweetened beverages, should be limited. Published by Elsevier Inc.

Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers.

PubMed

Rizwanullah, Md; Amin, Saima; Ahmad, Javed

2017-01-01

In the present study, rosuvastatin calcium-loaded nanostructured lipid carriers were developed and optimized for improved efficacy. The ROS-Ca-loaded NLC was prepared using melt emulsification ultrasonication technique and optimized by Box-Behnken statistical design. The optimized NLC composed of glyceryl monostearate (solid lipid) and capmul MCM EP (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and tween 80 (1%) as surfactant. The mean particle size, polydispersity index (PDI), zeta potential (ζ) and entrapment efficiency (%) of optimized NLC formulation was observed to be 150.3 ± 4.67 nm, 0.175 ± 0.022, -32.9 ± 1.36 mV and 84.95 ± 5.63%, respectively. NLC formulation showed better in vitro release in simulated intestinal fluid (pH 6.8) than API suspension. Confocal laser scanning showed deeper permeation of formulation across rat intestine compared to rhodamine B dye solution. Pharmacokinetic study on female albino Wistar rats showed 5.4-fold increase in relative bioavailability with NLC compared to API suspension. Optimized NLC formulation also showed significant (p < 0.01) lipid lowering effect in hyperlipidemic rats. Therefore, NLC represents a great potential for improved efficacy of ROS-Ca after oral administration.

Development of ionic-complex-based nanostructured lipid carriers to improve the pharmacokinetic profiles of breviscapine

PubMed Central

Li, Mei; Zheng, Yong; Shan, Feng-ying; Zhou, Jing; Gong, Tao; Zhang, Zhi-rong

2013-01-01

Aim: Breviscapine isolated from the Chinese herb Erigeron breviscapus (Vant) Hand-Mazz is widely used to treat cardiovascular and cerebrovascular diseases. The aim of this study was to improve the pharmacokinetic profiles of breviscapine using nanostructured lipid carrier based on an ionic complex formation. Methods: Breviscapine nanostructured lipid carrier (Bre-NLC) was prepared using the thin film homogenization method. The morphology of Bre-NLCs was determined using transmission electron microscopy. The mean particle size, polydispersity index, zeta-potential analysis and entrapment efficiency were analized. In vitro release was studied using the dialysis method. In vitro stability was studied in fresh plasma and liver slurry of rats. In vivo pharmacokinetics was analyzed in rats after intravenous injection of a dose equivalent to breviscapine (10 mg/kg). Results: The Bre-NLCs were spherical with a mean particle size of ∼170 nm, a zeta potential of ∼20 mV and a high entrapment efficiency of ∼89%. Compared with a commercially available solution, a substantial decrease in the cumulative release of breviscapine was found for the Bre-NLCs. The NLC has a significantly protective effect against the liver enzyme degradation of breviscapine. After intravenous administration in rats, the Bre-NLCs exhibited a 32 times increase in the AUC0–t and a 12 times increase in T1/2 as compared to the commercially available breviscapine solution. Conclusion: The results demonstrate that the NLC has great potential to use as a novel sustained release system for breviscapine. PMID:23770990

Differential effects of pair housing on voluntary nicotine consumption: a comparison between male and female adolescent rats.

PubMed

Lee, Hyunchan; Jang, Minji; Kim, Woonhee; Noh, Jihyun

2017-08-01

Tobacco smoking occurs in a wide array of social circumstances. Social support for quitting is generally used to stop smoking, while peer interactions may be a crucial factor in triggering tobacco use among adolescents. To determine the role of social factors on nicotine dependence, we compared single- and pair-housed rats subjected to voluntary oral nicotine consumption tests. Six-week-old adolescent rats were subjected to experimental procedures and assigned to one of the following groups: a male single group, a male pair group with a sibling, a female single group, and a female pair group with a sibling. To measure voluntary nicotine intake, we adopted a two-bottle free-choice paradigm for each two days using 25 μg/ml and 100 μg/ml nicotine solution. There were no differences in change in body weight or food intake between the two groups of either sex. Pair-housed female rats showed a reduction in nicotine consumption and preference for both low- and high-dose nicotine solution, while pair-housed male rats showed only reduced consumption and preference for high-dose nicotine solution, but not low-dose solution, as compared to single-housed male rats. Nicotine consumption is sex-dependently controlled by the social circumstances of rats. This study broadens our perspectives on the role of social interactions as a therapeutic strategy to treat nicotine addiction-related behaviors depending on sex.

High-fructose corn syrup-induced hepatic dysfunction in rats: improving effect of resveratrol.

PubMed

Sadi, Gokhan; Ergin, Volkan; Yilmaz, Guldal; Pektas, M Bilgehan; Yildirim, O Gokhan; Menevse, Adnan; Akar, Fatma

2015-09-01

The increased consumption of high-fructose corn syrup (HFCS) may contribute to the worldwide epidemic of fatty liver. In this study, we have investigated whether HFCS intake (20% beverages) influences lipid synthesis and accumulation in conjunction with insulin receptor substrate-1/2 (IRS-1; IRS-2), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1) and inducible NOS (iNOS) expressions in liver of rats. Resveratrol was tested for its potential efficacy on changes induced by HFCS. Animals were randomly divided into four groups as control, resveratrol, HFCS and resveratrol plus HFCS (resveratrol + HFCS). HFCS was given as 20% solutions in drinking water. Feeding of all rats was maintained by a standard diet that enriched with or without resveratrol for 12 weeks. Dietary HFCS increased triglyceride content and caused mild microvesicular steatosis in association with up-regulation of fatty acid synthase and sterol regulatory element binding protein (SREBP)-1c in liver of rats. Moreover, HFCS feeding impaired hepatic expression levels of IRS-1, eNOS and SIRT1 mRNA/proteins, but did not change iNOS level. Resveratrol promoted IRS, eNOS and SIRT1, whereas suppressed SREBP-1c expression in rats fed with HFCS. Resveratrol supplementation considerably restored hepatic changes induced by HFCS. The improvement of hepatic insulin signaling and activation of SIRT1 by resveratrol may be associated with decreased triglyceride content and expression levels of the lipogenic genes of the liver.

Safety of oral sulfates in rats and dogs contrasted with phosphate-induced nephropathy in rats.

PubMed

Pelham, Russell W; Russell, Robert G; Padgett, Eric L; Reno, Frederick E; Cleveland, Mark vB

2009-01-01

An oral sulfate salt solution (OSS), under development as a bowel cleansing agent for colonoscopy in humans, is studied in rats and dogs. In rats, amaximumpractical oral OSS dose (5 g/kg/d) is compared with an oral sodium phosphate (OSP) solution, both at about 7 times the clinical dose. OSS induces the intended effects of loose stools and diarrhea. In rats, higher urine sodium and potassium accompany higher clearance rates, considered adaptive to the osmotic load of OSS. OSS for 28 days is well tolerated in rats and dogs. In contrast, OSP causes increased mortality, reduced body weight and food consumption, severe kidney tubular degeneration, and calcium phosphate deposition in rats. These are accompanied by mineralization in the stomach and aorta, along with cardiac and hepatic degeneration and necrosis. The greater safety margin of OSS over OSP at similarmultiples of the clinical dose indicates its suitability for human use.

Anti-apoptotic effect of insulin in the control of cell death and neurologic deficit after acute spinal cord injury in rats.

PubMed

Wu, Xing-Huo; Yang, Shu-Hua; Duan, De-Yu; Cheng, Heng-Hui; Bao, Yu-Ting; Zhang, Yukun

2007-09-01

Recent studies confirmed that the new cell survival signal pathway of Insulin-PI3K-Akt exerted cyto-protective actions involving anti-apoptosis. This study was undertaken to investigate the potential neuroprotective effects of insulin in the pathogenesis of spinal cord injury (SCI) and evaluate its therapeutic effects in adult rats. SCI was produced by extradural compression using modified Allen's stall with damage energy of 40 g-cm force. One group of rats was subjected to SCI in combination with the administration of recombinant human insulin dissolved in 50% glucose solution at the dose of 1 IU/kg day, for 7 days. At the same time, another group of rats was subjected to SCI in combination with the administration of an equal volume of sterile saline solution. Functional recovery was evaluated using open-field walking, inclined plane tests, and motor evoked potentials (MEPs) during the first 14 days post-trauma. Levels of protein for B-cell lymphoma/leukemia-2 gene (Bcl-2), Caspase-3, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were quantified in the injured spinal cord by Western blot analysis. Neuronal apoptosis was detected by TUNEL, and spinal cord blood flow (SCBF) was measured by laser-Doppler flowmetry (LDF). Ultimately, the data established the effectiveness of insulin treatment in improving neurologic recovery, increasing the expression of anti-apoptotic bcl-2 proteins, inhibiting caspase-3 expression decreasing neuronal apoptosis, reducing the expression of proinflammatory cytokines iNOS and COX-2, and ameliorating microcirculation of injured spinal cord after moderate contusive SCI in rats. In sum, this study reported the beneficial effects of insulin in the treatment of SCI, with the suggestion that insulin should be considered as a potential therapeutic agent.

Preoperative oral carbohydrate improved postoperative insulin resistance in rats through the PI3K/AKT/mTOR pathway.

PubMed

Wang, Zhiguo; Liu, Yiqing; Li, Qi; Ruan, Canping; Wu, Bin; Wang, Qiang; Hu, Zhiqian; Qin, Huanlong

2015-01-01

Preoperative oral carbohydrate (OCH) improves postoperative insulin resistance (PIR) and insulin sensitivity. However, the exact mechanisms involved in the improvement of PIR with respect to preoperative OCH are still not clear. The aim of this study was to investigate the involvement of preoperative OCH and PI3K/AKT/mTOR pathway in reducing PIR in rats. Forty male Sprague-Dawley rats were randomly assigned to PreOp, glucose, saline, and fasting groups. Rats in the PreOp, glucose, and saline groups received OCH, 5% glucose solution, and saline, respectively. Rats in the fasting group did not receive anything but were fasted 3 h before surgery. Blood glucose, insulin and leucine levels, and insulin resistance, secretion, and sensitivity indexes were measured before and after surgery. mRNA and protein (total and phosphorylated) levels of mTOR, IRS-1, PI3K, PKB/AKT, and GlUT4 were measured using real-time polymerase chain reaction and Western blot in skeletal muscles. In the PIR experiment, blood glucose, serum insulin, insulin resistance, and serum leucine levels were all significantly lower in the PreOp group than in the other 3 groups (P<0.05) after surgery. HOMA-ISI were higher in the PreOp group vs the other 3 groups after surgery (P<0.05), and HOMA-b in the PreOp group was higher than that in the other 3 groups at 30 and 120 min after surgery. Additionally, post-operative phosphorylated IRS-1, PI3K, and AKT protein levels were significantly higher in the PreOp group than in the other 3 groups (P<0.05), but no significant differences were observed in their respective protein levels (P>0.05). OCH decreases postoperative insulin resistance and improves postoperative insulin sensitivity in skeletal muscles through the PI3K/AKT/mTOR pathway.

Evaluation of taurine as an osmotic agent for peritoneal dialysis solution.

PubMed

Nishimura, Hideki; Ikehara, Osamu; Naito, Takashi; Higuchi, Chieko; Sanaka, Tsutomu

2009-01-01

The development of a glucose-free peritoneal dialysis (PD) solution is important because glucose has been associated with functional and morphological damage to the peritoneal membrane. The ultrafiltration (UF) and biocompatibility of new PD solutions containing taurine (PD-taurine) instead of glucose as an osmolite were tested in a rat PD model. To determine the solution's UF ability, different concentrations of taurine in PD solutions were compared to glucose-based PD solutions (PD-glucose) by giving single intraperitoneal injections for 2, 4, and 6 hours. To examine the biocompatibility of PD-taurine, the rats were divided into 3 groups: a 3.86% PD-glucose group, a 3.5% PD-taurine group and a not dialyzed group. The rats were given 10-mL injections of PD fluids intraperitoneally 3 times daily for 7 days. A peritoneal equilibration test (PET) was performed using a 1.9% xylitol solution at the time the rats were sacrificed. Mesothelial cell monolayers were obtained from the animals and studied based on a population analysis. The net UF of PD-taurine increased in a dose-dependent manner; the 3.5% PD-taurine solution was equivalent to the 3.86% PD-glucose solution after 4 hours. The PET showed that the drainage volume and the D(4)/D(0) ratio for xylitol after 4 hours with PD-taurine solution were significantly greater than with the PD-glucose solution (p < 0.001 and p < 0.001 respectively). Mesothelial and fibroblast-like cell proliferation was significantly less with PD-taurine than with PD-glucose (p < 0.01). These results indicate that PD-taurine resulted in net UF equivalent to that of PD-glucose and was more biocompatible than PD-glucose with respect to the peritoneal membrane.

Effect of topical applications of neutral sodium fluoride on dental careis in the rat.

PubMed

Poulsen, S; Larson, R H

1975-01-01

A study on various regimens by which the same total amount of neutral sodium fluoride is applied to the teeth of rats showed that greater effects were observed after frequent application of 0.2% solutions than after less frequent application of more concentrated solutions.

The consummatory and motivational behaviors for natural rewards following long-term withdrawal from morphine: no anhedonia but persistent maladaptive behaviors for high-value rewards.

PubMed

Li, Yingying; Zheng, Xigeng; Xu, Na; Zhang, Yue; Liu, Zhengkui; Bai, Yunjing

2017-04-01

The negative affective state, e.g., anhedonia, emerges after abstinence from abused drugs may be linked to the motivational processes of drug craving and relapse. Although anhedonia diminishes over time with drug abstinence, it is not yet rather explicit whether anhedonia exists or not following protracted withdrawal. The behavioral responses to natural rewards were examined after 2 to 3 weeks withdrawal from morphine. Male rats were pretreated with either a binge-like morphine paradigm or daily saline injection for 5 days. The consummatory and motivational behaviors for three natural rewards (sucrose solutions 4, 15, and 60%, social stimulus: male rat, and sexual stimulus: estrous female rat) were examined under varied testing conditions. The morphine-withdrawn rats significantly increased their intake of 15% sucrose solution during the 1-h consumption test and their operant responding for 15% sucrose solution under a progressive ratio (PR) schedule of reinforcement. When obtaining a reinforcer was associated with a 0.5 mA foot shock under a PR-punishment schedule, the morphine-withdrawn rats showed a higher performance for 60% sucrose solution. Meanwhile, the morphine-withdrawn rats displayed a higher motivation to sexual stimulus during the free-approach test and more approaching behaviors towards sexual stimulus in a conflict-based approach test (concurrent presence of reward and aversive stimulus). No anhedonia-like behavior but sensitized behaviors for natural rewards were found after long-term morphine withdrawal. Notably, the morphine-withdrawn rats displayed persistent motivated behaviors for high-value rewards (60% sucrose and sexual stimulus) in the conflict tests suggesting impairments in inhibitory control in morphine-treated rats.

Ameliorative effect of black grape juice on systemic alterations and mandibular osteoradionecrosis induced by whole brain irradiation in rats.

PubMed

Freitas, Robson B; González, Paquita; Martins, Nara Maria B; Andrade, Edson R; Cesteros Morante, María Jesús; Conles Picos, Iban; Costilla García, Serafín; Bauermann, Liliane F; Barrio, Juan Pablo

2017-02-01

Whole brain irradiation (WBI) causes a variety of secondary side-effects including anorexia and bone necrosis. We evaluated the radiomodifying effect of black grape juice (BGJ) on WBI alterations in rats measuring food and water intake, body weight, hemogram, and morphological and histological mandibular parameters. Forty male rats (200-250 g) were exposed to eight sessions of cranial X-ray irradiation. The total dose absorbed was 32 Gy delivered over 2 weeks. Four groups were defined: (i) NG: non-irradiated, glucose and fructose solution-supplemented (GFS); (ii) NJ: non-irradiated, BGJ-supplemented; (iii) RG: irradiated, GFS-supplemented; and (iv) RJ: irradiated, BGJ-supplemented. Rats received daily BGJ or GFS dosing by gavage starting 4 days before, continuing during, and ending 4 days after WBI. RJ rats ingested more food and water and showed less body weight loss than RG rats during the irradiation period. Forty days after WBI, irradiated animals started losing weight again compared with controls as a consequence of masticatory hypofunction by mandibular osteoradionecrosis (ORN). Osteoclastic activity and inflammation were apparent in RG rat mandibles. BGJ was able to attenuate the severity of ORN as well as to improve white and red blood cell counts. Fractionated whole brain irradiation induces mandibular changes that interfere with normal feeding. BGJ can be used to mitigate systemic side-effects of brain irradiation and ORN.

Protective effect of pumpkin seed extract on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide.

PubMed

Aghaei, S; Nikzad, H; Taghizadeh, M; Tameh, A A; Taherian, A; Moravveji, A

2014-10-01

Cancer treatment with cyclophosphamide (CP) may result in reproductive toxicity as one of its side effects. The pumpkin seed is a rich natural source of antioxidant. We have assessed the possible protective efficacy of pumpkin seed extract on sperm characteristics, biochemical parameters and epididymal histology of CP-treated rats. Male adult Wistar rats were categorised into four groups. Group 1 served as control and received intraperitoneal (IP) injection of isotonic saline solution. Group 2 rats were treated with CP by IP injection in a single dose of 100 mg/kg body weight, only once. Group 3 and 4 received CP plus 300 and 600 mg/kg pumpkin seed extract respectively. Six weeks after treatment, sperm characteristics, biochemical parameters and histopathological changes were examined. Results showed that, sperm characteristics in CP-treated rats were significantly decreased. Biochemical analysis results showed that the co-administration of 300 mg pumpkin seed extract could increase the total antioxidant capacity (TAC) level significantly. In CP-treated rats, histopathological changes such as vacuolisation, disorganisation and separation of epididymal epithelium were observed as well. Interestingly, pumpkin seed extract could improve the above-mentioned parameters remarkably in CP-treated rats. Our findings indicated that pumpkin seed extract might be used as protective agent against CP-induced reproductive toxicity. © 2013 Blackwell Verlag GmbH.

The Influence of Chitosan Cross-linking on the Properties of Alginate Microparticles with Metformin Hydrochloride-In Vitro and In Vivo Evaluation.

PubMed

Szekalska, Marta; Sosnowska, Katarzyna; Zakrzeska, Agnieszka; Kasacka, Irena; Lewandowska, Alicja; Winnicka, Katarzyna

2017-01-22

Sodium alginate is a polymer with unique ability to gel with different cross-linking agents in result of ionic and electrostatic interactions. Chitosan cross-linked alginate provides improvement of swelling and mucoadhesive properties and might be used to design sustained release dosage forms. Therefore, the aim of this research was to develop and evaluate possibility of preparing chitosan cross-linked alginate microparticles containing metformin hydrochloride by the spray-drying method. In addition, influence of cross-linking agent on the properties of microparticles was evaluated. Formulation of microparticles prepared by the spray drying of 2% alginate solution cross-linked by 0.1% chitosan was characterized by good mucoadhesive properties, high drug loading and prolonged metformin hydrochloride release. It was shown that designed microparticles reduced rat glucose blood level, delayed absorption of metformin hydrochloride and provided stable plasma drug concentration. Additionally, histopathological studies of pancreas, liver and kidneys indicated that all prepared microparticles improved degenerative changes in organs of diabetic rats. Moreover, no toxicity effect and no changes in rats behavior after oral administration of chitosan cross-linked alginate microparticles were noted.

Improved oral bioavalability of mebudipine upon administration in PhytoSolve and Phosal-based formulation (PBF).

PubMed

Khani, Samira; Keyhanfar, Fariborz

2014-02-01

The aim of this investigation was to examine the efficacy of PhytoSolve and Phosal-based formulation (PBF) to enhance the oral bioavailability of mebudipine, which is a poorly water-soluble calcium channel blocker. The solubility of mebudipine in various oils was determined. PhytoSolve was prepared with a medium-chain triglyceride (MCT) oil (20%), soybean phospholipids (5%), and a 70% fructose solution (75%). The influence of the weight ratio of Phosal 50PG to glycerol in PBF on the mean globule size was studied with dynamic light scattering. The optimized formulation was evaluated for robustness toward dilution, transparency, droplet size, and zeta potential. The in vivo oral absorption of different mebudipine formulations (PhytoSolve, PBF, oily solution, and suspension) were evaluated in rats. The optimized PBF contained Phosal 50PG/glycerol in a 6:4 ratio (w/w). The PBF and PhytoSolve formulations were miscible with water in any ratio and did not demonstrate any phase separation or drug precipitation over 1 month of storage. The mean particle size of PhytoSolve and PBF were 138.5 ± 9.0 and 74.4 ± 2.5 nm, respectively. The in vivo study demonstrated that the oral bioavailability of PhytoSolve and PBF in rats was significantly higher than that of the other formulations. The PhytoSolve and PBF formulations of mebudipine are found to be more bioavailable compared with suspension and oily solutions during an in vivo study in rats. These formulations might be new alternative carriers that increase the oral bioavailability of poorly water-soluble molecules, such as mebudipine.

Cocaine self-administration punished by i.v. histamine in rat models of high and low drug abuse vulnerability: Effects of saccharin preference, impulsivity, and sex

PubMed Central

Holtz, Nathan A.; Anker, Justin J.; Regier, Paul S.; Claxton, Alex; Carroll, Marilyn E.

2015-01-01

A key feature of substance use disorders is continued drug consumption despite aversive consequences. This has been modeled in the animal laboratory by pairing drug self-administration with electric shock, thereby punishing drug intake (Deroche-Gamonet et al. 2004). In the present experiments, we examined the effects of punishment on i.v. cocaine self-administration by adding histamine to the cocaine solution in three different animal models of high and low vulnerability to drug abuse: rats selectively bred for high (HiS) and low (LoS) saccharin consumption, rats selected for high (HiI) and low (LoI) impulsivity, and sex differences. Animals were allowed to self-administer cocaine (0.4 mg/kg/infusion) to establish a baseline of operant responding. Histamine (4.0 mg/kg/infusion) was then added directly into the cocaine solution and its consequent effects on self-administration were compared to baseline. The histamine + cocaine solution was then replaced with a cocaine-only solution, and the rats' operant responding was again measured and compared to baseline. Concurrent histamine exposure was effective in reducing cocaine consumption in all groups of rats; however, LoS and female rats took longer to return to baseline levels of cocaine consumption after histamine was removed compared to HiS and male rats. These data suggest the reduction of drug self-administration by aversive consequences may differ in groups that vary in drug use vulnerability, and these results may inform pharmacological strategies that enhance the negative aspects of drug consumption. PMID:23948673

Tezosentan, a Novel Endothelin Receptor Antagonist, Markedly Reduces Rat Hepatic Ischemia and Reperfusion Injury in Three Different Models

PubMed Central

Farmer, Douglas G.; Kaldas, Fady; Anselmo, Dean; Katori, Masamichi; Shen, Xiu-Da; Lassman, Charles; Kaldas, Marian; Clozel, Martine; Busuttil, Ronald W.; Kupiec-Weglinski, Jerzy

2010-01-01

This study investigated the effects of dual endothelin (ET) receptor blockade in rat models of liver ischemia and reperfusion injury (IRI). Three models of IRI were used: (1) in vivo total hepatic warm ischemia with portal shunting for 60 minutes with control (saline) and treatment groups (15 mg/kg tezosentan intravenously prior to reperfusion), (2) ex vivo hepatic perfusion after 24 hours of cold storage in University of Wisconsin solution with control and treatment groups (10 mg/kg tezosentan in the perfusate), and (3) syngeneic liver transplantation (LT) after 24 hours of cold storage in University of Wisconsin solution with control and treatment groups (10 mg/kg tezosentan intravenously prior to reperfusion). Tezosentan treatment significantly improved serum transaminase and histology after IRI in all 3 models. This correlated with reduced vascular resistance, improved bile production, and an improved oxygen extraction ratio. Treatment led to a reduction in neutrophil infiltration and interleukin-1 beta and macrophage inflammatory protein 2 production. A reduction in endothelial cell injury as measured by purine nucleoside phosphorylase was seen. Survival after LT was significantly increased with tezosentan treatment (90% versus 50%). In conclusion, this is the first investigation to examine dual receptor ET blockade in 3 models of hepatic IRI and the first to use the parenterally administered agent tezosentan. The results demonstrate that in both warm and cold IRI tezosentan administration improves sinusoidal hemodynamics and is associated with improved tissue oxygenation and reduced endothelial cell damage. In addition, reduced tissue inflammation, injury, and leukocyte chemotactic signaling were seen. These results provide compelling data for the further investigation of the use of tezosentan in hepatic IRI. PMID:19025917

Autologous bone marrow stem cell transplantation attenuates hepatocyte apoptosis in a rat model of ex vivo liver resection and liver autotransplantation.

PubMed

Xu, Tubing; Wang, Xiaojun; Chen, Geng; He, Yu; Bie, Ping

2013-10-01

To investigate the efficacy of autologous bone marrow stem cell (BMSC) transplantation in the treatment of hepatic injury in ex vivo liver resection and liver autotransplantation (ELRLA). Rat hepatic fibrosis was induced by intraperitoneal injection of 50% CCl4-olive oil solution at a dose of 2 mL/kg twice weekly for 4 wk. ELRLA was performed 3 d post the last injection of CCl4. Six rats in each group were killed 12, 24, 48, 72, and 168 h after the operation. Hepatocyte apoptosis was determined by TUNEL assay. The expression of Bcl-2, Bax, transforming growth factor (TGF) β1, TGFβ1 receptor1/2, and phosphorylated p38 MAPK were determined by Western blot. Autologous BMSC transplantation significantly inhibited the increase of alanine aminotransferease and aspartate aminotransferase at 12, 24, and 48 h post operation and attenuated ELRLA-induced hepatocyte apoptosis. In BMSC-treated rats, the expression of Bcl-2 was significantly upregulated, whereas there were no obvious changes in Bax level. The expression of TGFβ1 was significantly upregulated in the rat liver after the surgery. Autologous BMSC transplantation significantly downregulated the TGFβ1 levels at 48, 72, and 168 h post surgery. However, autologous BMSC transplantation showed little effect on the levels of TGFβ receptor 1/2 at all the time points observed. Furthermore, autologous BMSC transplantation significantly inhibited the activation of p38 MAPK. Autologous BMSC transplantation may reduce ELRLA-induced liver injury and improve survival rates in hepatic fibrosis rats. Autologous BMSC transplantation may be useful to improve the outcome of patients who undergo ELRLA. Copyright © 2013 Elsevier Inc. All rights reserved.

Methylphenidate clinically oral doses improved brain and heart glutathione redox status and evoked renal and cardiac tissue injury in rats.

PubMed

Loureiro-Vieira, Sara; Costa, Vera Marisa; Duarte, José Alberto; Duarte-Araújo, Margarida; Gonçalves-Monteiro, Salomé; Maria de Lourdes, Bastos; Carvalho, Félix; Capela, João Paulo

2018-04-01

Methylphenidate (MPH) is a first-line stimulant drug to treat attention deficit hyperactivity disorder (ADHD). Overdiagnosis of ADHD and MPH abuse lead to serious concerns about the possible long-term adverse consequences of MPH in healthy children and adolescents. We aimed to evaluate MPH effects in adolescent male Wistar rats (postnatal day 40) using an oral dose scheme (2 daily MPH doses 5 mg/kg in a 5% sucrose solution, 5 h apart, for 7 days) that mimics the therapeutic doses given to human adolescents. Twenty-four hours after the last MPH administration, rats were sacrificed and brain areas [cerebellum, prefrontal cortex (PFC), hippocampus, and striatum], peripheral organs (liver, heart, and kidneys), and blood were collected for biochemical and histological analysis. MPH treatment did not alter rats' body temperature or weight, neither food or water intake throughout the experiment. The ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) significantly increased in the PFC and hippocampus of MPH-treated rats, meanwhile protein carbonylation remained unchanged in the brain. In the heart, the GSH/GSSG ratio and GSH levels were significantly increased, with decreased GSSG, while histology revealed significant damage, namely interstitial edema, vascular congestion, and presence of a fibrin-like material in the interstitial space. In the kidneys, MPH treatment resulted in extensive necrotic areas with cellular disorganization and cell infiltration, and immunohistochemistry analysis revealed a marked activation of nuclear factor-ĸB. This study showed that clinically relevant oral MPH doses improve the GSH redox status in the brain and heart, but evoke heart and kidney tissue damage to adolescent rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A Latent Cue Preference Based on Sodium Depletion in Rats

ERIC Educational Resources Information Center

Stouffer, Eric M.; White, Norman M.

2005-01-01

Three experiments show latent (or incidental) learning of salt-cue relationships using a conditioned cue-preference paradigm. Rats drank a salt solution while confined in one compartment and water in an adjacent, distinct compartment on alternate days. When given access to the two compartments with no solutions present, sodium-deprived rats…

Few effects of multi-generational dietary exposure to genistein or nonylphenol on sodium solution intake in male and female Sprague-Dawley rats.

PubMed

Ferguson, Sherry A; Delclos, K Barry; Newbold, Retha R; Flynn, Katherine M

2009-01-01

Previous work in our laboratory indicated that lifelong dietary exposure to estrogen-like endocrine disrupters increased sodium solution intake in adult male and female rats. Here, we sought to discern the critical periods necessary for this alteration as well as establish the effects of lower dietary concentrations of genistein and nonylphenol. Male and female Sprague-Dawley rats (F0) consumed phytoestrogen-free chow containing 0, 5, 100, or 500 ppm genistein (approximately equal to 0.0, 0.4, 8.0, and 40.0 mg/kg/day) or 0, 25, 200, or 750 ppm nonylphenol (approximately equal to 0.0, 2.0, 16.0, and 60.0 mg/kg/day). Rats were mated within treatment groups and offspring (F1) maintained on the same diets. Mating for the F1, F2, and F3 (genistein only) was within treatment groups. At postnatal day (PND) 21, the F3 generation began to consume unadulterated phytoestrogen-free chow such that genistein exposure occurred only in utero and preweaning. The F4 generation was never directly exposed to genistein. On PNDs 65-68, intake of regular water and a 3.0% sodium chloride solution was measured for F1-F4 generations (genistein portion) or F1-F2 (nonylphenol portion). Although body weights were decreased by the highest dietary concentrations of genistein and nonylphenol, there were only minimal effects of exposure on sodium solution intake. As expected, intake was highest in female rats. With previous data, these results indicate that the dietary concentrations necessary to increase adult sodium solution intake in rats are greater than 500 ppm genistein and 750 ppm nonylphenol and such effects do not appear to increase across generations.

Coconut water solutions for the preservation of spleen, ovary, and skin autotransplants in rats.

PubMed

Schettino César, J M; Petroianu, A; de Souza Vasconcelos, L; Cardoso, V N; das Graças Mota, L; Barbosa, A J A; Vianna Soares, C D; Lima de Oliveira, A

2015-03-01

The purpose of this study was to evaluate the efficacy of coconut water in the preservation of spleen, ovary, and skin autotransplantations in rats. Fifty female Wistar rats were divided randomly into 5 groups on the basis of the following tissue graft preservation solutions: group 1, lactated Ringer's; group 2, Belzer's solution; group 3, mature coconut water; group 4, green coconut water; and group 5, modified green coconut water. In group 5, the green coconut water solution was modified to obtain the same electrolyte composition as Belzer's solution. The spleen, ovaries, and a skin fragment were removed from each animal, stored for 6 hours in one of the solutions, and then re-implanted. The recoveries of tissue functions were assessed 90 days after surgery by means of spleen scintigraphy and blood tests. The implanted tissues were collected for histological analyses. Higher immunoglobulin G levels were observed in the animals of group 5 than in the animals of group 1. Differences in follicle-stimulating hormone levels were observed between groups 1 and 2 (P < .001), between groups 4 and 2 (P = .03), and between groups 5 and 2 (P = .01). The spleen scintigraphy results did not differ among the groups. The ovarian tissue was better preserved in the mature coconut water group (P < .007). Solutions containing coconut water allowed for the preservation of the spleen, ovaries, and skin for 6 hours, and the normal functions of these tissues were maintained in rats. Copyright © 2015 Elsevier Inc. All rights reserved.

Interaction of Vasopressin and Splenda on Glucose Metabolism and Long-term Preferences under Ad-libitum and Food-restricted Conditions.

PubMed

Murphy, H M; Wideman, C H; Cleary, A M

1999-01-01

Previous research has demonstrated that vasopressin-containing rats are capable of adapting to the stress of food restriction; whereas, vasopressin-deficient rats cannot adapt to this stressor. In the present study, the value of using a low-calorie (Splenda) or no-calorie (Equal) artificial sweetener to reverse the deleterious effects of food restriction in vasopressin-deficient rats was examined. In association with this effect, the role of vasopressin in long-term preferences for the two artificial sweeteners was studied. Vasopressin-deficient, Brattleboro (DI) rats and vasopressin-containing, Long-Evans (LE) rats underwent an habituation phase during which they had ad-libitum access to food. This was followed by an experimental phase during which the rats were divided into four groups. (1) DI rats continued with ad-libitum feeding, (2) LE rats continued with ad-libitum feeding, (3) DI rats subjected to 23 h of food restriction, and (4) LE rats subjected to 23 h of food restriction. All rats had ad-libitum access to an 8% Splenda solution, a 1% Equal solution, and water throughout both phases of the experiment. The deleterious effects of food restriction were completely reversed in DI rats, including survival, no stomach pathology, and normal plasma levels of glucose and urea nitrogen.

Hyperoxygenated hydrogen-rich solution suppresses shock- and resuscitation-induced liver injury.

PubMed

Dang, Yangjie; Liu, Ting; Mei, Xiaopeng; Meng, Xiangzhong; Gou, Xingchun; Deng, Bin; Xu, Hao; Xu, Lixian

2017-12-01

It is not known whether simultaneous delivery of hydrogen and oxygen can reduce injury caused by hemorrhagic shock and resuscitation (HSR). This study investigated the therapeutic potential of hyperoxygenated hydrogen-rich solution (HHOS), a combined hydrogen/oxygen carrier, in a rat model of HSR-induced liver injury. Rats (n = 60) were randomly divided into 5 groups (n = 6 per group at each time point). One group underwent sham operation, and the others were subjected to severe hemorrhagic shock and then treated with lactated Ringer's solution (LRS), hydrogen-rich solution, hyperoxygenated solution, or HHOS. At 2 and 6 h after resuscitation, blood samples (n = 6) were collected from the femoral artery and serum concentrations of alanine aminotransferase and aspartate aminotransferase (AST) were measured. Rats were then sacrificed, and histopathological changes in the liver were evaluated by quantifying the percentage of apoptotic cells by caspase-3 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Inflammation was assessed by assessing malondialdehyde content and tumor necrosis factor-α, and interleukin (IL)-6 expression. Compared to lactated Ringer's solution, hydrogen-rich solution, or hyperoxygenated solution groups, serum AST and alanine aminotransferase levels and IL-6, tumor necrosis factor-α, and malondialdehyde expression in liver tissue were decreased by HHOS treatment. The number of caspase-3- and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells was decreased (P < 0.05) by HHOS treatment, 2 and 6 h after resuscitation. HHOS has protective effects against liver injury in a rat model of HSR. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

PubMed

Wu, Meng-Huang; Shih, Ming-Hung; Hsu, Wei-Bin; Dubey, Navneet Kumar; Lee, Wen-Fu; Lin, Tsai-Yu; Hsieh, Meng-Yow; Chen, Chin-Fu; Peng, Kuo-Ti; Huang, Tsung-Jen; Shi, Chung-Sheng; Guo, Ren-Shyang; Cai, Chang-Jhih; Chung, Chiu-Yen; Wong, Chung-Hang

2017-01-01

This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolac-embedded 2, 2'-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Pro-inflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1β) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1β while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

PLGA nanoparticles for the oral delivery of 5-Fluorouracil using high pressure homogenization-emulsification as the preparation method and in vitro/in vivo studies.

PubMed

Li, XueMing; Xu, YuanLong; Chen, GuoGuang; Wei, Ping; Ping, QiNeng

2008-01-01

The objective of the present study was to incorporate the hydrophilic anti-cancer drug 5-Fluorouracil(5-FU) into poly(lactide-co-glycolide) (PLGA) nanoparticles(NP) to improve the oral bioavailability. Owing to the high solubility of 5-FU in basic water, the water-in-oil-in-water (w/o/w) emulsification process has been chosen as one of the most appropriate method for the encapsulation of 5-FU, and the ammonia solution was used as the inner aqueous phase solvent to increase the solubility of 5-FU. In order to reach submicron size as well as increasing the grade of monodispersity compared to previous preparation techniques, we prepared 5-FU loaded PLGA-NP by a high-pressure emulsification-solvent evaporation process. The PLGA-NPs were characterized with respect to their morphology, particle size, size distribution, 5-FU encapsulation efficiency, in vitro and in vivo studies in rats. In vitro release of 5-FU from nanoparticles appeared to have two components with an initial rapid release due to the surface associated drug and followed by a slower exponential release of 5-FU, which was dissolved in the core. The in vivo research was studied in male Sprague-Dawley rats after an oral 5-FU dose of 45 mg/kg. Single oral administration of 5-FU loaded PLGA-NP to rats produced bioavailability, which was statistically higher than 5-FU solution as negative control. And the MRT (mean residence time) of 5-FU loaded PLGA-NP was significantly (P < 0.05) modified. Thus, it is possible to design a controlled drug delivery system for oral 5-FU delivery, improving therapy efficiency by possible reduction of time intervals between peroral administrations and reduction of local gastrointestinal side effects.

Effects of aging on mineralocorticoid-induced salt appetite in rats

PubMed Central

Beltz, Terry G.; Johnson, Alan Kim

2013-01-01

This work examined the effects of age on salt appetite measured in the form of daily saline (i.e., 0.3 M NaCl) drinking in response to administration of deoxycorticosterone acetate (DOCA; 5 mg/kg body wt) using young (4 mo), “middle-aged” adult (12 mo), and old (30 mo) male Brown Norway rats. Water and sodium intakes, excretions, and balances were determined daily. The salt appetite response was age dependent with “middle-aged” rats ingesting the most saline solution followed in order by young and then old rats. While old rats drank the least saline solution, the amounts of saline ingested still were copious and comprise an unambiguous demonstration of salt appetite in old rats. Middle-aged rats had the highest saline preference ratios of the groups under baseline conditions and throughout testing consistent with an increased avidity for sodium taste. There were age differences in renal handling of water and sodium that were consistent with a renal contribution to the greater saline intakes by middle-aged rats. There was evidence of impaired renal function in old rats, but this did not account for the reduced saline intakes of the oldest rats. PMID:24133100

Effects of β-hydroxy-β-methyl butyrate on working memory and cognitive flexibility in an animal model of aging.

PubMed

Hankosky, Emily R; Sherrill, Luke K; Ruvola, Lauren A; Haake, Rachel M; Kim, Taehyeon; Hammerslag, Lindsey R; Kougias, Daniel G; Juraska, Janice M; Gulley, Joshua M

2017-09-01

Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) on working memory and cognitive flexibility. Beginning ∼12 months of age, male and female Long-Evans rats were given twice daily access to sipper tubes containing calcium HMB (450 mg/kg) or vehicle (285 mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process.

Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide.

PubMed

Aghaie, Somaieh; Nikzad, Hossein; Mahabadi, Javad Amini; Taghizadeh, Mohsen; Azami-Tameh, Abolfazl; Taherian, Aliakbar; Sajjadian, Seyyed Mohammad Sajjad; Kamani, Mehran

2016-09-01

Reproductive toxicity is one of the side effects of cyclophosphamide (CP) in cancer treatment. Pumpkin seeds and Zingiber officinale are natural sources of antioxidants. We investigated the possible protective effect of combined pumpkin seed and Zingiber officinale extracts on sperm characteristics, epididymal histology and biochemical parameters of CP-treated rats. Male adult Wistar rats were divided randomly into six groups. Group 1, as a control, received an isotonic saline solution injection intraperitoneally (IP). Group 2 were injected IP with a single dose of CP (100 mg/kg) once. Groups 3 and 4 received CP plus 300 and 600 mg/kg combined pumpkin seed and Zingiber officinale extract (50:50). Groups 5 and 6 received only 300 and 600 mg/kg combined pumpkin seed and Zingiber officinale extract. Six weeks after treatment, sperm characteristics, histopathological changes and biochemical parameters were assessed. In CP-treated rats, motile spermatozoa were decreased, and abnormal or dead spermatozoa increased significantly (P < 0.001) but administration of the mixed extract improved sperm parameters. Epididymal epithelium and fibromascular thickness were also improved in extract-treated rats compared to control or CP groups. Biochemical analysis showed that the administration of combined extracts could increase the total antioxidant capacity (TAC) level significantly in groups 3, 4, 5 and 6. Interestingly, the mixed extract could decrease most of the side effects of CP such as vacuolization and separation of epididymal tissue. Our findings indicated that the combined extracts might be used as a protective agent against CP-induced reproductive toxicity.

Caffeine dependence in rats: effects of exposure duration and concentration.

PubMed

Dingle, Rachel N; Dreumont-Boudreau, Sarah E; Lolordo, Vincent M

2008-09-03

Groups of rats were chronically exposed to a 1.0-g/L caffeine solution for 5, 10, 15 or 20 days. Upon removal of caffeine, rats were given brief exposure to a novel flavour CS (withdrawal CS) followed by 12 days of plain water and then brief exposure to a second flavour CS (neutral CS). Only rats exposed to 20 days of caffeine strongly preferred the neutral CS to the withdrawal CS in a 2-bottle test. In Experiment 2, groups of rats were chronically exposed to caffeine at one of four concentrations (1.0, 0.5, 0.25, or 0.125 g/L) for 21 days, after which withdrawal and neutral CSs were established. Only rats that drank the highest caffeine concentration, 1.0 g/L, preferred the neutral CS to the withdrawal CS. This suggests that long exposure to a strong caffeine solution is required in order to induce dependence in rats such that a CS associated with the withdrawal of caffeine becomes avoided.

Delay discounting of oral morphine and sweetened juice rewards in dependent and non-dependent rats.

PubMed

Harvey-Lewis, Colin; Perdrizet, Johnna; Franklin, Keith B J

2014-07-01

Opioid-dependent humans are reported to show accelerated delay discounting of opioid rewards when compared to monetary rewards. It has been suggested that this may reflect a difference in discounting of consumable and non-consumable goods not specific to dependent individuals. Here, we evaluate the discounting of similar morphine and non-morphine oral rewards in dependent and non-dependent rats We first tested the analgesic and rewarding effects of our morphine solution. In a second experiment, we assigned rats randomly to either dependent or non-dependent groups that, 30 min after daily testing, received 30 mg/kg subcutaneous dose of morphine, or saline, respectively. Delay discounting of drug-free reward was examined prior to initiation of the dosing regimen. We tested discounting of the morphine reward in half the rats and retested the discounting of the drug-free reward in the other half. All tests were run 22.5 h after the daily maintenance dose. Rats preferred the morphine cocktail to the drug-free solution and consumed enough to induce significant analgesia. The control quinine solution did not produce these effects. Dependent rats discounted morphine rewards more rapidly than before dependence and when compared to discounting drug-free rewards. In non-dependent rats both reward types were discounted similarly. These results show that morphine dependence increases impulsiveness specifically towards a drug reward while morphine experience without dependence does not.

[Metabolism of thyroid gland cells as affected by prolactin and emotional-physical stress].

PubMed

Strizhkov, V V

1991-01-01

A study was made of the role of prolactin (PRL) in the regulation of thyroid function in intact animals and in those exposed to stress (swimming was used as physical exercise). A single daily dose of 125 micrograms of PRL per 100 g of body mass was injected subcutaneously in 0.5 ml of saline solution during a week to male rats (control: intact rats; injection of 0.5 ml of saline solution subcutaneously). Redox enzymes; succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, NAD.H2 and NADP.H2, ATPase and monoamine oxidase, total protein, RNA and glycogen in glandular cells were investigated histochemically 24 h after the last injection of PRL or saline, 30 min., 1, 2, 3, 5 and 7 hours after swimming or right after complete fatigue (in the presence of experimental hyperprolactinemia). A conclusion has been made that one of the most important mechanisms of the adaptive effect of PRL is its ability to suppress thyroid function, thus decreasing the metabolism level, which results in reduction of oxygen consumption and improves body tolerance to stress.

Reinforcement active learning in the vibrissae system: optimal object localization.

PubMed

Gordon, Goren; Dorfman, Nimrod; Ahissar, Ehud

2013-01-01

Rats move their whiskers to acquire information about their environment. It has been observed that they palpate novel objects and objects they are required to localize in space. We analyze whisker-based object localization using two complementary paradigms, namely, active learning and intrinsic-reward reinforcement learning. Active learning algorithms select the next training samples according to the hypothesized solution in order to better discriminate between correct and incorrect labels. Intrinsic-reward reinforcement learning uses prediction errors as the reward to an actor-critic design, such that behavior converges to the one that optimizes the learning process. We show that in the context of object localization, the two paradigms result in palpation whisking as their respective optimal solution. These results suggest that rats may employ principles of active learning and/or intrinsic reward in tactile exploration and can guide future research to seek the underlying neuronal mechanisms that implement them. Furthermore, these paradigms are easily transferable to biomimetic whisker-based artificial sensors and can improve the active exploration of their environment. Copyright © 2012 Elsevier Ltd. All rights reserved.

The comparison of methylene blue and vitamin E in prevention of abdominal postoperative adhesion formation in rat uterine horn models: Biochemical and histopathologic evaluation.

PubMed

Yildiz, Hamit; Durmus, Ali Said; Simsek, Halil; Yaman, Ihsan

2011-02-01

To compare the effects of vitamin E and 1% methylen blue solutions on prevention of experimentally induced adhesions in rats. Thirty seven female Spraque Dawley rats were randomized into four groups. First group was kept as sham operated group. An adhesion model was constituted on the left uterine horn of the other groups. The lesion areas of rats from the second, the third and the fourth groups were coated with 2 ml 0.9 % saline solution (C group), 10 mg vitamin E (VE group) and 1% methylen blue solutions (MB group), respectively. Histopathologically, adhesion scores, mononuclear cell infiltration, oedema and fibrosis were more prominent in the MB group compared with C and VE groups. There were no significant differences between the groups in tissue glutathione peroxidase (GPx), catalase (CAT) activities and glutation (GSH) level, these parameters were slightly increased in group with VE supplementation though. The administration of VE and MB significantly decreased NO (P<0.01) levels when compared to the C group. The level of malondialdehyde (MDA) in the VE group was significantly lower (P<0.05) than those of the Sh and C groups. Intraperitoneal methylen blue solutions treatments were more effective according to vitamin E in preventing the formation of intra-abdominal adhesion in a rat uterine horn model.

Attenuation of Multiple Organ Damage by Continuous Low-Dose Solvent-Free Infusions of Resveratrol after Severe Hemorrhagic Shock in Rats

PubMed Central

Kirsch, Michael; Petrat, Frank

2017-01-01

Therapeutic effects of continuous intravenous infusions of solvent-free low doses of resveratrol on organ injury and systemic consequences resulting from severe hemorrhagic shock in rats were studied. Hemorrhagic shock was induced by withdrawing arterial blood until a mean arterial blood pressure (MAP) of 25–30 mmHg was reached. Following a shock phase of 60 min, rats were resuscitated with the withdrawn blood plus lactated Ringer’s. Resveratrol (20 or 60 μg/kg × h) was continuously infused intravenously starting with the resuscitation phase (30 min) and continued until the end of the experiment (total treatment time 180 min). Animals of the shock control group received 0.9% NaCl solution. After the observation phase (150 min), rats were sacrificed. Resveratrol significantly stabilized the MAP and peripheral oxygen saturation after hemorrhagic shock, decreased the macroscopic injury of the small intestine, significantly attenuated the shock-induced increase in tissue myeloperoxidase activity in the small intestine, liver, kidney and lung, and diminished tissue hemorrhages (particularly in the small intestine and liver) as well as the rate of hemolysis. Already very low doses of resveratrol, continuously infused during resuscitation after severe hemorrhagic shock, can significantly improve impaired systemic parameters and attenuate multiple organ damage in rats. PMID:28817064

Biomaterials for the Decorporation of Sr-85 in the Rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levitskaia, Tatiana G.; Creim, Jeffrey A.; Curry, Terry L.

2010-09-01

Although four stable isotopes of strontium occur naturally, strontium-90 is produced by nuclear fission and is present in surface soil around the world as a result of fallout from atmospheric nuclear weapons tests. It can easily transfer to man in the event of a nuclear/radiological emergency or through the plant-animal-human food chain causing long-term exposures. Strontium is chemically and biologically similar to calcium, and is incorporated primarily into bone following internal deposition. Alginic acid (alginate) obtained from seaweed (kelp) extract selectively binds ingested strontium in the GI tract blocking its systemic uptake and reducing distribution to bone in rats, whilemore » other natural polysaccharides including chitosan and hyaluronic acid had little in vivo affinity for strontium. Alginate exhibits the unique ability to discriminate between strontium and calcium and has been previously shown to reduce intestinal absorption and skeletal retention of strontium without changing calcium metabolism. In our studies, the effect of commercially available alginate on strontium intestinal absorption was examined. One problem associated with alginate treatment is its limited solubility and gel formation in water. The aqueous solubility of sodium alginate was improved in a sodium chloride/sodium bicarbonate electrolyte solution containing low molecular weight polyethylene glycol (PEG). Furthermore, oral administration of the combined alginate/electrolyte//PEG solution synergistically accelerated removal of internal strontium in rats when compared to treatment with individual sodium alginate/electrolyte or electrolyte/PEG solutions. Importantly, both alginate and PEG are nontoxic, readily available materials that can be easily administered orally in case of a national emergency when potentially large numbers of the population may require medical treatment for internal depositions. Our results suggest further studies to optimize in vivo decorporation performance of engineered alginate material via modification of its chemical and physicochemical properties is warranted.« less

The surface alloying effect of silicon in a binary NiTi-base alloy on the corrosion resistance and biocompatibility of the material

NASA Astrophysics Data System (ADS)

Psakhie, S. G.; Lotkov, A. I.; Meisner, L. L.; Meisner, S. N.; Matveeva, V. A.

2013-02-01

The corrosion resistance behavior and cytotoxicity of binary NiTi-base alloy specimens subjected to surface modification by silicon ion beams and the proliferative ability of mesenchymal stem cells of rat marrow on an ion-implanted surface of the alloy have been studied. The silicon ion beam processing of specimen surfaces is shown to bring about a nearly two-fold improvement in the corrosion resistance of the material to attack by aqueous solutions of NaCl (artificial body fluid) and human plasma and a drastic decrease in the nickel concentration after immersion of the specimens into the solutions for ˜3400 and ˜6000 h, respectively (for the artificial plasma solution, a nearly 20-fold decrease in the Ni concentration is observed.)

Dissociation of conditioned taste avoidance from conditioned disgust reactions induced by wheel running in rats.

PubMed

Grant, Virginia L; McDonald, Sarah V; Sheppard, Robyn C; Caldwell, Catherine L; Heeley, Thomas H; Brown, Adam R; Martin, Gerard M

2012-06-01

It is well established that wheel running in rats produces conditioned taste avoidance; that is, rats that run in wheels after consuming a novel-tasting solution later consume less of that solution than rats that do not run. In experiment 1, we found that wheel running also produces conditioned disgust reactions, indicated by gapes elicited by both the taste and context that were experienced before running. Experiment 2 showed that the conditioned disgust reactions were likely not due to running itself but to a by-product of running, the rocking of the wheel that occurs when the running stops. When rocking was reduced, the disgust reactions were also reduced, but consumption of the taste solution was not changed, showing dissociation of conditioned taste avoidance and disgust. These findings indicate that the taste avoidance induced by wheel running itself is more like the taste avoidance produced by rewarding drugs than that produced by nausea-inducing drugs. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Bacopa monnieri extract increases rat coronary flow and protects against myocardial ischemia/reperfusion injury.

PubMed

Srimachai, Sirintorn; Devaux, Sylvie; Demougeot, Celine; Kumphune, Sarawut; Ullrich, Nina D; Niggli, Ernst; Ingkaninan, Kornkanok; Kamkaew, Natakorn; Scholfield, C Norman; Tapechum, Sompol; Chootip, Krongkarn

2017-02-20

This study explored Bacopa monnieri, a medicinal Ayurvedic herb, as a cardioprotectant against ischemia/reperfusion injury using cardiac function and coronary flow as end-points. In normal isolated rat hearts, coronary flow, left ventricular developed pressure, heart rate, and functional recovery were measured using the Langendorff preparation. Hearts were perfused with either (i) Krebs-Henseleit (normal) solution, (control), or with 30, 100 μg/ml B. monnieri ethanolic extract (30 min), or (ii) with normal solution or extract for 10 min preceding no-perfusion ischemia (30 min) followed by reperfusion (30 min) with normal solution. Infarct volumes were measured by triphenyltetrazolium staining. L-type Ca 2+ -currents (I Ca, L ) were measured by whole-cell patching in HL-1 cells, a mouse atrial cardiomyocyte cell line. Cytotoxicity of B. monnieri was assessed in rat isolated ventricular myocytes by trypan blue exclusion. In normally perfused hearts, B. monnieri increased coronary flow by 63 ± 13% (30 μg/ml) and 216 ± 21% (100 μg/ml), compared to control (5 ± 3%) (n = 8-10, p < 0.001). B. monnieri treatment preceding ischemia/reperfusion improved left ventricular developed pressure by 84 ± 10% (30 μg/ml), 82 ± 10% (100 μg/ml) and 52 ± 6% (control) compared to pre- ischemia/reperfusion. Similarly, functional recovery showed a sustained increase. Moreover, B. monnieri (100 μg/ml) reduced the percentage of infarct size from 51 ± 2% (control) to 25 ± 2% (n = 6-8, p < 0.0001). B. monnieri (100 μg/ml) reduced I Ca, L by 63 ± 4% in HL-1 cells. Ventricular myocyte survival decreased at higher concentrations (50-1000 μg/ml) B. monnieri. B. monnieri improves myocardial function following ischemia/reperfusion injury through recovery of coronary blood flow, contractile force and decrease in infarct size. Thus this may lead to a novel cardioprotectant strategy.

Multidirectional approach to study peritoneal dialysis fluid biocompatibility in a chronic peritoneal dialysis model in the rat.

PubMed

Wieczorowska-Tobis, K; Polubinska, A; Wisniewska, J; Pawlaczyk, K; Kuzlan-Pawlaczyk, M; Filas, V; Breborowicz, A; Oreopoulos, D G

2001-03-01

Peritoneal dialysis causes the functional and morphological changes in the peritoneum that result from the bioincompatibility of dialysis solutions. We present a model of chronic peritoneal dialysis in the rat that can be used for testing the biocompatibility of dialysis fluids. Methods and Results. Long-term exposure of the peritoneum to dialysis solutions can be performed in rats with implanted peritoneal catheters. Sampling of the dialysate allows the evaluation of intraperitoneal inflammation by examining cell differential and dialysate cytokine levels. Peritoneal permeability can be evaluated at designed time intervals with the peritoneal equilibration test (PET). At the end of dialysis, peritoneal histology is studied with light and electron microscopy. Such a multidirectional approach is an effective way to test biocompatibility of dialysis solutions.

[A comparative study on behaviors of two depression models in rats induced by chronic forced swimming stress].

PubMed

Han, Ming-Fei; Gao, Dong; Sun, Xue-Li

2010-01-01

To compare the behaviors of rats with depressions induced by chronic forced swimming stress under two different conditions. Eighteen male rats were randomly divided into 3 groups, with 6 rats in each group. The rats in the control group (C group) were not forced into swimming, while the rats in the stress groups (S1 and S2) were forced to swim for 14 consecutive days. The rats in S1 group and S2 group swam for five minutes every morning, in water with (23 +/- 1) degree C, and (10 +/- 0.5) degree C in temperature, respectively. The weight gain, food intake, open-field test and saccharin solution test were observed on the seventh day and fourteenth day. On the seventh day following chronic swim stress, the rats in the S2 group had significant lower ratio in weight gain and food intake than the controls (P < 0.05). On the fourteenth day, the rats in the S2 group had significant lower ratio in weight gain (12.26 +/- 4.04)%, food intake (9.49 +/- 0.96)%, sucrose intake (28.63 +/- 3.51) g, and preference for saccharin solution (76.25 +/- 2.51)%, and less number of crossing (12.17 +/- 9.00) and times of rearing (3.17 +/- 3.60) than the controls (P < 0.05). The rats in the S1 group had significant lower ratio in weight gain and food intake than the controls on the seventh day following forced swimming. On the fourteenth day, the rats in the S1 group still had lower ratio in weight gain, but had higher ratio in food intake and preference for saccharin solution, and greater number of crossing than the controls. Chronic forced swimming at a lower temperature could induce depression better than at a higher temperature.

Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

PubMed Central

Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

2014-01-01

The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

Improved biochemical preservation of lung slices during cold storage.

PubMed

Bull, D A; Connors, R C; Reid, B B; Albanil, A; Stringham, J C; Karwande, S V

2000-05-15

Development of lung preservation solutions typically requires whole-organ models which are animal and labor intensive. These models rely on physiologic rather than biochemical endpoints, making accurate comparison of the relative efficacy of individual solution components difficult. We hypothesized that lung slices could be used to assess preservation of biochemical function during cold storage. Whole rat lungs were precision cut into slices with a thickness of 500 microm and preserved at 4 degrees C in the following solutions: University of Wisconsin (UW), Euro-Collins (EC), low-potassium-dextran (LPD), Kyoto (K), normal saline (NS), or a novel lung preservation solution (NPS) developed using this model. Lung biochemical function was assessed by ATP content (etamol ATP/mg wet wt) and capacity for protein synthesis (cpm/mg protein) immediately following slicing (0 h) and at 6, 12, 18, and 24 h of cold storage. Six slices were assayed at each time point for each solution. The data were analyzed using analysis of variance and are presented as means +/- SD. ATP content was significantly higher in the lung slices stored in NPS compared with all other solutions at each time point (P < 0.0001). Protein synthesis was significantly higher in the lung slices stored in NPS compared with all other solutions at 6, 12, and 18 h of preservation (P < 0.05). This lung slice model allows the rapid and efficient screening of lung preservation solutions and their components using quantifiable biochemical endpoints. Using this model, we have developed a novel solution that improves the biochemical preservation of lung slices during cold storage. Copyright 2000 Academic Press.

Influence of administration vehicles and drug formulations on the pharmacokinetic profile of lamotrigine in rats.

PubMed

Castel-Branco, M M; Figueiredo, I V; Falcão, A C; Macedo, T R A; Caramona, M M

2002-10-01

Given that administration vehicles and drug formulations can affect drug bioavailability, their influence on the pharmacokinetic profile of lamotrigine (LTG), a new-generation anti-epileptic drug, was studied in rats. Three different formulations administered intraperitoneally at a dose of 10 mg/kg were used: (1) LTG suspended in a 0.25% methylcelulose solution, (2) LTG dissolved in a 50% propylene glycol solution, and (3) LTG isethionate dissolved in distilled water. Plasma and brain homogenate levels were determined in order to evaluate vehicle-dependent drug absorption. The results demonstrated rapid absorption of LTG when it was administered as an aqueous solution, in contrast to a slower and more erratic absorption after the injection of either the lipophilic solution or the suspension. A plasma peak was achieved 15 min post-dose with the aqueous solution, with a brain peak being achieved 15 min later, while with the other formulations both plasma and brain homogenate peaks were reached 2 h after LTG administration. This study suggests that LTG isethionate dissolved in distilled water is the most suitable formulation for successful LTG pharmacokinetic studies in rats.

Cryopreservation of Hepatocyte Microbeads for Clinical Transplantation

PubMed Central

Jitraruch, Suttiruk; Hughes, Robin D.; Filippi, Celine; Lehec, Sharon C.; Glover, Leanne; Mitry, Ragai R.

2017-01-01

Intraperitoneal transplantation of hepatocyte microbeads is an attractive option for the management of acute liver failure. Encapsulation of hepatocytes in alginate microbeads supports their function and prevents immune attack of the cells. Establishment of banked cryopreserved hepatocyte microbeads is important for emergency use. The aim of this study was to develop an optimized protocol for cryopreservation of hepatocyte microbeads for clinical transplantation using modified freezing solutions. Four freezing solutions with potential for clinical application were investigated. Human and rat hepatocytes cryopreserved with University of Wisconsin (UW)/10% dimethyl sulfoxide (DMSO)/5% (300 mM) glucose and CryoStor CS10 showed better postthawing cell viability, attachment, and hepatocyte functions than with histidine–tryptophan–ketoglutarate/10% DMSO/5% glucose and Bambanker. The 2 freezing solutions that gave better results were studied with human and rat hepatocytes microbeads. Similar effects on cryopreserved microbead morphology (external and ultrastructural), viability, and hepatocyte-functions post thawing were observed over 7 d in culture. UW/DMSO/glucose, as a basal freezing medium, was used to investigate the additional effects of cytoprotectants: a pan-caspase inhibitor (benzyloxycarbonyl-Val-Ala-dl-Asp-fluoromethylketone [ZVAD]), an antioxidant (desferoxamine [DFO]), and a buffering and mechanical protectant (human serum albumin [HSA]) on RMBs. ZVAD (60 µM) had a beneficial effect on cell viability that was greater than with DFO (1 mM), HSA (2%), and basal freezing medium alone. Improvements in the ultrastructure of encapsulated hepatocytes and a lower degree of cell apoptosis were observed with all 3 cytoprotectants, with ZVAD tending to provide the greatest effect. Cytochrome P450 activity was significantly higher in the 3 cytoprotectant groups than with fresh microbeads. In conclusion, developing an optimized cryopreservation protocol by adding cytoprotectants such as ZVAD could improve the outcome of cryopreserved hepatocyte microbeads for future clinical use. PMID:28901189

Levosimendan improves postresuscitation outcomes in a rat model of CPR.

PubMed

Huang, Lei; Weil, Max Harry; Sun, Shijie; Cammarata, Gianluca; Cao, Lan; Tang, Wanchun

2005-11-01

In this study we sought to determine whether a calcium sensitizer, levosimendan, would have a more favorable effect on postresuscitation myocardial function and, consequently, postresuscitation survival than beta-adrenergic dobutamine. The extreme decrease in survival before hospital discharge of resuscitated victims is attributed, in part, to postresuscitation myocardial failure, and dobutamine has been recommended for the management of postresuscitation myocardial failure. We studied a total of 15 animals. Ventricular fibrillation was induced in Sprague-Dawley rats weighing 450 to 550 g. Cardiopulmonary resuscitation (CPR), including chest compressions and mechanical ventilation, was begun after 8 minutes of untreated cardiac arrest. Electrical defibrillation was attempted after 6 minutes of CPR. Each animal was resuscitated. Animals were randomized to undergo treatment with levosimendan, dobutamine, or saline-solution placebo. These agents were administered 10 minutes after the return of spontaneous circulation. Levosimendan was administered in a loading dose of 12 microg kg(-1) over a 10-minute period, followed by infusion of 0.3 microg kg(-1) min(-1) over the next 230 minutes. Dobutamine was continuously infused at a dosage of 3 microg kg(-1) min(-1). Saline-solution placebo was administered in the same volume and over the same amount of time as levosimendan. Levosimendan and dobutamine produced comparable increases in cardiac output and rate of left-ventricular pressure increase. However, administration of levosimendan resulted in lower heart rates and lesser increases in left ventricular diastolic pressure compared with both dobutamine and placebo. The duration of postresuscitation survival was significantly greater with levosimendan (16 +/- 2 hours), intermediate with dobutamine (11 +/- 2 hours) and least with saline-solution placebo (8 +/- 1 hour). Levosimendan and dobutamine both improved postresuscitation myocardial function. However, levosimendan produced more favorable postresuscitation myocardial function and increased the duration of postresuscitation survival.

Pumpkin polysaccharide modifies the gut microbiota during alleviation of type 2 diabetes in rats.

PubMed

Liu, Guimei; Liang, Li; Yu, Guoyong; Li, Quanhong

2018-04-24

Pumpkin polysaccharide is able to alleviate diabetes, but understanding of the underlining mechanism is still limited. In this study, we hypothesized that the alleviating effects of pumpkin polysaccharide is modulated via changes in the gut microbiota and short-chain fatty acid (SCFA) production in type 2 diabetic rats. After the type 2 diabetic model successfully was established, three groups of high-fat diet induced diabetic rats were intragastrically administered pumpkin polysaccharide, metformin, or saline solution respectively. We utilized 16S rRNA gene sequencing and multivariate statistics to analyze the structural and key species of gut microbiota in the type 2 diabetic rats. The results revealed that pumpkin polysaccharide alleviated the type 2 diabetes by improving the insulin tolerance and decreasing the levels of serum glucose (GLU), total cholesterol (TC), and low-density lipoprotein (LDL-C), while increasing the levels of high-density lipoprotein (HDL-C). Simultaneously, pumpkin polysaccharide changed the structure of gut microbiota and had selective enrichment in key species of Bacteroidetes, Prevotella, Deltaproteobacteria, Oscillospira, Veillonellaceae, Phascolarctobacterium, Sutterella, and Bilophila. The correlations between the key species and SCFA production indicated the underlining mechanisms of pumpkin polysaccharide on type 2 diabetes. Copyright © 2018. Published by Elsevier B.V.

Higher-Order Motion-Compensation for In Vivo Cardiac Diffusion Tensor Imaging in Rats

PubMed Central

Welsh, Christopher L.; DiBella, Edward V. R.; Hsu, Edward W.

2015-01-01

Motion of the heart has complicated in vivo applications of cardiac diffusion MRI and diffusion tensor imaging (DTI), especially in small animals such as rats where ultra-high-performance gradient sets are currently not available. Even with velocity compensation via, for example, bipolar encoding pulses, the variable shot-to-shot residual motion-induced spin phase can still give rise to pronounced artifacts. This study presents diffusion-encoding schemes that are designed to compensate for higher-order motion components, including acceleration and jerk, which also have the desirable practical features of minimal TEs and high achievable b-values. The effectiveness of these schemes was verified numerically on a realistic beating heart phantom, and demonstrated empirically with in vivo cardiac diffusion MRI in rats. Compensation for acceleration, and lower motion components, was found to be both necessary and sufficient for obtaining diffusion-weighted images of acceptable quality and SNR, which yielded the first in vivo cardiac DTI demonstrated in the rat. These findings suggest that compensation for higher order motion, particularly acceleration, can be an effective alternative solution to high-performance gradient hardware for improving in vivo cardiac DTI. PMID:25775486

Decline of umami preference in aged rats.

PubMed

Miura, Hirohito; Ooki, Makoto; Kanemaru, Norikazu; Harada, Shuitsu

2014-08-08

The effects of aging on the umami sensation were compared between the preference and neural responses from the greater superficial petrosal nerve (GSP innervating the soft palate) and the chorda tympani nerve (CT innervating the fungiform papillae) in the Sprague Dawley rat. A two-bottle preference test revealed that younger rats (5-12 weeks) preferred significantly 0.001 M 5'-inosine monophosphate (IMP), 0.01 M mono sodium glutamate (MSG), and binary mixtures of 0.001 M IMP+0.01 M MSG than deionized water. However, aged rats (21-22 months) showed no significant preference to these umami solutions compared to deionized water. Among the other four basic taste stimuli, there were no significant differences in preference between young and aged rats. Regardless of the age of the rat, neural responses from the GSP and CT produced robust integrated responses to all three umami solutions used in the two-bottle tests. These results indicate that the lack of preference to umami in aged rats is a central nervous system phenomenon and suggests that the loss of preference to umami taste in aged rats is caused by homeostatic changes in the brain incurred by aging. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Modification of Rat Lung Decellularization Protocol Based on Dynamic Conductometry of Working Solution.

PubMed

Kuevda, E V; Gubareva, E A; Gumenyuk, I S; Sotnichenko, A S; Gilevich, I V; Nakokhov, R Z; Rusinova, T V; Yudina, T G; Red'ko, A N; Alekseenko, S N

2017-03-01

We modified the protocol of obtaining of biological scaffolds of rat lungs based on dynamic recording of specific resistivity of working detergent solution (conductometry) during perfusion decellularization. Termination of sodium deoxycholate exposure after attaining ionic equilibrium plateau did not impair the quality of decellularization and preserved structural matrix components, which was confirmed by morphological analysis and quantitative assay of residual DNA.

Short-term periodic consumption of multiprobiotic from childhood improves insulin sensitivity, prevents development of non-alcoholic fatty liver disease and adiposity in adult rats with glutamate-induced obesity.

PubMed

Savcheniuk, Oleksandr; Kobyliak, Nazarii; Kondro, Maryana; Virchenko, Oleksandr; Falalyeyeva, Tetyana; Beregova, Tetyana

2014-07-16

Today the impairment of metabolism and obesity are being extensively investigated due to the significant increase of the prevalence of these diseases. There is scientific evidence that probiotics are beneficial for human health. Thus, the aim of the study was to investigate the effect of multiprobiotic "Symbiter acidophilic concentrated" on obesity parameters in the rats under experimental obesity. The study was carried out on 60 newborn Wistar rats, divided into 3 groups, 20 animals in each (females - n = 10, males - n = 10): intact rats, monosodium glutamate (MSG-) and MSG + probiotic group. Rats of intact group were administered with saline (8 μl/g, subcutaneously (s.c.)). Newborns rats of MSG-group and MSG + probiotic group were injected with a solution of MSG (4.0 mg/g) s.c. at 2nd - 10th postnatal days. The MSG + probiotic group was treated with 140 mg/kg (1.4 × 10(10) CFU/kg) of multiprobiotic "Symbiter". MSG-group was treated with 2.5 ml/kg of water (per os) respectively. Administration was started at the age of 4 weeks just after wean and continued for 3 month intermittently alternating two-week course of introduction with two-week course of break. Neonatal treatment with MSG caused a stunted growth in both MSG-groups, which manifested with significantly smaller naso-anal length compared to adult intact rats. There was no significant difference in weight between intact and MSG-groups on 120th day. The adiponectin level in the serum of rats with MSG-induced obesity decreased by 2.43 times (p = 0.001) in males and 1.75 (p = 0.020) in females. Concentration of leptin in adipose tissue were significantly higher by 45.9% (p = 0.019) and 61.2% (p = 0.009) respectively in males and females compared to intact rats. Our study has indicated that daily oral administration of multiprobiotic to neonatal MSG-treated rats by 2-week courses led to significant reduce of total body and VAT weight with subsequent improvement in insulin sensitivity and prevention of non-alcoholic fatty liver (NAFLD) development. These results have shown that periodic treatment with multiprobiotic prevents the MSG-induced obesity and NAFLD development.

Short-term periodic consumption of multiprobiotic from childhood improves insulin sensitivity, prevents development of non-alcoholic fatty liver disease and adiposity in adult rats with glutamate-induced obesity

PubMed Central

2014-01-01

Background Today the impairment of metabolism and obesity are being extensively investigated due to the significant increase of the prevalence of these diseases. There is scientific evidence that probiotics are beneficial for human health. Thus, the aim of the study was to investigate the effect of multiprobiotic “Symbiter acidophilic concentrated” on obesity parameters in the rats under experimental obesity. Methods The study was carried out on 60 newborn Wistar rats, divided into 3 groups, 20 animals in each (females – n = 10, males – n = 10): intact rats, monosodium glutamate (MSG-) and MSG + probiotic group. Rats of intact group were administered with saline (8 μl/g, subcutaneously (s.c.)). Newborns rats of MSG-group and MSG + probiotic group were injected with a solution of MSG (4.0 mg/g) s.c. at 2nd – 10th postnatal days. The MSG + probiotic group was treated with 140 mg/kg (1.4 × 1010 CFU/kg) of multiprobiotic “Symbiter”. MSG-group was treated with 2.5 ml/kg of water (per os) respectively. Administration was started at the age of 4 weeks just after wean and continued for 3 month intermittently alternating two-week course of introduction with two-week course of break. Results Neonatal treatment with MSG caused a stunted growth in both MSG-groups, which manifested with significantly smaller naso-anal length compared to adult intact rats. There was no significant difference in weight between intact and MSG-groups on 120th day. The adiponectin level in the serum of rats with MSG-induced obesity decreased by 2.43 times (p = 0.001) in males and 1.75 (p = 0.020) in females. Concentration of leptin in adipose tissue were significantly higher by 45.9% (p = 0.019) and 61.2% (p = 0.009) respectively in males and females compared to intact rats. Our study has indicated that daily oral administration of multiprobiotic to neonatal MSG-treated rats by 2-week courses led to significant reduce of total body and VAT weight with subsequent improvement in insulin sensitivity and prevention of non-alcoholic fatty liver (NAFLD) development. Conclusions These results have shown that periodic treatment with multiprobiotic prevents the MSG-induced obesity and NAFLD development. PMID:25030027

Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S.

Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days.more » Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid {beta}-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid {beta}-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights: >Fructose administration as a liquid solution to Sprague-Dawley male rats induced hypertriglyceridemia, hyperleptinemia, hepatic steatosis and necroinflammation. >Atorvastatin administration: >Abolished histological sings of necroinflammation and reduced plasma and liver triglyceride concentrations. >Reduced the expression of phospho-I{kappa}B >Reduced the expression of fructokinase, a key enzyme controlling fructose metabolism« less

Voluntary alcohol intake in two rat lines selectively bred for learned helpless and non-helpless behavior.

PubMed

Vengeliene, Valentina; Vollmayr, Barbara; Henn, Fritz A; Spanagel, Rainer

2005-03-01

A high comorbidity between depression and alcoholism has been reported in several studies, but the mechanisms underlying this relationship remain unknown. We tested whether learned helplessness in rats as a model for depression is associated with enhanced alcohol intake and relapse behavior. Congenital learned helplessness (cLH) and congenital non-learned helplessness (cNLH) rats were selectively bred for differences in an escape paradigm. Sucrose preference was tested at the first hour of the dark phase. In order to study an association with alcohol drinking behavior, rats underwent a free-choice procedure with access to water, and 5% and 20% alcohol solutions for 6 weeks. After acquisition of alcohol drinking behavior, the alcohol deprivation effect (ADE) was assessed. Sensitivity to the sedative-hypnotic effect of alcohol was measured by loss of the righting reflex. cLH rats showed significantly lower preference for sucrose solutions during the second half hour of the dark phase than cNLH rats. Alcohol intake of male cLH rats was not significantly different from that of male cNLH rats. In contrast, cLH female rats consumed higher amounts of alcohol than female cNLH rats. The ADE was more pronounced in female animals, although the magnitude of the ADE was similar in both cNLH and cLH female rats. The time to regain the righting reflex was significantly higher in both male and female cLH rats than in cNLH rats. In summary, these data suggest that an inborn depressive-like behavior in female rats is associated with enhanced alcohol intake.

Intravenous administration of oxytocin in rats acutely decreases deprivation-induced chow intake, but it fails to affect consumption of palatable solutions.

PubMed

Klockars, Anica; Brunton, Chloe; Li, Lu; Levine, Allen S; Olszewski, Pawel K

2017-07-01

Despite its limited ability to cross the blood-brain barrier, peripherally administered oxytocin (OT) acutely decreases food intake, most likely via the brainstem and hypothalamic mechanisms. Studies performed to date have focused mainly on the effects of subcutaneous or intraperitoneal OT on the consumption of only solid calorie-dense diets (either standard or high-fat), whereas it is unknown whether, similarly to central OT, peripherally administered peptide reduces intake of calorie-dilute and non-caloric palatable solutions. In this project, we established that 0.1μg/kg intravenous (IV) OT is the lowest anorexigenic dose, decreasing deprivation-induced standard chow intake by ca. 40% in rats and its effect does not stem from aversion. We then used this dose in paradigms in which effects of centrally acting OT ligands on consumption of palatable solutions had been previously reported. We found that IV OT did not change episodic intake of individually presented palatable solutions containing 10% sucrose, 0.1% saccharin, combined 10% sucrose-0.1% saccharin or 4.1%. Intralipid and it failed to affect daily scheduled consumption of a sucrose solution in non-deprived rats. In a two-bottle choice test, IV OT did not shift animals' preference from sucrose to Intralipid. Finally, OT injected IV prior to the simultaneous presentation chow and a sucrose solution in food-deprived rats significantly decreased chow intake, whereas sugar water consumption remained unchanged. We conclude that IV OT reduces deprivation-induced chow intake without causing aversion, but the dose effective in decreasing energy-driven consumption of high-calorie food fails to affect consumption of palatable calorie-dilute solutions. Copyright © 2017 Elsevier Inc. All rights reserved.

A Novel Newborn Rat Kernicterus Model Created by Injecting a Bilirubin Solution into the Cisterna Magna

PubMed Central

Song, Sijie; Hu, Ying; Gu, Xianfang; Si, Feifei; Hua, Ziyu

2014-01-01

Background Kernicterus still occurs around the world; however, the mechanism of bilirubin neurotoxicity remains unclear, and effective treatment strategies are lacking. To solve these problems, several kernicterus (or acute bilirubin encephalopathy) animal models have been established, but these models are difficult and expensive. Therefore, the present study was performed to establish a novel kernicterus model that is simple and affordable by injecting unconjugated bilirubin solution into the cisterna magna (CM) of ordinary newborn Sprague-Dawley (SD) rats. Methods On postnatal day 5, SD rat pups were randomly divided into bilirubin and control groups. Then, either bilirubin solution or ddH2O (pH = 8.5) was injected into the CM at 10 µg/g (bodyweight). For model characterization, neurobehavioral outcomes were observed, mortality was calculated, and bodyweight was recorded after bilirubin injection and weaning. Apoptosis in the hippocampus was detected by H&E staining, TUNEL, flow cytometry and Western blotting. When the rats were 28 days old, learning and memory ability were evaluated using the Morris water maze test. Results The bilirubin-treated rats showed apparently abnormal neurological manifestations, such as clenched fists, opisthotonos and torsion spasms. Bodyweight gain in the bilirubin-treated rats was significantly lower than that in the controls (P<0.001). The early and late mortality of the bilirubin-treated rats were both dramatically higher than those of the controls (P = 0.004 and 0.017, respectively). Apoptosis and necrosis in the hippocampal nerve cells in the bilirubin-treated rats were observed. The bilirubin-treated rats performed worse than the controls on the Morris water maze test. Conclusion By injecting bilirubin into the CM, we successfully created a new kernicterus model using ordinary SD rats; the model mimics both the acute clinical manifestations and the chronic sequelae. In particular, CM injection is easy to perform; thus, more stable models for follow-up study are available. PMID:24796550

Rat organic solute carrier protein 1 (rOscp1) mediated the transport of organic solutes in Xenopus laevis oocytes: isolation and pharmacological characterization of rOscp1.

PubMed

Izuno, Hisanori; Kobayashi, Yasuna; Sanada, Yutaka; Nihei, Daisuke; Suzuki, Masako; Kohyama, Noriko; Ohbayashi, Masayuki; Yamamoto, Toshinori

2007-09-22

Rat organic solute carrier protein 1 (rOscp1) was isolated from a rat testis cDNA library. Isolated rOscp1 cDNA consisted of 1089 base pairs that encoded a 363-amino acid protein, and the amino acid sequence was 88% and 93% identical to that of human OSCP1 (hOSCP1) and mouse Oscp1 (mOscp1), respectively. The message for rOscp1 is highly detected in rat testis. When expressed in X. oocytes, rOscp1 mediated the high affinity transport of p-aminohippurate (PAH) with a Km value of 15.7+/-1.9 microM, and rOscp1-mediated organic solutes were exhibited in time- and Na+-independent manners. rOscp1 also transported various structurally heterogenous compounds such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), and taurocholate with some differences in substrate specificity compared with hOSCP1. Immunohistochemical analysis revealed that the rOscp1 protein is localized in the basal membrane side of Sertoli cells as observed in mouse testis [Kobayashi et al., 2007; Kobayashi, Y., Tsuchiya, A., Hayashi, T., Kohyama, N., Ohbayashi, M., Yamamoto, T., 2007. Isolation and characterization of polyspecific mouse organic solute carrier protein 1 (mOscp1). Drug Metabolism and Disposition 35 (7), 1239-1245]. Thus, the present results indicate that a newly isolated cDNA clone, rOscp1, is a polyspecific organic solute carrier protein with some differences in substrate specificity compared with human and mouse OSCP1.

Exposure to predator odor influences the relative use of multiple memory systems: role of basolateral amygdala.

PubMed

Leong, Kah-Chung; Packard, Mark G

2014-03-01

In a dual-solution plus-maze task in which both hippocampus-dependent place learning and dorsolateral striatal-dependent response learning provide an adequate solution, the relative use of multiple memory systems can be influenced by emotional state. Specifically, pre-training peripheral or intra-basolateral (BLA) administration of anxiogenic drugs result in the predominant use of response learning. The present experiments were designed to extend these findings by examining whether exposure to a putatively ethologically valid stressor would also produce a predominant use of response learning. In experiment 1, adult male Long-Evans rats were exposed to either a predator odor (trimethylthiazoline [TMT], a component of fox feces) or distilled water prior to training in a dual-solution water plus maze task. On a probe trial 24h following task acquisition, rats previously exposed to TMT predominantly displayed response learning relative to control animals. In experiment 2, rats trained on a single-solution plus maze task that required the use of response learning displayed enhanced acquisition following pre-training TMT exposure. In experiment 3, rats exposed to TMT or distilled water were trained in the dual-solution task and received post-training intra-BLA injections of the sodium channel blocker bupivacaine (1.0% solution, 0.5 μl) or saline. Relative to control animals, rats exposed to TMT predominantly displayed response learning on the probe trial, and this effect was blocked by neural inactivation of the BLA. The findings indicate that (1) the use of dorsal striatal-dependent habit memory produced by emotional arousal generalizes from anxiogenic drug administration to a putatively ecologically valid stressor (i.e. predator odor), and (2) the BLA mediates the modulatory effect of exposure to predator odor on the relative use of multiple memory systems. Copyright © 2013 Elsevier Inc. All rights reserved.

The type of caloric sweetener added to water influences weight gain, fat mass, and reproduction in growing Sprague-Dawley female rats.

PubMed

Light, Heather R; Tsanzi, Embedzayi; Gigliotti, Joseph; Morgan, Keri; Tou, Janet C

2009-06-01

Caloric sweetened beverages have been suggested to be a major dietary contributor to weight gain, particularly among adolescents. Dietary recommendations are for moderating intakes of added sugars; however, the question remains whether certain types of sugars should be limited. The objective of this study was to determine the effect of drinking different caloric sweetened beverages on the development of adiposity, metabolic, and endocrine disorders. Young (age 28 days) female Sprague-Dawley rats (n = 8-9 rats/group) were randomly assigned to drink either deionized distilled water (ddH2O) or ddH2O sweetened with 13% (w/v) glucose, sucrose, fructose or high fructose corn syrup 55 (HFCS-55) for 8 weeks. Rats drinking caloric sweetened solutions failed to completely compensate for liquid calories ingested by reducing their consumption of solid food. This resulted in greater total energy intake compared to the ddH2O control; however, there was no significant difference in total energy intake between rats drinking sucrose, fructose or HFCS-55. Of the different caloric sweeteners, only rats drinking HFCS-55 had greater (P < 0.05) final body weights and fat mass compared to the rats drinking ddH2O or glucose solution. This may have occurred because drinking HFCS-55 solution promoted a faster body weight gain. Adiposity induced by caloric sweetened water was not accompanied by metabolic disorders indicated by the absence of dyslipidemia and no differences in fasting serum glucose, insulin or C-peptide among the treatment groups. However, rats drinking HFCS-55 showed lengthened estrous cycles due to prolonged estrus. Based on this study, the type of caloric sweetener added to beverages should be considered when making dietary recommendation for reducing excess body weight and related health risk.

Strychnos nux-vomica extract and its ultra-high dilution reduce voluntary ethanol intake in rats.

PubMed

Sukul, N C; Ghosh, S; Sinhababu, S P; Sukul, A

2001-04-01

To see whether Strychnos nux-vomica extract (mother tincture [MT]), its potency Nux 30c, and its principal alkaloid, strychnine, could reduce voluntary ethanol intake in rats. To analyze the solution structure of Nux MT, Nux 30c, 90% ethanol, and ethanol 30c by means of electronic (ES) and nuclear nuclear magnetic resonance (NMR) spectra. Potentially alcoholic rats were first given 20% ethanol and then kept on a two-choice bottle, one with 20% ethanol and another with tap water. These rats were given the following oral treatments for 15 days: group 1, control; group 2, strychnine at 0.36 mg/kg per day; group 3, ethanolic extract of S. nux-vomica seeds (Nux MT) at 3.6 mg/kg per day; and group 4, Nux 30c at 0.05 mL/d per rat. Nux 30c was prepared by successive dilution of Nux MT and 90% ethanol (1:100) and sonication at 20 kHz for 30 seconds in 30 steps. Both Nux MT and Nux 30c significantly reduced ethanol intake and increased water intake in rats. ES of two dilutions of Nux MT and Nux 30c showed intersections at more than one point suggesting existence of molecular complexes. ES of Nux MT in CCl4 showed a red shift when 90% ethanol was added indicating molecular complexation and charge transfer interaction between ethanol and Nux compounds. NMR spectra of Nux MT, 90% ethanol, ethanol 30c, and Nux 30c indicated a change in solution structure of the medium (90% ethanol) of Nux 30c. Nux MT and Nux 30c could reduce ethanol intake in rats. The altered solution structure of Nux 30c is thought to mimic Nux MT and produce ethanol aversion in rats.

New researches on teratogenic effects of singulair using optical methods

NASA Astrophysics Data System (ADS)

Valiulis, A.; Gaidelis, P.; Januskevicius, A.

2005-11-01

It was proved that singulair does not cause macroscopical and histological alterations on the animals, but it is not known its influence on the molecular level. The purpose of our work is to explore teratogenic effects of singulair on the animals by using our non-standard method (which is preciser than standard method, because it showes not only macroscopical, but also and molecular alterations in the damage tissue), hoping, that it would be the help for the pregnant women to decide can they take this drug or not. We injected singulair (25 mg/kg of rat) to one group of pregnant rats in rareripe period (from the first to the eight day) of embryogenesis. Another group of pregnant rats got injections of teratogenic substance ochratoxin A (25 pg/kg of rat) in the same period of embryogenesis. The third group got injections of physiological solution. There were taken 10 rats to everyone group. In the end of rareripe period we took a blood sample from each rat of the rats and wrote a spectrum of everyone sample by using spectrophotometer. We got, that spectra of solutions from the first and the third group were very similar (there were no statistical difference) and spectra of solutions from the second group were very similar (there were no statistical difference), but statistical difference was between the first and the third group together and the second group in the zone of 200-350 nm. At the twentieth day of pregnancy we made Caesarean section to all of the rats, compared embryos interpendent and did not find any defects in anyone of them through all the first and the third group, but everyone embryo from the second group had a lot of defects.

Comparison of three chronic dialysis models.

PubMed

Peng, W X; Guo, Q Y; Liu, S M; Liu, C Z; Lindholm, B; Wang, T

2000-01-01

The chronic peritoneal dialysis model is important for understanding the pathophysiology of peritoneal transport and for studying biocompatibility of peritoneal dialysis solutions. In this study, we compared three different chronic peritoneal dialysis models. A peritoneal catheter was placed in 23 male Sprague-Dawley rats, 12 of which had an intact omentum (model 1) and 11 of which received an omentectomy (model 2). Seven other rats, without a catheter, received a daily intraperitoneal injection (model 3). Each rat received a daily infusion of 25 mL of 3.86% glucose dialysis solution either through the catheter (models 1 and 2) or through injection (model 3) for 4 weeks. Then, a 4-hour dwell study using 3.86% glucose solution with an intraperitoneal volume marker and frequent dialysate and blood sampling was performed in each rat. The intraperitoneal volume was significantly lower in all the dialysis groups as compared to a control group (n = 6) in which the rats had no chronic dialysate exposure. The peritoneal fluid absorption rate, as well as the direct lymphatic absorption rate, was significantly higher in the three dialysis groups as compared to the control group. In general, no significant differences were seen in any of the parameters among the three dialysis models. Owing to catheter obstruction, three rats in model 1 and four rats in model 2 were lost during dialysis. Histological examination showed no significant differences among the three dialysis groups. Our results suggest that omentectomy may not be necessary in the chronic peritoneal dialysis model when using dialysate infusion and no drainage. Based on the present study, we think that perhaps model 1 may be the method of choice to test new peritoneal dialysis solutions. However, owing to its simplicity, model 3 could also be used if great care is taken to avoid puncturing the intestine or injecting into the abdominal wall.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meisner, L. L., E-mail: llm@isps.tsc.ru; Meisner, S. N.; National Research Tomsk State University, 36, Lenina Avenue, Tomsk, 634050

The corrosion resistance behavior and cytotoxicity of binary NiTi-base alloy specimens subjected to surface modification by silicon ion beams and the proliferative ability of mesenchymal stem cells (MSC) of rat marrow on an ion-implanted surface of the alloy have been studied. The silicon ion beam processing of specimen surfaces is shown to bring about a nearly two-fold improvement in the corrosion resistance of the material to attack by acqueous solutions of NaCl and human plasma and a drastic decrease in the nickel concentration after immersion of the specimens into the solutions for ∼3400 and ∼6000 h, respectively. It is foundmore » that MSC proliferation strongly depends on the surface structure, roughness and chemical condition of NiTi implants.« less

Butanol fraction of Parkia biglobosa (Jacq.) G. Don leaves enhance pancreatic β-cell functions, stimulates insulin secretion and ameliorates other type 2 diabetes-associated complications in rats.

PubMed

Ibrahim, Mohammed Auwal; Habila, James Dama; Koorbanally, Neil Anthony; Islam, Md Shahidul

2016-05-13

Ethnopharmacological surveys have reported that Parkia biglobosa (Jacq.) G. Don (Leguminosae) is among the plants commonly used in the traditional management of diabetes mellitus in Nigeria and Togo. This study investigated the anti-diabetic activity of the butanol fraction of P. biglobosa leaves (PBBF) in a type 2 diabetes (T2D) model of rats and a possible bioactive compound in the fraction. T2D was induced by feeding rats with a 10% fructose solution ad libitum for two weeks followed by an intraperitoneal injection of 40mg/kg body weight streptozotocin and the animals were orally treated with 150 and 300mg/kg BW of the PBBF for five days in a week. Another group of rats was non-diabetic but similarly administered with 300mg/kg BW of the PBBF. Food and fluid intakes, body weight changes and blood glucose levels were monitored during the experiment while other relevant diabetes-associated parameters were measured at the end of the experiment. The PBBF treatments significantly (P<0.05) decreased the blood glucose levels and improved the glucose tolerance ability compared to untreated diabetic rats. Furthermore, the treatments were found to improve pancreatic β cell function (HOMA-β), stimulate insulin secretions, decrease insulin resistance (HOMA-IR), restore liver glycogen, ameliorate serum dyslipidaemia and prevent hepatic and renal damages compared to untreated diabetic rats. Phytochemical analysis of the fraction led to the isolation of lupeol which inhibited α-glucosidase and α-amylase in non-competitive and uncompetitive inhibition patterns respectively. It was concluded that PBBF possessed remarkable anti-T2D activity which is mediated through modulation of β-cell function and stimulation of insulin secretion and the lower dose (150mg/kg BW) was found optimum for anti-T2D activity compared to the high dose (300mg/kg BW) in this study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Over-expressed Bax inhibitor 1 (BI-1) inhibits apoptosis of hippocampal neurons via endoplasmic reticulum IRE1-JNK pathway in rats with subarachnoid hemorrhage].

PubMed

Liu, Jiaxin; Zhou, Shuai; Qian, Xiying; Zhang, Yueting; Zhao, Jianhua

2017-10-01

Objective To investigate the protective effect of lentivirus-mediated BI-1 overexpression on hippocampal neurons in rats with subarachnoid hemorrhage (SAH) and the relationship with endoplasmic reticulum IRE1-JNK signaling pathway. Methods The lentivirus solution of BI-1 over-expression was injected into the brain of rats 24 hours before SAH rat model was established by intravascular puncture method. At 24 hours after modeling, the brain water content and neurological score of the rats were measured. The apoptosis of hippocampal neurons was detected by TUNEL assay. Western blotting was used to detect the expressions of BI-1 protein and endoplasmic reticulum stress (ERS) marker proteins GRP78 and IRE1. ERS in hippocampal neurons of the rats with SAH was intervened by IRE1α-specific inhibitor KIRA6, and then the protein expressions of p-IRE1, p-JNK, Bax, Bcl2 and caspase-3 were detected by Western blotting. Results BI-1 over-expression improved neurobehavioral score, decreased brain water content and hippocampal neuron apoptosis rate, and also down-regulated GRP78 and IRE1 protein levels in the rats with SAH. Both the interference of KIRA6 and the over-expression of BI-1 inhibited the expressions of p-IRE1, p-JNK, Bax and caspase-3, and promoted the expression of anti-apoptotic protein Bcl2. Conclusion Over-expression of BI-1 can inhibit the apoptosis of hippocampal neurons in rats with SAH by inhibiting the activation of ERS-mediated IRE1-JNK signaling pathway, thus ultimately attenuating the early brain injury following SAH.

The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes.

PubMed

Bergantin, Leandro Bueno; Figueiredo, Leonardo Bruno; Godinho, Rosely Oliveira

2011-12-01

The molecular regulation of skeletal muscle proteolysis and the pharmacological screening of anticatabolic drugs have been addressed by measuring tyrosine release from prepubertal rat skeletal muscles, which are thin enough to allow adequate in vitro diffusion of oxygen and substrates. However, the use of muscle at accelerated prepubertal growth has limited the analysis of adult muscle proteolysis or that associated with aging and neurodegenerative diseases. Here we established the adult rat lumbrical muscle (4/hindpaw; 8/rat) as a new in situ experimental model for dynamic measurement of skeletal muscle proteolysis. By incubating lumbrical muscles attached to their individual metatarsal bones in Tyrode solution, we showed that the muscle proteolysis rate of adult and aged rats (3-4 to 24 mo old) is 45-25% of that in prepubertal animals (1 mo old), which makes questionable the usual extrapolation of proteolysis from prepubertal to adult/senile muscles. While acute mechanical injury or 1- to 7-day denervation increased tyrosine release from adult lumbrical muscle by up to 60%, it was reduced by 20-28% after 2-h incubation with β-adrenoceptor agonists, forskolin or phosphodiesterase inhibitor IBMX. Using inhibitors of 26S-proteasome (MG132), lysosome (methylamine), or calpain (E64/leupeptin) systems, we showed that ubiquitin-proteasome is accountable for 40-50% of total lumbrical proteolysis of adult, middle-aged, and aged rats. In conclusion, the lumbrical model allows the analysis of muscle proteolysis rate from prepubertal to senile rats. By permitting eight simultaneous matched measurements per rat, the new model improves similar protocols performed in paired extensor digitorum longus (EDL) muscles from prepubertal rats, optimizing the pharmacological screening of drugs for anticatabolic purposes.

High-monosaccharide intake inhibits anorexigenic hypothalamic insulin response in male rats.

PubMed

Ramos, Viviane Wagner; Batista, Leandro Oliveira; Cordeiro, Elisaldo Mendes; Oliveira, Gustavo Vieira; Albuquerque, Kelse Tibau

2018-06-01

The aim of this research is to evaluate if intake of 20% fructose solution is able to change the anorexigenic hypothalamic insulin action. Thirty day-old male Wistar rats were randomly assigned to one of the following groups: standard chow and water for the rats (Control group, C) and standard chow and 20% fructose solution for the rats (Fructose group, F).These treatments lasted 8 weeks. Three-month-old rats from group C and F received insulin or saline intracerebroventricular injections for evaluation of 24 h food intake, phosphorylated forms of the IR (p-IR) and Akt (p-Akt) proteins and quantified hypothalamic insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) proteins. Insulin injection was able to decrease food intake in group C compared to 0.9% saline. However, insulin infusion failed to inhibit 24 h food intake in group F compared to 0.9% saline. The hypothalamic content of the IRS-1 was 37% higher in group F as well as p-Akt protein was significant higher vs. group C. We concluded that the 20% fructose solution compromised insulin signaling considering that it inhibited the anorexigenic hypothalamic response to acute injection of this hormone and increase of IRS-1 and p-Akt content.

Effect of exposure to similar flavours in sensory specific satiety: Implications for eating behaviour.

PubMed

González, Ana; Recio, Sergio Andrés; Sánchez, Jesús; Gil, Marta; de Brugada, Isabel

2018-08-01

Sensory-specific satiety (SSS) refers to a decline in pleasantness of eaten foods in comparison to other non-ingested meals. Although SSS is specific to the eaten food, it can also generalize to other meals that share similar properties to the satiated food. It is possible that this phenomenon could become more specific after extensive experience, as repeated exposure to an assortment of similar food could cause perceptual learning (i.e. an increase in the distinctiveness of each specific item). This in turn would reduce generalization from the consumed food to other similar products, so they will be more readily consumed. To assess this hypothesis, two experiments were carried out using rats as experimental subjects and flavoured solutions as stimuli. In Experiment 1 our main goal was to find the basic SSS effect with two different solutions. As expected, the results showed that rats tended to consume a higher amount of non-sated solutions in comparison to sated ones. Experiment 2 evaluated how repeated exposure to two similar solutions affected generalization of the SSS. Results showed that rats that did not have extensive exposure to the flavoured solutions showed no preference for the non-sated drink. However, rats that had repeated exposure to the flavours showed SSS. The results suggest that easy and continuous access to a high variety of similar unhealthy foods might have long-term effects on food consumption, and highlight a potential mechanism linking obesogenic environments with dietary habits. Copyright © 2018. Published by Elsevier Ltd.

Adolescent Alcohol Drinking Renders Adult Drinking BLA-Dependent: BLA Hyper-Activity as Contributor to Comorbid Alcohol Use Disorder and Anxiety Disorders

PubMed Central

Moaddab, Mahsa; Mangone, Elizabeth; McDannald, Michael A.

2017-01-01

Adolescent alcohol drinking increases the risk for alcohol-use disorder in adulthood. Yet, the changes in adult neural function resulting from adolescent alcohol drinking remain poorly understood. We hypothesized that adolescent alcohol drinking alters basolateral amygdala (BLA) function, making alcohol drinking BLA-dependent in adulthood. Male, Long Evans rats were given voluntary, intermittent access to alcohol (20% ethanol) or a bitter, isocaloric control solution, across adolescence. Half of the rats in each group received neurotoxic BLA lesions. In adulthood, all rats were given voluntary, intermittent access to alcohol. BLA lesions reduced adult alcohol drinking in rats receiving adolescent access to alcohol, but not in rats receiving adolescent access to the control solution. The effect of the BLA lesion was most apparent in high alcohol drinking adolescent rats. The BLA is essential for fear learning and is hyper-active in anxiety disorders. The results are consistent with adolescent heavy alcohol drinking inducing BLA hyper-activity, providing a neural mechanism for comorbid alcohol use disorder and anxiety disorders. PMID:29135933

Protective effect of mannitol, glucose-fructose-sucrose-maltose mixture, and natural honey hyperosmolar solutions against ethanol-induced gastric mucosal damage in rats.

PubMed

Gharzouli, K; Gharzouli, A; Amira, S; Khennouf, S

2001-06-01

We have previously shown that natural honey is able to protect the rat stomach against acute ethanol- and indomethacin-induced lesions. The present investigations were undertaken to examine the role of intraluminal osmolality in this protective effect. Mannitol, glucose-fructose-sucrose-maltose mixture (GFSM) and natural honey (300, 600, 1800 mOsmol/kg water) were given orally to rats 30 min before administration of 70% ethanol for a further 15-min period. Lesions area of the excised stomachs were evaluated. Pylorus-ligated stomachs were filled with mannitol, GFSM mixture and honey (1800 mOsmol/kg water) to test the effect of the hyperosmolar solutions on gastric fluid content and acid secretion. The rate of gastric emptying of the three test solutions (1800 mOsmol/kg) was measured by the phenol red method. Intragastric administration of mannitol, GFSM mixture or honey prevented the formation of mucosal lesions in an osmolality-dependent manner. Using the pylorus-ligated stomach model, the test solutions led to a net increase of luminal fluid volume without affecting acid content. Hyperosmolar solutions presented a delayed gastric emptying if compared to a nonnutrient solution made of carboxymethyl cellulose. The observed results suggest that hyperosmolar solutions can prevent the formation of hemorrhagic lesions by luminal dilution of the necrotising agent and acid, an effect which may be potentiated by a lowered gastric emptying rate.

Improved biochemical preservation of heart slices during cold storage.

PubMed

Bull, D A; Reid, B B; Connors, R C; Albanil, A; Stringham, J C; Karwande, S V

2000-01-01

Development of myocardial preservation solutions requires the use of whole organ models which are animal and labor intensive. These models rely on physiologic rather than biochemical endpoints, making accurate comparison of the relative efficacy of individual solution components difficult. We hypothesized that myocardial slices could be used to assess preservation of biochemical function during cold storage. Whole rat hearts were precision cut into slices with a thickness of 200 microm and preserved at 4 degrees C in one of the following solutions: Columbia University (CU), University of Wisconsin (UW), D5 0.2% normal saline with 20 meq/l KCL (QNS), normal saline (NS), or a novel cardiac preservation solution (NPS) developed using this model. Myocardial biochemical function was assessed by ATP content (etamoles ATP/mg wet weight) and capacity for protein synthesis (counts per minute (cpm)/mg protein) immediately following slicing (0 hours), and at 6, 12, 18, and 24 hours of cold storage. Six slices were assayed at each time point for each solution. The data were analyzed using analysis of variance and are presented as the mean +/- standard deviation. ATP content was higher in the heart slices stored in the NPS compared to all other solutions at 6, 12, 18 and 24 hours of cold storage (p < 0.05). Capacity for protein synthesis was higher in the heart slices stored in the NPS compared to all other solutions at 6, 12, and 18 hours of cold storage (p < 0.05). CONCLUSIONS This myocardial slice model allows the rapid and efficient screening of cardiac preservation solutions and their components using quantifiable biochemical endpoints. Using this model, we have developed a novel preservation solution which improves the biochemical function of myocardial slices during cold storage.

Effect of apitherapy products against carbon tetrachloride-induced toxicity in Wistar rats.

PubMed

Andriţoiu, Călin Vasile; Andriţoiu, Vasile; Cuciureanu, Magdalena; Nica-Badea, Delia; Bibire, Nela; Popa, Marcel

2014-01-01

The present paper aimed to evaluate the influence of apitherapy diet in Wistar rats with carbon tetrachloride induced hepatotoxicity, by the means of biochemical determinations and histopathological changes of liver, spleen, pancreas and testicular tissue. The experiment was carried out on six groups of male Wistar rats. Hepatic lesions were induced by intraperitoneal injection of carbon tetrachloride (dissolved in paraffin oil, 10% solution), 2 mL per 100 g, every two days, for two weeks. Hepatoprotection was achieved with two-apitherapy diet formulations (containing honey, pollen, propolis, Apilarnil, with/without royal jelly), that have been administered for six up to nine weeks. The biochemical results revealed that the two-apitherapy diet formulations had a positive effect improving the enzymatic, lipid, and protein profiles, coagulation, mineral parameters and also the bilirubin levels, after six weeks of treatment. The histopathological results demonstrated the benefit of the two-apitherapy diet formulations on reducing the toxicity of liver, spleen and pancreas in laboratory animals, after six and nine weeks, respectively. In conclusion, apitherapy products have a hepatoprotective effect in carbon tetrachloride-induced hepatopathy.

Improvement of semi-quantitative small-animal PET data with recovery coefficients: a phantom and rat study.

PubMed

Aide, Nicolas; Louis, Marie-Hélène; Dutoit, Soizic; Labiche, Alexandre; Lemoisson, Edwige; Briand, Mélanie; Nataf, Valérie; Poulain, Laurent; Gauduchon, Pascal; Talbot, Jean-Noël; Montravers, Françoise

2007-10-01

To evaluate the accuracy of semi-quantitative small-animal PET data, uncorrected for attenuation, and then of the same semi-quantitative data corrected by means of recovery coefficients (RCs) based on phantom studies. A phantom containing six fillable spheres (diameter range: 4.4-14 mm) was filled with an 18F-FDG solution (spheres/background activity=10.1, 5.1 and 2.5). RCs, defined as measured activity/expected activity, were calculated. Nude rats harbouring tumours (n=50) were imaged after injection of 18F-FDG and sacrificed. The standardized uptake value (SUV) in tumours was determined with small-animal PET and compared to ex-vivo counting (ex-vivo SUV). Small-animal PET SUVs were corrected with RCs based on the greatest tumour diameter. Tumour proliferation was assessed with cyclin A immunostaining and correlated to the SUV. RCs ranged from 0.33 for the smallest sphere to 0.72 for the largest. A sigmoidal correlation was found between RCs and sphere diameters (r(2)=0.99). Small-animal PET SUVs were well correlated with ex-vivo SUVs (y=0.48x-0.2; r(2)=0.71) and the use of RCs based on the greatest tumour diameter significantly improved regression (y=0.84x-0.81; r(2)=0.77), except for tumours with important necrosis. Similar results were obtained without sacrificing animals, by using PET images to estimate tumour dimensions. RC-based corrections improved correlation between small-animal PET SUVs and tumour proliferation (uncorrected data: Rho=0.79; corrected data: Rho=0.83). Recovery correction significantly improves both accuracy of small-animal PET semi-quantitative data in rat studies and their correlation with tumour proliferation, except for largely necrotic tumours.

The ototoxic effect of intratympanic terbinafine applied in the middle ear of rats

PubMed Central

2013-01-01

Background Otomycosis is defined as an infection of the external ear canal with fungal agents. The treatment of the disease is cleansing and drying of the external ear canal, identification and treatment of any predisposing factors and application of topical antifungal agents. Terbinafine is used as an antifungal agent to treat otomycosis. We proposed to investigate the probable ototoxic effect of terbinafine solution on auditory brain stem response (ABR) and distortion product otoacoustic emission (DPOAE) when applied intratympanically in the middle ear of rats. Methods The experiment was performed on 30 female Wistar albino rats. Thirty animals were divided into three groups of 10 animals each. 1% terbinafine solution was administered to the first group (group T). The second group (group G) was administered 40 mg/ml gentamicin solution (ototoxic control). The third group (group S) was administered saline solution (negative control). Baseline DPOAE measurements and ABR testing from the left ears were obtained from the animals in all groups under general anesthesia. Ear solutions were applied in the middle ear intratympanically with a dental needle. Treatment was initiated after baseline measurements and repeated once every two days for fifteen days. Results Pre and post-treatment DPOAE responses for all tested frequencies of group T and Group S showed no statistically significant difference. However, the group G demonstrated a significant change in ABR thresholds and DPOAE responses. Conclusions Terbinafine solution is a broad spectrum antifungal agent effective in the treatment of otomycosis. The present study demonstrated that its direct administration in the middle ear of rats does not affect inner ear function as measured by ABR and DPOAE responses. PMID:23663536

Efficacy of methylene blue in an experimental model of calcium channel blocker-induced shock.

PubMed

Jang, David H; Donovan, Sean; Nelson, Lewis S; Bania, Theodore C; Hoffman, Robert S; Chu, Jason

2015-04-01

Calcium channel blocker poisonings account for a substantial number of reported deaths from cardiovascular drugs. Although supportive care is the mainstay of treatment, experimental therapies such as high-dose insulin-euglycemia and lipid emulsion have been studied in animal models and used in humans. In the most severe cases, even aggressive care is inadequate and deaths occur. In both experimental models and clinical cases of vasodilatory shock, methylene blue improves hemodynamic measures. It acts as a nitric oxide scavenger and inhibits guanylate cyclase that is responsible for the production of cyclic guanosine monophosphate (cGMP). Excessive cGMP production is associated with refractory vasodilatory shock in sepsis and anaphylaxis. The aim of this study is to determine the efficacy of methylene blue in an animal model of amlodipine-induced shock. Sprague-Dawley rats were anesthetized, ventilated, and instrumented for continuous blood pressure and pulse rate monitoring. The dose of amlodipine that produced death within 60 minutes was 17 mg/kg per hour (LD50). Rats were divided into 2 groups: amlodipine followed by methylene blue or amlodipine followed by normal saline solution, with 15 rats in each group. Rats received methylene blue at 2 mg/kg during 5 minutes or an equivalent amount of normal saline solution in 3 intervals from the start of the protocol: minutes 5, 30, and 60. The animals were observed for a total of 2 hours after the start of the protocol. Mortality risk and survival time were analyzed with Fisher's exact test and Kaplan-Meier survival analysis with the log rank test. Overall, 1 of 15 rats (7%) in the saline solution-treated group survived to 120 minutes compared with 5 of 15 (33%) in the methylene blue-treated group (difference -26%; 95% confidence interval [CI] -54% to 0.3%). The median survival time for the normal saline solution group was 42 minutes (95% CI 28.1 to 55.9 minutes); for the methylene blue group, 109 minutes (95% CI 93.9 to 124.1 minutes). Pulse rate and mean arterial pressure (MAP) differences between groups were analyzed until 60 minutes. Pulse rate was significantly higher in the methylene blue-treated group beginning 25 minutes after the start of the amlodipine infusion (95% CI 30 to 113 minutes) that was analyzed until 60 minutes. MAP was significantly higher in the methylene blue-treated group starting 25 minutes after the amlodipine infusion (95% CI 2 to 30 minutes) that was analyzed until 60 minutes. Methylene blue did not result in a significant difference in mortality risk. There was an increased pulse rate, MAP, and median survival time in the methylene blue group. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Complex motivated behaviors for natural rewards following a binge-like regimen of morphine administration: mixed phenotypes of anhedonia and craving after short-term withdrawal

PubMed Central

Bai, Yunjing; Li, Yingying; Lv, Yaodi; Liu, Zhengkui; Zheng, Xigeng

2014-01-01

The anhedonia-like behaviors following about 1-week withdrawal from morphine were examined in the present study. Male rats were pretreated with either a binge-like morphine paradigm or daily saline injection for 5 days. Three types of natural reward were used, food reward (2.5, 4, 15, 30, 40, and 60% sucrose solutions), social reward (male rat) and sexual reward (estrous female rat). For each type of natural stimulus, consummatory behavior and motivational behaviors under varied testing conditions were investigated. The results showed that the morphine-treated rats significantly reduced their consumption of 2.5% sucrose solution during the 1-h consumption testing and their operant responding for 15, 30, and 40% sucrose solutions under a fixed ratio 1 (FR1) schedule. However, performance under a progressive ratio (PR) schedule increased in morphine-treated rats reinforced with 60% sucrose solution, but not in those reinforced with sucrose concentrations lower than 60%. Pretreatment with morphine significantly decreased the male rats' ejaculation frequency (EF) during the 1-h copulation testing, and impaired the maintenance of appetitive motivations to sexual and social stimuli under a free-approach condition. Moreover, the morphine-treated rats demonstrated a diminished motivation to approach social stimulus in the effort-based appetitive behavior test but showed a remarkable increase in motivation to approach sexual stimulus in the risky appetitive behavior test. These results demonstrated some complex motivated behaviors following about 1 week of morphine withdrawal: (1) The anhedonia-like behavior was consistently found in animals withdrawn from morphine. However, for a given reward, there was often a dissociation of the consummatory behaviors from the motivational behaviors, and whether the consummatory or the motivational anhedonia-like behaviors could be discovered heavily depended on the type and magnitude of the reward and the type of testing task; (2) These anhedonia-like behaviors coexisted with a craving for the high-incentive reward which was evidenced by the increased PR performance for the 60% sucrose solution and the heightened risky appetitive behavior for the sexual stimulus. The craving for the high-incentive reward alongside with the impaired inhibitory control in drug-withdrawn subjects might form one of psychological mechanisms underlying drug relapse after withdrawal. PMID:24550799

The protective effect of dexmedetomidine in a rat ex vivo lung model of ischemia-reperfusion injury.

PubMed

Zhou, Yan; Zhou, Xinqiao; Zhou, Wenjuan; Pang, Qingfeng; Wang, Zhiping

2018-01-01

To investigate the effect of dexmedetomidine (Dex) in a rat ex vivo lung model of ischemia-reperfusion injury. An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury. Drugs were added to the perfusion solution for reperfusion. Lung injury was assessed by histopathological changes, airway pressure (Res), lung compliance (Compl), perfusion flow (Flow), pulmonary venous oxygen partial pressure (PaO2), and lung wet/dry (W/D) weight ratio. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), 78 kDa glucose-regulated protein (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured, respectively. The introduction of Dex attenuated the post-ischemia-reperfusion lung damage and MDA level, improved lung histology, W/D ratio, lung injury scores and SOD activity. Decreased mRNA and protein levels of GRP78 and CHOP compared with the IR group were observed after Dex treatment. The effect of Dex was dosage-dependence and a high dose of Dex (10 nM) was shown to confer the strongest protective effect against lung damage (P<0.05). Yohimbine, an α2 receptor antagonist, significantly reversed the protective effect of Dex in lung tissues (P<0.05). Dex reduced ischemia-reperfusion injury in rat ex vivo lungs.

Polyethylene glycol rinse solution: An effective way to prevent ischemia-reperfusion injury

PubMed Central

Zaouali, Mohamed Amine; Bejaoui, Mohamed; Calvo, Maria; Folch-Puy, Emma; Pantazi, Eirini; Pasut, Gianfranco; Rimola, Antoni; Ben Abdennebi, Hassen; Adam, René; Roselló-Catafau, Joan

2014-01-01

AIM: To test whether a new rinse solution containing polyethylene glycol 35 (PEG-35) could prevent ischemia-reperfusion injury (IRI) in liver grafts. METHODS: Sprague-Dawley rat livers were stored in University of Wisconsin preservation solution and then washed with different rinse solutions (Ringer’s lactate solution and a new rinse solution enriched with PEG-35 at either 1 or 5 g/L) before ex vivo perfusion with Krebs-Heinseleit buffer solution. We assessed the following: liver injury (transaminase levels), mitochondrial damage (glutamate dehydrogenase activity), liver function (bile output and vascular resistance), oxidative stress (malondialdehyde), nitric oxide, liver autophagy (Beclin-1 and LCB3) and cytoskeleton integrity (filament and globular actin fraction); as well as levels of metalloproteinases (MMP2 and MMP9), adenosine monophosphate-activated protein kinase (AMPK), heat shock protein 70 (HSP70) and heme oxygenase 1 (HO-1). RESULTS: When we used the PEG-35 rinse solution, reduced hepatic injury and improved liver function were noted after reperfusion. The PEG-35 rinse solution prevented oxidative stress, mitochondrial damage, and liver autophagy. Further, it increased the expression of cytoprotective heat shock proteins such as HO-1 and HSP70, activated AMPK, and contributed to the restoration of cytoskeleton integrity after IRI. CONCLUSION: Using the rinse solution containing PEG-35 was effective for decreasing liver graft vulnerability to IRI. PMID:25473175

[Effects of Salvianolate on Myosin Heavy Chain in Cardiomyocytes of Congestive Heart Failure Rats].

PubMed

Chen, Cheng; Zou, Xiang-gu; Qiu, Shan-dong; Chen, Hui; Chen, Yong-zhong; Lin, Xiu-ming

2015-07-01

To explore the effect of Salvianolate on myosin heavy chain (MHC) in cardiomyocytes of congestive heart failure (CHF) rats. Sixty male SD rats were divided into 6 groups according to random digit table, i.e., the normal control group (NCG), the model group, the Captopril group (CAG), the low dose Salvianolate group (LSG), the high dose Salvianolate group (HSG), the Captopril and high dose Salvianolate group (CSG), 10 in each group. CHF rat model was established with peritoneal injection of adriamycin in all rats except those in the NCG. Equal volume of normal saline was peritoneally injected to rats in the NCG, once per week for 6 successive weeks. Corresponding medication was started from the 5th week of injecting adriamycin. Rats in the CAG were administered with Captopril solution at the daily dose of 10 mg/kg by gastrogavage. Rats in the LSG and the HSG were administered with Salvianolate solution at the daily dose of 24.219 mg/kg and 48.438 mg/kg respectively by gastrogavage. Salvianolate was dissolved in 2 mL 5% glucose solution and administered by peritoneal injection. Rats in the CSG were peritoneally injected with high dose Salvianolate solution and administered with Captopril solution by gastrogavage. Two mL normal saline was peritoneally injected to rats in the model group, once per day for 8 successive weeks. Eight weeks later, the cardiac function and myocardial hypertrophy indices were detected by biological signal collecting and processing system. mRNA expression levels of alpha-MHC and beta-MHC in cardiac muscle were detected by fluorescence quantitative PCR. Expressions of protein kinase C (PKC) in cardiac muscle were detected by Western blot. Compared with the normal control group, heart mass index (HMI) and left ventricular mass index (LVMI) obviously increased in the model group (P < 0.01). Compared with the model group, HMI and LVMI decreased in HSG, CAG, and CSG groups (P < 0.05, P < 0.01). It was more obviously lowered in the CSG group than in the CAG group (P < 0.05). Compared with the NCG, the mRNA expression level of alpha-MHC in cardiac muscle decreased, the mRNA expression level of p-MHC and the expression of PKC in cardiac muscle increased in the model group (P < 0.01). Compared with the model group, the mRNA expression level of alpha-MHC in cardiac muscle was increased, and the mRNA expression level of beta-MHC and the expression of PKC in cardiac muscle were decreased in HSG, CAG, and CSG groups (P < 0.05, P < 0.01). There was statistical difference between the CSG group and the CAG group (P < 0.05). Salvianolate could up-regulate the mRNA expression level of alpha-MHC, and down-regulate the mRNA expression level of beta-MHC in cardiac muscle. Its mechanism might be related to decreasing the expression of PKC.

Toxicology and carcinogenesis studies of a nondecolorized [corrected] whole leaf extract of Aloe barbadensis Miller (Aloe vera) in F344/N rats and B6C3F1 mice (drinking water study).

PubMed

Boudreau, M D; Beland, F A; Nichols, J A; Pogribna, M

2013-08-01

Extracts from the leaves of the Aloe vera plant (Aloe barbadensis Miller) have long been used as herbal remedies and are also now promoted as a dietary supplement, in liquid tonics, powders or tablets, as a laxative and to prevent a variety of illnesses. We studied the effects of Aloe vera extract on rats and mice to identify potential toxic or cancer-related hazards. We gave solutions of nondecolorized extracts of Aloe vera leaves in the drinking water to groups of rats and mice for 2 years. Groups of 48 rats received solutions containing 0.5%, 1% or 1.5% of Aloe vera extract in the drinking water, and groups of mice received solutions containing 1%, 2%, or 3% of Aloe vera extract. Similar groups of animals were given plain drinking water and served as the control groups. At the end of the study tissues from more than 40 sites were examined for every animal. In all groups of rats and mice receiving the Aloe vera extract, the rates of hyperplasia in the large intestine were markedly increased compared to the control animals. There were also increases in hyperplasia in the small intestine in rats receiving the Aloe vera extract, increases in hyperplasia of the stomach in male and female rats and female mice receiving the Aloe vera extract, and increases in hyperplasia of the mesenteric lymph nodes in male and female rats and male mice receiving the Aloe vera extract. In addition, cancers of the large intestine occurred in male and female rats given the Aloe vera extract, though none had been seen in the control groups of rats for this and other studies at this laboratory. We conclude that nondecolorized Aloe vera caused cancers of the large intestine in male and female rats and also caused hyperplasia of the large intestine, small intestine, stomach, and lymph nodes in male and female rats. Aloe vera extract also caused hyperplasia of the large intestine in male and female mice and hyperplasia of the mesenteric lymph node in male mice and hyperplasia of the stomach in female mice.

Oral intake of hydrogen-rich water inhibits intimal hyperplasia in arterialized vein grafts in rats

PubMed Central

Sun, Qiang; Kawamura, Tomohiro; Masutani, Kosuke; Peng, Ximei; Sun, Qing; Stolz, Donna B.; Pribis, John P.; Billiar, Timothy R.; Sun, Xuejun; Bermudez, Christian A.; Toyoda, Yoshiya; Nakao, Atsunori

2012-01-01

Aims Arterialized vein grafts often fail due to intimal hyperplasia. Hydrogen potently protects organs and cells from many insults via its anti-inflammatory and antioxidant properties. We investigated the efficacy of oral administration of hydrogen-rich water (HW) for prevention of intimal hyperplasia. Methods and results The inferior vena cava was excised, stored in cold Ringer solution for 2 h, and placed as an interposition graft in the abdominal aorta of syngeneic Lewis rats. HW was generated by immersing a magnesium stick in tap water (Mg + 2H2O → Mg (OH)2 + H2). Beginning on the day of graft implantation, recipients were given tap water [regular water (RW)], HW or HW that had been subsequently degassed water (DW). Six weeks after grafting, the grafts in the rats given RW or DW had developed intimal hyperplasia, accompanied by increased oxidative injury. HW significantly suppressed intimal hyperplasia. One week after grafting, the grafts in HW-treated rats exhibited improved endothelial integrity with less platelet and white blood cell aggregation. Up-regulation of the mRNAs for intracellular adhesion molecules was attenuated in the vein grafts of the rats receiving HW. Activation of p38 mitogen-activated protein kinase, matrix metalloproteinase (MMP)-2, and MMP-9 was also significantly inhibited in grafts receiving HW. In rat smooth muscle cell (A7r5) cultures, hydrogen treatment for 24 h reduced smooth muscle cell migration. Conclusion Drinking HW significantly reduced neointima formation after vein grafting in rats. Drinking HW may have therapeutic value as a novel therapy for intimal hyperplasia and could easily be incorporated into daily life. PMID:22287575

Effect of vitamin E on lead exposure-induced learning and memory impairment in rats.

PubMed

Khodamoradi, Nasrin; Komaki, Alireza; Salehi, Iraj; Shahidi, Siamak; Sarihi, Abdolrahman

2015-05-15

Chronic lead (Pb(2+)) exposure has been associated with learning and memory impairments, whereas vitamin E improves cognitive deficits. In this study, using a passive avoidance learning model in rats, we investigated the effects of vitamin E on Pb(2+) exposure-induced learning and memory impairments in rats. In the present study, 56 Wistar male rats (weighting 230-250g) were divided into eight groups (n=7). The Pb(2+) exposure involved gavages of lead acetate solution using three different doses (0.05%, 0.1%, and 0.2%) and the vitamin E consisted of three different doses (10, 25, 50μg/rat) for 30days. After the 30-day period, the rats were tested using a passive avoidance task (acquisition test). In a retrieval test conducted 48h after the training, step through latency (STL) and time in the dark compartment (TDC) were recorded. The statistical analysis of data was performed using ANOVA followed by Tukey's post hoc analysis. In all cases, differences were considered significant if p<0.05. The results of the present study showed that chronic exposure to high doses of Pb(2+) significantly increased both the number of trails required for learning and the TDC, whereas it decreased the STL in the passive avoidance test. Administration of vitamin E ameliorated the effects of Pb(2+) on animal behavior in the passive avoidance learning and memory task. Our results indicate that impairments of learning and memory in Pb(2+)-exposed rats are dose dependent and can be inhibited by antioxidants such as vitamin E. Copyright © 2015 Elsevier Inc. All rights reserved.

[Comparative study of the long-term behavioral effects of noopept and piracetam in adult male rats and female rats in postnatal period].

PubMed

Voronina, T A; Guzevatykh, L S; Trofimov, S S

2005-01-01

Adult male and female rats were treated with the peptide nootrope drug noopept (daily dose, 0.1 mg/kg) and piracetam (200 mg/kg). In the period from 8th to 20th day, both drugs (cognitive enhancers) suppressed the horizontal and vertical activity and the anxiety in test animals as compared to the control group treated with 0.9 % aqueous NaCl solution. Early postnatal injections of the nootropes influenced neither the morphology development nor the behavior of adult female rats in the plus maze, extrapolational escape, passive avoidance, and pain sensitivity threshold tests. Animals in the "intact" group (having received neither drugs not physiological solution, that is, developing in a poor sensor environment), showed less pronounced habituation in the open field test as compared to the control and drug treated groups.

Re-thinking the role of the dorsal striatum in egocentric/response strategy.

PubMed

Botreau, Fanny; Gisquet-Verrier, Pascale

2010-01-01

Rats trained in a dual-solution cross-maze task, which can be solved by place and response strategies, predominantly used a response strategy after extensive training. This paper examines the involvement of the medial and lateral dorsal striatum (mDS and lDS) in the choice of these strategies after partial and extensive training. Our results show that rats with lDS and mDS lesions used mainly a response strategy from the early phase of training. We replicated these unexpected data in rats with lDS lesions and confirmed their tendency to use the response strategy in a modified cross-maze task. When trained in a dual-solution water-maze task, however, control and lesioned rats consistently used a place strategy, demonstrating that lDS and mDS lesioned rats can use a place strategy and that the shift towards a response strategy did not systematically result from extensive training. The present data did not show any clear dissociation between the mDS and lDS in dual solution tasks. They further indicate that the dorsal striatum seems to determine the strategies adopted in a particular context but cannot be considered as a neural support for the response memory system. Accordingly, the role of the lateral and medial part of the dorsal striatum in egocentric/response memory should be reconsidered.

Allogenic Myocytes and Mesenchymal Stem Cells Partially Improve Fatty Rotator Cuff Degeneration in a Rat Model.

PubMed

Güleçyüz, Mehmet F; Macha, Konstanze; Pietschmann, Matthias F; Ficklscherer, Andreas; Sievers, Birte; Roßbach, Björn P; Jansson, Volkmar; Müller, Peter E

2018-05-31

Rotator cuff (RC) tears result not only in functional impairment but also in RC muscle atrophy, muscle fattening and eventually to muscle fibrosis. We hypothesized that allogenic bone marrow derived mesenchymal stem cells (MSC) and myocytes can be utilized to improve the rotator cuff muscle fattening and increase the atrophied muscle mass in a rat model. The right supraspinatus (SSP) tendons of 105 inbred rats were detached and muscle fattening was provoked over 4 weeks; the left side remained untouched (control group). The animals (n = 25) of the output group were euthanized after 4 weeks for reference purposes. The SSP-tendon of one group (n = 16) was left unoperated to heal spontaneously. The SSP-tendons of the remaining 64 rats (4 groups with n = 16) were repaired with transosseous sutures. One group received a saline solution injection in the SSP muscle belly, two other groups received 5 × 10 6 allogenic myocytes and 5 × 10 6 allogenic MSC injections from donor rats, respectively, and one group received no additional treatment. After 4 weeks of healing, the supraspinatus muscle mass was compared quantitatively and histologically to all the treated groups and to the untreated contralateral side. In the end of the experiments at week 8, the myocyte and MCS treated groups showed a significantly higher muscle mass with 0.2322 g and 0.2257 g, respectively, in comparison to the output group (0.1911 g) at week 4 with p < 0.05. There was no statistical difference between the repaired, treated, or spontaneous healing groups at week 8. Supraspinatus muscle mass of all experimental groups of the right side was significantly lower compared to the untreated contralateral muscle mass. This defect model shows that the injection of allogenic mycocytes and MSC in fatty infiltrated SSP muscles is better than no treatment and can partially improve the SSP muscle belly fattening. Nevertheless, a full restoration of the degenerated and fattened rotator cuff muscle to its original condition is not possible using myocytes and MSC in this model.

Taurine alleviates malathion induced lipid peroxidation, oxidative stress, and proinflammatory cytokine gene expressions in rats.

PubMed

Ince, Sinan; Arslan-Acaroz, Damla; Demirel, Hasan Huseyin; Varol, Nuray; Ozyurek, Hatice Arzu; Zemheri, Fahriye; Kucukkurt, Ismail

2017-12-01

The present study was considered to evaluate the protective effect of taurine on malathion-induced toxicity in rats. Totally, 48 male rats were divided into 6 equal groups: 0.5ml physiological salt solution was given orally to control rats. 0.5ml corn oil was given orally to rats in corn oil group. Malathion at dose of 27mg/kg (1/50 of LD 50 ) was dissolved in 0.5ml corn oil and given to orally rats in malathion group. The other groups; malathion (27mg/kg) and taurine (dissolved in 0.5ml physiological salt solution) at dose of 50, 100, and 200mg/kg were given orally to rats for 30days, respectively. Malathion treatment decreased acetylcholinesterase levels in serum (30%) and liver (25%) compared to the control group. Malathion resulted in a significant increase in malondialdehyde levels whereas decreased glutathione levels, superoxide dismutase, and catalase activities in rats. Also, IF-γ, IL1-β, TNF-α, and NFĸB mRNA expression levels were found to be increased 5, 1.7, 2.3, and 2.5 fold in malathion treated rats compared to control, respectively. However, treatment of taurine, in a dose-dependent manner, resulted in a reversal of malathion-induced lipid peroxidation, antioxidant enzyme activities, and mRNA expression levels of proinflammatory cytokines. Moreover, taurine demonstrated preventive action against malathion-induced histopathological changes in rat tissues. In conclusion, taurine exhibited a protective effect in rats against malathion-induced lipid peroxidation, besides it ameliorated antioxidant status, decreased mRNA expression levels of proinflammatory cytokine and repaired rat tissues. Copyright © 2017. Published by Elsevier Masson SAS.

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

PubMed Central

Levy, AnneMarie; Limebeer, Cheryl L.; Ferdinand, Justin; Shillingford, Ucal; Parker, Linda A.; Leri, Francesco

2014-01-01

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e. 8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e. one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets. PMID:24561923

Post-oral infusion sites that support glucose-conditioned flavor preferences in rats.

PubMed

Ackroff, Karen; Yiin, Yeh-Min; Sclafani, Anthony

2010-03-03

Rats learn to prefer a flavored solution (CS+) paired with a gastrointestinal glucose infusion over an alternate flavor (CS-) paired with a non-caloric infusion. Prior work implicates a post-gastric site of glucose action, which is the focus of this study. In Exp. 1, male rats (8-10/group) were infused in the duodenum (ID), mid-jejunum (IJ), or distal ileum (II) with 8% glucose or water as they drank saccharin-sweetened CS+ and CS- solutions, respectively, in one-bottle 30-min sessions. Two-bottle tests (no infusions) were followed by a second train-test cycle. By the second test, the ID and IJ groups preferred the CS+ (69%, 67%) to the CS- but the II group did not (48%). Satiation tests showed that ID and IJ infusions of glucose reduced intake of a palatable solution similarly, while II infusions were ineffective. In Exp. 2, rats (10/group) drank CS solutions in one-bottle, 30-min sessions and were given 2-h ID or hepatic portal vein (HP) infusions. The CS+ and CS- were paired with 10 ml infusions of 10% glucose and 0.9% saline, respectively. Following 8 training sessions, the ID group preferred the CS+ (67%) to the CS- but the HP group did not (47%) in a two-bottle test. The similar CS+ preferences displayed by ID and IJ, but not II groups implicate the jejunum as a critical site for glucose-conditioned preferences. A pre-absorptive glucose action is indicated by the CS+ preference displayed by ID but not HP rats in Exp. 2. Our data were obtained with non-nutritive CS solutions. HP glucose infusions are reported to condition preferences for a flavored food that itself has pre- and post-absorptive actions. Thus, there may be multiple sites for glucose conditioning with the upper or mid-intestines being the first site of action. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Effect of Diet on Preference and Intake of Sucrose in Obese Prone and Resistant Rats

PubMed Central

Duca, Frank A.; Swartz, Timothy D.; Covasa, Mihai

2014-01-01

Increased orosensory stimulation from palatable diets and decreased feedback from gut signals have been proposed as contributing factors to obesity development. Whether altered taste functions associated with obesity are common traits or acquired deficits to environmental factors, such as a high-energy (HE)-diet, however, is not clear. To address this, we examined preference and sensitivity of increasing concentrations of sucrose solutions in rats prone (OP) and resistant (OR) to obesity during chow and HE feeding and measured lingual gene expression of the sweet taste receptor T1R3. When chow-fed, OP rats exhibited reduced preference and acceptance of dilute sucrose solutions, sham-fed less sucrose compared to OR rats, and had reduced lingual T1R3 gene expression. HE-feeding abrogated differences in sucrose preference and intake and lingual T1R3 expression between phenotypes. Despite similar sucrose intakes however, OP rats consumed significantly more total calories during 48-h two-bottle testing compared to OR rats. The results demonstrate that OP rats have an innate deficit for sweet taste detection, as illustrated by a reduction in sensitivity to sweets and reduced T1R3 gene expression; however their hyperphagia and subsequent obesity during HE-feeding is most likely not due to altered consumption of sweets. PMID:25329959

Pre-exposure to wheel running disrupts taste aversion conditioning.

PubMed

Salvy, Sarah-Jeanne; Pierce, W David; Heth, Donald C; Russell, James C

2002-05-01

When rats are given access to a running wheel after drinking a flavored solution, they subsequently drink less of that flavor solution. It has been suggested that running produces a conditioned taste aversion (CTA). This study explored whether CTA is eliminated by prior exposure to wheel running [i.e., unconditioned stimulus (UCS) pre-exposure effect]. The rats in the experimental group (UW) were allowed to wheel run for 1 h daily for seven consecutive days of pre-exposure. Rats in the two other groups had either access to locked wheels (LW group) or were maintained in their home cages (HC group) during the pre-exposure days. All rats were then exposed to four paired and four unpaired trials using a "ABBAABBA" design. Conditioning trials were composed of one flavored liquid followed by 60-min access to wheel running. For the unpaired trials, rats received a different flavor not followed by the opportunity to run. All rats were then initially tested for water consumption followed by tests of the two flavors (paired or unpaired) in a counterbalanced design. Rats in the UW group show no CTA to the liquid paired with wheel running, whereas LW and HC groups developed CTA. These results indicate that pre-exposure to wheel running (i.e., the UCS), eliminates subsequent CTA.

Injectable caltrop fruit saponin protects against ischemia-reperfusion injury in rat brain.

PubMed

Yan, Ling-Geng; Lu, Yin; Zheng, Shi-Zhong; Wang, Ai-Yun; Li, Meng-Qiu; Ruan, Jun-Shan; Zhang, Lei

2011-01-01

The present study aimed to investigate the protective effects of injectable caltrop fruit saponin preparation (ICFSP) on ischemia-reperfusion injury in rat brain. Rats were injected with ICFSP and then subjected to cerebral ischemia-reperfusion injury induced by middle cerebral artery occlusion. Then the neurological deficit score was evaluated by Bederson's method. The infarct size was assessed by TTC staining. The content of malondialdehyde (MDA) and nitric oxide (NO), and the activity of superoxide dismutase (SOD) in rat cerebrum were measured with kits, and the content of 6 K prostaglandin F1α (6-K-PGF 1α), thromboxane B2 (TXB2) and endothelin (ET) in blood plasma was measured by radioimmunoassay. The results demonstrated that ICFSP led to a decrease in infarct size (p < 0.01), neurological deficit score (p < 0.05) and plasma content of TXB2 and ET (p < 0.05), and an increase of the plasma level of 6-K-PGF 1α (p < 0.05) and SOD activity in cerebrum, where the MDA and NO content were decreased. The treatment improved forelimb function. ICFSP showed a similar potency compared to that of Ligustrazine hydrochloride parenteral solution (LHPS) and nimodipine (Nim). We concluded that ICFSP protects the brain damage caused by ischemia-reperfusion injury in rats, and this may be closely related to the regulation of reactive oxygen species (MDA and SOD activity) and NO levels in the rat cerebrum, as well as vasoactive factors in the plasma (6-K-PGF 1α, TXB2 and ET).

Assessment of the biopotency of follitropin alfa and lutropin alfa combined in one injection: a comparative trial in Sprague-Dawley rats

PubMed Central

Alper, Michael; Meyer, Randal; Dekkers, Chris; Ezcurra, Diego; Schertz, Joan; Kelly, Eduardo

2008-01-01

Background The current study was designed to determine if follitropin alfa (recombinant human follicle-stimulating hormone; r-hFSH) and lutropin alfa (recombinant human luteinizing hormone; r-hLH) biopotencies were unchanged by reconstituting in sterile water for injection and mixing prior to injection. Methods The biopotencies of r-hFSH and r-hLH were determined following injection of female Sprague-Dawley rats with a mixture of follitropin alfa revised formulation female (RFF) and lutropin alfa (1:1, r-hFSH:r-hLH). Biopotencies of follitropin alfa RFF and lutropin alfa were measured using ovarian weight and ascorbic acid depletion assays, respectively, and compared with a reference standard. Stock mixtures of follitropin alfa RFF and lutropin alfa (1:1) were prepared within 1 h prior to each respective assay's injection and stored at 6 +/- 2°C. Separate low dose (follitropin alfa RFF 1.5 IU/rat, lutropin alfa 2 IU/rat) and high dose (follitropin alfa RFF 3 IU/rat, lutropin alfa 8 IU/rat) treatments were prepared from stock mixtures or individual solutions by diluting with 0.22% bovine serum albumin saline solution and injected within 1 h of preparation. The main outcome measures were ovarian weight and ovarian ascorbic acid depletion. Results FSH bioactivities were similar (p > 0.10) between the individual follitropin alfa RFF test solution (84.2 IU) and follitropin alfa RFF/lutropin alfa (87.6 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2°C. LH bioactivities were similar (p > 0.10) between lutropin alfa (94.7 IU) test solution and lutropin alfa/follitropin alfa RFF (85.3 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2°C for not more than 1 h prior to injection. Conclusion Mixing follitropin alfa RFF and lutropin alfa did not alter the bioactivity of either FSH or LH. PMID:18647398

Effects of Multiple Intra-articular Injections of 0.5% Bupivacaine on Normal and Osteoarthritic Joints in Rats.

PubMed

Iwasaki, Koji; Sudo, Hideki; Kasahara, Yasuhiko; Yamada, Katsuhisa; Ohnishi, Takashi; Tsujimoto, Takeru; Iwasaki, Norimasa

2016-10-01

To determine the in vivo effects of multiple local anesthetic injections of 0.5% bupivacaine on normal and osteoarthritic articular cartilage. Rats with normal knee joints received an intra-articular injection of 0.9% saline solution or 0.5% bupivacaine in their right knees joint once a week for 5 consecutive weeks, starting 4 weeks after the beginning of the experiment. Rats were humanely killed at 8, 16, and 24 weeks. In a parallel experiment, rats underwent anterior cruciate ligament transection to induce osteoarthritic changes. These rats were subjected to the same protocol as those with normal knee joints, starting 4 weeks after the procedure. Static weight-bearing tests were performed on both hind limbs to evaluate changes in weight-bearing ability throughout the experiments. Rats were humanely killed at 8 and 16 weeks. Cell viability was assessed with confocal microscopy, using samples from the distal femur. Histologic assessment of osteoarthritis was performed using samples from the tibial plateau based on the Osteoarthritis Research Society International (OARSI) cartilage histopathology assessment system (i.e., OARSI score). Static weight-bearing tests showed no significant changes after intra-articular injection of saline solution or bupivacaine, and bupivacaine injection did not increase weight bearing compared with saline solution injection, regardless of whether there were osteoarthritic changes. There were also no significant differences in cell viability, cell density, or OARSI scores between the saline solution and bupivacaine groups at each time point, regardless of whether osteoarthritic changes were induced. This study suggested that single or intermittent intra-articular bupivacaine injections might not have deleterious effects on either osteoarthritic or normal joints. There is no strong evidence that intra-articular bupivacaine injection induces degenerative changes in articular cartilage. Therefore, these results may apply to normal and osteoarthritic joints. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Study on 41Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

NASA Astrophysics Data System (ADS)

Shen, Hongtao; Pang, Fangfang; Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang; Pang, Yijun; Yang, Xianlin; Ruan, Xiangdong; Liu, Manjun; Xia, Chunbo

2015-10-01

The annual incidence of new cancer patients in China is about 2 million, 30-40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of 41Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague-Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl2 solution (containing 1.4 mg Ca and 5nCi 41Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for 41Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of 41Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that 41Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

Daily Access to Sucrose Impairs Aspects of Spatial Memory Tasks Reliant on Pattern Separation and Neural Proliferation in Rats

ERIC Educational Resources Information Center

Reichelt, Amy C.; Morris, Margaret J.; Westbrook, Reginald Frederick

2016-01-01

High sugar diets reduce hippocampal neurogenesis, which is required for minimizing interference between memories, a process that involves "pattern separation." We provided rats with 2 h daily access to a sucrose solution for 28 d and assessed their performance on a spatial memory task. Sucrose consuming rats discriminated between objects…

MSG intake suppresses weight gain, fat deposition, and plasma leptin levels in male Sprague-Dawley rats.

PubMed

Kondoh, Takashi; Torii, Kunio

2008-09-03

Monosodium l-glutamate (MSG), an umami taste substance, may be a key molecule coupled to a food intake signaling pathway, possibly mediated through a specific l-glutamate (GLU) sensing mechanism in the gastrointestinal tract. Here we investigated the effect of the spontaneous ingestion of a 1% MSG solution and water on food intake and body weight in male Sprague-Dawley rats fed diets of varying caloric density, fat and carbohydrate contents. Fat mass and lean mass in the abdomen, blood pressure, and several blood metabolic markers were also measured. Rats given free access to MSG and water showed a high preference (93-97%) for the MSG solution, regardless of the diet they consumed. Rats ingesting MSG had a significantly smaller weight gain, reduced abdominal fat mass, and lower plasma leptin levels, compared to rats ingesting water alone. Naso-anal length, lean mass, food and energy intakes, blood pressure, blood glucose, and plasma levels of insulin, triglyceride, total cholesterol, albumin, and GLU were not influenced by the ingestion of the MSG solution. These same effects were observed in a study of adult rats. Together, these results suggest that MSG ingestion reduces weight gain, body fat mass, and plasma leptin levels. Moreover, these changes are likely to be mediated by increased energy expenditure, not reduced energy intake or delayed development. Conceivably, these effects of MSG might be mediated via gut GLU receptors functionally linked to afferent branches of the vagus nerve in the gut, or the afferent sensory nerves in the oral cavity.

Stabilization of a supersaturated solution of mefenamic acid from a solid dispersion with EUDRAGIT(®) EPO.

PubMed

Kojima, Taro; Higashi, Kenjirou; Suzuki, Toyofumi; Tomono, Kazuo; Moribe, Kunikazu; Yamamoto, Keiji

2012-10-01

The stabilization mechanism of a supersaturated solution of mefenamic acid (MFA) from a solid dispersion with EUDRAGIT(®) EPO (EPO) was investigated. The solid dispersions were prepared by cryogenic grinding method. Powder X-ray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid- and solution-state NMR spectroscopies were used to characterize the solid dispersions. Dissolution tests in acetate buffer (pH 5.5) revealed that solid dispersion showed > 200-fold higher concentration of MFA. Supersaturated solution was stable over 1 month and exhibited improved oral bioavailability of MFA in rats, with a 7.8-fold higher area under the plasma concentration-versus-time curve. Solid-state (1)H spin-lattice relaxation time (T(1)) measurement showed that MFA was almost monomolecularly dispersed in the EPO polymer matrix. Intermolecular interaction between MFA and EPO was indicated by solid-state infrared and (13)C-T(1) measurements. Solution-state (1)H-NMR measurement demonstrated that MFA existed in monomolecular state in supersaturated solution. (1)H-T(1) and difference nuclear Overhauser effect measurements indicated that cross relaxation occurred between MFA and EPO due to the small distance between them. The formation and high stability of the supersaturated solution were attributable to the specifically formed intermolecular interactions between MFA and EPO.

[Gene transfer-induced human heme oxygenase-1 over-expression protects kidney from ischemia-reperfusion injury in rats].

PubMed

Lü, Jin-xing; Yan, Chun-yin; Pu, Jin-xian; Hou, Jian-quan; Yuan, He-xing; Ping, Ji-gen

2010-12-14

To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (P<0.01). Immunohistochemically, we found that the rats treated with Ad-hHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.

Reduced-calorie avocado paste attenuates metabolic factors associated with a hypercholesterolemic-high fructose diet in rats.

PubMed

Pahua-Ramos, María Elena; Garduño-Siciliano, Leticia; Dorantes-Alvarez, Lidia; Chamorro-Cevallos, German; Herrera-Martínez, Julieta; Osorio-Esquivel, Obed; Ortiz-Moreno, Alicia

2014-03-01

The objective of this study was to evaluate the effect of reduced-calorie avocado paste on lipid serum profile, insulin sensitivity, and hepatic steatosis in rats fed a hypercholesterolemic-high fructose diet. Thirty five male Wistar rats were randomly separated in five groups: Control group (ground commercial diet); hypercholesterolemic diet plus 60% fructose solution (HHF group); hypercholesterolemic diet plus 60% fructose solution supplemented with avocado pulp (HHF+A group); hypercholesterolemic diet plus 60% fructose solution supplemented with reduced-calorie avocado paste (HHF+P group); and hypercholesterolemic diet plus 60% fructose solution supplemented with a reduced-calorie avocado paste plus fiber (HHF+FP group). The A, P, and FP were supplemented at 2 g/kg/d. The study was carried out for seven weeks. Rats belonging to the HHF group exhibited significantly (P ≤ 0.05) higher total cholesterol, triglycerides, and insulin levels in serum as well as lower insulin sensitivity than the control group. Supplementation with reduced-calorie avocado paste showed a significant (P ≤ 0.05) decrease in total cholesterol (43.1%), low-density lipoprotein (45.4%), and triglycerides (32.8%) in plasma as well as elevated insulin sensitivity compared to the HHF group. Additionally, the liver enzymes alanine aminotransferase and aspartate aminotransferase decreased significantly in the HHF-P group (39.8 and 35.1%, respectively). These results are likely due to biocompounds present in the reduced-calorie avocado paste, such as polyphenols, carotenoids, chlorophylls, and dietary fibre, which are capable of reducing oxidative stress. Therefore, reduced-calorie avocado paste attenuates the effects of a hypercholesterolemic-high fructose diet in rats.

Differences in bingeing behavior and cocaine reward following intermittent access to sucrose, glucose or fructose solutions

PubMed Central

Rorabaugh, Jacki M.; Stratford, Jennifer M.; Zahniser, Nancy R.

2015-01-01

Daily intermittent access to sugar solutions results in intense bouts of sugar intake (i.e. bingeing) in rats. Bingeing on sucrose, a disaccharide of glucose and fructose, has been associated with a “primed” mesolimbic dopamine (DA) pathway. Recent studies suggest glucose and fructose engage brain reward and energy sensing mechanisms in opposing ways and may drive sucrose intake through unique neuronal circuits. Here, we examined in male Sprague-Dawley rats whether or not (1) intermittent access to isocaloric solutions of sucrose, glucose or fructose results in distinctive sugar bingeing profiles and (2) previous sugar bingeing alters cocaine locomotor activation and/or reward, as determined by conditioned place preference (CPP). To encourage bingeing, rats were given 24-h access to water and 12 h-intermittent access to chow plus an intermittent bottle that contained water (control) or 8% solutions of sucrose, glucose or fructose for 9 days, followed by ad libitum chow diet and a 10 day cocaine (15 mg/kg; i.p.) CPP paradigm. By day 4 of the sugar bingeing diet, sugar bingeing in the fructose group surpassed the glucose group, with the sucrose group being intermediate. All three sugar groups had similar chow and water intake throughout the diet. In contrast, controls exhibited chow bingeing by day 5 without altering water intake. Similar magnitudes of cocaine CPP were observed in rats with a history of sucrose, fructose or chow (control) bingeing. Notably, the glucosebingeing rats did not demonstrate a significant cocaine CPP despite showing similar cocaine-induced locomotor activity as the other diet groups. Overall, these results show that fructose and glucose, the monosaccharide components of sucrose, produce divergent degrees of bingeing and cocaine reward. PMID:26079112

In vivo evaluation of an oral drug delivery system for peptides based on S-protected thiolated chitosan.

PubMed

Dünnhaupt, Sarah; Barthelmes, Jan; Iqbal, Javed; Perera, Glen; Thurner, Clemens C; Friedl, Heike; Bernkop-Schnürch, Andreas

2012-06-28

The aim of the present study was the development and evaluation in vitro as well as in vivo of an oral delivery system based on a novel type of thiolated chitosan, so-called S-protected thiolated chitosan, for the peptide drug antide. The sulfhydryl ligand thioglycolic acid (TGA) was covalently attached to chitosan (CS) in the first step of modification. In the second step, these thiol groups of thiolated chitosan were protected by disulfide bond formation with the thiolated aromatic residue 6-mercaptonicotinamide (6-MNA). Absorptive transport studies of antide were evaluated ex vivo using rat intestinal mucosa. Matrix tablets of each polymer sample were prepared and their effect on the absorption of antide evaluated in vivo in male Sprague-Dawley rats. In addition, tablets were examined in terms of their disintegration, swelling and drug release behavior. The resulting S-protected thiomer (TGA-MNA) exhibited 840μmol of covalently linked 6-MNA per gram thiomer. Based on the implementation of this hydrophobic ligand on the thiolated backbone, the disintegration behavior was reduced greatly and a controlled release of the peptide could be achieved. Furthermore, permeation studies with TGA-MNA on rat intestine revealed a 4.5-fold enhanced absorptive transport of the peptide in comparison to antide in solution. Additional in vivo studies confirmed the potential of this novel conjugate. Oral administration of antide in solution led to only very small detectable quantities in plasma with an absolute and relative bioavailability (BA) of 0.003 and 0.03%, only. In contrast, with antide incorporated in TGA-MNA matrix tablets an absolute and relative BA of 1.4 and 10.9% could be reached, resulting in a 421-fold increased area under the plasma concentration time curve (AUC) compared to the antide solution. According to these results, S-protected thiolated chitosan as oral drug delivery system might be a valuable tool for improving the bioavailability of peptides. Copyright © 2012 Elsevier B.V. All rights reserved.

Voluntary ethanol consumption differs in adolescent and adult male rats using a modified sucrose-fading paradigm.

PubMed

Maldonado, Antoniette M; Finkbeiner, Lauren M; Alipour, Kent K; Kirstein, Cheryl L

2008-09-01

Initiation of alcohol consumption during adolescence is high, which usually begins with consumption of highly concentrated sweetened alcoholic beverages in adolescent humans. Enhanced voluntary ethanol (EtOH) intake has been observed previously in adolescent relative to adult rats under continuous access conditions using sweetened EtOH solutions. The present set of experiments investigated patterns of voluntary EtOH intake in adolescent and adult rats using sweetened EtOH solutions in a limited access paradigm. Rats were trained with modified sucrose-substitution protocols that ended at either 5% sucrose-20% EtOH (5S/20E) (Exp. 1) or 5% sucrose-10% EtOH (5S/10E) (Exp. 2). Voluntary EtOH consumption differences between the 2 age groups were apparent at higher (i.e., 10 and 20%), but not lower (i.e., 2 and 5%) EtOH concentrations. Adolescent rats consumed more EtOH on a g/kg basis only at 20% EtOH (Exp. 1). Adolescent rats voluntarily consumed more EtOH than adults when maintained at 5S/10E (Exp. 2). To assess whether these age-related differences in voluntary EtOH intake were concentration dependent, rats were trained with 5S/20E and subsequently trained with decreasing EtOH concentrations (i.e., 5S/10E and 5S/5E). Adolescents consumed more EtOH when initially presented with the 5S/10E and 5S/20E EtOH concentrations, and subsequently at the lower 5S/5E EtOH concentration (Exp. 3). There were no differences in preference for the sucrose-only solution, however adolescents tended to consume more sucrose at the 5S sucrose concentration (Exp. 4). Given that adolescents consumed more EtOH at the 5S/10E and 5S/20E, but not at the 5S/5E EtOH concentrations, preference for sucrose does not solely explain the age differences in voluntary EtOH intake observed. Overall, results replicate previous work, demonstrating adolescent rats consume more EtOH relative to adults. However, the present results were observed using sweetened EtOH solutions in a limited access paradigm. The present modified sucrose-substitution paradigm may serve as a valid model of human adolescent drinking behavior.

Cryopreservation of isolated primary rat hepatocytes: enhanced survival and long-term hepatospecific function.

PubMed

Sosef, Meindert N; Baust, John M; Sugimachi, Keishi; Fowler, Alex; Tompkins, Ronald G; Toner, Mehmet

2005-01-01

To investigate the long-term effect of cryopreservation on hepatocyte function, as well as attempt to improve cell viability and function through the utilization of the hypothermic preservation solution, HypoThermosol (HTS), as the carrier solution. Advances in the field of bioartificial liver support have led to an increasing demand for successful, efficient means of cryopreservation of hepatocytes. Fresh rat hepatocytes were cryopreserved in suspension in culture media (Media-cryo group) or HTS (HTS-cryo group), both supplemented with 10% DMSO. Following storage up to 2 months in liquid nitrogen, cells were thawed and maintained in a double collagen gel culture for 14 days. Hepatocyte yield and viability were assessed up to 14 days postthaw. Serial measurements of albumin secretion, urea synthesis, deethylation of ethoxyresorufin (CYT P450 activity), and responsiveness to stimulation with interleukin-6 (IL-6) were performed. Immediate postthaw viability was 60% in Media-cryo and 79% in HTS-cryo, in comparison with control (90%). Albumin secretion, urea synthesis and CYT P450 activity yielded 33%, 55%, and 59% in Media-cryo and 71%, 80%, and 88% in HTS-cryo, respectively, compared with control (100%). Assessment of cellular response to IL-6 following cryopreservation revealed a similar pattern of up-regulation in fibrinogen production and suppression of albumin secretion compared with nonfrozen controls. This study demonstrates that isolated rat hepatocytes cryopreserved using HTS showed high viability, long-term hepatospecific function, and response to cytokine challenge. These results may represent an important step forward to the utilization of cryopreserved isolated hepatocytes in bioartificial liver devices.

Umbilical cord blood cells regulate endogenous neural stem cell proliferation via hedgehog signaling in hypoxic ischemic neonatal rats.

PubMed

Wang, Xiao-Li; Zhao, Yan-Song; Hu, Ming-Ying; Sun, Ye-Quan; Chen, Yu-Xi; Bi, Xue-Hui

2013-06-26

Umbilical cord blood mononuclear cells (UCBMC) transplantation may improve hypoxia-induced brain injury in neonatal rats, but the mechanism is unclear. This study examines whether UCBMC promote neural stem cell (NSC) proliferation via the Sonic hedgehog (Shh) signaling pathway. The rats underwent left carotid ligation followed by hypoxic stress. UCBMC were transplanted 24h after hypoxia ischemia (HI), and immunohistochemistry, immmunoblotting, and morphology analyses were performed at different time points after transplantation. Increased numbers of NSCs were observed in the subventrical zone (SVZ) of the HI+UCBMC group, but these increases were attenuated by cyclopamine treatment. There were significant increases in Shh and Gli1 protein levels after transplantation in the HI group treated with UCBMC compared to HI rats treated with phosphate-buffered solution (PBS). Significantly more Gli1(+)DAPI(+) cells were observed in the SVZ of the HI+UCBMC group compared to the HI+PBS and N+UCBMC groups, but few Gli1(+)DAPI(+) cells were found in the SVZ of the HI+cyclopamine+UCBMC group. The HI+UCBMC group had significantly less neuronal loss in the cortex and CA1 sector of the hippocampus compared to the HI+PBS group, but more neuron loss was observed in the HI+cyclopamine+UCBMC group compared to HI+UCBMC. These results indicate that UCBMC may promote NSC proliferation and alleviate brain injury in HI neonatal rats via Shh signaling. Copyright © 2013 Elsevier B.V. All rights reserved.

Lemon juice has protective activity in a rat urolithiasis model.

PubMed

Touhami, Mohammed; Laroubi, Amine; Elhabazi, Khadija; Loubna, Farouk; Zrara, Ibtissam; Eljahiri, Younes; Oussama, Abdelkhalek; Grases, Félix; Chait, Abderrahman

2007-10-05

The use of herbal medicines (medicinal plants or phytotherapy) has recently gained popularity in Europe and the United States. Nevertheless the exact mechanism of the preventive effects of these products is still far to be clearly established, being its knowledge necessary to successfully apply these therapies to avoid stone formation. The effect of oral lemon juice administration on calcium oxalate urolithiasis was studied in male Wistar rats. Rats were rendered nephrolithic by providing drinking water containing 0.75% ethylene glycol [v/v] (EG) and 2% ammonium chloride [w/v] (AC) for 10 days. In addition to EG/AC treatment, three groups of rats were also gavage-administered solutions containing 100%, 75% or 50% lemon juice [v/v] (6 microl solution/g body weight). Positive control rats were treated with EG/AC but not lemon juice. Negative control rats were provided with normal drinking water, and were administered normal water by gavage. Each group contained 6 rats. After 10 days, serum samples were collected for analysis, the left kidney was removed and assessed for calcium levels using flame spectroscopy, and the right kidney was sectioned for histopathological analysis using light microscopy. Analysis showed that the rats treated with EG/AC alone had higher amounts of calcium in the kidneys compared to negative control rats. This EG/AC-induced increase in kidney calcium levels was inhibited by the administration of lemon juice. Histology showed that rats treated with EG/AC alone had large deposits of calcium oxalate crystals in all parts of the kidney, and that such deposits were not present in rats also treated with either 100% or 75% lemon juice. These data suggest that lemon juice has a protective activity against urolithiasis.

High-performance porous polylactide stereocomplex crystallite scaffolds prepared by solution blending and salt leaching.

PubMed

Xie, Yan; Lan, Xiao-Rong; Bao, Rui-Ying; Lei, Yang; Cao, Zhi-Qiang; Yang, Ming-Bo; Yang, Wei; Wang, Yun-Bing

2018-09-01

Biodegradable stereocomplex crystallite polylactide (SC-PLA) porous scaffolds with well-defined pore structures, high heat resistance, mechanical strength, and solvent resistance together with good biocompatibility, were obtained through solution casting of mixed poly(l-lactide) and poly(d-lactide) solution and subsequent leaching of sodium chloride particles. The pore structure of the SC-PLA scaffolds can be perfectly maintained after a high-pressure sterilization treatment at 121 °C, owing to the extensive formation of stereocomplex crystallites in the scaffolds. In vivo pilot study demonstrates that the fibroblasts of rats can infiltrate into the SC-PLA scaffolds well through the open pores. Degradation tests in phosphate-buffered saline solution reveal that the structure of SC-PLA scaffolds was quite stable due to the enhanced hydrolysis-resistance and improved mechanical properties of the scaffolds. These results reveal that SC-PLA scaffolds with good biocompatibility are potentially to be used as implanted biomaterials for the regeneration and restoration of tissues or organs. Copyright © 2018 Elsevier B.V. All rights reserved.

Age-related peculiarities of contractile activity of rat myocardium during blockade of hyperpolarization-activated currents.

PubMed

Zefirov, T L; Gibina, A E; Sergejeva, A M; Ziyatdinova, N I; Zefirov, A L

2007-09-01

Contractile activity of atrial and ventricular myocardial strips isolated from rats of various age was examined under conditions of blockade of non-selective hyperpolarization-activated cation currents. Addition of ZD7288, a blocker of non-selective hyperpolarization-activated cation currents, to the perfusion solution increased the contraction force of atrial and ventricular strips in 1-, 8-, and 20-week rats, but produced an opposite effect on contractile activity of atrial and ventricular strips in 3-week rats.

Impaired responses to sweet taste in vitamin A-deficient rats.

PubMed

Reifen, R; Agami, O; Weiser, H; Biesalski, H; Naim, M

1998-01-01

In brief-exposure, two-choice preference tests (sucrose solution v water), vitamin A-deficient (VAD) rats exhibited a decreased preference for sucrose relative to control rats. There was no difference in total fluid intake from both choices between the two groups, nor was any significant difference found in circumvallate taste papilla keratin size. It is concluded that the impaired preference for sucrose in VAD rats is due to a specific impairment in taste sensation rather than general malaise.

[EFFECT OF ACETYLCYSTEINE, CORVITIN AND THEIR COMBINATION ON THE FUNCTIONAL STATE OF LIVER IN RATS WITH PARACETAMOL INDUCED TOXIC HEPATITIS].

PubMed

Ghonghadze, M; Antelava, N; Liluashvili, K; Okujava, M; Pachkoria, K

2017-02-01

Nowadays drug-induced hepatotoxicity is urgent problem worldwide. Currently more than 1000 drugs are hepatotoxic and most often are the reason of acute fulminant hepatitis and hepatocellular failure, the states requiring liver transplantation. The paracetamol induced liver toxicity is related with accumulation of its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is the free radical and enhances peroxidation of lipids, disturbs the energy status and causes death of hepatocytes. During our research we investigated and assessed the efficacy of acetylcysteine, corvitin and their combination in rat model of paracetamol induced acute toxic hepatitis. The study was performed on mature white male Wistar rates with body mass 150-180 g. 50 rats were randomly divided into 5 groups (10 rats in each group). To get the model of acute toxic hepatitis single intraperitoneal injection of paracetamol solution was used (750 mg/kg). Toxic hepatitis was treated with intrapertoneal administration of 40mg/kg acetylcysteine or 100mg/kg corvitin, as well as with combination of these drugs. Monotherapy with acetylcysteine and corvitin of paracetamol induced toxic hepatitis improved the liver function, decreased relative mass of the liver and animal mortality. The treatment of toxic hepatitis was most effective in the case of simultaneous administration of acetylcysteine and corvitin. The normal value of laboratory tests (ALT, ACT, alkaline phosphatase, total and unconjugated bilirubin) was reached and mortality was not more observed. On the bases of obtained data was concluded that acetylcysteine and corvitin have almost equal hepatoprotective activity. The combination of two drugs actually improves the liver function. The most pronounced hepatoprotective effect may be due to synergic action of acetylcysteine and corvitin and such regime can be recommended for correction of liver function.

Direct intraperitoneal resuscitation with lidocaine, methylene blue and pentoxiphylline combination does not decreases inflammation after intestinal ischemia-reperfusion injury in rats.

PubMed

Gandini, Marco; Cerri, Simona; Pregel, Paola; Giusto, Gessica; Vercelli, Cristina; Iussich, Selina; Tursi, Massimiliano; Farca, Anna Maria

2016-05-01

To evaluate the effects of an intraperitoneal solution of methylene blue (MB), lidocaine and pentoxyphylline (PTX) on intestinal ischemic and reperfusion injury. Superior mesenteric artery was isolated and clamped in 36 adult male Sprague Dawley rats. After 60 minutes, clamp was removed and a group received intraperitoneally UNITO solution (PTX 25mg/kg + lidocaine 5mg/kg + MB 2mg/kg), while the other group was treated with warm 0.9% NaCl solution. Rats were euthanized 45 min after drug administration. Lung and bowel were collected for histological evaluation (using Park's score) and determination of myeloperoxidase (MPO) and malondialdehyde (MDA) levels. Control samples showed lymphoplasmocytic infiltrate and crypt necrosis of villi. MPO and MDA measurements shown no differences between treated and control groups. The combination of lidocaine, methylene blue and pentoxyphylline administered intraperitoneally at the studied dose, did not decreased histological lesion scores and biochemical markers levels in intestinal ischemia/reperfusion injury.

In-vitro terahertz spectroscopy of rat skin under the action of dehydrating agents

NASA Astrophysics Data System (ADS)

Kolesnikov, Aleksandr S.; Kolesnikova, Ekaterina A.; Tuchina, Daria K.; Terentyuk, Artem G.; Nazarov, Maxim; Skaptsov, Alexander A.; Shkurinov, Alexander P.; Tuchin, Valery V.

2014-01-01

In the paper we present the results of study of rat skin and rat subcutaneous tumor under the action of dehydrating agents in terahertz (THz) range (15-30 THz). Frustrated Total Internal Reflection (FTIR) spectra were obtained with infrared Fourier spectrometer Nicolet 6700 and then they were recalculated in the transmittance spectra with Omnic software. Experiments were carried out with healthy and xenografted tumor in skin tissue in vitro. As the dehydrating agents 100% glycerol, 40%-water glucose solution, PEG-600, and propylene glycol were used. To determine the effect of the optical clearing agent (OCA), the alterations of terahertz transmittance for the samples were analyzed. The results have shown that PEG-600 and 40%-glucose water solution are the most effective dehydrating agent. The transmittance of healthy skin after PEG-600 application increased approximately by 6% and the transmittance of tumor tissue after PEG- 600 and 40%-glucose water solution application increased approximately by 8%. Obtained data can be useful for further application of terahertz radiation for tumor diagnostics.

Mannitol Improves Brain Tissue Oxygenation in a Model of Diffuse Traumatic Brain Injury.

PubMed

Schilte, Clotilde; Bouzat, Pierre; Millet, Anne; Boucheix, Perrine; Pernet-Gallay, Karin; Lemasson, Benjamin; Barbier, Emmanuel L; Payen, Jean-François

2015-10-01

Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury. Experimental study. Neurosciences and physiology laboratories. Adult male Wistar rats. Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult. Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats. The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue without evidence of brain ischemia. Our findings indicate that an antiedematous agent such as mannitol can improve brain tissue oxygenation, possibly by limiting astrocyte swelling and restoring capillary perfusion.

Exercise training and muscle microvascular oxygenation: functional role of nitric oxide

PubMed Central

Hirai, Daniel M.; Copp, Steven W.; Ferguson, Scott K.; Holdsworth, Clark T.; McCullough, Danielle J.; Behnke, Bradley J.; Musch, Timothy I.

2012-01-01

Exercise training induces multiple adaptations within skeletal muscle that may improve local O2 delivery-utilization matching (i.e., Po2mv). We tested the hypothesis that increased nitric oxide (NO) function is intrinsic to improved muscle Po2mv kinetics from rest to contractions after exercise training. Healthy young Sprague-Dawley rats were assigned to sedentary (n = 18) or progressive treadmill exercise training (n = 10; 5 days/wk, 6–8 wk, final workload of 60 min/day at 35 m/min, −14% grade) groups. Po2mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP, NO donor; 300 μM), and NG-nitro-l-arginine methyl ester (l-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained rats had greater peak oxygen uptake (V̇o2peak) than their sedentary counterparts (81 ± 1 vs. 72 ± 2 ml·kg−1·min−1, respectively; P < 0.05). Exercise-trained rats had significantly slower Po2mv fall throughout contractions (τ1; time constant for the first component) during control (sedentary: 8.1 ± 0.6; trained: 15.2 ± 2.8 s). Compared with control, SNP slowed τ1 to a greater extent in sedentary rats (sedentary: 38.7 ± 5.6; trained: 26.8 ± 4.1 s; P > 0.05) whereas l-NAME abolished the differences in τ1 between sedentary and trained rats (sedentary: 12.0 ± 1.7; trained: 11.2 ± 1.4 s; P < 0.05). Our results indicate that endurance exercise training leads to greater muscle microvascular oxygenation across the metabolic transient following the onset of contractions (i.e., slower Po2mv kinetics) partly via increased NO-mediated function, which likely constitutes an important mechanism for training-induced metabolic adaptations. PMID:22678970

Improvement in hemodynamic performance, exercise capacity, inflammatory profile, and left ventricular reverse remodeling after intracoronary delivery of mesenchymal stem cells in an experimental model of pressure overload hypertrophy.

PubMed

Molina, Ezequiel J; Palma, Jon; Gupta, Dipin; Torres, Denise; Gaughan, John P; Houser, Steven; Macha, Mahender

2008-02-01

In a rat model of pressure overload hypertrophy, we studied the effects of intracoronary delivery of mesenchymal stem cells on hemodynamic performance, exercise capacity, systemic inflammation, and left ventricular reverse remodeling. Sprague-Dawley rats underwent aortic banding and were followed up by echocardiographic scanning. After a decrease in fractional shortening of 25% from baseline, animals were randomized to intracoronary injection of mesenchymal stem cells (MSC group; n = 28) or phosphate-buffered saline solution (control group; n = 20). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of inflammatory markers were performed before the rats were humanely killed on postoperative day 7, 14, 21, or 28. Injection of mesenchymal stem cells improved systolic function in the MSC group compared with the control group (mean +/- standard deviation: maximum dP/dt 3048 +/- 230 mm Hg/s vs 2169 +/- 97 mm Hg/s at 21 days and 3573 +/- 741 mm Hg/s vs 1363 +/- 322 mm Hg/s at 28 days: P < .001). Time to exhaustion was similarly increased in the MSC group compared with controls (487 +/- 35 seconds vs 306 +/- 27 seconds at 28 days; P < .01). Serum levels of interleukins 1 and 6, tumor necrosis factor-alpha, and brain natriuretic peptide-32 were significantly decreased in animals treated with mesenchymal stem cells. Stem cell transplantation improved left ventricular fractional shortening at 21 and 28 days. Left ventricular end-systolic and end-diastolic diameters were also improved at 28 days. In this model of pressure overload hypertrophy, intracoronary delivery of mesenchymal stem cells during heart failure was associated with an improvement in hemodynamic performance, maximal exercise tolerance, systemic inflammation, and left ventricular reverse remodeling. This study suggests a potential role of this treatment strategy for the management of hypertrophic heart failure resulting from pressure overload.

Pyruvate dose response studies targeting the vital signs following hemorrhagic shock

PubMed Central

Sharma, Pushpa; Vyacheslav, Makler; Carissa, Chalut; Vanessa, Rodriguez; Bodo, Mike

2015-01-01

Objectives: To determine the optimal effective dose of sodium pyruvate in maintaining the vital signs following hemorrhagic shock (HS) in rats. Materials and Methods: Anesthetized, male Sprague-Dawley rats underwent computer-controlled HS for 30 minute followed by fluid resuscitation with either hypertonic saline, or sodium pyruvate solutions of 0.5 M, 1.0 M, 2.0 M, and 4.0 M at a rate of 5ml/kg/h (60 minute) and subsequent blood infusion (60 minute). The results were compared with sham and non- resuscitated groups. The animals were continuously monitored for mean arterial pressure, systolic and diastolic pressure, heart rate, pulse pressure, temperature, shock index and Kerdo index (KI). Results: The Sham group remained stable throughout the experiment. Non-resuscitated HS animals did not survive for the entire experiment due to non-viable vital signs and poor shock and KI. All fluids were effective in normalizing the vital signs when shed blood was used adjunctively. Sodium pyruvate 2.0 M was most effective, and 4.0 M solution was least effective in improving the vital signs after HS. Conclusions: Future studies should be directed to use 2.0 M sodium pyruvate adjuvant for resuscitation on multiorgan failure and survival rate in HS. PMID:26229300

Enhanced in vivo absorption of CB-1 antagonist in rats via solid solutions prepared by hot-melt extrusion.

PubMed

Ranzani, L S; Font, J; Galimany, F; Santanach, A; Gomez-Gomar, A M; Casadevall, G; Gryczke, A

2011-06-01

The aim of the present work was to investigate in vitro dissolution properties of three binary solid solutions prepared by a hot-melt extrusion (HME) process with vinyl pirrolidone--vinyl acetate copolymer (Kollidon VA 64), ethyl acrylate, methyl methacrylate polymer (Eudragit E) polyetilenglicol 8000 (PEG 8000) with a cannabinoid type 1 (CB-1) antagonist. Hansen solubility parameters were calculated from the chemical structures of the drug and the individual polymers in order to predict miscibility. Solid state characterizations of drug substance, physical blends and HME formulations were performed with differential scanning calorimetry. The dissolution testing conducted under sink conditions revealed that the dissolution rate of HME formulations improved around 1.8-fold vs drug substance. Supersaturation dissolution study demonstrated that HME formulations composed by Eudragit E and Kollidon VA64 increased drug solubility between 30- and 35-fold, respectively comparing to the drug substance. Physical and chemical stability of formulations were studied at 40°C/75%HR with open dish during 15 days. The formulation composed by the drug and Eudragit E at 10:90 was evaluated for in vivo drug absorption in male Wistar-Hannover rats and it was found to increase CB-1 absorption threefold greater than pure drug oral suspension.

D-optimal experimental approach for designing topical microemulsion of itraconazole: Characterization and evaluation of antifungal efficacy against a standardized Tinea pedis infection model in Wistar rats.

PubMed

Kumar, Neeraj; Shishu

2015-01-25

The study aims to statistically develop a microemulsion system of an antifungal agent, itraconazole for overcoming the shortcomings and adverse effects of currently used therapies. Following preformulation studies like solubility determination, component selection and pseudoternary phase diagram construction, a 3-factor D-optimal mixture design was used for optimizing a microemulsion having desirable formulation characteristics. The factors studied for sixteen experimental trials were percent contents (w/w) of water, oil and surfactant, whereas the responses investigated were globule size, transmittance, drug skin retention and drug skin permeation in 6h. Optimized microemulsion (OPT-ME) was incorporated in Carbopol based hydrogel to improve topical applicability. Physical characterization of the formulations was performed using particle size analysis, transmission electron microscopy, texture analysis and rheology behavior. Ex vivo studies carried out in Wistar rat skin depicted that the optimized formulation enhanced drug skin retention and permeation in 6h in comparison to conventional cream and Capmul 908P oil solution of itraconazole. The in vivo evaluation of optimized formulation was performed using a standardized Tinea pedis model in Wistar rats and the results of the pharmacodynamic study, obtained in terms of physical manifestations, fungal-burden score, histopathological profiles and oxidative stress. Rapid remission of Tinea pedis from rats treated with OPT-ME formulation was observed in comparison to commercially available therapies (ketoconazole cream and oral itraconazole solution), thereby indicating the superiority of microemulsion hydrogel formulation over conventional approaches for treating superficial fungal infections. The formulation was stable for a period of twelve months under refrigeration and ambient temperature conditions. All results, therefore, suggest that the OPT-ME can prove to be a promising and rapid alternative to conventional antifungal therapies against superficial fungal infections. Copyright © 2014 Elsevier B.V. All rights reserved.

Critical role of NMDA but not opioid receptors in the acquisition of fat-conditioned flavor preferences in rats.

PubMed

Dela Cruz, J A D; Bae, V S; Icaza-Cukali, D; Sampson, C; Bamshad, D; Samra, A; Singh, S; Khalifa, N; Touzani, K; Sclafani, A; Bodnar, R J

2012-11-01

Animals learn to prefer flavors associated with the intake of dietary fats such as corn oil (CO) solutions. We previously reported that fat-conditioned flavor preferences in rats were relatively unaffected by systemic treatment with dopamine D1 and D2 antagonsits. The present study examined whether systemic opioid (naltrexone, NTX) or NMDA (MK-801) receptor antagonists altered the acquisition and/or expression of CO-CFP. The CFP was produced by training rats to drink one novel flavor (CS+, e.g., cherry) mixed in a 3.5% CO solution and another flavor (CS-, e.g., grape) in a 0.9% CO solution. In expression studies, food-restricted rats drank these solutions in one-bottle sessions (2 h) over 10 d. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 0.9% CO solutions occurred 0.5h after systemic administration of vehicle (VEH), NTX (0.1-5 mg/kg) or MK-801 (50-200 μg/kg). Rats displayed a robust CS+ preference following VEH treatment (85-88%) which was significantly though moderately attenuated by NTX (69-70%). The lower doses of MK-801 slightly reduced the CS+ preference; the high dose blocked the CS+ preference (49%) but also markedly reduced overall CS intake. In separate acquisition studies, rats received VEH or NTX (0.1, 0.5, 1mg/kg) or MK-801 (100 μg/kg) 0.5h prior to 1-bottle training trials with CS+/3.5% CO and CS-/0.9% CO training solutions. Additional Limited VEH groups were trained with intakes limited to that of the NTX and MK-801 groups. Subsequent two-bottle CS+ vs. CS- tests were conducted without injections. Significant and persistent CS+ preferences were observed in VEH (77-84%) and Limited VEH (88%) groups. NTX treatment during training failed to block the acquisition of CO-CFP although the magnitude of the CS+ preference was reduced by 0.5 (70%) and 1.0 (72%) mg/kg doses relative to the Limited VEH treatment (88%). In contrast, MK-801 (100 μg/kg) treatment during training blocked the acquisition of the CO-CFP. These data suggest a critical role for NMDA, but not opioid receptor signaling in the acquisition of a fat conditioned flavor preferences, and at best limited involvement of NMDA and opioid receptors in the expression of a previously learned preference. Copyright © 2012 Elsevier Inc. All rights reserved.

Ultrastructural liver changes in the experimental thyrotoxicosis.

PubMed

Pasyechko, Nadiya Vasylivna; Kuleshko, Iryna Ihorivna; Kulchinska, Veronika Mykolaiivna; Naumova, Liudmyla Valeriivna; Smachylo, Iryna Volodymyrivna; Bob, Anzhela Olehivna; Radetska, Liudmyla Volodymyrivna; Havryliuk, Mykhailo Yevhenovych; Sopel, Olha Mykolaiivna; Mazur, Liudmyla Petrivna

Aim of the study is to evaluate ultrastructural changes of rat liver in experimental thyrotoxicosis. For the study, 36 male rats have been utilized, weighing approximately 150-190 g, which were divided into three groups: the first, control group (12 animals) was composed of healthy rats that received intragastric sodium chloride 0.9% solution, the second group (12 animals) - animals with experimental thyrotoxicosis, which received intragastric solution of L-thyroxine at the rate of 200 μg/kg for 2 weeks, and the third group (12 animals) - rats with experimental thyrotoxicosis, which received intragastric solution of L-thyroxine at the rate of 200 μg/kg for 4 weeks. For electron-microscopic studies small pieces of liver tissue were taken at the end of the 2nd and 4th weeks of the experiment. The material was studied and documented in electron micrographs by using a TEM-125K electron microscope. In experiment in white male rats the electron-microscopic state of the liver in thyrotoxicosis has been studied. It has been established that thyrotoxicosis is accompanied by the significant changes of the hepatocytes ultrastructure, blood and bile capillaries. Experimental thyrotoxicosis causes significant damage of the liver plasma membranes and intracellular structural components of hepatocytes and endothelial cells. In experimental thyrotoxicosis, on the background of microcirculatory disorders, significant damage of plasmatic and intracellular organoid membranes of hepatocytes in the liver develops, which has an adverse effect on the functionality of the organ. The found ultrastructural changes are aggravated depending on the duration of thyrotoxicosis.

Conditions sufficient for the production of oral cocaine or lidocaine self-administration in preference to water.

PubMed

Falk, J L; Siris, A; Lau, C E

1996-03-01

Groups of rats were given a chronic history of drinking cocaine solutions of different concentrations in daily, 3-h schedule induced polydipsia sessions. Animals failed to develop a preference for cocaine solution to concurrently presented water. Schedule-induction conditions were maintained, and the animals were divided into separate groups, drinking either cocaine or lidocaine placed in a highly acceptable vehicle (glucose-saccharin solution). Animals preferred their respective drug solutions to concurrently presented water, and these preferences remained stable after the glucose-saccharin vehicle was gradually faded to water, leaving only cocaine or lidocaine, respectively, in the solution. Thus a stable preference for drug solution to water could be instituted in rats for either cocaine or lidocaine solution (putative reinforcing and nonreinforcing agents, respectively) given an appropriate associative history, with high intakes maintained by schedule-induction. Conditions sufficient for the initiation of an oral preference and high intake for a putatively reinforcing drug cannot be assumed to occur owing to the drug's reinforcing property in the absence of demonstrating the ineffectiveness of an appropriate negative control substance.

Taste-aversion-prone (TAP) rats and taste-aversion-resistant (TAR) rats differ in ethanol self-administration, but not in ethanol clearance or general consumption.

PubMed

Orr, T Edward; Whitford-Stoddard, Jennifer L; Elkins, Ralph L

2004-05-01

Taste-aversion (TA)-prone (TAP) rats and TA-resistant (TAR) rats have been developed by means of bidirectional selective breeding on the basis of their behavioral responses to a TA conditioning paradigm. The TA conditioning involved the pairing of an emetic-class agent (cyclophosphamide) with a novel saccharin solution as the conditioned stimulus. Despite the absence of ethanol in the selective breeding process, these rat lines differ widely in ethanol self-administration. In the current study, blood alcohol concentrations (BACs) were determined after 9 days of limited (2 h per day) access to a simultaneous, two-bottle choice of a 10% ethanol in water solution [volume/volume (vol./vol.)] or plain water. The BACs correlated highly with ethanol intake among TAR rats, but an insufficient number of TAP rats yielded measurable BACs to make the same comparison within this rat line. The same rats were subsequently exposed to 24-h access of a two-bottle choice (10% ethanol or plain water) for 8 days. Ethanol consumption during the 24-h access period correlated highly with that seen during limited access. Subsequent TA conditioning with these rats yielded line-typical differences in saccharin preferences. In a separate group of rats, ethanol clearance was determined by measuring BACs at 1, 4, and 7 h after injection of a 2.5-g/kg dose of ethanol. Ethanol clearance was not different between the two lines. Furthermore, the lines did not differ with respect to food and water consumption. Therefore, the TAP rat-TAR rat differences in ethanol consumption cannot be attributed to line differences in ethanol metabolism or in general consummatory behavior. The findings support our contention that the line differences in ethanol consumption are mediated by differences in TA-related mechanisms. The findings are discussed with respect to genetically based differences in the subjective experience of ethanol.

Pontine and Thalamic Influences on Fluid Rewards: I. Operant Responding for Sucrose and Corn Oil

PubMed Central

Liang, Nu-Chu; Freet, Christopher S.; Grigson, Patricia S; Norgren, Ralph

2011-01-01

The reward strength of orosensory sucrose and corn oil was measured using fixed and progressive ratio operant schedules. Because the orosensory effects of the stimuli were of interest, Experiment 1 compared operant responses for sucrose in sham and real feeding rats. The results demonstrated that rats would work for sucrose solutions without the accompanying postingestive effects. Furthermore, the break points for high concentrations of sucrose (1.0 M or 2.0 M) were significantly higher in sham feeding rats than in real feeding controls. Experiment 2 investigated the role of the parabrachial nucleus (PBN) and of the thalamic orosensory area (TOA) in sucrose and corn oil reward. During free access, rats with PBN lesions (PBNx) licked significantly less sucrose solution than their controls, but both groups ingested a similar volume of corn oil emulsion. When an operant was imposed, these same PBNx rats failed to respond for sucrose and continued only modestly for corn oil. In contrast, the TOA lesioned rats (TOAx) showed no impairment in responding for sucrose or corn oil during either the free access or operant sessions. Furthermore, rats with TOA lesions demonstrated significantly higher break points for sucrose than did their controls. Together, the data imply that the PBN but not the TOA is critical for the perception of, or responding to the reward value of sucrose and corn oil. PMID:21703290

Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring.

PubMed

Abd Elfatah, Azza A M; Ghaly, Inas S; Hanafy, Safaa M

2012-10-01

The present study evaluated the effect of aspartame intake on the histological and genetic structures of mother albino rats and their offspring. Sixty adult female albino rats and 180 of their offspring were equally divided into two groups (control and treated), each group divided into three subgroups. Each subgroup consisted of 10 pregnant rats and 30 of their offspring. The experimental design divided into three periods: (1) the gestation period (subgroup one), (2) the gestation period and three weeks after delivery (subgroup two) and (3) animals in the third subgroup treated as subgroup two then left till the end of the ninth week after delivery. Each pregnant rat in the treated subgroups was given a single daily dose of 1 mL aspartame solution (50.4 mg) by gastric gavage throughout the time intervals of experimental design. At the end of each experimental period for control and treated subgroups, the liver of half of both control and treated groups were subjected for histological study while the liver and bone marrow of the other halves were subjected for cytogenetic studies. Body weight of both groups were recorded individually twice weekly in the morning before offering the diet. The results revealed that the rats and their offspring in the subgroups of control animals showed increases in body weight, normal histological sections, low chromosomal aberration and low DNA fragmentation. The treated animals in the three subgroups rats and their offspring revealed decreases in body weight, high histological lesions, increases in the chromosomal aberration and DNA fragmentation compared with control groups. In conclusion, the consumption of aspartame leads to histopathological lesions in the liver and alterations of the genetic system in the liver and bone marrow of mother albino rats and their offspring. These toxicological changes were directly proportional to the duration of its administration and improved after its withdrawal.

In-vivo study for anti-hyperglycemic potential of aqueous extract of Basil seeds (Ocimum basilicum Linn) and its influence on biochemical parameters, serum electrolytes and haematological indices.

PubMed

Chaudhary, Sachin; Semwal, Amit; Kumar, Hitesh; Verma, Harish Chandra; Kumar, Amit

2016-12-01

The study introduced anti-hyperglycemic influence of aqueous extract of Ocimum basilicum seeds (AEOBS) in Streptozotocin (STZ) induced diabetic rats and estimating its potential to ameliorate altered level of biochemical parameters, serum electrolytes level and haematological indices along with its effect on body weight of treated rats. The albino rats were selected to observe oral glucose tolerance test by oral intake of aq. glucose solution (4g/kg, body weight) in normal rats and estimation of blood glucose level after administration of AEOBS at 250mg/kg, 500mg/kg and standard drug glibenclamide at 0.6mg/kg, body weight. Antidiabetic activity was evaluated in chronic study models by STZ induced diabetes in rats followed by blood glucose estimation. Chronic study model was selected to carry out further studies to evaluate the effect of AEOBS at 250mg/kg, 500mg/kg and standard drug on body weight, alterations in biochemical parameters including AST, ALT, ALP, total bilirubin and total protein, alterations in serum electrolytes like Na + , K + , Cl - , HCO 3 - along with estimation of haematological indices like red blood cells (RBC), white blood cells (WBC), hemoglobin (Hb), lymphocytes, neutrophils, eosinophils, monocytes and basophils. AEOBS significantly reduced the blood glucose level of diabetic rats at both doses. Body weight was also improved significantly. Similarly, the levels of biochemical parameters, serum electrolytes, and haematological indices were significantly ameliorated at both doses of AEOBS. The histopathological results revealed reconstitution of pancreatic islets towards normal cellular architecture in rats treated with AEOBS. The results illustrated that AEOBS have eminent antidiabetic potential in STZ effectuated diabetes in rats and can be extensively used for the treatment of diabetes mellitus-II and its associated complications including anaemia, diabetic nephropathy, liver dysfunction, and immunosuppression. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Reduced carotid baroreceptor distensibility-induced baroreflex resetting contributes to impairment of sodium regulation in rats fed a high-fat diet.

PubMed

Abe, Chikara; Nagai, Yuko; Yamaguchi, Aoi; Aoki, Hitomi; Shimizu, Shuji; Akiyama, Tsuyoshi; Kawada, Toru; Sugimachi, Masaru; Morita, Hironobu

2015-04-15

Decreased carotid arterial compliance has been reported in obese subjects and animals. Carotid baroreceptors are located at the bifurcation of the common carotid artery, and respond to distension of the arterial wall, suggesting that higher pressure is required to obtain the same distension in obese subjects and animals. A hyperosmotic NaCl solution induces circulatory volume expansion and arterial pressure (AP) increase, which reflexively augment renal excretion. Thus, we hypothesized that sodium regulation via the baroreflex might be impaired in response to chronic hyperosmotic NaCl infusion in rats fed a high-fat diet. To examine this hypothesis, we used rats fed a high-fat (Fat) or normal (NFD) diet, and measured mean AP, water and sodium balance, and renal function in response to chronic infusion of hyperosmotic NaCl solution via a venous catheter. Furthermore, we examined arterial baroreflex characteristics with static open-loop analysis and distensibility of the common carotid artery. Significant positive water and sodium balance was observed on the 1st day of 9% NaCl infusion; however, this disappeared by the 2nd day in Fat rats. Mean AP was significantly higher during 9% NaCl infusion in Fat rats compared with NFD rats. In the open-loop analysis of carotid sinus baroreflex, a rightward shift of the neural arc was observed in Fat rats compared with NFD rats. Furthermore, distensibility of the common carotid artery was significantly reduced in Fat rats. These results indicate that a reduced baroreceptor distensibility-induced rightward shift of the neural arc might contribute to impairment of sodium regulation in Fat rats. Copyright © 2015 the American Physiological Society.

Jew's mellow leaves (Corchorus olitorius) suppress elevation of postprandial blood glucose levels in rats and humans.

PubMed

Innami, Satoshi; Ishida, Hiroshi; Nakamura, Kahoru; Kondo, Mika; Tabata, Kimiko; Koguchi, Takashi; Shimizu, Jun; Furusho, Tadasu

2005-01-01

The study was performed to explore the suppressive effect of Jew's mellow leaves (JML) on postprandial blood glucose levels in rats and humans. A soluble dietary fiber (SDF) was extracted from the freeze-dried JML powder. An elevation of the postprandial blood glucose level in rats given 1% or 2% JML-SDF solution orally together with 20% glucose solution was significantly suppressed as compared with that observed in the control rats given only glucose solution. When seven healthy young male adults ingested 225 mL of JML mixed juice containing 15 g of freeze-dried powder with 75 g of glucose in the fasting state in the morning, the elevation of the postprandial blood glucose level was significantly suppressed as compared with the control subjects. The diffusion rate of glucose and the permeation rate of glucose in the cultured Caco-2 cells were both significantly reduced by the addition of appropriate amounts of JML-SDF when compared to the controls. These results indicate that the effective substance in JML for suppressing blood glucose elevation is a kind of mucilaginous SDF. The mechanism by which this suppression occurs may be largely attributable to the delayed absorption of glucose from the intestinal membrane in the upper digestive tract by viscous SDF.

Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

PubMed

Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

2011-01-01

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

[Analysis of healing in the Alba Linea with the use of Orbignya phalerata (babassu) water extract. Controlled study in rats].

PubMed

Brito Filho, Sebastião Barreto de; Matias, Jorge Eduardo F; Stahlke Júnior, Henrique Jorge; Torres, Orlando Jorge Martins; Timi, Jorge Rufino Ribas; Tenório, Sérgio Bernardo; Tâmbara, Elizabeth Milla; Carstens, Angelo G; Campos, Richard Vieira; Myamoto, Márcio

2006-01-01

The babassu mesocarp (Orbignya phalerata) has been used in experimental research studies focused on its antiinflammatory action. In state of Maranhão--Brazil it is widely used not only as food, but also as popular medicine in wound healing process. To evaluate the action of Orbignya phalerata extract in macroscopic, histologic and tensiometric aspects in the healing process of median laparotomy in rats. Forty male adult Wistar rats were submitted to an incision in the alba linea, sutured back in one plan with separated stitches of polypropylene 5-0. After regular procedure, the animals were divided into two groups of 20 rats each. To the group named control an intraperitoneal, dose of 1.0 ml of saline solution per kilogram of body weight was done. To the experimental group, the same thing was also done, but instead of saline solution it was injected water solution of babassu, in a dose of 50 mg/kg. The animals were observed in the following days. All of them were killed within a three and seven day post-operative period schedule, and then a histological and tensiometric analysis was carried out. On macroscopic examination no relevant adherence, between the alba linea and the abdominal organs in the study groups, was found. Histological evaluation presented marginal significant effects (p=0.86) to acute inflammation and significant effects (p=0.003) to giant cell reaction in both control and experimental three days groups. Significant difference was observed to acute inflammation in both seven days control and experimental groups. In the intragroup analysis (control three and seven) some marginal significant effect was in relationship to acute and chronic inflammation. In the inter-experimental groups analysis, only the giant cell reactions (0.002) and colagenization had significant results. The tensiometric evaluation showed in the seven day experimental group more resistance then others. The macroscopic and histological evaluation didn't show any significant difference between the experimental and control groups, but the tensiometric evaluation at the 7th day experimental group had significant difference compared to the control group, signaling that the use of the extract of babassu intraperitoneally injected can improve the healing process.

Intraoperative bowel irrigation improves anastomotic collagen metabolism in the left-sided colonic obstruction but not covering colostomy.

PubMed

Duraker, N; Bender, O; Memişoğlu, K; Yalçiner, A

1998-01-01

This study investigated the effects of intraoperative colonic irrigation and proximal diverting end colostomy after segmental bowel resection in experimental left-colonic obstruction on anastomotic healing. Simple obstruction of descending colon was performed in male Sprague-Dawley rats. After 24 h we performed segmental colonic resection and anastomosis in the control group (n = 15); resection, anastomosis, and covering colostomy in the colostomy group (n = 14); resection and anastomosis after antegrade colonic lavage through cecum by using isotonic saline solution in the irrigation group (n = 13). In rats that were killed 7 days later anastomotic dehiscence and bursting pressure and tissue hydroxyproline concentration at the anastomosis were measured. No significant differences were observed between groups in terms of anastomotic dehiscence, bursting site, or pressure. The hydroxyproline concentration was significantly higher in the irrigation group than the control group (P = 0.025) and the colostomy group (P = 0.029), but no difference was noted between the control group and the colostomy group. These findings suggest that intraoperative antegrade colonic irrigation in the acute left-sided colonic obstruction positively affects collagen metabolism at the anastomotic site; if the anastomosis is performed without bowel cleansing, covering colostomy does not improve collagen metabolism.

Gold nanoparticles induce DNA damage in the blood and liver of rats

NASA Astrophysics Data System (ADS)

Cardoso, Eria; Londero, Eduardo; Ferreira, Gabriela Kozuchovski; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rohr, Paula; da Silva, Luciano; Andrade, Vanessa M.; da Silva Paula, Marcos Marques

2014-11-01

The potential of gold nanoparticles (GNPs) for use in different biological applications has led to a strong interest in the study of their possible deleterious effects in biological systems and how these effects may be mitigated. This study was undertaken to investigate the effects of the acute and chronic administration of GNPs with mean diameters of 10 and 30 nm on deoxyribonucleic acid (DNA) damage in the blood and liver of adult rats. For the acute administration, Wistar adult rats received a single intraperitoneal injection of either GNPs or a saline solution. For the chronic administration, Wistar adult rats received a daily single injection of the same GNPs or saline solution for 28 days. Twenty-four hours after either the single (acute) or final injection (chronic), the rats were euthanised by decapitation, and the blood and liver were isolated for the evaluation of DNA damage. In this study, we demonstrated that the acute and chronic administration of GNPs 10 and 30 nm in size increased the frequency of DNA damage and the damage index in the blood and liver of adult rats. These findings suggest that the DNA damage may be caused by oxidative stress, which occurred regardless of the type of administration and GNP size.

Gaussian beam in two-photon fluorescence imaging of rat brain microvessel

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Rodríguez-Contreras, Adrián; Alfano, Robert R.

2014-12-01

The critical optical properties of a Gaussian laser beam in two-photon or multiphoton fluorescence imaging, including the beam spot size, depth of focus, and intensity profile, are investigated for spatially locating nanoscale solutes in and surrounding the microvessels of rat brain.

Some factors affecting performance of rats in the traveling salesman problem.

PubMed

Bellizzi, C; Goldsteinholm, K; Blaser, R E

2015-11-01

The traveling salesman problem (TSP) is used to measure the efficiency of spatial route selection. Among researchers in cognitive psychology and neuroscience, it has been utilized to examine the mechanisms of decision making, planning, and spatial navigation. While both human and non-human animals produce good solutions to the TSP, the solution strategies engaged by non-human species are not well understood. We conducted two experiments on the TSP using Long-Evans laboratory rats as subjects. The first experiment examined the role of arena walls in route selection. Rats tend to display thigmotaxis in testing conditions comparable to the TSP, which could produce results similar to a convex hull type strategy suggested for humans. The second experiment examined the role of turn angle between targets along the optimal route, to determine whether rats exhibit a preferential turning bias. Our results indicated that both thigmotaxis and preferential turn angles do affect performance in the TSP, but neither is sufficient as a predictor of route choice in this task.

17β-Estradiol protects the liver against cold ischemia/reperfusion injury through the Akt kinase pathway.

PubMed

Yang, Xiaohua; Qin, Lei; Liu, Jianxia; Tian, Liping; Qian, Haixin

2012-12-01

Hepatic ischemia-reperfusion (IR) injury occurs during liver resection and transplantation. Recent studies have shown that 17β-estradiol (E2) can protect the heart and liver against warm IR. The present study focused on the cytoprotective effects of E2 on cold IR injury to the liver. Sprague-Dawley male rats were randomly divided into three groups: sham, IR, and IR plus E2. The model of rat orthotopic liver transplantation was used. The rats in the IR plus E2 group were intraperitoneally injected with E2 (100 μg/kg/d) for 7 d before surgery. The sham and IR group received the same quantity of saline. The donor livers were then orthotopically transplanted into rats after cold ischemia preservation for 4 h at 4°C lactated Ringer's solution. After 6 h reperfusion, liver function, bile flow volume, hepatocyte apoptosis, and activation of Akt, glycogen synthase kinase-3β, and Bcl-2-associated death promoter were assessed. The survival rate of the rats was also investigated. The administration of E2 significantly prolonged the survival of liver grafts by improving liver function and decreasing hepatocyte apoptosis. Rats undergoing E2 demonstrated a greater level activation of Akt in the liver compared with the IR group. In addition, E2 also inhibited the activities of glycogen synthase kinase-3β, Bcl-2-associated death promoter, and caspase-3-induced by IR injury. E2 pretreatment attenuated the hepatocellular damage caused by hepatic cold IR injury through the Akt pathway. Estrogen therapy might be important in clinical settings associated with cold IR injury during liver transplantation. Copyright © 2012 Elsevier Inc. All rights reserved.

Efficacy of the injectable calcium phosphate ceramics suspensions containing magnesium, zinc and fluoride on the bone mineral deficiency in ovariectomized rats.

PubMed

Otsuka, Makoto; Oshinbe, Ayako; Legeros, Racquel Z; Tokudome, Yoshihiro; Ito, Atsuo; Otsuka, Kuniko; Higuchi, William I

2008-01-01

The purpose of this study was to evaluate the therapeutic efficacy of a new calcium phosphate (CaP)-based formulation in improving the bone mineral deficiency in ovariectomized (OVX) rats. The ions release experiments for CaP preparations (G2: 0.46% Mg, 5.78% Zn, and 2.5% F; G3:3.1% Mg, 0.03% Zn, and 3.01% F; G4: 1.25% Mg, 1.77% Zn, 1.35% F) and of a Zn-TCP (G1: 6.17% Zn) powders, the initial Mg and Zn ion release rates of MZF-CaPs were performed in acetate buffer at pH 4.5 (37 degrees C). Wistar rats were divided into six groups including a normal (not OVX) group (GN) and a control, OVX group (GC). Rats in groups GC, G1, G2, G3, G4 were OVX. Suspensions consisting of CaP preparations (G2, G3, G4) and of a Zn-TCP (G1) powders were injected in the right thighs of OVX rats in all groups except for GN and GC, once a week for 4 weeks. GN and GC rats were injected with saline solutions. Plasma was analyzed for Zn land alkaline phosphatase levels. The bone mineral density (BMD) was measured using DEXA and the bone (femur) strength determined using three-point-bending analysis. G1 and G2 groups showed high plasma Zn levels. The area under the curve of plasma Zn was significantly greater in the G1, G2, and GN groups than in the G3, G4, and GC groups (p < 0.05). The BMD and bone mechanical strength of the right femur were significantly higher in the G1, G2, G3, and G4 groups than GC group on day 28. The right femur had significantly greater BMD and bone mechanical strength than the left femur in G1, G2, G3, and G4 groups. However, there was no significant difference in the BMD of the right femur between the G1, G2, G3, and G4 groups. Results indicate that the new injectable CaP formulations are effective in improving bone properties of OVX rats and may be useful in osteoporosis therapy. (c) 2007 Wiley-Liss, Inc.

[The influence of low-energy millimeter electromagnetic waves on the stability of DNA molecules in solution].

PubMed

Babaian; Markarian, A Sh; Kalantarian, V P; Kazarian, R S; Parsadanian, M A; Vardevanian, P O

2007-01-01

The influence of low-energy millimeter electromagnetic waves on aqueous saline solution of DNA from the liver of healthy rats and rats with sarcoma 45 has been investigated. The characteristic parameters of irradiated and unirradiated DNA, melting temperature, and the range of melting were obtained from melting curves. The duration of exposure did not practically affect the range of melting, while the thermostability of DNA increased; as irradiation duration increased to 90 min, the melting temperature of tumor increased by approximately 1.5 degrees C. It was assumped that the increase in the thermostability of DNA is due to a more effective stabilization of the DNA double helix caused by the dehydration of Na(+)- ions present in the solution.

Pharmacokinetics and Bioavailability of the GnRH Analogs in the Form of Solution and Zn2+-Suspension After Single Subcutaneous Injection in Female Rats.

PubMed

Suszka-Świtek, Aleksandra; Ryszka, Florian; Dolińska, Barbara; Dec, Renata; Danch, Alojzy; Filipczyk, Łukasz; Wiaderkiewicz, Ryszard

2017-04-01

Although many synthetic gonadoliberin analogs have been developed, only a few of them, including buserelin, were introduced into clinical practice. Dalarelin, which differs from buserelin by just one aminoacid in the position 6 (D-Ala), is not widely used so far. Gonadotropin-releasing hormone (GnRH) analogs are used to treat many different illnesses and are available in different forms like solution for injection, nasal spray, microspheres, etc. Unfortunately, none of the above drug formulations can release the hormones for 24 h. We assumed that classical suspension could solve this problem. Two sets of experiments were performed. In the first one, buserelin and dalarelin were injected into mature female rats in two forms: suspension, in which the analogs are bounded by Zn 2+ ions and solution. The pharmacokinetic parameters and bioavailability of the analogs were calculated, based on their concentration in the plasma measured by high-performance liquid chromatography method (HPLC). In the second experiment, the hormones in two different forms were injected into superovulated immature female rats and then the concentration of Luteinizing hormone (LH), Follicle-stimulating hormone (FSH) and 17β-estradiol in the serum was measured by radioimmunological method. The Extent of Biological Availability (EBA), calculated on the base of AUC 0-∞ , showed that in the form of solution buserelin and dalarelin display, respectively, only 13 and 8 % of biological availability of their suspension counterparts. Comparing both analogs, the EBA of dalarelin was half (53 %) that of buserelin delivered in the form of solution and 83 % when they were delivered in the form of suspension. The injection of buserelin or dalarelin, in the form of solution or suspension, into superovulated female rats increased LH, FSH and estradiol concentration in the serum. However, after injection of the analogs in the form of suspension, the high concentration of LH and FSH in the serum persisted longer. Performed studies indicate that GnRH analogs in the form of suspension have higher bioavailability than their solution counterparts. It influences the effects of their action, especially in relation to LH and FSH.

Effect of Neonatal Clomipramine Treatment on Consummatory Successive Negative Contrast

ERIC Educational Resources Information Center

Ruetti, Eliana; Burgueno, Adriana L.; Justel, Nadia R.; Pirola, Carlos J.; Mustaca, Alba E.

2013-01-01

Neonatal administration of clomipramine (CLI) produces physiological, neuroendocrinal and behavioral abnormalities in rats when they reach adulthood, which are similar to those observed in animal models of depression. In consummatory successive negative contrast (cSNC), rats that have had experience drinking 32% sucrose solution drink…

FACTORS DETERMINING DEGREE OF INFLATION IN INTRATRACHEALLY FIXED RAT LUNGS

EPA Science Inventory

The total lung capacity (TLC) of rats was measured in vivo and was compared to the displacement volume of the lungs following intratracheal fixation with glutaraldehyde or formaldehyde solution. When glutaraldehyde was used the speed of infusion of the fixative was an important f...

Lack of functionally active sweet taste receptors in the jejunum in vivo in the rat.

PubMed

Chaudhry, Rizwan M; Garg, Alok; Abdelfatah, Mohamed M; Duenes, Judith A; Sarr, Michael G

2013-08-01

When studied in enterocyte-like cell lines (Caco-2 and RIE cells), agonists and antagonists of the sweet taste receptor (STR) augment and decrease glucose uptake, respectively. We hypothesize that exposure to STR agonists and antagonists in vivo will augment glucose absorption in the rat. About 30-cm segments of jejunum in anesthetized rats were perfused with iso-osmolar solutions containing 10, 35, and 100 mM glucose solutions (n = 6 rats, each group) with and without the STR agonist 2 mM acesulfame potassium and the STR inhibitor 10 μM U-73122 (inhibitor of the phospholipase C pathway). Carrier-mediated absorption of glucose was calculated by using stereospecific and nonstereospecific (14)C-d-glucose and (3)H-l-glucose, respectively. Addition of the STR agonist acesulfame potassium to the 10, 35, and 100 mM glucose solutions had no substantive effects on glucose absorption from 2.1 ± 0.2 to 2.0 ± 0.3, 5.8 ± 0.2 to 4.8 ± 0.2, and 15.5 ± 2.3 to 15.7 ± 2.7 μmoL/min/30-cm intestinal segment (P > 0.05), respectively. Addition of the STR inhibitor (U-73122) also had no effect on absorption in the 10, 35, and 100 mM solutions from 2.3 ± 0.1 to 2.1 ± 0.2, 7.7 ± 0.5 to 7.2 ± 0.5, and 15.7 ± 0.9 to 15.2 ± 1.1 μmoL/min/30-cm intestinal segment, respectively. Provision of glucose directly into rat jejunum does not augment glucose absorption via STR-mediated mechanisms within the jejunum in the rat. Our experiments show either no major role of STRs in mediating postprandial augmentation of glucose absorption or that proximal gastrointestinal tract stimulation of STR or other luminal factors may be required for absorption of glucose to be augmented by STR. Copyright © 2013 Elsevier Inc. All rights reserved.

HSD is a better resuscitation fluid for hemorrhagic shock with pulmonary edema at high altitude.

PubMed

Liu, Liang-Ming; Hu, De-Yao; Zhou, Xue-Wu; Liu, Jiang-Cang; Li, Ping

2008-12-01

To investigate the fluid tolerance of hemorrhagic shock with pulmonary edema (HSPE) at high altitude in unacclimated rats and the beneficial effect of 7.5% hypertonic saline/6% dextran (HSD). One hundred seventy-six Sprague-Dawley rats, transported to LaSa, Tibet, 3,760 m above the sea level, were anesthetized with sodium pentobarbital (30 mg/kg, i.p.) within 1 week. Hemorrhagic shock with pulmonary edema was induced by bloodletting (50 mmHg for 1 h) plus intravenous injection of oleic acid (50 microL/kg). Seventy-seven rats were equally divided into 11 groups (n = 7/group) including sham-operated control group; hemorrhagic shock control group; HSPE control group; HSPE plus 0.5-, 1.0-, 1.5-, 2.0-, or 3.0-fold volumes of lactated Ringer's solution (LR) groups; and HSPE plus 4, 6, and 8 mL/kg of HSD groups. Hemodynamic parameters including mean arterial blood pressure, left intraventricular systolic pressure, and the maximal change rate of intraventricular pressure rise or decline (+/-dp/dtmax) were observed at baseline and at 15, 30, 60, and 120 min after infusion; blood gases were measured at 30 and 120 min after infusion, and the water content of lung and brain was determined at 120 min after infusion. Additional 99 rats were used to observe the effect of these treatments on the survival time of HSPE rats; 0.5 volume of LR infusion slightly increased the mean arterial blood pressure, left intraventricular systolic pressure, and +/-dp/dtmax and prolonged the survival time of HSPE animals as compared with the HSPE group (P < 0.05 - 0.01); it did not increase the water content of lung and brain and had no marked influences on blood gases. One volume of LR infusion had somewhat improved the hemodynamic parameters for HSPE animals, but had no apparent effect on the survival time and the water content of lung and brain. Lactate Ringer's solution infusion, 1.5, 2, and 3 volumes, significantly deteriorated the hemodynamic parameters, increased the water content of lung, and decreased the survival time of HSPE animals. Hypertonic saline/6% dextran (4 - 8 mL/kg) significantly increased the hemodynamic parameters, improved the blood gases, decreased the water content of lung and brain, and prolonged the survival time of HSPE rats. Among the three dosages of HSD, 6 mL/kg of HSD had the best effect. The tolerance of fluid infusion for hemorrhagic shock with pulmonary edema at high altitude is significantly decreased. More than one volume of LR infusion would aggravate the pulmonary edema and exacerbate the resuscitation effect, but only one volume of LR cannot reach the effective volume resuscitation. Small volume of HSD could better resuscitate hemorrhagic shock with pulmonary edema at high altitude.

Acute and chronic ethanol intake: effects on spatial and non-spatial memory in rats.

PubMed

García-Moreno, Luis M; Cimadevilla, Jose M

2012-12-01

Abusive alcohol consumption produces neuronal damage and biochemical alterations in the mammal brain followed by cognitive disturbances. In this work rats receiving chronic and acute alcohol intake were evaluated in a spontaneous delayed non-matching to sample/position test. Chronic alcohol-treated rats had free access to an aqueous ethanol solution as the only available liquid source from the postnatal day 21 to the end of experiment (postnatal day 90). Acute alcoholic animals received an injection of 2 g/kg ethanol solution once per week. Subjects were evaluated in two tests (object recognition and spatial recognition) based on the spontaneous delayed non-matching to sample or to position paradigm using delays of 1 min, 15 min and 60 min. Results showed that chronic and acute alcohol intake impairs the rats' performance in both tests. Moreover, chronic alcohol-treated rats were more altered than acute treated animals in both tasks. Our results support the idea that chronic and acute alcohol administration during postnatal development caused widespread brain damage resulting in behavioral disturbances and learning disabilities. Copyright © 2012 Elsevier Inc. All rights reserved.

A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB.

PubMed

Iannone, Michelangelo; Cosco, Donato; Cilurzo, Felisa; Celia, Christian; Paolino, Donatella; Mollace, Vincenzo; Rotiroti, Domenicantonio; Fresta, Massimo

2010-01-18

The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood-brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80-coated poly-L-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-L-lactid acid nanoparticles (5mg/kg), a saline solution of tacrine (5mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine-lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Prolonged nerve block by microencapsulated bupivacaine prevents acute postoperative pain in rats.

PubMed

Ohri, Rachit; Blaskovich, Phillip; Wang, Jeffrey Chi-Fei; Pham, Lan; Nichols, Gary; Hildebrand, William; Costa, Daniel; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary

2012-01-01

To minimize acute postoperative pain, a new formulation of slowly released bupivacaine was developed. Bupivacaine was microencapsulated at 60% (wt/wt) in poly-lactide-co-glycolide polymers and characterized for physicochemical properties and bupivacaine release kinetics. This formulation was injected around the rat sciatic nerve to produce an antinociceptive effect to toe pinch. Mechanical hyperalgesia following lateral plantar paw incision in rats was assessed for 7 to 14 days when the bupivacaine slow-release formulation was placed at the ipsilateral sciatic nerve and compared with the hyperalgesia that developed with various controls. Bupivacaine was released in vitro at a relatively constant rate over a period of ≈ 72 to 96 hours. Complete antinociception, shown as no response to toe pinch, lasted for 23 ± 7 hours, with a half-recovery time of 42 ± 8 hours after sciatic nerve injection of 0.4 mL of the microspheres delivering 34 mg of bupivacaine. Solutions of 0.5% (wt/vol) bupivacaine-HCl (0.1 mL) produced complete antinociception for less than 2 hours and recovery half-times of 2 hours. Postincisional mechanical hyperalgesia, shown by increased withdrawal responses to von Frey filaments, was absent for 24 hours and was lower than control for 96 hours, when the sciatic nerve was blocked by bupivacaine microspheres, whereas the 0.5% bupivacaine solution reduced postincisional pain for only 4 hours. Corresponding to its far greater functional blocking time, the microsphere-bupivacaine formulation was able to significantly reduce postoperative pain below control levels for up to 4 days. These findings of several days of postoperative pain relief, for an injectable formulation containing a single active agent, present an improved and potentially promising therapy to prevent acute pain after surgery.

Nitric oxide synthase gene transfer for erectile dysfunction in a rat model.

PubMed

Chancellor, M B; Tirney, S; Mattes, C E; Tzeng, E; Birder, L A; Kanai, A J; de Groat, W C; Huard, J; Yoshimura, N

2003-05-01

To determine whether over-expression of nitric oxide synthase (NOS) in the corpus cavernosum of the penis improves erectile function, as NO is an important transmitter for genitourinary tract function, mediating smooth muscle relaxation and being essential for penile erection. The inducible form of the enzyme NOS (iNOS) was introduced into the corpus cavernosum of adult Sprague-Dawley rats (250-300 g) by injecting a solution of plasmid, adenovirus or adenovirus-transduced myoblast cells (adeno-myoblasts). Plasmid, adenovirus and adeno-myoblasts encoding the expression of the beta-galactosidase reporter gene were also injected into rats. Throughout the corpora cavernosum there was expression of beta-galactosidase after injecting each of the three solutions. Maximum staining was greatest for adeno-myoblast, then adenovirus and then plasmid. The mean (sd) basal intracavernosal pressure (ICP) of iNOS-treated animals (adenovirus and adeno-myoblast) increased to 55 (23) cmH2O, compared with naive animals with a basal ICP of 5 (6) cmH2O (P = 0.001). Stimulating the cavernosal nerve (15 Hz, 1.5 ms, 10-40 V, 1 min) resulted in a doubling of the ICP (adenovirus and adeno-myoblast) from the basal level of the iNOS-treated animals. Direct in situ measurement of NO showed the release of 1-1.3 micro mol/L in the adeno-myoblast penis. Myoblast-mediated gene therapy was more successful for delivering iNOS into the corpus cavernosum than direct adenovirus injection or plasmid transfection. Surprisingly, implanting muscle cells into the penis is not only feasible but also beneficial. Gene therapy for NOS may open new avenues of treatment for erectile dysfunction. Control of NOS expression would be necessary to prevent priapism.

Pre-Clinical Study for the Antidiabetic Potential of Selenium Nanoparticles.

PubMed

Ahmed, Hanaa H; Abd El-Maksoud, Mohamed Diaa; Abdel Moneim, Ahmed E; Aglan, Hadeer A

2017-06-01

This research was delineated to explore the efficacy of selenium nanoparticles delivered in liposomes (L-Se) in the mitigation of type-2 diabetes mellitus. Adult female Wistar rats were assigned into four groups: group I, the normal control group in which the rats received normal saline solution orally; group II, the diabetic control group in which the rats were injected intraperitoneally with a single dose of streptozotocin (STZ) for induction of diabetes; group III, the metformin (Met)-treated group in which the diabetic rats were treated orally with Met; and group IV, the L-Se-treated group in which the diabetic rats were treated orally with L-Se. All treatments were delivered for 21 days. Blood and pancreas tissue samples were obtained for biochemical analysis, immunohistochemical examinations, and histopathological investigation. The L-Se-treated group showed significant drop in serum glucose and pancreatic malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), and prostaglandin F2α (PGF2α) levels associated with significant rise in serum insulin and pancreatic glutathione, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) values, in addition to significant improvement in the immunohistochemical indices (insulin and glucagon). Aforementioned results are appreciated by the histopathological findings of pancreatic tissue. In conclusion, our data have brought about compelling evidence favoring the antidiabetic potency of elemental selenium nanoparticles delivered in liposomes through preservation of pancreatic β cell integrity with consequent increment of insulin secretion and in turn glucose depletion, repression of oxidative stress, potentiation of the antioxidant defense system, and inhibition of pancreatic inflammation.

Memory inhibition as a critical factor preventing creative problem solving.

PubMed

Gómez-Ariza, Carlos J; Del Prete, Francesco; Prieto Del Val, Laura; Valle, Tania; Bajo, M Teresa; Fernandez, Angel

2017-06-01

The hypothesis that reduced accessibility to relevant information can negatively affect problem solving in a remote associate test (RAT) was tested by using, immediately before the RAT, a retrieval practice procedure to hinder access to target solutions. The results of 2 experiments clearly showed that, relative to baseline, target words that had been competitors during selective retrieval were much less likely to be provided as solutions in the RAT, demonstrating that performance in the problem-solving task was strongly influenced by the predetermined accessibility status of the solutions in memory. Importantly, this was so even when participants were unaware of the relationship between the memory and the problem-solving procedures in the experiments. This finding is consistent with an inhibitory account of retrieval-induced forgetting effects and, more generally, constitutes support for the idea that the activation status of mental representations originating in a given task (e.g., episodic memory) can unwittingly have significant consequences for a different, unrelated task (e.g., problem solving). (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Acute elevations in salt intake and reduced renal mass hypertension compromise arteriolar dilation in rat cremaster muscle.

PubMed

Frisbee, J C; Lombard, J H

1999-05-01

Alterations in arteriolar reactivity to dilator agonists were assessed in the skeletal muscle microcirculation of normotensive male Sprague-Dawley rats fed either high- (4% NaCl; HS) or low- (0. 4% NaCl; LS) salt diets and in reduced renal mass hypertensive rats (RRM-HT) on a high-salt diet for 3 days. An in situ cremaster muscle preparation was superfused with physiological salt solution, transilluminated, and viewed via television microscopy. A videomicrometer was used to measure changes in diameter of distal arterioles in response to increasing concentrations of acetylcholine (ACH), iloprost (ILO), cholera toxin (CT), forskolin (FOR), and sodium nitroprusside (SNP). Arteriolar dilation in response to ACH, ILO, and CT was significantly reduced in both HS and RRM-HT rats, while responses to FOR and SNP were decreased in RRM-HT rats only. The maximum dilation of the arterioles (determined during superfusion of the muscle with Ca2+-free solution containing 10(-4) M adenosine) was similar in the normotensive control animals on LS and HS diets, but was reduced in the RRM-HT rats, suggesting that early anatomic remodeling of the vessel wall may be occurring with RRM-HT. We conclude that arteriolar reactivity to endothelium-dependent and -independent vasodilator agonists is impaired as early as 3 days after the development of RRM hypertension or commencement of a high-salt diet in normotensive rats. Structural remodeling of the arteriolar wall, although becoming evident in the hypertensive rats, takes longer to develop than the impaired vasodilator reactivity. Copyright 1999 Academic Press.

Can overeating induce conditioned taste avoidance in previously food restricted rats?

PubMed

Hertel, Amanda; Eikelboom, Roelof

2010-03-30

While feeding is rewarding, the feeling of satiation has been theorized to have a mixed affect. Using a food restriction model of overeating we examined whether bingeing was capable of supporting conditioned taste avoidance (CTA). Adult male Sprague-Dawley rats were maintained on either an ad lib (n=8) or restricted (50% of regular consumption; n=24) food access for 20 days. On Days 9, 14, and 19 all rats were given access to a novel saccharin solution in place of water, and two groups of food restricted rats were given access to either 100% of regular food consumption or ad lib food. Ad lib access in the restricted rats induced significant overeating on all three exposures. After all rats were returned to ad lib feeding, a 24h two-bottle saccharin/water choice test displayed significantly reduced saccharin consumption in the overeating rats, compared to those in the other 3 groups. To determine whether this avoidance was due to a learned association, a second experiment used a latent inhibition paradigm, familiarizing half the rats with the saccharin for 8 days prior to pairing it with overeating. Using the design of Experiment 1, with only the continuously ad lib and the restricted to ad lib feeding groups, it was found that the overeating-induced saccharin avoidance was attenuated by the pre-exposure. These results suggest that self-induced overeating is capable of supporting a learned avoidance of a novel solution suggestive of a conditioned satiety or taste avoidance. (c) 2009 Elsevier Inc. All rights reserved.

Time course and pattern of compensatory ingestive behavioral adjustments to lysine deficiency in rats.

PubMed

Markison, S; Thompson, B L; Smith, J C; Spector, A C

2000-05-01

We and others have demonstrated that rats deficient in an essential amino acid (EAA) will consume sufficient quantities of the lacking nutrient to produce repletion when it is made available in solution. In the current series of experiments, we made rats deficient in lysine (LYS) by limiting the level of this EAA in the diet. We then examined licking behavior during approximately 23-h two-bottle intake tests over 4 consecutive days. In three separate experiments, rats were presented with the following: 1) 0.1 mol/L LYS and water, 2) 0.2 mol/L threonine (THR) and water and 3) 0.1 mol/L LYS and 0.2 mol/L THR. Lysine-deficient (LYS-DEF) rats drink significantly more LYS than did nondepleted controls (CON) when this amino acid was available. Meal pattern analysis revealed that the enhanced intake of LYS occurred as a function of a greater number of ingestive bouts, not changes in bout size. A cumulative analysis of LYS intake between CON and LYS-DEF rats revealed that a potentiation of intake developed within 30 min of sampling the solution when LYS and water were available and within 90 min when LYS and THR were the contrasting choices. In conclusion, increased LYS intake in the deficient rats occurs relatively rapidly and appears to be at least somewhat specific. Moreover, LYS deficiency does not seem to enhance the palatability of the limiting amino acid as judged by behaviors such as lick rate and bout size. Instead, LYS-DEF rats relieve the deficiency by increasing the number of drinking episodes initiated.

Supercooling as a Viable Non-Freezing Cell Preservation Method of Rat Hepatocytes

PubMed Central

Usta, O. Berk; Kim, Yeonhee; Ozer, Sinan; Bruinsma, Bote G.; Lee, Jungwoo; Demir, Esin; Berendsen, Tim A.; Puts, Catheleyne F.; Izamis, Maria-Louisa; Uygun, Korkut; Uygun, Basak E.; Yarmush, Martin L.

2013-01-01

Supercooling preservation holds the potential to drastically extend the preservation time of organs, tissues and engineered tissue products, and fragile cell types that do not lend themselves well to cryopreservation or vitrification. Here, we investigate the effects of supercooling preservation (SCP at -4oC) on primary rat hepatocytes stored in cryovials and compare its success (high viability and good functional characteristics) to that of static cold storage (CS at +4oC) and cryopreservation. We consider two prominent preservation solutions a) Hypothermosol (HTS-FRS) and b) University of Wisconsin solution (UW) and a range of preservation temperatures (-4 to -10 oC). We find that there exists an optimum temperature (-4oC) for SCP of rat hepatocytes which yields the highest viability; at this temperature HTS-FRS significantly outperforms UW solution in terms of viability and functional characteristics (secretions and enzymatic activity in suspension and plate culture). With the HTS-FRS solution we show that the cells can be stored for up to a week with high viability (~56%); moreover we also show that the preservation can be performed in large batches (50 million cells) with equal or better viability and no loss of functionality as compared to smaller batches (1.5 million cells) performed in cryovials. PMID:23874947

A comparative study of charge movement in rat and frog skeletal muscle fibres.

PubMed

Hollingworth, S; Marshall, M W

1981-12-01

1. The middle of the fibre voltage--clamp technique (Adrian & Marshall, 1977), modified where necessary for electrically short muscle fibres, has been used to measure non-linear charge movements in mammalian fast twitch (rat extensor digitorum longus), mammalian slow twitch (rat soleus) and frog (sartorius) muscles. 2. The maximum amount of charge moved in mammalian fast twitch muscle at 2 degrees C in hypertonic solution, was 3--5 times greater than in slow twitch muscle. The voltage distribution of fast twitch charge was 10--15 mV more positive when compared to slow twitch. 3. In both mammalian muscle types hypertonic Ringer solution negatively shifted the voltage distribution of charge some 6 mV. The steepness of charge moved around mechanical threshold was unaffected by hypertonicity. 4. The amount of charge in frog sartorius fibres at 2 degrees C in hypertonic solution was about half of that in rat fast twitch muscle; the voltage distribution of the frog charge was similar to rat soleus muscle. 5. Warming between 2 and 15 degrees C had no effect on either the amount of steady-state distribution of charge in mammalian or frog muscles. 6. At 2 degrees C, the kinetics of charge movement in fast and slow twitch mammalian muscles were similar and 2--3 times faster than frog muscle at the same temperature. In fast and slow mammalian fibres at 2 degrees C similar times were taken to shift the same fractions of the total amount of charge. The Q10 of charge movement kinetics was between 1.2 and 2.0 in the three muscles studied.

Self-nanoemulsifying drug delivery system for enhanced bioavailability and improved hepatoprotective activity of biphenyl dimethyl dicarboxylate.

PubMed

El-Laithy, Hanan M

2008-07-01

Biphenyl Dimethyl Dicarboxylate (BDD) is insoluble in aqueous solution and the bioavailability after oral administration is low. Self-nanoemulsifying drug delivery system (SNEDDS) containing BDD has been successfully prepared using carefully selected ingredients which are less affected by pH and ionic strength changes to improve its bioavailability. SNEDDS is an isotropic mixture of lipid, surfactant, and cosurfactant which are spontaneously emulsified in aqueous medium under gentle digestive motility in the gastrointestinal tract. Pseudo ternary phase diagrams composed of various excipients were plotted to identify self -nano -emulsifying area. Droplet size changes upon dilution with aqueous media and in vitro release of BDD from SNEDDS in 0.1N HCl and phosphate buffer (pH 7.4) were studied and compared with commercial chinese pilules and Pennel capsules. The hepatoprotective activity upon oral administration of SNEDDS against carbon tetrachloride-induced oxidative stress in albino rats was assessed by measuring biochemical parameters like serum glutamic oxalacetate transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH). Results showed that using a proper ratio of Tween 80 to Transcutol as surfactant and co-surfactant respectively and Miglyol 812 as oil to surfactants mixture resulted in production of infinitely diluted formulations in nano droplet size range. BDD self nano emulsified formula composed of 20% Miglyol 812, 60% Tween 80 and 20% Transcutol released 99% of the drug very rapidly within 10-15 minutes regardless of the pH condition. The oral absorption and bioavailability of BDD self nano emulsified formula in albino rats were significantly enhanced (P<0.01) with an average improvement of 1.7 and 6-folds that of commercial chinese pilules and Pennel capsules respectively. This improvement was also confirmed histopathologically in chemically injured rats and by the significant decrease in elevated liver enzymes level.

Increase in insulin sensitivity by the association of chicoric acid and chlorogenic acid contained in a natural chicoric acid extract (NCRAE) of chicory (Cichorium intybus L.) for an antidiabetic effect.

PubMed

Ferrare, Karine; Bidel, Luc P R; Awwad, Abdulmomem; Poucheret, Patrick; Cazals, Guillaume; Lazennec, Françoise; Azay-Milhau, Jacqueline; Tournier, Michel; Lajoix, Anne-Dominique; Tousch, Didier

2018-04-06

Chicory (Cichorium intybus L.) is an indigenous vegetable widely cultivated in Europe, America and Asia. In ancient times, the leaves, flowers, seeds, and roots have been used as a wealth of health benefits including its tonic effects, the ability to ease digestive problems and to detoxify liver. In Indian traditional therapy, chicory was known to possess antidiabetic effect. In the traditional medicine of Bulgaria and Italy, chicory was used as hypoglycemic decoctions. We wanted to obtain the complete chemical composition of the natural chicoric acid extract (NCRAE), a chicory root extract rich in chicoric acid, which previously showed its glucose tolerance effect in normal rats. To investigate if the whole NCRAE is required to be effective, we performed a comparative in vivo experiment on STZ diabetic rats treated either with NCRAE or a mixture composed of the two major compounds of NCRAE. LC-MS method has been used to analyze the exhaustive composition of NCRAE: we have determined that chicoric acid and chlorogenic acid represented 83.8% of NCRAE. So, we have prepared a solution mixture of chicoric acid and chlorogenic acid named SCCAM, in order to compare in vivo the antidiabetic effects of this last and NCRAE in streptozotocin diabetic rats. In vitro experiments were performed on L6 cell line both for glucose uptake and for the protective effect against H 2 O 2 oxidative stress. Also, we have evaluated DPPH and ORAC (Oxygen Radical Absorbance Capacity) antioxidative capacities of the two compositions. The LC-MS analysis confirmed the high abundance of chicoric acid (64.2%) in NCRAE and a second part of NCRAE is composed of caffeoylquinic acids (CQAs) at 19.6% with among them the chlorogenic acid. This result has permitted us to prepare a mixture of synthetic L-chicoric acid (70%) and synthetic chlorogenic acid (30%): the solution is designated SCCAM. Our results showed that both NCRAE and SCCAM are able to improve a glucose tolerance in STZ diabetic rats after a subchronic administration of seven days. Alone NCRAE allows to significantly decrease the basal hyperglycemia after six days of treatment. To explain these difference of effects between NCRAE and SCCAM, we have compared their in vitro effects on the L6 muscle cell line both for the insulin sensitizing effect and for their protective action in pretreatment against H 2 O 2 . We have also compared their antioxidant capacities. In conclusion, we demonstrated that NCRAE, a natural extract of chicory (Cichorium intybus) rich in CRA and CQAs improves glucose tolerance and reduces the basal hyperglycemia in STZ diabetic rats. Copyright © 2018 Elsevier B.V. All rights reserved.

Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats

PubMed Central

2013-01-01

Introduction The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. Methods Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. Results We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood–brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. Conclusions Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus. PMID:24131855

Speech sound discrimination training improves auditory cortex responses in a rat model of autism

PubMed Central

Engineer, Crystal T.; Centanni, Tracy M.; Im, Kwok W.; Kilgard, Michael P.

2014-01-01

Children with autism often have language impairments and degraded cortical responses to speech. Extensive behavioral interventions can improve language outcomes and cortical responses. Prenatal exposure to the antiepileptic drug valproic acid (VPA) increases the risk for autism and language impairment. Prenatal exposure to VPA also causes weaker and delayed auditory cortex responses in rats. In this study, we document speech sound discrimination ability in VPA exposed rats and document the effect of extensive speech training on auditory cortex responses. VPA exposed rats were significantly impaired at consonant, but not vowel, discrimination. Extensive speech training resulted in both stronger and faster anterior auditory field (AAF) responses compared to untrained VPA exposed rats, and restored responses to control levels. This neural response improvement generalized to non-trained sounds. The rodent VPA model of autism may be used to improve the understanding of speech processing in autism and contribute to improving language outcomes. PMID:25140133

Consequences of Adolescent Exposure to the Cannabinoid Receptor Agonist WIN55,212-2 on Working Memory in Female Rats.

PubMed

Kirschmann, Erin K; McCalley, Daniel M; Edwards, Caitlyn M; Torregrossa, Mary M

2017-01-01

Marijuana is a prevalent illicit substance used by adolescents, and several studies have indicated that adolescent use can lead to long-term cognitive deficits including problems with attention and memory. However, preclinical animal studies that observe cognitive deficits after cannabinoid exposure during adolescence utilize experimenter administration of doses of cannabinoids that may exceed what an organism would choose to take, suggesting that contingency and dose are critical factors that need to be addressed in translational models of consequences of cannabinoid exposure. Indeed, we recently developed an adolescent cannabinoid self-administration paradigm in male rats, and found that prior adolescent self-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) resulted in improved working memory performance in adulthood. In addition, the doses self-administered were not as high as those that are found to produce memory deficits. However, given known sex differences in both drug self-administration and learning and memory processes, it is possible that cannabinoid self-administration could have different cognitive consequences in females. Therefore, we aimed to explore the effects of self-administered vs. experimenter-administered WIN in adolescent female rats on adult cognitive function. Female rats were trained to self-administer WIN daily throughout adolescence (postnatal day 34-59). A control group self-administered vehicle solution. The acute effects of adolescent WIN self-administration on memory were determined using a short-term spatial memory test 24 h after final SA session; and the long-term effects on cognitive performance were assessed during protracted abstinence in adulthood using a delayed-match-to-sample working memory task. In a separate experiment, females were given daily intraperitoneal (IP) injections of a low or high dose of WIN, corresponding to self-administered and typical experimenter-administered doses, respectively, or its vehicle during adolescence and working memory was assessed under drug-free conditions in adulthood. While self-administration of WIN in adolescence had no significant effects on short-term spatial memory or adult working memory, experimenter administration of WIN resulted in improved adult working memory performance that was more pronounced in the low dose group. Thus, low-dose adolescent WIN exposure, whether self-administered or experimenter-administered, results in either improvements or no change in adult working memory performance in female rats, similar to previous results found in males.

Novelty-induced locomotion is positively associated with cocaine ingestion in adolescent rats; anxiety is correlated in adults

PubMed Central

Walker, Q. David; Schramm-Sapyta, Nicole L.; Caster, Joseph M.; Waller, Samuel T.; Brooks, Matthew P.; Kuhn, Cynthia M.

2009-01-01

The present studies assessed the roles of sex, age, novelty-seeking and plus-maze behavior on cocaine drinking in rats. Cocaine/saccharin solution was available in three daily, 5-hour sessions then a saccharin-only solution was also available in following sessions. In the one-bottle drinking phase, early and late adolescent males, post-natal day 28 (PN28) and PN42, consumed more cocaine/saccharin solution than young adults (PN65), but females did not exhibit significant age differences. Adolescents of both sexes consumed more cocaine/saccharin than adults during choice drinking. Saccharin availability in the two-bottle trials decreased cocaine/saccharin consumption in PN28 and PN65 rats. After a drug-free period, cocaine-stimulated locomotion was lower in cocaine/saccharin drinking than saccharin-only males, indicating tolerance. We tested the hypothesis that individual differences in pre-screened behavioral traits would correlate with cocaine/saccharin consumption in PN28 and PN65 male rats. High locomotor responses to novelty were associated with greater cocaine/saccharin drinking in adults in one-bottle sessions. In the subsequent choice drinking phase, correlations were age-specific. Adolescents with high novelty-induced locomotion and adults that spent less time on open arms of the elevated plus-maze drank more cocaine/saccharin. Thus, behavioral phenotypes correlated with individual differences in cocaine/saccharin consumption in an age-related manner. PMID:18790706

A comparative histological study of alginate beads as a promising controlled release delivery for mefenamic acid.

PubMed

Sevgi, Ferhan; Kaynarsoy, Buket; Ozyazici, Mine; Pekcetin, Cetin; Ozyurt, Dogan

2008-01-01

The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 x 2(2) factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1)) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.

Improved Butanol-Methanol (BUME) Method by Replacing Acetic Acid for Lipid Extraction of Biological Samples.

PubMed

Cruz, Mutya; Wang, Miao; Frisch-Daiello, Jessica; Han, Xianlin

2016-07-01

Extraction of lipids from biological samples is a critical step in lipidomics, especially for shotgun lipidomics where lipid extracts are directly infused into a mass spectrometer. The butanol-methanol (BUME) extraction method was originally developed to extract lipids from plasma samples with 1 % acetic acid. Considering some lipids are sensitive to acidic environments, we modified this protocol by replacing acetic acid with lithium chloride solution and extended the modified extraction to tissue samples. Although no significant reduction of plasmalogen levels in the acidic BUME extracts of rat heart samples was found, the modified method was established to extract various tissue samples, including rat liver, heart, and plasma. Essentially identical profiles of the majority of lipid classes were obtained from the extracts of the modified BUME and traditional Bligh-Dyer methods. However, it was found that neither the original, nor the modified BUME method was suitable for 4-hydroxyalkenal species measurement in biological samples.

Improved Butanol-Methanol (BUME) Method by Replacing Acetic Acid for Lipid Extraction of Biological Samples

PubMed Central

Cruz, Mutya; Wang, Miao; Frisch-Daiello, Jessica; Han, Xianlin

2016-01-01

Extraction of lipids from biological samples is a critical step in lipidomics, especially for shotgun lipidomics where lipid extracts are directly infused into a mass spectrometer. The butanol-methanol (BUME) extraction method was originally developed to extract lipids from plasma samples with 1% acetic acid. Considering some lipids are sensitive to acidic environments, we modified this protocol by replacing acetic acid with lithium chloride solution and extended the modified extraction to tissue samples. Although no significant reduction of plasmalogen levels in the acidic BUME extracts of rat heart samples was found, the modified method was established to extract various tissue samples, including rat liver, heart, and plasma. Essentially identical profiles of the majority of lipid classes were obtained from the extracts of the modified BUME and traditional Bligh-Dyer methods. However, it was found that neither the original, nor the modified BUME method was suitable for 4-hydroxyalkenal species measurement in biological samples. PMID:27245345

In vitro and in vivo biological activities of anthocyanins from Nitraria tangutorun Bobr. fruits.

PubMed

Ma, Tao; Hu, Na; Ding, Chenxi; Zhang, Qiulong; Li, Wencong; Suo, Yourui; Wang, Honglun; Bai, Bo; Ding, Chenxu

2016-03-01

Anthocyanins are the main compounds in Nitraria tangutorun Bobr. The enrichment and purification of anthocyanins on macroporous resins were investigated. Regarding anthocyanin purification, static adsorption and desorption were studied. The optimal experimental conditions were the following: resin type: X-5; static adsorption time: 6h; desorption solution: ethanol-water-HCl (80:19:1, V/V/V; pH 1); desorption time: 40min. Furthermore, the in vitro and in vivo biological activities of the anthocyanins were evaluated. The anthocyanins showed ideal scavenging effects on free radicals in vitro, especially on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl free radical (OH). In the animal experiment, blood lipid metabolism of hyperlipidemia rats was regulated by anthocyanin contents. The superoxide dismutase (SOD) activity and the total antioxidant capacity (TAC) of hyperlipidemia rats were also improved by anthocyanins. These results showed that anthocyanins from N. tangutorun Bobr. fruits had potential biological activities in vivo as well as in vitro. Copyright © 2015. Published by Elsevier Ltd.

Effects of taurine on plasma glucose concentration and active glucose transport in the small intestine.

PubMed

Tsuchiya, Yo; Kawamata, Koichi

2017-11-01

Taurine lowers blood glucose levels and improves hyperglycemia. However, its effects on glucose transport in the small intestine have not been investigated. Here, we elucidated the effect of taurine on glucose absorption in the small intestine. In the oral glucose tolerance test, addition of 10 mmol/L taurine suppressed the increase in hepatic portal glucose concentrations. To investigate whether the suppressive effect of taurine occurs via down-regulation of active glucose transport in the small intestine, we performed an assay using the everted sac of the rat jejunum. Addition of taurine to the mucosal side of the jejunum suppressed active glucose transport via sodium-glucose cotransporter 1 (SGLT1). After elimination of chloride ions from the mucosal solution, taurine did not show suppressive effects on active glucose transport. These results suggest that taurine suppressed the increase in hepatic portal glucose concentrations via suppression of SGLT1 activity in the rat jejunum, depending on chloride ions. © 2017 Japanese Society of Animal Science.

New tris(dopamine) derivative as an iron chelator. Synthesis, solution thermodynamic stability, and antioxidant research.

PubMed

Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Lei, Shan; Tang, Xingyan; Liang, Hua; Liu, Qiangqiang; Gong, Mei; Peng, Rufang

2017-06-01

A new tris(dopamine) derivative, containing three dopamine chelate moieties which were attached to a trimesic acid molecular scaffold, has been prepared and fully characterized by NMR, FTIR and HRMS. The solution thermodynamic stability of the chelator with Fe(III), Mg(II), Zn(II) and Fe(II) ions was investigated. Results demonstrated that the chelator exhibited effective binding ability and improved selectivity to Fe(III) ion. The chelator possessed affinity similar to that of diethylenetriaminepentaacetic acid chelator for Fe(III) ion. The high affinity could be attributed to the favorable geometric arrangement between the chelator and Fe(III) ion coordination preference. The chelator also exhibited high antioxidant activity and nontoxicity to neuron-like rat pheochromocytoma cells. Hence, the chelator could be used as chelating agent for iron overload situations without depleting essential metal ions, such as Mg(II) and Zn(II) ions. Copyright © 2017. Published by Elsevier Inc.

Pulmonary preservation studies: effects on endothelial function and pulmonary adenine nucleotides.

PubMed

Paik, Hyo Chae; Hoffmann, Steven C; Egan, Thomas M

2003-02-27

Lung transplantation is an effective therapy plagued by a high incidence of early graft dysfunction, in part because of reperfusion injury. The optimal preservation solution for lung transplantation is unknown. We performed experiments using an isolated perfused rat lung model to test the effect of lung preservation with three solutions commonly used in clinical practice. Lungs were retrieved from Sprague-Dawley rats and flushed with one of three solutions: modified Euro-Collins (MEC), University of Wisconsin (UW), or low potassium dextran and glucose (LPDG), then stored cold for varying periods before reperfusion with Earle's balanced salt solution using the isolated perfused rat lung model. Outcome measures were capillary filtration coefficient (Kfc), wet-to-dry weight ratio, and lung tissue levels of adenine nucleotides and cyclic AMP. All lungs functioned well after 4 hr of storage. By 6 hr, UW-flushed lungs had a lower Kfc than LPDG-flushed lungs. After 8 hr of storage, only UW-flushed lungs had a measurable Kfc. Adenine nucleotide levels were higher in UW-flushed lungs after prolonged storage. Cyclic AMP levels correlated with Kfc in all groups. Early changes in endothelial permeability seemed to be better attenuated in lungs flushed with UW compared with LPDG or MEC; this was associated with higher amounts of adenine nucleotides. MEC-flushed lungs failed earlier than LPDG-flushed or UW-flushed lungs. The content of the solution may be more important for lung preservation than whether the ionic composition is intracellular or extracellular.

Lung preservation with Euro-Collins, University of Wisconsin, Wallwork, and low-potassium-dextran solution. Université++ Paris-Sud Lung Transplant Group.

PubMed

Xiong, L; Mazmanian, M; Chapelier, A R; Reignier, J; Weiss, M; Dartevelle, P G; Hervé, P

1994-09-01

Using isolated rat lungs, we compared prevention of ischemia-reperfusion injury provided by flushing the lungs with modified Euro-Collins solution (EC), University of Wisconsin solution (UW), low-potassium-dextran solution (LPD), or Wallwork solution (WA). After 4 hours' and 6 hours' cold ischemia, reperfusion injury was assessed on the basis of changes in filtration coefficients (Kfc) and pressure-flow curves, characterized by the slope of the curves (incremental resistance) and the extrapolation of this slope to zero flow (pulmonary pressure intercept [Ppi]). After 4 hours, Kfc and Ppi were higher with EC than with UW, LPD, and WA, and the incremental resistance was higher with EC and UW. After 6 hours, Kfc and incremental resistance Ppi were higher with LPD than with WA. Because ischemia-reperfusion injury is associated with decreased endothelial synthesis of prostacyclin and nitric oxide, we tested whether the addition of prostacyclin or the nitric oxide precursor L-arginine to WA would improve preservation. The Kfc and Ppi were lower with both treatments. In conclusion, ischemia-reperfusion injury was best prevented by using WA. The favorable effect of prostacyclin or L-arginine emphasizes the role played by endothelial dysfunction in ischemia-reperfusion injury.

In vivo evaluation of thiolated poly(acrylic acid) as a drug absorption modulator for MRP2 efflux pump substrates.

PubMed

Greindl, Melanie; Föger, Florian; Hombach, Juliane; Bernkop-Schnürch, Andreas

2009-08-01

Recently, several polymers have been reported to modulate drug absorption by inhibition of intestinal efflux pumps such as multidrug resistance proteins (MRPs) and P-glycoprotein (P-gp). The aim of the present study was to evaluate the efficiency of thiolated poly(acrylic acid) (PAA-Cys) to act as a drug absorption modulator for MRP2 efflux pump substrates in vivo, using sulforhodamine 101 as representative MRP2 substrate. In vitro, the permeation-enhancing effect of unmodified PAA and PAA(250)-Cys(,) displaying 580 micromol free thiol groups per gram polymer, was evaluated by using freshly excised rat intestinal mucosa mounted in Ussing-type chambers. In comparison to that of the buffer control, the sulforhodamine 101 transport in the presence of 0.5% unmodified PAA(250) and 0.5% (w/v) PAA(250)-Cys was 1.3- and 4.0-fold improved, respectively. In vivo, sulforhodamine 101 solutions containing 4% (w/v) unmodified PAA(250) or 4% (w/v) thiolated PAA(250) were orally given to rats. The PAA(250)-Cys solution increased the area under the plasma concentration-time curve (AUC(0-12)) of sulforhodamine 101 3.8-fold in comparison to control and 2.2-fold in comparison to unmodified PAA(250). This in vivo study revealed that PAA(250)-Cys significantly increased the oral bioavailability of MRP2 substrate sulforhodamine 101.

Self-Nanoemulsifying Drug Delivery System for Resveratrol: Enhanced Oral Bioavailability and Reduced Physical Fatigue in Rats

PubMed Central

Yen, Ching-Chi; Hsu, Mei-Chich; Wu, Yu-Tse

2017-01-01

Resveratrol (RES), a natural polyphenolic compound, exerts anti-fatigue activity, but its administration is complicated by its low water solubility. To improve RES bioavailability, this study developed a self-nanoemulsifying drug delivery system (SNEDDS) for RES and evaluated its anti-fatigue activity and rat exercise performance by measuring fatigue-related parameters, namely lactate, ammonia, plasma creatinine phosphokinase, and glucose levels and the swimming time to exhaustion. Through solubility and emulsification testing, the optimized SNEDDS composed of Capryol 90, Cremophor EL, and Tween 20 was developed; the average particle size in this formulation, which had favorable self-emulsification ability, was approximately 41.3 ± 4.1 nm. Pharmacokinetic studies revealed that the oral bioavailability of the optimized RES-SNEDDS increased by 3.2-fold compared with that of the unformulated RES-solution. Pretreatment using the RES-SNEDDS before exercise accelerated the recovery of lactate after exercise; compared with the vehicle group, the plasma ammonia level in the RES-SNEDDS group significantly decreased by 65.4%, whereas the glucose level significantly increased by approximately 1.8-fold. Moreover, the swimming time to exhaustion increased by 2.1- and 1.8-fold, respectively, compared with the vehicle and RES-solution pretreatment groups. Therefore, the developed RES-SNEDDS not only enhances the oral bioavailability of RES but may also exert anti-fatigue pharmacological effect. PMID:28841149

Lever conditioned stimulus-directed autoshaping induced by saccharin-ethanol unconditioned stimulus solution: effects of ethanol concentration and trial spacing.

PubMed

Tomie, Arthur; Festa, Eugene D; Sparta, Dennis R; Pohorecky, Larissa A

2003-05-01

Two experiments were designed to evaluate whether brief access to a saccharin-ethanol solution would function as an effective unconditioned stimulus (US) in Pavlovian-autoshaping procedures. In these experiments, the insertion of a lever conditioned stimulus (CS) was followed by the brief presentation of a sipper tube containing saccharin-ethanol US solution. Experience with this Pavlovian-autoshaping procedure engendered lever CS-directed autoshaping conditioned responses (CRs) in all rats. In Experiment 1, the concentration of ethanol [0%, 2%, 4%, 6%, or 8% (vol./vol.)] in 0.1% saccharin was systematically increased within subjects across autoshaping sessions to evaluate the relation between a rat's drinking and lever pressing. In Experiment 2, the mean intertrial interval (ITI) duration (60, 90, 120 s) was systematically increased within subjects across autoshaping sessions to evaluate the effect of ITI duration on drinking and lever pressing. A pseudoconditioning control group received lever CS randomly with respect to the saccharin-ethanol US solution. In Experiment 1, lever-press autoshaping CRs developed in all rats, and the tendency of a rat to drink an ethanol concentration was predictive of the performance of lever-press autoshaping CRs. In Experiment 2, longer ITIs induced more lever CS-directed responding, and CS-US paired procedures yielded more lever CS-directed responding than that observed in CS-US random procedures. Saccharin-ethanol is an effective US in Pavlovian-autoshaping procedures, inducing more CS-directed responding than in pseudoconditioning controls receiving CS-US random procedures. More lever CS-directed responding was observed when there was more drinking of the saccharin-ethanol US solution (Experiment 1); when the CS and US were paired, rather than random (Experiment 2); and with longer mean ITI durations (Experiment 2). This pattern of results is consistent with the hypothesis that lever CS-directed responding reflects performance of Pavlovian-autoshaping CRs.

DHA-supplemented diet increases the survival of rats following asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation.

PubMed

Kim, Junhwan; Yin, Tai; Shinozaki, Koichiro; Lampe, Joshua W; Becker, Lance B

2016-11-04

Accumulating evidence illustrates the beneficial effects of dietary docosahexaenoic acid (DHA) on cardiovascular diseases. However, its effects on cardiac arrest (CA) remain controversial in epidemiological studies and have not been reported in controlled animal studies. Here, we examined whether dietary DHA can improve survival, the most important endpoint in CA. Male Sprague-Dawley rats were randomized into two groups and received either a control diet or a DHA-supplemented diet for 7-8 weeks. Rats were then subjected to 20 min asphyxia-induced cardiac arrest followed by 30 min cardiopulmonary bypass resuscitation. Rat survival was monitored for additional 3.5 h following resuscitation. In the control group, 1 of 9 rats survived for 4 h, whereas 6 of 9 rats survived in the DHA-treated group. Surviving rats in the DHA-treated group displayed moderately improved hemodynamics compared to rats in the control group 1 h after the start of resuscitation. Rats in the control group showed no sign of brain function whereas rats in the DHA-treated group had recurrent seizures and spontaneous respiration, suggesting dietary DHA also protects the brain. Overall, our study shows that dietary DHA significantly improves rat survival following 20 min of severe CA.

Memory Inhibition as a Critical Factor Preventing Creative Problem Solving

ERIC Educational Resources Information Center

Gómez-Ariza, Carlos J.; del Prete, Francesco; Prieto del Val, Laura; Valle, Tania; Bajo, M. Teresa; Fernandez, Angel

2017-01-01

The hypothesis that reduced accessibility to relevant information can negatively affect problem solving in a remote associate test (RAT) was tested by using, immediately before the RAT, a retrieval practice procedure to hinder access to target solutions. The results of 2 experiments clearly showed that, relative to baseline, target words that had…

Cocaine Self-Administration Alters the Relative Effectiveness of Multiple Memory Systems during Extinction

ERIC Educational Resources Information Center

Gabriele, Amanda; Setlow, Barry; Packard, Mark G.

2009-01-01

Rats were trained to run a straight-alley maze for an oral cocaine or sucrose vehicle solution reward, followed by either response or latent extinction training procedures that engage neuroanatomically dissociable "habit" and "cognitive" memory systems, respectively. In the response extinction condition, rats performed a runway approach response…

A histological and micro-CT investigation in to the effect of NGF and EGF on the periodontal, alveolar bone, root and pulpal healing of replanted molars in a rat model - a pilot study

PubMed Central

2014-01-01

Background This study aims to investigate, utilising micro-computed tomography (micro-CT) and histology, whether the topical application of nerve growth factor (NGF) and/or epidermal growth factor (EGF) can enhance periodontal, alveolar bone, root and pulpal tissue regeneration while minimising the risk of pulpal necrosis, root resorption and ankylosis of replanted molars in a rat model. Methods Twelve four-week-old male Sprague-Dawley rats were divided into four groups: sham, collagen, EGF and NGF. The maxillary right first molar was elevated and replanted with or without a collagen membrane impregnated with either the growth factors EGF or NGF, or a saline solution. Four weeks after replantation, the animals were sacrificed and the posterior maxilla was assessed using histological and micro-CT analysis. The maxillary left first molar served as the control for the corresponding right first molar. Results Micro-CT analysis revealed a tendency for all replanted molars to have reduced root length, root volume, alveolar bone height and inter-radicular alveolar bone volume. It appears that the use of the collagen membrane had a negative effect while no positive effect was noted with the incorporation of EGF or NGF. Histologically, the incorporation of the collagen membrane was found to negatively affect pulpal, root, periodontal and alveolar bone healing with pulpal inflammation and hard tissue formation, extensive root resorption and alveolar bone fragmentation. The incorporation of EGF and NGF did not improve root, periodontal or alveolar bone healing. However, EGF was found to improve pulp vascularisation while NGF-improved pulpal architecture and cell organisation, although not to the level of the control group. Conclusions Results indicate a possible benefit on pulpal vascularisation and pulpal cell organisation following the incorporation of EGF and NGF, respectively, into the alveolar socket of replanted molars in the rat model. No potential benefit of EGF and NGF was detected in periodontal or root healing, while the use of a collagen membrane carrier was found to have a negative effect on the healing response. PMID:24393534

Comparative analysis of tissue reactions to anesthetic solutions: histological analysis in subcutaneous tissue of rats.

PubMed Central

Ribeiro, Paulo Domingos; Sanches, Marcio Giampietro; Okamoto, Tetuo

2003-01-01

Postanesthetic pain is a relatively common complication after local anesthesia. This complication may be caused by the anesthetic technique or by the anesthetic solution used. Tissue reactions induced by the anesthetic solutions may be one of the factors resulting in pain after anesthesia. The objective of this study was to comparatively analyze tissue reactions induced by different anesthetic solutions in the subcutaneous tissue of rats. The following solutions were utilized: 2% lidocaine without vasoconstrictor; a 0.5% bupivacaine solution with 1:200,000 adrenaline; a 4% articaine solution and 2% mepivacaine, both with 1:100,000 adrenaline; and a 0.9% sodium chloride solution as a control. Sterilized absorbent paper cones packed inside polyethylene tubes were soaked in the solutions and implanted in the subcutaneous region. The sacrifice periods were 1, 2, 5, and 10 days after surgery. The specimens were prepared and stained with hematoxylin and eosin for histological analysis. The results showed that there is a difference in tissue irritability produced by the local anesthetic solutions. The results also showed that there is no relation between the concentration of the drug and the inflammatory intensity, that the mepivacaine and articaine solutions promoted less inflammatory reaction than the bupivacaine, and that the lidocaine solution produced the least intense inflammation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:14959905

Alteration of renal function of rats following spaceflight.

PubMed

Wade, C E; Morey-Holton, E

1998-10-01

Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

Alteration of renal function of rats following spaceflight

NASA Technical Reports Server (NTRS)

Wade, C. E.; Morey-Holton, E.

1998-01-01

Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

Embryotoxicity of benzalkonium chloride in vaginally treated rats.

PubMed

Buttar, H S

1985-12-01

The effects of the spermicide benzalkonium chloride (BKC) were studied on the conceptus of rat. Single doses (0, 25, 50, 100 or 200 mg kg-1) of aqueous solutions of BKC were administered intravaginally (1 ml kg-1) on gestational day 1. The vulval metallic clips, used to prevent leakage of the solution, were removed 24 h post-treatment. Fetuses were obtained and examined for malformations on day 21 of gestation. slight to copious amounts of vaginal discharge and vaginitis were noticed in rats treated with the two largest doses of BKC. A dose-related increase in resorptions and fetal death, reduction in litter size and weight were observed in BKC-treated dams. The conceptus loss seemed to occur both before and after implantation. BKC did not cause any discernible visceral malformations, although minor sternal defects occurred in fetuses exposed to 100 and 200 mg kg-1 of the spermicide. These results suggest that single vaginal application of BKC is embryo- and fetocidal in the rat at a dose about 143 times higher than that recommended for controlling conception in women.

Ethanol-induced conditioned taste aversion in Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats.

PubMed

Dyr, Wanda; Wyszogrodzka, Edyta; Paterak, Justyna; Siwińska-Ziółkowska, Agnieszka; Małkowska, Anna; Polak, Piotr

2016-03-01

The aversive action of the pharmacological properties of ethanol was studied in selectively bred Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats. For this study, a conditioned-taste aversion test was used. Male WHP and WLP rats were submitted to daily 20-min sessions for 5 days, in which a saccharin solution (1.0 g/L) was available (pre-conditioning phase). Next, this drinking was paired with the injection of ethanol (0, 0.5, 1.0 g/kg), intraperitoneally [i.p.] immediately after removal of the saccharin bottle (conditioning phase). Afterward, the choice between the saccharin solution and water was extended for 18 subsequent days for 20-min daily sessions (post-conditioning phase). Both doses of ethanol did not produce an aversion to saccharin in WLP and WHP rats in the conditioning phase. However, injection of the 1.0 g/kg dose of ethanol produced an aversion in WLP rats that was detected by a decrease in saccharin intake at days 1, 3, 7, and 10 of the post-conditioning phase, with a decrease in saccharin preference for 16 days of the post-conditioning phase. Conditioned taste aversion, measured as a decrease in saccharin intake and saccharin preference, was only visible in WHP rats at day 1 and day 3 of the post-conditioning phase. This difference between WLP and WHP rats was apparent despite similar blood ethanol levels in both rat lines following injection of 0.5 and 1.0 g/kg of ethanol. These results may suggest differing levels of aversion to the post-ingestional effects of ethanol between WLP and WHP rats. These differing levels of aversion may contribute to the selected line difference in ethanol preference in WHP and WLP rats. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel sustained-release formulation of recombinant human growth hormone and its pharmacokinetic, pharmacodynamic and safety profiles.

PubMed

Wei, Yi; Wang, Yuxia; Kang, Aijun; Wang, Wei; Ho, Sa V; Gao, Junfeng; Ma, Guanghui; Su, Zhiguo

2012-07-02

An effective and safe formulation of sustained-release rhGH for two months using poly(monomethoxypolyethylene glycol-co-D,L-lactide) (mPEG-PLA, PELA) microspheres was developed to reduce the frequency of medication. The rhGH-loaded PELA microspheres with a narrow size distribution were successfully prepared by a double emulsion method combined with a premix membrane emulsification technique without any exogenous stabilizing excipients. The narrow size distribution of the microspheres would guarantee repeatable productivity and release behavior. Moreover, the amphiphilic PELA improved the bioactivity retention of protein drugs since it prevented protein contact with the oil/water interface and the hydrophobic network, and modulated diffusion of acidic degradation products from the carrier system. These PELA microspheres were compared in vivo with commercial rhGH solution, conventional poly(D,L-lactic acid) (PLA) and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres. Administration of rhGH-PELA could extend the duration of rhGH release (for up to 56 days) and increase area under the curve (AUC) compared to rhGH solution, PLA or PLGA microspheres in Sprague-Dawley (SD) rats. In addition, rhGH-PELA microspheres induced a greater response in total insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) than other rhGH formulations. With a hypophysectomized SD rat model, the pharmacological efficacy of rhGH-PELA microspheres was shown to be better than that from daily administration of rhGH solutions over 6 days based on body weight gain and width of the tibial growth plate. Histological examination of the injection sites indicated a significantly milder inflammatory response than that observed after injection of PLA and PLGA microspheres. Neither anti-rhGH antibodies nor the toxic effects on heart, liver and kidney were detectable after administration of rhGH-PELA microspheres in SD rats. These results suggest that rhGH-PELA microspheres have the potential to be clinically effective and safe when administered only once every two months, a dose regimen for better patient acceptance and compliance.

Effects of Alcohol Injection in Rat Sciatic Nerve

PubMed Central

Mazoch, Mathew J.; Cheema, Gulraiz A.; Suva, Larry J.; Thomas, Ruth L.

2015-01-01

Background Previous studies have shown that the injection of dehydrated alcohol has been successful for the treatment of Morton's neuroma in the foot. In this study, we determined the cellular effect of injection of alcohol into and around the sciatic nerve of rats, and measured the extent of cell necrosis and/or any associated histologic or inflammatory changes. Methods Twenty-two male (~375g) Wistar rats were randomized into two groups each receiving alcohol injections into or around the sciatic nerve after nerve exposure under sterile technique. Group 1 rats were injected with a 0.5ml solution of 0.5% Marcaine in the left sciatic nerve as a control group. In the right sciatic nerve a 0.5ml solution of 4% ethanol with 0.5% Marcaine was injected. Group 2 rats received 0.5ml of 20%ethanol with 0.5% Marcaine injected into the left sciatic nerve and 0.5 ml of 30% ethanol with 0.5% Marcaine injected into the right sciatic nerve. In each group, the rats were placed in 3 subgroups: intraneural, perineural, perimuscular injections. All rats were sacrificed and tissue harvested for histologic evaluation at day 10 post injection. Results No evidence of alcohol-associated cell necrosis, apoptosis or apparent inflammation was observed in histologic specimens of any injected nerves, perineural tissue, or muscles in controls or experimental groups regardless of concentration of ethanol injected on day 10. Conclusion We concluded that alcohol injection (≤30% ethanol) into and/or around the sciatic nerve or the adjacent muscle of rats has no histologic evidence of necrosis or inflammation to the nerve or surrounding tissue. There was no observable histological change in apoptosis, or cell number, in response to the alcohol injection. PMID:25097192

Hydration status affects urea transport across rat urothelia.

PubMed

Spector, David A; Deng, Jie; Stewart, Kerry J

2011-12-01

Although mammalian urinary tract epithelium (urothelium) is generally considered impermeable to water and solutes, recent data suggest that urine constituents may be reabsorbed during urinary tract transit and storage. To study water and solute transport across the urothelium in an in vivo rat model, we instilled urine (obtained during various rat hydration conditions) into isolated in situ rat bladders and, after a 1-h dwell, retrieved the urine and measured the differences in urine volume and concentration and total quantity of urine urea nitrogen and creatinine between instilled and retrieved urine in rat groups differing by hydration status. Although urine volume did not change >1.9% in any group, concentration (and quantity) of urine urea nitrogen in retrieved urine fell significantly (indicating reabsorption of urea across bladder urothelia), by a mean of 18% (489 mg/dl, from an instilled 2,658 mg/dl) in rats receiving ad libitum water and by a mean of 39% (2,544 mg/dl, from an instilled 6,204 mg/dl) in water-deprived rats, but did not change (an increase of 15 mg/dl, P = not significant, from an instilled 300 mg/dl) in a water-loaded rat group. Two separate factors affected urea nitrogen reabsorption rates, a urinary factor related to hydration status, likely the concentration of urea nitrogen in the instilled urine, and a bladder factor(s), also dependent on the animal's state of hydration. Urine creatinine was also absorbed during the bladder dwell, and hydration group effects on the concentration and quantity of creatinine reabsorbed were qualitatively similar to the hydration group effect on urea transport. These findings support the notion(s) that urinary constituents may undergo transport across urinary tract epithelia, that such transport may be physiologically regulated, and that urine is modified during transit and storage through the urinary tract.

The effect of Chinese Jinzhida recipe on the hippocampus in a rat model of diabetes-associated cognitive decline

PubMed Central

2013-01-01

Background To investigate the effects of treatment with Multi component Chinese Medicine Jinzhida (JZD) on behavioral deficits in diabetes-associated cognitive decline (DACD) rats and verify our hypothesis that JZD treatment improves cognitive function by suppressing the endoplasmic reticulum stress (ERS) and improving insulin signaling transduction in the rats’ hippocampus. Methods A rat model of type 2 diabetes mellitus (T2DM) was established using high fat diet and streptozotocin (30 mg/kg, ip). Insulin sensitivity was evaluated by the oral glucose tolerance test and the insulin tolerance test. After 7 weeks, the T2DM rats were treated with JZD. The step-down test and Morris water maze were used to evaluate behavior in T2DM rats after 5 weeks of treatment with JZD. Levels of phosphorylated proteins involved in the ERS and in insulin signaling transduction pathways were assessed by Western blot for T2DM rats’ hippocampus. Results Compared to healthy control rats, T2DM rats initially showed insulin resistance and had declines in acquisition and retrieval processes in the step-down test and in spatial memory in the Morris water maze after 12 weeks. Performance on both the step-down test and Morris water maze tasks improved after JZD treatment. In T2DM rats, the ERS was activated, and then inhibited the insulin signal transduction pathways through the Jun NH2-terminal kinases (JNK) mediated. JZD treatment suppressed the ERS, increased insulin signal transduction, and improved insulin resistance in the rats’ hippocampus. Conclusions Treatment with JZD improved cognitive function in the T2DM rat model. The possible mechanism for DACD was related with ERS inducing the insulin signal transduction dysfunction in T2DM rats’ hippocampus. The JZD could reduce ERS and improve insulin signal transduction and insulin resistance in T2DM rats’ hippocampus and as a result improved the cognitive function. PMID:23829668

Protective role of caffeic acid on lambda cyhalothrin-induced changes in sperm characteristics and testicular oxidative damage in rats.

PubMed

Abdallah, Fatma Ben; Fetoui, Hamadi; Zribi, Nassira; Fakhfakh, Feiza; Keskes, Leila

2012-08-01

The synthetic pyrethroids are expected to cause deleterious effects on most of the organs and especially on the male reproductive system. The current study was performed to assess the adverse effect of lambda cyhalothrin (LC) on reproductive organs and fertility in male rats and to evaluate the protective role of caffeic acid phenethyl ester (CAPE) in alleviating the detrimental effect of LC on male fertility. A total of 48 male rats were divided into 4 groups (12 rats each): control group received distilled water ad libitum and 1 ml of vehicle solution given intraperitoneally (i.p.); CAPE-treated group received a single i.p. dose of CAPE (10 μmol kg⁻¹ day⁻¹); LC-treated group received 668 ppm of LC through drinking water; and CAPE + LC-treated group received an i.p. injection of CAPE (10 μmol kg⁻¹ day⁻¹) 12 h before the LC administration. The experiment was conducted for 10 consecutive weeks. LC caused a significant increase in testicular malondialdehyde, catalase, superoxide dismutase, glutathione-S-transferase activities, and sperm abnormalities and a significant reduction in testicular glutathione concentration, sperm count, sperm motility, and a live sperm percentage. Conversely, treatment with CAPE improved the reduction in the sperm characteristics, LC-induced oxidative damage of testes and the testicular histopathological alterations. Results indicate that LC exerts significant harmful effects on the male reproductive system and that CAPE reduced the deleterious effects of LC on male fertility.

Salt appetite is reduced by a single experience of drinking hypertonic saline in the adult rat.

PubMed

Greenwood, Michael P; Greenwood, Mingkwan; Paton, Julian F R; Murphy, David

2014-01-01

Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions.

Resistance to Reperfusion Injury Following Short Term Postischemic Administration of Natural Honey in Globally Ischemic Isolated Rat Heart

PubMed Central

Vaez, Haleh; Samadzadeh, Mehrban; Zahednezhad, Fahimeh; Najafi, Moslem

2012-01-01

Purpose: Results of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Methods: Male Wistar rats were divided into five groups (n=10-13). The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibrate for 30 min then subjected to 30 min global ischemia. In the control group, the hearts were reperfused with drug free normal Krebs-Henseleit (K/H) solution before ischemia and during 120 min reperfusion. In the treatment groups, reperfusion was initiated with K/H solution containing different concentration of honey (0.25, 0.5, 1 and 2%) for 15 min and was resumed until the end of 120 min with normal K/H solution. Results: In the control group, VEBs number was 784±199, while in honey concentration of 0.25, 0.5, 1 and 2%, it decreased to 83±23 (P<0.001), 138±48 (P<0.01), 142±37 (P<0.001) and 157±40 (P<0.01), respectively. Number and duration of VT and time spent in reversible VF were also reduced by honey. In the control group, the infarct size was 54.1±7.8%, however; honey (0.25, 0.5, 1 and 2%) markedly lowered the value to 12.4±2.4, 12.7±3.3, 11.3±2.6 and 7.9±1.7 (P<0.001), respectively. Conclusion: Postischemic administration of natural honey in global ischemia showed protective effects against ischemia/reperfusion (I/R) injuries in isolated rat heart. Antioxidant and radical scavenging activity, lipoperoxidation inhibition, reduction of necrotized tissue, presence of rich energy sources, various type of vitamins, minerals and enzymes and formation of NO-contain metabolites may probably involve in those cardioprotective effects. PMID:24312792

D-sorbose inhibits disaccharidase activity and demonstrates suppressive action on postprandial blood levels of glucose and insulin in the rat.

PubMed

Oku, Tsuneyuki; Murata-Takenoshita, Yoko; Yamazaki, Yuko; Shimura, Fumio; Nakamura, Sadako

2014-11-01

In an attempt to develop D-sorbose as a new sweetener that could help in preventing lifestyle-related diseases, we investigated the inhibitory effect of D-sorbose on disaccharidase activity, using the brush border membrane vesicles of rat small intestines. The inhibitory effect was compared with that of L-sorbose and other rare sugars, and the small intestinal disaccharidases in rats was compared with that of humans as well. In humans and the small intestines of rats, d-sorbose strongly inhibited sucrase activity and weakly inhibited maltase activity. Inhibition by D-sorbose of sucrase activity was similar to that of L-arabinose, and the K(i) of D-sorbose was 7.5 mM. Inhibition by D-sorbose was very strong in comparison with that of L-sorbose (K(i), 60.8 mM), whereas inhibition of d-tagatose was between that of D-sorbose and L-sorbose. The inhibitory mode of D-sorbose for sucrose and maltase was uncompetitive, and that of L-sorbose was competitive. To determine a suppressive effect on postprandial blood levels of glucose and insulin via inhibition of sucrase activity, sucrose solution with or without D-sorbose was administered to rats. Increments in the blood levels of glucose and insulin were suppressed significantly after administration of sucrose solution with D-sorbose to rats, in comparison to administration of sucrose solution without D-sorbose. In contrast, the suppressive effect of L-sorbose on postprandial blood levels of glucose and insulin was very weak. These results suggest that D-sorbose may have an inhibitory effect on disaccharidase activity and could be used as a sweetener to suppress the postprandial elevation of blood levels of glucose and insulin. The use of D-sorbose as a sweetener may contribute to the prevention of lifestyle-related diseases, such as type 2 diabetes mellitus. Copyright © 2014 Elsevier Inc. All rights reserved.

Salt Appetite Is Reduced by a Single Experience of Drinking Hypertonic Saline in the Adult Rat

PubMed Central

Greenwood, Michael P.; Greenwood, Mingkwan; Paton, Julian F. R.; Murphy, David

2014-01-01

Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions. PMID:25111786

Improvement of aqueous solubility and rectal absorption of 6-mercaptopurine by addition of sodium benzoate.

PubMed

Takeichi, Y; Kimura, T

1994-10-01

The solubility of 6-mercaptopurine (6-MP) in water increased as the concentration of sodium benzoate or sodium hippurate in the solution increased. The solubility of 6-MP in 20% (w/v) sodium benzoate or sodium hippurate solution was about 6-fold larger than that of 6-MP alone. The stability constant of the soluble complex of 6-MP with sodium benzoate was estimated to be 2-8 M-1 from (1) phase-solubility study and (2) analysis of chemical shifts observed in 1H-NMR. Partition of 6-MP from the saturated solution to n-octanol was also greatly increased by the addition of sodium benzoate or sodium hippurate, the degree being less in the latter. Administration of 6-MP with 20% (w/v) sodium benzoate to rat rectum resulted in enhanced absorption and the area under the plasma concentration-time curve was comparable to that obtained by intravenous administration (bioavailability = 100%), while the bioavailability after intrarectal administration of 6-MP with 20% (w/v) sodium hippurate was only 9%. The reason for the difference was discussed.

Gelatin and galactomannan-based scaffolds: Characterization and potential for tissue engineering applications.

PubMed

Siqueira, Nataly M; Paiva, Bruno; Camassola, Melissa; Rosenthal-Kim, Emily Q; Garcia, Ketlin C; dos Santos, Francisco P; Soares, Rosane M D

2015-11-20

In this work, we produced gelatin films containing different concentrations of galactomannan by casting solutions. The films were crosslinked by immersion in 30mM solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC). The crosslinking of gelatin-containing films was confirmed by the reduction of free amine band intensity (3400-3200cm(-1)) in the GEL IR, as well as by the evaluation of its behavior when immersed in phosphate-buffer solution. The crosslinking of galactomannan film was confirmed by the formation of new ether bonds, as observed by increasing intensity of the band at 1148cm(-1), and the reduction of OH band intensity (3600-3200cm(-1)). The presence of galactomannan and the crosslinking mediated by EDC were responsible to improve elasticity in the gelatin-based films. The samples did not show cytotoxicity during 24h or 48h. In addition, rat mesenchymal stem cells adhered to the films regardless of galactomannan concentration. The results indicated that the gelatin/galactomannan films are potential biomaterials for use as scaffolds for tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Major Royal Jelly Proteins on Spatial Memory in Aged Rats: Metabolomics Analysis in Urine.

PubMed

Chen, Di; Liu, Fang; Wan, Jian-Bo; Lai, Chao-Qiang; Shen, Li-Rong

2017-04-19

Royal jelly (RJ) produced by worker honeybees is the sole food for the queen bee throughout her life as well as the larvae of worker bees for the first 3 days after hatching. Supplementation of RJ in the diet has been shown to increase spatial memory in rodents. However, the key constituents in RJ responsible for improvement of cognitive function are unknown. Our objective was to determine if the major royal jelly proteins (MRJPs) extracted from RJ can improve the spatial memory of aged rats. The spatial memory assay using the Morris water maze test was administered once to rats after a 14-week feeding. Metabolomics analysis based on quadrupole time-of-flight mass spectrometry was conducted to examine the differences in compounds from urine. Aged male rats fed MRJPs showed improved spatial memory up to 48.5% when compared to the control male aged rats fed distilled water. The metabolite pattern of the MRJPs-fed aged rats was regressed to that of the young rats. Compounds altered by MRJPs were mapped to nicotinate and nicotinamide metabolism, cysteine taurine metabolism, and energy metabolism pathways. In summary, MRJPs may improve spatial memory and possess the potential for prevention of cognitive impairment via the cysteine and taurine metabolism and energy metabolism pathways in aged rats.

Stress triggers anhedonia in rats bred for learned helplessness.

PubMed

Enkel, Thomas; Spanagel, Rainer; Vollmayr, Barbara; Schneider, Miriam

2010-05-01

Congenitally helpless (cLH) rats, a well-accepted model for depression, show reduced consumption of sweet solutions only under single-housing conditions, indicating anhedonia under stress. We investigated if anhedonic-like behaviour, measured by a reduction of sweetened-condensed milk (SCM) intake and the pleasure-attenuated startle response (PAS), could be induced by an electric foot-shock stress challenge in group-housed rats. After foot-shock stress, reduced SCM intake was observed in cLH rats compared to non-helpless (cNLH) rats. Furthermore, cLH rats also showed a decreased PAS, indicating deficient reward perception. In summary, we demonstrate that a predisposition for learned helplessness interacts with stress to trigger anhedonic-like behaviour in cLH rats. These findings further add to the validity of congenitally learned helplessness as an animal model of depression, since gene-environment interactions are considered to play a role in the etiology of this disorder.

Sucrose or sucrose and caffeine differentially impact memory and anxiety-like behaviours, and alter hippocampal parvalbumin and doublecortin.

PubMed

Xu, Tanya J; Reichelt, Amy C

2018-04-11

Caffeinated sugar-sweetened "energy" drinks are a subset of soft drinks that are popular among young people worldwide. High sucrose diets impair cognition and alter aspects of emotional behaviour in rats, however, little is known about sucrose combined with caffeine. Rats were allocated to 2 h/day 10% sucrose (Suc), 10% sucrose plus 0.04% caffeine (CafSuc) or control (water) conditions. The addition of caffeine to sucrose appeared to increase the rewarding aspect of sucrose, as the CafSuc group consumed more solution than the Suc group. After 14 days of intermittent Suc or CafSuc access, anxiety was assessed in the elevated plus maze (EPM) prior to their daily solution access, whereby CafSuc and Suc rats spent more time in the closed arms, indicative of increased anxiety. Following daily solution access, CafSuc, but not Suc, rats showed reduced anxiety-like behaviour in the open-field. Control and CafSuc rats displayed intact place and long-term object memory, while Suc showed impaired memory performance. Sucrose reduced parvalbumin immunoreactivity in the hippocampus, but no differences were observed between Control and CafSuc conditions. Parvalbumin reactivity in the basolateral amygdala did not differ between conditions. Reduced doublecortin immunoreactivity in the dentate gyrus relative to controls was seen in the CafSuc, but not Suc, treatment conditions. These findings indicate that the addition of caffeine to sucrose attenuated cognitive deficits. However, the addition of caffeine to sucrose evoked anxiety-like responses under certain testing conditions, suggesting that frequent consumption of caffeinated energy drinks may promote emotional alterations and brain changes compared to standard soft drinks. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of different freezing rates during cryopreservation of rat mesenchymal stem cells using combinations of hydroxyethyl starch and dimethylsulfoxide

PubMed Central

2012-01-01

Background Mesenchymal stem cells (MSCs) are increasingly used as therapeutic agents as well as research tools in regenerative medicine. Development of technologies which allow storing and banking of MSC with minimal loss of cell viability, differentiation capacity, and function is required for clinical and research applications. Cryopreservation is the most effective way to preserve cells long term, but it involves potentially cytotoxic compounds and processing steps. Here, we investigate the effect of decreasing dimethyl sulfoxide (DMSO) concentrations in cryosolution by substituting with hydroxyethyl starch (HES) of different molecular weights using different freezing rates. Post-thaw viability, phenotype and osteogenic differentiation capacity of MSCs were analysed. Results The study confirms that, for rat MSC, cryopreservation effects need to be assessed some time after, rather than immediately after thawing. MSCs cryopreserved with HES maintain their characteristic cell surface marker expression as well as the osteogenic, adipogenic and chondrogenic differentiation potential. HES alone does not provide sufficient cryoprotection for rat MSCs, but provides good cryoprotection in combination with DMSO, permitting the DMSO content to be reduced to 5%. There are indications that such a combination would seem useful not just for the clinical disadvantages of DMSO but also based on a tendency for reduced osteogenic differentiation capacity of rat MSC cryopreserved with high DMSO concentration. HES molecular weight appears to play only a minor role in its capacity to act as a cryopreservation solution for MSC. The use of a ‘straight freeze’ protocol is no less effective in maintaining post-thaw viability of MSC compared to controlled rate freezing methods. Conclusion A 5% DMSO / 5% HES solution cryopreservation solution using a ‘straight freeze’ approach can be recommended for rat MSC. PMID:22889198

Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

PubMed

Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit

2011-01-01

Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.

Increased Renal Solute Excretion in Rats Following Space Flight

NASA Technical Reports Server (NTRS)

Wade, Charles E.; Moore, A. L.; Morey-Holton, E.

1995-01-01

Following space flight a diuresis, due to an increase in free water clearance, has been suggested in humans. To assess the effects of space flight on renal function, rats were flown in space for 14 days. Rats were divided into three groups; vivarium controls (V;n=6; housed 2/shoe box cage), flight controls (FC;n=6; group housed in a flight cage), and flight animals (F;n=6). Upon landing all animals were placed into individual metabolic cages. Urine was collected daily for 7 days and every other day for 14 days. Urine output was increased (p less than 0.05; ANOVA) following flight for 3 days. On postflight day 1, flow rates were, V=6.8 plus or minus 0.9, FC=8.711.8 and F=16.6 plus or minus 2.7 microliter/min. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate (V=7.9 plus or minus 0.9, FC=6.1 plus or minus 0.7 and F=13.5 plus or minus 0.7 uOsm/min). Creatinine excretion rate was increased over the first two postflight days. In the absence of changes in plasma creatinine, Na+, or K+ (samples obtained immediately post flight from similar rats compared to Day 14), GFR was increased following space flight. The increased excretion of solute was thus the result of increased delivery and decreased reabsorption. Osmotic clearance was increased (V=28, FC=27 and F=51 microliter/min), while free water clearance was decreased post flight (V=-21,FC=-18 and F=-34 microliter/min). In rats, the postflight diuresis is the result of an increase in solute (osmotic) excretion with an accompanying reduction in free water clearance.

Optimization of SDS exposure on preservation of ECM characteristics in whole organ decellularization of rat kidneys.

PubMed

He, M; Callanan, A; Lagaras, K; Steele, J A M; Stevens, M M

2017-08-01

Renal transplantation is well established as the optimal form of renal replacement therapy but is restricted by the limited pool of organs available for transplantation. The whole organ decellularisation approach is leading the way for a regenerative medicine solution towards bioengineered organ replacements. However, systematic preoptimization of both decellularization and recellularization parameters is essential prior to any potential clinical application and should be the next stage in the evolution of whole organ decellularization as a potential strategy for bioengineered organ replacements. Here we have systematically assessed two fundamental parameters (concentration and duration of perfusion) with regards to the effects of differing exposure to the most commonly used single decellularizing agent (sodium dodecyl sulphate/SDS) in the perfusion decellularization process for whole rat kidney ECM bioscaffolds, with findings showing improved preservation of both structural and functional components of the whole kidney ECM bioscaffold. Whole kidney bioscaffolds based on our enhanced protocol were successfully recellularized with rat primary renal cells and mesenchymal stromal cells. These findings should be widely applicable to decellularized whole organ bioscaffolds and their optimization in the development of regenerated organ replacements for transplantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1352-1360, 2017. © 2016 Wiley Periodicals, Inc.

Effect of apitherapy formulations against carbon tetrachloride-induced toxicity in Wistar rats after three weeks of treatment.

PubMed

Andritoiu, Calin Vasile; Ochiuz, Lacramioara; Andritoiu, Vasile; Popa, Marcel

2014-08-29

The human body is exposed nowadays to increasing attacks by toxic compounds in polluted air, industrially processed foods, alcohol and drug consumption that increase liver toxicity, leading to more and more severe cases of hepatic disorders. The present paper aims to evaluate the influence of the apitherapy diet in Wistar rats with carbon tetrachloride-induced hepatotoxicity, by analyzing the biochemical determinations (enzymatic, lipid and protein profiles, coagulation parameters, minerals, blood count parameters, bilirubin levels) and histopathological changes at the level of liver, spleen and pancreas. The experiment was carried out on six groups of male Wistar rats. Hepatic lesions were induced by intraperitoneal injection of carbon tetrachloride (dissolved in paraffin oil, 10% solution). Two mL per 100 g were administered, every 2 days, for 2 weeks. Hepatoprotection was achieved with two apitherapy diet formulations containing honey, pollen, propolis, Apilarnil, with/without royal jelly. Biochemical results reveal that the two apitherapy diet formulations have a positive effect on improving the enzymatic, lipid, and protein profiles, coagulation, mineral and blood count parameters and bilirubin levels. The histopathological results demonstrate the benefits of the two apitherapy diet formulations on reducing toxicity at the level of liver, spleen and pancreas in laboratory animals.

Prolonged oral administration of potassium upon aldosterone biosynthesis by rat glomerulosa tissue in vitro.

PubMed

Regöly-Mérei, J; Sólyom, J

1975-01-01

Steroid production rate of adrenals derived from rats drinking a 0.3 M KC1 + 5% glucose solution for 7 days was compared to that of control rats drinking a 5% glucose solution in order to investigate the effect of potassium loading upon the early and late step of aldosterone biosynthesis. Following potassium loading the quartered adrenals produced more aldosterone but less corticosterone as compared to the control. Potassium loading resulted in an increased aldosterone production rate by capsular adrenals (z. glomerulosa) provided that the corticosterone concentration in the incubation medium was elevated either by incubating it together with the decapsulated adrenal or adding exogenous corticosterone (4--16 mug/ml) to the medium. The corticosterone to aldosterone converting capacity of capsular adrenals is markedly higher in the potassium-loaded rats than in the controls. In the first 15 minutes of incubation the corticosterone production rate of the two groups was equal, aldosterone production rate by capsular adrenals of potassium-loaded rats, being higher than that of control animals. Corticosterone output of capsular adrenals from potassium-loaded rats decreased more rapidly in course of the incubation than it did in control tissue. These results suggest that the increase in aldosterone secretion in vivo following potassium loading is due to the stimulation of conversion of corticosterone to aldosterone in the glomerulosa cells. However, the endogenous corticosterone production during the incubation of glomerulosa cells from pottasium-loaded rats decreases so rapidly that the cells are not capable of producing more aldosterone than the control ones in spite of activated 18-hydroxylase.

Detection of cocaine and benzoylecgonine in formalin fixed rat tissues.

PubMed

Hilal, Ahmet; Dağlioğlu, Nebīle; Battal, Dīlek; Yener, Fadīle; Dağlioğlu, Kenan

2009-09-01

The stability of drugs in formalin solution is an important factor in forensic investigation. Tissues (liver, lung, kidney, brain) taken from rats, which have been poisoned acutely with cocaine, were preserved in two different conditions, analyzed by GC-MS, and then compared. Organs of the first group were preserved and stored at -20 degrees C without adding formalin, whereas the organs of the second group were preserved and stored in formalin solution at room temperature (25 degrees C). Serum samples were taken immediately after poisoning and studied as well. In specimens stored at -20 degrees C, cocaine and its metabolite benzoylecgonine were detected in the tissues. Only benzoylecgonine was detected both in tissues and their formalin solution. It was observed that the distribution of cocaine in tissues had differed depending on the preservation conditions. The formalin solution in which benzoylecgonine was mostly detected was from liver. As a result, cocaine was detected in tissues stored at -20 degrees C. It is recommended that both the formalin-fixed tissues and formalin solution should be analyzed concurrently to assure the accurate results (LOD = 3 ng/ml).

Cross-linked polyhemoglobin-superoxide dismutase-catalase supplies oxygen without causing blood-brain barrier disruption or brain edema in a rat model of transient global brain ischemia-reperfusion.

PubMed

Powanda, D Douglas; Chang, Thomas M S

2002-01-01

In strokes, myocardial infarctions, severe sustained hemorrhagic shock, and donor organs, inadequate blood supply results in lack of oxygen to the tissue (ischemia). If ischemia is sustained, reperfusion with the needed oxygen can result in tissue injury (ischemia-reperfusion injury) due to formation of reactive oxygen species. We are studying an oxygen-carrying solution with anitoxidant activity formed by cross-linking hemoglobin, superoxide dismutase, and catalase to form PolyHb-SOD-CAT. The present report studies its effect on the blood-brain barrier and cerebral edema when used in a transient global brain ischemia-reperfusion rat model. We compare this solution to sham-control, oxygenated saline, stroma-free hemoglobin (SF-Hb), polymerized hemoglobin (PolyHb), and a mixture of SF-Hb, SOD, and CAT in free solution. The results show that the cross-linked PolyHb-SOD-CAT solution, unlike the other solutions, can supply oxygen to ischemic tissues without causing reperfusion injury in the transient global brain ischemia-reperfusion model.

Morphometric and microscopic evaluation of the effect of a solution of alendronate as an intracanal therapeutic agent in rat teeth submitted to late reimplantation.

PubMed

Mori, Graziela Garrido; Garcia, Roberto Brandão; Gomes de Moraes, Ivaldo; Bramante, Clóvis Monteiro; Bernardineli, Norberti

2007-08-01

The use of substances that inhibit root resorption may be an alternative for cases of unsuccessful reimplants. Hence, the purpose of this study was to test a solution of alendronate, a resorption inhibitor, as an intracanal therapeutic agent for teeth submitted to late reimplantation. Thirty rat maxillary right central incisors were avulsed and kept dry for 30 min. The teeth were instrumented, and the root surfaces treated with 1% hypochlorite solution followed by application of 2% sodium fluoride. Thereafter, the teeth were divided in two groups according to the intracanal dressing: (i) group I, solution of alendronate and (ii) group II, calcium hydroxide paste. Teeth were then reimplanted in their respective sockets. The animals were killed at 15, 30 and 60 days after reimplantation and the samples processed for morphometric and microscopic analysis. The results demonstrated that the solution of alendronate and the calcium hydroxide paste limited the root resorption, yet did not impair its occurrence. It may be concluded that alendronate and calcium hydroxide paste demonstrated similar behavior.

Topical HPMC/S-Nitrosoglutathione Solution Decreases Inflammation and Bone Resorption in Experimental Periodontal Disease in Rats

PubMed Central

Martins, Conceição S.; Leitão, Renata F. C.; Costa, Deiziane V. S.; Melo, Iracema M.; Santos, Glaylton S.; Lima, Vilma; Baldim, Victor; Wong, Deysi V. T.; Bonfim, Luana E.; Melo, Cíntia B.; Brito, Gerly A. C.

2016-01-01

S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor, which exerts antioxidant, anti-inflammatory, and microbicidal actions. Intragingival application of GSNO was already shown to decrease alveolar bone loss, inflammation and oxidative stress in an experimental periodontal disease (EPD) model. In the present study, we evaluated the potential therapeutic effect of topical applications of hydroxypropylmethylcellulose (HPMC)/GSNO solutions on EPD in Wistar rats. EPD was induced by placing a sterilized nylon (3.0) thread ligature around the cervix of the second left upper molar of the animals, which received topical applications of a HPMC solutions containing GSNO 2 or 10 mM or vehicle (HPMC solution), 1 h prior to the placement of the ligature and then twice daily until sacrifice on day 11. Treatment with HPMC/GSNO 10 mM solution significantly reduced alveolar bone loss, oxidative stress and TNF-α e IL-1β levels in the surrounding gingival tissue, and led to a decreased transcription of RANK and TNF-α genes and elevated bone alkaline phosphatase, compared to the HPMC group. In conclusion, topical application of HPMC/GSNO solution is a potential treatment to reduce inflammation and bone loss in periodontal disease. PMID:27116554

Topical HPMC/S-Nitrosoglutathione Solution Decreases Inflammation and Bone Resorption in Experimental Periodontal Disease in Rats.

PubMed

Martins, Conceição S; Leitão, Renata F C; Costa, Deiziane V S; Melo, Iracema M; Santos, Glaylton S; Lima, Vilma; Baldim, Victor; Wong, Deysi V T; Bonfim, Luana E; Melo, Cíntia B; G de Oliveira, Marcelo; Brito, Gerly A C

2016-01-01

S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor, which exerts antioxidant, anti-inflammatory, and microbicidal actions. Intragingival application of GSNO was already shown to decrease alveolar bone loss, inflammation and oxidative stress in an experimental periodontal disease (EPD) model. In the present study, we evaluated the potential therapeutic effect of topical applications of hydroxypropylmethylcellulose (HPMC)/GSNO solutions on EPD in Wistar rats. EPD was induced by placing a sterilized nylon (3.0) thread ligature around the cervix of the second left upper molar of the animals, which received topical applications of a HPMC solutions containing GSNO 2 or 10 mM or vehicle (HPMC solution), 1 h prior to the placement of the ligature and then twice daily until sacrifice on day 11. Treatment with HPMC/GSNO 10 mM solution significantly reduced alveolar bone loss, oxidative stress and TNF-α e IL-1β levels in the surrounding gingival tissue, and led to a decreased transcription of RANK and TNF-α genes and elevated bone alkaline phosphatase, compared to the HPMC group. In conclusion, topical application of HPMC/GSNO solution is a potential treatment to reduce inflammation and bone loss in periodontal disease.

Aggravation of cold-induced injury in Vero-B4 cells by RPMI 1640 medium - identification of the responsible medium components.

PubMed

Pless-Petig, Gesine; Metzenmacher, Martin; Türk, Tobias R; Rauen, Ursula

2012-10-10

In modern biotechnology, there is a need for pausing cell lines by cold storage to adapt large-scale cell cultures to the variable demand for their products. We compared various cell culture media/solutions for cold storage of Vero-B4 kidney cells, a cell line widely used in biotechnology. Cold storage in RPMI 1640 medium, a recommended cell culture medium for Vero-B4 cells, surprisingly, strongly enhanced cold-induced cell injury in these cells in comparison to cold storage in Krebs-Henseleit buffer or other cell culture media (DMEM, L-15 and M199). Manufacturer, batch, medium supplements and the most likely components with concentrations outside the range of the other media/solutions (vitamin B12, inositol, biotin, p-aminobenzoic acid) did not cause this aggravation of cold-induced injury in RPMI 1640. However, a modified Krebs-Henseleit buffer with a low calcium concentration (0.42 mM), a high concentration of inorganic phosphate (5.6 mM), and glucose (11.1 mM; i.e. concentrations as in RPMI 1640) evoked a cell injury and loss of metabolic function corresponding to that observed in RPMI 1640. Deferoxamine improved cell survival and preserved metabolic function in modified Krebs-Henseleit buffer as well as in RPMI 1640. Similar Ca2+ and phosphate concentrations did not increase cold-induced cell injury in the kidney cell line LLC-PK1, porcine aortic endothelial cells or rat hepatocytes. However, more extreme conditions (Ca2+ was nominally absent and phosphate concentration raised to 25 mM as in the organ preservation solution University of Wisconsin solution) also increased cold-induced injury in rat hepatocytes and porcine aortic endothelial cells. These data suggest that the combination of low calcium and high phosphate concentrations in the presence of glucose enhances cold-induced, iron-dependent injury drastically in Vero-B4 cells, and that a tendency for this pathomechanism also exists in other cell types.

DDPH ameliorated oxygen and glucose deprivation-induced injury in rat hippocampal neurons via interrupting Ca2+ overload and glutamate release.

PubMed

He, Zhi; Lu, Qing; Xu, Xulin; Huang, Lin; Chen, Jianguo; Guo, Lianjun

2009-01-28

Our previous work has demonstrated that DDPH (1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenylethylamino) propane hydrochloride), a competitive alpha(1)-adrenoceptor antagonist, could improve cognitive deficits, reduce histopathological damage and facilitate synaptic plasticity in vivo possibly via increasing NR2B (NMDA receptor 2B) expression and antioxidation of DDPH itself. The present study further evaluated effects of DDPH on OGD (Oxygen and glucose deprivation)-induced neuronal damage in rat primary hippocampal cells. The addition of DDPH to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and LDH (lactate dehydrogenase) release experiments. The effects of DDPH on intracellular calcium concentration were explored by Fura-2 based calcium imaging techniques and results showed that DDPH at the dosages of 5 microM and 10 microM suppressed the increase of intracellular calcium ([Ca(2+)](i)) stimulated by 50 mM KCl in Ca(2+)-containing extracellular solutions. However, DDPH couldn't suppress the increase of [Ca(2+)](i) induced by both 50 microM glutamate in Ca(2+)-containing extracellular solutions and 20 microM ATP (Adenosine Triphosphate) in Ca(2+)-free solution. These results indicated that DDPH prevented [Ca(2+)](i) overload in hippocampal neurons by blocking Ca(2+) influx (voltage-dependent calcium channel) but not Ca(2+) mobilization from the intracellular Ca(2+) store in endoplasm reticulum (ER). We also demonstrated that DDPH could decrease glutamate release when hippocampal cells were subjected to OGD. These observations demonstrated that DDPH protected hippocampal neurons against OGD-induced damage by preventing the Ca(2+) influx and decreasing glutamate release.

Beneficial effect of D-allose for isolated islet culture prior to islet transplantation.

PubMed

Kashiwagi, Hirotaka; Asano, Eisuke; Noguchi, Chisato; Sui, Li; Hossain, Akram; Akamoto, Shintaro; Okano, Keiichi; Tokuda, Masaaki; Suzuki, Yasuyuki

2016-01-01

Pretransplant restoration of islets damaged during isolation remains to be solved. In this study, we examined the effect of D-allose on islets isolated from rat pancreata prior to islet transplantation. Rat islets isolated from fresh pancreata were cultured overnight in Roswell Park Memorial Institute 1640 solution in the absence (group 1) or presence (group 2) of D-allose. Then we assessed stimulation index of insulin, and cure rate after islet transplantation to diabetic nude mice. We also measured malondialdehyde level and caspase 3 activity of islets after the overnight culture for assessment of the oxidative stress and the apoptosis. D-allose significantly improved insulin secretion of islets. The stimulation index in group 2 was significantly higher than in group 1. Cure rate after transplantation in group 2 was higher than in group 1 especially in the first week. The malondialdehyde level in group 2 was significantly lower than in group 1. But the caspase 3 activities in both groups did not differ. D-allose treatment of isolated islet culture prior to transplantation restored islet function and increased successful transplant rate. The results of this study suggested that D-allose improved function of damaged islets through its anti-oxidative activity. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats

NASA Technical Reports Server (NTRS)

Brooks-Asplund, Esther M.; Shoukas, Artin A.; Kim, Soon-Yul; Burke, Sean A.; Berkowitz, Dan E.

2002-01-01

We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.

The Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester Diminishes the Immunomodulatory Effects of Parental Arginine in Rats with Subacute Peritonitis

PubMed Central

Lo, Hui-Chen; Hung, Ching-Yi; Huang, Fu-Huan; Su, Tzu-Cheng; Lee, Chien-Hsing

2016-01-01

The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days. Non-surgical and sham-operated rats with no cecal puncture were given a chow diet and parenteral nutrition, respectively. Parenteral feeding elevated the white blood cell numbers and subacute peritonitis augmented the parenteral nutrition-induced alterations in the loss of body weight gain, splenomegaly, and splenocyte decreases. Parenteral arginine significantly increased the B-leukocyte level, decreased the natural killer T (NKT)-leukocyte and splenocyte levels, alleviated the loss in body weight gain and total and cytotoxic T-splenocyte levels, and attenuated the increases in plasma nitrate/nitrite and interferon-gamma production by T-splenocytes. L-NAME infusion significantly decreased NKT-leukocyte level, tumor-necrosis factor (TNF)-alpha production by T-splenocytes and macrophages, and interferon-gamma production by T-leukocytes, monocytes, and T-splenocytes, as well as increased interleukin-6 production by T-leukocytes and monocytes and nitrate/nitrite production by T-leukocytes. Combined treatment significantly decreased plasma nitrate/nitrite, the NKT-leukocyte level, and TNF-alpha production by T-splenocytes. Parenteral arginine may attenuate immune impairment and L-NAME infusion may augment leukocyte proinflammatory response, eliminate splenocyte proinflammatory and T-helper 1 responses, and diminish arginine-induced immunomodulation in combined treatment in subacute peritonitic rats. PMID:27007815

Beneficial effects of exercise and its molecular mechanisms on depression in rats

PubMed Central

Zheng, Hang; Liu, Yanyou; Li, Wei; Yang, Bo; Chen, Dengbang; Wang, Xiaojia; Jiang, Zhou; Wang, Hongxing; Wang, Zhengrong; Cornelisson, G.; Halberg, F.

2008-01-01

Exercise showed the beneficial effects on mental health in depressed sufferers, whereas, its underlying mechanisms remained unresolved. This study utilized the chronic unpredictable stress (CNS) animal model of depression to evaluate the effects of exercise on depressive behaviors and spatial performance in rats. Furthermore, we tested the hypothesis that the capacity of exercise to reverse the harmful effects of CNS was relative to the hypothalamo–pituitary–adrenal (HPA) system and brain-derived neurotrophic factor (BDNF) in the hippocampus. Animal groups were exposed to CNS for 4 weeks with and without access to voluntary wheel running. Stressed rats consumed significantly less of a 1% sucrose solution during CNS and exhibited a significant decrease in open field behavior. On the other hand, they showed impaired spatial performance in Morris water maze test 2 weeks after the end of CNS. Further, CNS significantly decreased hippocampal BDNF mRNA levels. However, voluntary exercise improved or even reversed these harmful behavioral effects in stressed rats. Furthermore, exercise counteracted a decrease in hippocampal BDNF mRNA caused by CNS. In addition, we also found that CMS alone increased circulating corticosterone (CORT) significantly and decreased hippocampal glucocorticoid receptor (GR) mRNA. At the same time, exercise alone increased CORT moderately and did not affect hippocampal GR mRNA levels. While, when both CNS and exercise were combined, exercise reduced the increase of CORT and the decrease of GR caused by CMS. The results demonstrated that: (1) exercise reversed the harmful effects of CNS on mood and spatial performance in rats and (2) the behavioral changes induced by exercise and/or CNS might be associated with hippocampal BDNF levels, and in addition, the HPA system might play different roles in the two different processes. PMID:16290283

Simultaneous infusion of glutamine and branched-chain amino acids (BCAA) to septic rats does not have more favorable effect on protein synthesis in muscle, liver, and small intestine than separate infusions.

PubMed

Holecek, Milan; Muthny, Tomas; Kovarik, Miroslav; Sispera, Ludek

2006-01-01

Glutamine and branched-chain amino acids (BCAA; valine, leucine, and isoleucine) are used as nutrition supplements in the treatment of proteocatabolic illness. We hypothesized that simultaneous administration of BCAA and glutamine affects protein metabolism more significantly than separate administration. In the present study, we evaluated their effect on protein synthesis in skeletal muscle, liver, and jejunum of septic rats. Twenty-four hours after induction of sepsis by subcutaneous injection of turpentine, the rats were infused for 6 hours with 5 mL of 1.75% glutamine, 1.75% BCAA, 1.75% glutamine+BCAA, or saline solution. The control group consisted of intact rats infused with saline. Protein synthesis was measured at the end of infusion by a "flooding method" with [3,4,5-(3)H]phenylalanine. In turpentine-treated animals, we observed a decrease in glutamine concentration in blood plasma and skeletal muscle, a decrease in BCAA concentration in liver and jejunum, and a decrease in protein synthesis in all tissues. Glutamine or glutamine+BCAA infusion increased glutamine concentration in plasma and muscle and stimulated protein synthesis in the liver. The BCAA infusion enhanced concentrations of BCAA in plasma and tissues, but the effect of BCAA on protein synthesis was insignificant. Synergistic effect of simultaneous infusion of glutamine and BCAA on protein synthesis was not observed. We conclude that glutamine infusion to rats with septic injury may significantly improve impaired protein synthesis in the liver and that there is no synergistic effect of glutamine and BCAA infusion on protein synthesis in skeletal muscle, liver, and jejunum.

In vitro and in vivo studies to assess the effectiveness of cholestyramine as a binding agent for fumonisins.

PubMed

Solfrizzo, M; Visconti, A; Avantaggiato, G; Torres, A; Chulze, S

2001-01-01

Several adsorbent materials were tested at I mg/ml for their in vitro capacity to adsorb fumonisin B1(FB1) from aqueous solutions. Cholestyramine showed the best adsorption capacity (85% from a solution containing 200 microg/ml FB1) followed by activated carbon (62% FB1). Bentonite adsorbed only 12% of the toxin from a solution containing 13 microg/ml FB1, while celite was not effective even at the lowest tested FB1 concentration (3.2 microg/ml). Cholestyramine was tested in vivo to evaluate its capacity to reduce the bioavailability of fumonisins (FBs) in rats fed diet contaminated with toxigenic Fusarium verticillioides culture material. Rats were exposed for one week to FBs-free diet, FBs-contaminated diet containing 6 or 20 microg/g FB1 + FB2 and the same FBs-contaminated diet added of 20 mg/g cholestyramine. The increase of sphinganine/sphingosine (SA/SO) ratio in urine and kidney of treated rats was used as specific and sensitive biomarker of fumonisin exposure. The addition of cholestyramine to the FBs-contaminated diets consistently reduced the effect of FBs by reducing significantly (P < 0.05) both urinary and renal SA/SO ratios.

Rats' preferences for high fructose corn syrup vs. sucrose and sugar mixtures.

PubMed

Ackroff, Karen; Sclafani, Anthony

2011-03-28

High fructose corn syrup (HFCS) has replaced sucrose in many food products, which has prompted research comparing these two sweeteners in rodents. The present study examined the relative palatability of HFCS and sucrose for rats, offering 11% carbohydrate solutions to match the content of common beverages for human consumption. The animals initially preferred HFCS to sucrose but after separate experience with each solution they switched to sucrose preference. Approximating the composition of HFCS with a mixture of fructose and glucose (55:45) yielded a solution that was less attractive than sucrose or HFCS. However, HFCS contains a small amount of glucose polymers, which are very attractive to rats. A 55:42:3 mixture of fructose, glucose and glucose polymers (Polycose) was equally preferred to HFCS and was treated similarly to HFCS in comparisons vs. sucrose. Post-oral effects of sucrose, which is 50% fructose and 50% glucose, may be responsible for the shift in preference with experience. This shift, and the relatively small magnitude of differences in preference for HFCS and sucrose, suggest that palatability factors probably do not contribute to any possible difference in weight gain responses to these sweeteners. Copyright © 2011 Elsevier Inc. All rights reserved.

The neuroprotective effects of oxaloacetate in closed head injury in rats is mediated by its blood glutamate scavenging activity: evidence from the use of maleate.

PubMed

Zlotnik, Alexander; Gruenbaum, Shaun E; Artru, Alan A; Rozet, Irene; Dubilet, Michael; Tkachov, Sergey; Brotfain, Evgeny; Klin, Yael; Shapira, Yoram; Teichberg, Vivian I

2009-07-01

Treatment with oxaloacetate after traumatic brain injury has been shown to decrease blood glutamate levels and protect against the neurotoxic effects of glutamate on the brain. A number of potential mechanisms have been suggested to explain oxaloacetate-induced neuroprotection. We hypothesize that the primary mechanism by which intravenous oxaloacetate provides neuroprotection is by activation of the blood glutamate-scavenging enzyme glutamate-oxaloacetate transaminase, increasing thereby the driving force for the efflux of excess glutamate from brain interstitial fluids into blood. If so, coadministration of maleate, a glutamate-oxaloacetate transaminase-blocker is expected to prevent the neuroprotective effects of oxaloacetate. A neurological severity score (NSS) was measured 1 hour after closed head injury (CHI) in rats. Then, rats received 30 microL/min/100 g infusion of saline, or 1 mmol/100 g solution of oxaloacetate, maleate, or a mixture of oxaloacetate and maleate. NSS was reassessed at 24 and 48 hour after CHI. Blood glutamate and glucose levels were measured at 0, 60, 90, and 120 minutes. NSS improved significantly at 24 hour (P<0.001) and 48 hour (P<0.001) only in the rats treated with oxaloacetate. Blood glutamate decreased significantly in the oxaloacetate-treated group at 90 minute (at the conclusion of oxaloacetate administration) (P<0.00001), but not in the control, maleate or oxaloacetate+maleate groups. A strong correlation r2=0.86 was found to exist between the percent decrease in blood glutamate levels and percent improvement in NSS. The results of this study demonstrate that the primary mechanism by which oxaloacetate provides neuroprotective activity after CHI is related to its blood glutamate scavenging activity. Management of blood glutamate concentration may have important implications in the treatment of acute brain conditions, including CHI and stroke.

Development of a novel niosomal system for oral delivery of Ginkgo biloba extract

PubMed Central

Jin, Ye; Wen, Jingyuan; Garg, Sanjay; Liu, Da; Zhou, Yulin; Teng, Lirong; Zhang, Weiyu

2013-01-01

Background The aim of this study was to develop an optimal niosomal system to deliver Ginkgo biloba extract (GbE) with improved oral bioavailability and to replace the conventional GbE tablets. Methods In this study, the film dispersion-homogenization method was used to prepare GbE niosomes. The resulting GbE niosome suspension was freeze-dried or spray-dried to improve the stability of the niosomes. GbE-loaded niosomes were formulated and characterized in terms of their morphology, particle size, zeta potential, entrapment efficiency, and angle of repose, and differential scanning calorimetry analysis was performed. In vitro release and in vivo distribution studies were also carried out. Results The particle size of the optimal delivery system prepared with Tween 80, Span 80, and cholesterol was about 141 nm. There was a significant difference (P < 0.05) in drug entrapment efficiency between the spray-drying method (about 77.5%) and the freeze-drying method (about 50.1%). The stability study revealed no significant change in drug entrapment efficiency for the GbE niosomes at 4°C and 25°C after 3 months. The in vitro release study suggested that GbE niosomes can prolong the release of flavonoid glycosides in phosphate-buffered solution (pH 6.8) for up to 48 hours. The in vivo distribution study showed that the flavonoid glycoside content in the heart, lung, kidney, brain, and blood of rats treated with the GbE niosome carrier system was greater than in the rats treated with the oral GbE tablet (P < 0.01). No flavonoid glycosides were detected in the brain tissue of rats given the oral GbE tablets, but they were detected in the brain tissue of rats given the GbE niosomes. Conclusion Niosomes are a promising oral system for delivery of GbE to the brain. PMID:23378764

188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas

PubMed Central

Allard, Emilie; Hindré, François; Passirani, Catherine; Lemaire, Laurent; Lepareur, Nicolas; Noiret, Nicolas; Menei, Philippe; Benoit, Jean-Pierre

2008-01-01

Purpose Lipid nanocapsules (LNC) entrapping lipophilic complexes of 188Re (188Re(S3CPh)2(S2CPh) [188Re-SSS]) were investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant gliomas. The present study was designed to evaluate the efficacy of intracerebral administration of 188Re-SSS LNC by means of convection-enhanced delivery (CED) on a 9L rat brain tumour model. Methods Female Fischer rats with 9L glioma were treated with a single injection of 188Re-SSS LNC by CED 6 days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8, and 3 Gy in comparison with blank LNC, perrhenate solution (4Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring 188Re elimination in faeces and urine over 72h after the CED injection. The therapeutic effect of 188Re-SSS LNC was assessed based on animal survival. Results CED of 188Re perrhenate solution resulted in rapid drug clearance with a brain T1/2 of 7h. In contrast, when administered in LNC, 188Re tissue retention was greatly prolonged, with only 10% of the injected dose being eliminated at 72h. Rat median survival was significantly improved for the group treated with 8Gy 188Re-SSS LNC compared to the control group and blank-LNC treated animals. The increase in the median survival time (ISTmedian) was about 80% compared to the control group; 33% of the animals were long-term survivors. The dose of 8Gy proved to be a very effective dose, between toxic (10–12Gy) and ineffective (3–4Gy) doses. Conclusions These findings show that CED of Rhenium-188-loaded lipid nanocapsules is a safe and potent antitumour system for treating malignant gliomas. Our data are the first to show the in vivo efficacy of Rhenium-188 internal radiotherapy for the treatment of brain malignancy. PMID:18465130

Preparation of intact monomeric collagen from rat tail tendon and skin and the structure of the nonhelical ends in solution.

PubMed

Chandrakasan, G; Torchia, D A; Piez, K A

1976-10-10

Procedures for the preparation of soluble collagen from rat skin and tail tendon were reviewed and revised to permit the preparation of native monomeric collagen with intact nonhelical ends. The degree of intactness was estimated from the tyrosine content, which is present only in the nonhelical ends, and by mobility of the COOH-terminal cyanogen bromide peptide of the alpha1 chain on sodium dodecyl sulfate gels. The amount of covalently cross-linked polymeric material present was estimated by molecular sieve chromatography of denatured samples. Rapid purification in the cold was sufficient to prevent or greatly reduce proteolytic alteration. Fractionation by salt precipitation at acid pH was effective in reducing the content of polymeric material. Rat tail tendon yielded completely intact native collagen, but some high molecular weight aggregates remained. Collagen from the skin of lathyritic rats was easier to obtain free of aggregates, but contained about 1 less tyrosine residue per alpha1 chain even when isolated in the presence of enzyme inhibitors. Proton NMR spectra of denatured acidic solutions of these preparations showed that 4 to 5 tyrosine residues per alpha chain were present, confirming the chemical analysis. Spectra of the native molecule showed that about the same number of tyrosine residues per chain are in rapid motion, unlike residues in the helical portion of the molecule, a result which shows that the nonhelical ends of the native molecule are unstructured in acidic solution.

Pharmacokinetic evaluation of β-caryophyllene alcohol in rats and beagle dogs.

PubMed

He, Jiake; Zhou, Sufeng; Li, Xiaonan; Wang, Chunfeng; Yu, Yang; Chen, Xijing; Lu, Yang

2017-09-11

1. β-caryophyllene alcohol (BCPA) has shown therapeutic promise in the treatment of asthma and inflammation with low toxicity. The aim of the current study was to report the pharmacokinetic profiles of BCPA in rats and dogs. 2. Following intravenous administration, BCPA exhibited moderate volumes of distribution (V z ) ranging from 5.63 to 8.97 L/kg in rats and low V z (2.89 ± 1.12 L/kg) in dogs. Systemic plasma clearance was high in both species, resulting in a short elimination half-life ranging from 29.6 to 48.3 min. In rats, the intravenous pharmacokinetics was dose dependent. The measured oral bioavailability was low in rats for BCPA solution (1.17 ± 0.78%), suspension (1.21 ± 0.33%) and PEG formulation (6.22 ± 2.63%). The bioavailability was lower in dogs for BCPA solution (0.12 ± 0.05%) and PEG formulation (0.25 ± 0.07%), indicating significant species difference. However, treatment of plasma samples with β-glucuronidase increased the systematic exposure of BCPA as assessed from AUC (0-∞) by 24.7- or 2.62-fold in rats and dogs, respectively, which suggested glucuronidation was a significant metabolic pathway for BCPA possibly due to first-pass metabolism. 3. In summary, this was the first preclinical pharmacokinetic investigation of BCPA in animals, providing vital knowledge for further preclinical research and subsequent clinical trials.

Melatonin Attenuates Histopathological Changes in the Hippocampus of Infantile Rats with Kaolin-Induced Hydrocephalus.

PubMed

Turgut, Mehmet; Baka, Meral; Uyanıkgil, Yiğit

2018-05-23

Hydrocephalus is defined as an incapacitating neurological disorder characterized by ventricular enlargement in children, but the effects of melatonin on this hydrocephalus have not yet been fully elucidated. In the present experiment, we attempted to investigate the effects of exogenous melatonin administration on hydrocephalus-induced hippocampal changes in infantile rats. In this study, we randomly divided 45 Swiss albino rats aged 2 weeks into 3 groups: group I, the control group received a sham injection with needle insertion only; groups II and III were given kaolin injections before treatment - group II, the hydrocephalus group, was treated with an isotonic NaCl solution, and group III, the hydrocephalus plus melatonin group, was treated with 0.5 mg/100 g body weight of exogenous melatonin. Both immunohistochemical and histological analyses were performed after hydrocephalus induction and melatonin administration. Immunohistochemical staining consisted anti-glial fibrillary acidic protein staining. The TUNEL technique was used for defining quantitate apoptosis. Melatonin administration significantly attenuated chronic hydrocephalus-induced histopathological changes in the hippocampal subregions of infantile rats. Compared to hydrocephalic rats treated with saline solution, melatonin significantly decreased the number of apoptotic cells and pyknotic index values of each hippocampal subregion after the kaolin-induced hydrocephalus (p < 0.001). The present results demonstrate that the chronic hydrocephalus-induced histopathological changes in the hippocampus were partially reversible with melatonin treatment, suggesting its neuroprotective effects in infantile rats. However, these findings need to be confirmed by further experimental studies and clinical trials. © 2018 S. Karger AG, Basel.

Comparison of histological effects of polydeoxyribonucleic acid and hyaluronic acid in experimentally induced osteoarthritis of the knee joints of rats

PubMed Central

Karahan, Nazım; Arslan, İlyas; Orak, Müfit; Midi, Ahmet; Yücel, İstemi

2017-01-01

Aim: The histological effects of intra-articular polydeoxyribonucleic acid and hyaluronic acid in experimentally induced osteoarthritis of the knee joints of rats were investigated. Methods: Thirty rats were divided into three groups, i.e. polydeoxyribonucleic acid group, hyaluronic acid group and saline group. Osteoarthritis of the knee joints of the rats were induced by acl- transection. The polydeoxyribonucleic group was injected with 100 µg (0.05 cc) polydeoxyribonucleic acid. The hyaluronic acid group was injected with 100 µg (0.05 cc) hyaluronic acid, and the saline group was injected with 50 µl (0.05 cc) of 0.9% sodium chloride solution. All of the rats were sacrificed on day 29 and the right knee joints were prepared, and evaluated histologically by Mankin classification. Findings: The differences in total Mankin scores between the three groups were statistically significant (P < 0.01). The differences in total Mankin scores between the polydeoxyribonucleic acid group and the hyaluronic acid group were statistically significant (P < 0.01). The differences in total Mankin scores between hyaluronic acid group and saline group were statistically significant (P < 0.01). Tidemark continuity in all the specimens of the polydeoxyribonucleic acid group was noteworthy. Conclusion: The present study shows that more chondroprotective effect and less degeneration was observed with intra-articularly delivered polydeoxyribonucleic acid compared to hyaluronic acid and saline solution in the experimentally induced osteoarthritis of the knee joints of rats.

The fine temporal structure of the rat licking pattern: what causes the variabiliy in the interlick intervals and how is it affected by the drinking solution?

PubMed

Lin, Xiong Bin; Pierce, Dwight R; Light, Kim Edward; Hayar, Abdallah

2013-10-01

Licking is a repetitive behavior controlled by a central pattern generator. Even though interlick intervals (ILIs) within bursts of licks are considered fairly regular, the conditions that affect their variability are unknown. We analyzed the licking pattern in rats that licked water, 10% sucrose solution, or 10% ethanol solution, in 90-min recording sessions after 4h of water deprivation. The histograms of ILIs indicate that licking typically occurred at a preferred ILI of about 130-140ms with evidence of bimodal or multimodal distributions due to occasional licking failures. We found that the longer the pause between bursts of licks, the shorter was the first ILI of the burst. When bursts of licks were preceded by a pause >4 s, the ILI was the shortest (~110ms) at the beginning of the burst, and then it increased rapidly in the first few licks and slowly in subsequent licks. Interestingly, the first ILI of a burst of licks was not significantly different when licking any of the 3 solutions, but subsequent licks exhibited a temporal pattern characteristic of each solution. The rapid deceleration in intraburst licking rate was due to an increase from ~27ms to ~56ms in the tongue-spout contact duration while the intercontact interval was only slightly changed (80-90ms). Therefore, the contact duration seems to be the major factor that increases the variability in the ILIs and could be another means for the rat to adjust the amount of fluid ingested in each individual lick.

[Study on effect of oil-bearing solution environment of Caryophylli Flos and other traditional Chinese medicines on system flux and oil recovery rate].

PubMed

Fan, Wen-Ling; Guo, Li-Wei; Lin, Ying; Shen, Jie; Cao, Gui-Ping; Zhu, Yun; Xu, Min; Yang, Lei

2013-10-01

The membrane enrichment process of traditional Chinese medicine volatile oil is environmental friendly and practical, with a good application prospect. In this article, oil-bearing solutions of eight traditional Chinese medicines, namely Caryophylli Flos, Schizonepetae Herba, Eupatorii Herb, Acori Talarinowii Rhizoma, Magnoliae Flos, Chrysanthemum indicum, Cyperi Rhizoma and Citri Reticulatae Pericarpium Viride, were taken as the experimental system. Under unified conditions (membrane: PVDF-14W, temperature: 40 degreeC, pressure: 0. 1 MPa, membrane surface speed: 150 r min- 1), trans-membrane was conducted for above eight oil-bearing solutions to explore the effect of their oil-bearing solution environment on system flux and oil recovery rate. The results showed that systems with smaller pH had a lower flux, without significant effect on oil recovery rate. Greater differences between the surface tension of solutions and that of pure water contributed to a lower oil recovery rate. The conductivity had no notable effect on membrane enrichment process. Systems with high turbidity had a lower flux, without remarkable effect on oil recovery rat. Heavy oils showed lower flux than light ones, but with a slightly higher oil recovery rat. Systems with higher viscosity had a lower flux than those with lower viscosity. Except for Magnoliae Flos volatile oil, all of the remaining volatile oils showed a much higher oil recovery rat than systems with high viscosity. The above results could provide data support and theoretical basis for the industrialization of membrane enrichment volatile oil technology.

Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour activity, cellular uptake and improved in vivo bioavailability.

PubMed

Sun, Jiabei; Bi, Chao; Chan, Hok Man; Sun, Shaoping; Zhang, Qingwen; Zheng, Ying

2013-11-01

The aim of the present study was to blend liquid lipids with solid lipids to encapsulate curcumin in solid lipid nanoparticles (SLNs), thereby improving the dispersibility and chemical stability of curcumin, prolonging its antitumour activity and cellular uptake and enhancing its bioavailability. Curcumin-loaded SLNs (C-SLNs) were prepared by high-pressure homogenisation with liquid lipid Sefsol-218(®). The morphology, stability and release of curcumin in the optimised formulation were investigated. The anti-cancer activity of the formulation was evaluated in MCF-7 cells. Fluorescence spectrophotometry was used to quantify cellular uptake of the drug. The pharmacokinetic profiles of curcumin in SLNs after intravenous administration were studied in rats. Blending Sefsol-218(®) into a lipid matrix reduced the particle size without improving drug loading. An optimised formulation consisting of Dynasan 114(®), Sefsol-218(®), and Pluronic F68(®) (630:70:300, w/w) loaded with 0.8% drug was prepared. This formulation could be dispersed in water with a mean particle size of 152.8 ± 4.7 nm and a 90% entrapment efficiency. Curcumin displayed a two-phase sustained release profile from C-SLNs with improved chemical stability. Compared to the solubilised solution, C-SLNs exhibited prolonged inhibitory activity in cancer cells, as well as time-dependent increases in intracellular uptake. After intravenous administration to rats, the bioavailability of curcumin was increased by 1.25-fold. C-SLNs with improved dispersibility and chemical stability in an aqueous system have been successfully developed. C-SLNs may represent a potentially useful cancer therapeutic curcumin delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

Essential Role of Growth Hormone and IGF-1 in Therapeutic Effect of Ghrelin in the Course of Acetic Acid-Induced Colitis.

PubMed

Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Kuśnierz-Cabala, Beata; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Gil, Krzysztof; Olszanecki, Rafał; Pihut, Małgorzata; Dembiński, Artur

2017-05-24

Previous studies have shown that ghrelin exhibits a protective and therapeutic effect in the gut. The aim of the present study was to examine whether administration of ghrelin affects the course of acetic acid-induced colitis and to determine what is the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this effect. In sham-operated or hypophysectomized male Wistar rats, colitis was induced by enema with 1 mL of 3% solution of acetic acid. Saline or ghrelin (given at the dose of 8 nmol/kg/dose) was administered intraperitoneally twice a day. Seven days after colitis induction, rats were anesthetized and the severity of the colitis was assessed. Treatment with ghrelin reduced the area of colonic mucosa damage in pituitary-intact rat. This effect was associated with increase in serum levels of GH and IGF-1. Moreover, administration of ghrelin improved blood flow in colonic mucosa and mucosal cell proliferation, as well as reduced mucosal concentration of proinflammatory interleukin-1β (IL-1β) and activity of myeloperoxidase. Hypophysectomy reduced serum levels of GH and IGF-1 and increased the area of colonic damage in rats with colitis. These effects were associated with additional reduction in mucosal blood follow and DNA synthesis when compared to pituitary-intact rats. Mucosal concentration of IL-1β and mucosal activity of myeloperoxidase were maximally increased. Moreover, in hypophysectomized rats, administration of ghrelin failed to affect serum levels of GH or IGF-1, as well as the healing rate of colitis, mucosal cell proliferation, and mucosal concentration of IL-1β, or activity of myeloperoxidase. We conclude that administration of ghrelin accelerates the healing of the acetic acid-induced colitis. Therapeutic effect of ghrelin in experimental colitis is mainly mediated by the release of endogenous growth hormone and IGF-1.

Effects of parenteral structured lipid emulsion on modulating the inflammatory response in rats undergoing a total gastrectomy.

PubMed

Lin, Ming-Tsan; Yeh, Sung-Ling; Tsou, Shung-Sheng; Wang, Ming-Yang; Chen, Wei-Jao

2009-01-01

Structured lipid emulsion improves the nitrogen balance and is rapidly cleared from the blood of moderately catabolic patients. However, the effects of structured lipids on inflammatory reactions during major surgery are not clear. This study investigated the effect of a parenteral structured triacylglycerol emulsion on leukocyte adhesion molecule expression and inflammatory mediator production in rats undergoing a total gastrectomy. Normal rats with internal jugular catheters were assigned to three experimental groups and received total parenteral nutrition. At the same time, a total gastrectomy was performed on the experimental groups. The total parenteral nutrition solutions were isonitrogenous and identical in nutrient compositions except for differences in the composition of the fat emulsion. Group 1 received a conventional fat emulsion with long-chain triacylglycerols (LCTs), group 2 received a physical mixture of medium-chain triacylglycerols (MCTs) and LCTs (MCT/LCT), and group 3 received structured lipids composed of MCTs and LCTs (STG). Half of the rats in each respective group were sacrificed 1 d and the other half 3 d after surgery to examine the analytical parameters. Plasma cholesterol and free fatty acid levels in the STG group were lower than those in the other groups after surgery. The STG group had lower leukocyte CD11a/CD18 expressions than the MCT/LCT group 3 d after surgery, and CD11b/CD18 expressions in the STG group were lower than those in the LCT group on postoperative days. The STG group had higher monocyte chemotactic protein-1 and macrophage inflammatory protein-2 levels in peritoneal lavage fluid than did the other two groups. These results suggest that, compared with the LCT and MCT/LCT groups, rats administered STG had lower plasma lipid concentrations and leukocyte integrin expressions. In addition, STG administration may cause increased recruiting of neutrophils and monocytes at the site of injury and enhance antipathogenicity in rats undergoing a total gastrectomy.

Parenteral glutamine supplementation in combination with enteral nutrition improves intestinal immunity in septic rats.

PubMed

Fan, Jun; Li, Guoping; Wu, Lidong; Tao, Shaoyu; Wang, Wei; Sheng, Zhiyong; Meng, Qingyan

2015-05-01

The gut-associated lymphoid tissue is continuously exposed to antigens in the gut lumen and becomes the first line of defense against enteric bacteria and associated toxin. The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation in combination with enteral nutrition (EN) on intestinal mucosal immunity in septic rats by cecal ligation and puncture (CLP). Male Sprague-Dawley rats were randomly assigned into four groups: A sham CLP + EN + saline group (n = 10), a sham CLP + EN + GLN group (n = 10), a CLP + EN + saline group (n = 10), and a CLP + EN + GLN group (n = 10). At 2 h after CLP or sham CLP, all rats in each of the four groups received an identical enteral nutrition solution as their base formula. Then, the rats in the sham CLP + EN + GLN group and CLP + EN + GLN group were given 0.35 g GLN/kg body weight daily for 7 d, all at the same time, via a tail vein injection; whereas those in the sham CLP + EN + saline group and CLP + EN + saline group were daily administered isovolumic sterile 0.9% saline for comparison. All rats in each of the four groups were given 290 kcal/kg body wt/d for 7 d. At the end of the seventh day after the nutritional program was finished, all rats were euthanized and the entire intestine was collected. Total Peyer's patches (PP) cell yield was counted by a hemocytometer. The percentage of PP lymphocyte subsets was analyzed by flow cytometry. The number of intestinal lamina propria IgA plasma cells was determined by the immunohistochemistry technique. The intestinal immunoglobulin A (IgA) levels were assessed by ELISA. PP apoptosis was evaluated by terminal deoxyuridine nick-end labeling. The results revealed total PP cell yield, the numbers of PP lymphocyte subsets, intestinal lamina propria IgA plasma cells, and intestinal IgA levels in the CLP + EN + GLN group were significantly increased when compared with the CLP + EN + saline group (P < 0.05). On the other hand, the number of TUNEL-stained cells within PPs in the CLP + EN + GLN group was markedly decreased as compared with the CLP + EN + saline group (P < 0.05). The results of this study show that parenteral glutamine supplementation in combination with enteral nutrition may attenuate PP apoptosis, increase PP cell yield and intestinal lamina propria IgA plasma cells, and subsequently improve intestinal mucosal immunity. Clinically, these results suggest therapeutic efforts at improving intestinal immunity may contribute to the prevention and treatment of sepsis. Copyright © 2015 Elsevier Inc. All rights reserved.

[Effect of Transcutaneuos Acupoint Electrostimulation on Serum Sex Hormone Levels and Expression of Ovarian Steroid Hormone Metabolic Enzymes in Polycystic Ovary Syndrome Rats].

PubMed

Zhou, Jian-yong; Zhang, Xiao-yue; Yu, Mei-ling; Lu, Sheng-feng; Chen, Xia

2016-02-01

To observe the effect of transcutaneuos acupoint electrostimulation(TAES) on ovarian serum sex hormone levels and ovarian follicle granular cell aromatase cytochrome P 450 (P 450 arom) protein and follicle theca cell cytochrome P 450 17 α-hydroxylase/c 17-20 lyase cytochrome P 450 (P 450 c 17 α) protein expression in polycystic ovary syndrome (PCOS)rats, so as to explore its mechanisms underlying improvement of PCOS. METHODS Forty SD rats were randomly divided into four groups: normal control, model, medication and TAES (10 rats/group). The PCOS model was established by giving (gavage) the animals with letrozole solution (1.0 mg/kg, once daily for 21 consecutive days). Rats of the medication group were treated with Clomiphene (1 mg/kg) once daily for 7 days, and those of the TAES group were treated with electrical stimulation (2 Hz, 3 mA) of "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) areas for 30 min, once daily for 7 consecutive days. The rats body weight and bilateral ovarian weight were detected, and the ovarian structure and follicular development degree were observed under light microscope after H. E. stain, and the serum testosterone (T), estradiol (E2), luteotrophic hormone (LH) and follicle-stimulating hormone (FSH) contents were detected using radioimmunoassay. The expression of ovarian P 450 arom (for production of estrogen)protein and P 450 c 17 α (for production of androgen) protein was detected by using immunohistochemical stain and Western blot, respectively. The body weight, bilateral ovary weight, serum T and LH contents, and ratio of LH/FSH, and ovarian P 450 c 17 α immunoactivity and protein expression levels in the model group were all significantly increased compared with the normal control group (P < 0.01), and the levels of serum E2 and ovarian P 450 arom immunoactivity and protein expression were significantly decreased after modeling (P < 0.01). Following the treatment, the increased body weight, ovary weight, serum T and LH contents, ratio of LH/FSH, and ovarian P 450 c 17 α immunoactivity and protein expression levels, and the decreased ovarian P 450 arom immunoactivity and protein expression levels were reversed in the TAES group (P < 0.01, P < 0.05) rather than in the medication group, except serum T and ratio of LH/FSH in the medication group. No significant differences were found between the medication and TAES groups in the serum T and ratio of LH/FSH (P > 0.05). In addition, the increased vesicular follicle number, the decreased corepus luteum number and the thickness of granular cell layer were markedly improved in the TAES group. TAES intervention can reduce both body weight and ovarian weight and regulate the levels of serum sex hormones and ovarian P 450 c 17 α and P 450 arom protein expression levels in PCOS rats, which may contribute to its effect in improving PCOS.

[Effect of different volumes of fluid resuscitation on hemorrhagic shock with pulmonary edema at high altitude in the unacclimated rat].

PubMed

Liu, Liang-ming; Hu, De-yao; Liu, Jian-cang; Li, Ping; Liu, Hou-dong; Xiao, Nan; Zhou, Xue-wu; Tian, Kun-lun; Huo, Xiao-ping; Shi, Quan-gui; He, Yan-mei; Yin, Zuo-ming

2003-05-01

To study the effects of different volumes of fluid resuscitation on hemorrhagic shock with pulmonary edema at high altitude in the unacclimated rat. One hundred and twenty-six SD rats transported to Lasa, Tibet, 3 760 meters above the sea level, were anesthetized one week later with sodium pentobarbital (30 mg/kg, intraperitoneal). Hemorrhagic shock with pulmonary edema model was induced by hemorrhage (50 mm Hg for 1 hour, 1 mmHg=0.133 kPa) plus intravenous injection of oleic acid (50 microl/kg). Experiments were then conducted in two parts. Sixty-three rats in part I were equally divided into nine groups (n=7): normal control, hemorrhagic shock control, hemorrhagic shock with pulmonary edema (HSPE) without fluid infusion, HSPE plus infusing lactated Ringer's solution (LR) with 0.5-, 1-, 1.5-, 2- or 3- fold volume shed blood, and 1 volume of LR plus mannitol (10 ml/kg). Hemodynamic parameters including mean arterial blood pressure (MAP), left intraventricular systolic pressure (LVSP) and the maximal change rate of intraventricular pressure rise or decline (+/- dp/dt max) were observed at 15, 30, 60 and 120 minutes after infusion, blood gases were measured at 30 and 120 minutes after infusion and the water content of lung and brain was determined at 120 minutes after infusion. In part II, additional 63 rats were used to observe the effect of different volumes of fluid resuscitation on survival time of HSPE rats. 0.5 volume of LR infusion significantly improved MAP, LVSP and +/- dp/dt max, prolonged the survival time of HSPE animals (all P<0.01), while it did not increase the water content of lung and brain and had no marked influence on blood gases. One volume of LR infusion slightly improved hemodynamic parameters, prolonged the survival time and increased the water content of lung. More than 1 volume of LR infusion including 1.5-, 2- and 3- fold volume LR deteriorated the hemodynamic parameters and decreased the survival time of shocked animal, meanwhile they apparently increased the water content of lung. One volume of LR plus mannitol (10 ml/kg) infusion did not improve the hemodynamic parameters and blood gases; also it did not decrease the water content of lung. The tolerance to fluid infusion for the unacclimated animal subjected to hemorrhagic shock with pulmonary edema at high altitude is significantly decreased. 0.5-1 volume of LR infusion appears to be beneficial effect on resuscitation at high altitude, while over 1 volume of LR infusion would aggravate pulmonary edema and exacerbate fluid resuscitation effect.

Effects of xylitol as a sugar substitute on diabetes-related parameters in nondiabetic rats.

PubMed

Islam, Md Shahidul

2011-05-01

Abstract The present study was examined the effects of xylitol feeding on diabetes-associated parameters in nondiabetic rats. Seven-week-old male Sprague-Dawley rats were randomly divided into three groups: control (five rats), sucrose (six rats), and xylitol (six rats). Animal had free access to a commercial rat pellet diet, and ad libitum water, 10% sucrose solution, and 10% xylitol solution were supplied to the control, sucrose, and xylitol groups, respectively. After 3 weeks of feeding of experimental diets, food intakes were significantly (P<.05) lower in the sucrose and xylitol groups compared with the control group. Drink intake was significantly higher in the sucrose group but significantly lower in the xylitol group compared with the control group. Body weight gain was significantly lower in the xylitol group compared with the sucrose group. Weekly nonfasting blood glucose was significantly increased, but fasting blood glucose was significantly decreased, in the sucrose group compared with the control and xylitol groups. Significantly better glucose tolerance was observed in the xylitol group compared with the control and sucrose groups. Serum insulin and fructosamine concentrations were not significantly influenced by the feeding of xylitol or sucrose. Relative liver weight and liver glycogen were significantly increased in the xylitol group compared with the sucrose group, whereas no difference was observed between the xylitol and control groups. Serum total cholesterol and low-density lipoprotein-cholesterol were significantly decreased in the sucrose and xylitol groups, and serum triglyceride of the xylitol group, but not the sucrose group, was significantly increased compared with the control group. Data of this study suggest that xylitol can be a better sweetener than sucrose to maintain diabetes-related parameters at a physiologically safer and stable condition.

Absorption, Distribution, Metabolism, and Excretion of the Androgen Receptor Inhibitor Enzalutamide in Rats and Dogs.

PubMed

Ohtsu, Yoshiaki; Gibbons, Jacqueline A; Suzuki, Katsuhiro; Fitzsimmons, Michael E; Nozawa, Kohei; Arai, Hiroshi

2017-08-01

Enzalutamide is an androgen receptor inhibitor that has been approved in several countries. Absorption, distribution, metabolism, and excretion (ADME) data in animals would facilitate understanding of the efficacy and safety profiles of enzalutamide, but little information has been reported in public. The purpose of this study was to clarify the missing ADME profile in animals. ADME of 14 C-enzalutamide after oral administration as Labrasol solution were investigated in non-fasted male Sprague-Dawley rats and beagle dogs. Plasma concentrations of 14 C-enzalutamide peaked in rats and dogs at 6-8 h after a single oral administration. In most tissues, radioactivity concentration peaked at 4 h after administration. Excluding the gastrointestinal tract, tissues with the highest concentration of radioactivity were liver, fat, and adrenal glands. The tissue concentrations of radioactivity declined below the limit of quantitation or <0.89 % of maximum concentration by 168 h post-dose. Two known metabolites (M1 and M2) and at least 15 novel possible metabolites were detected in this study. M1 was the most abundant metabolite in both rats and dogs. Unchanged drug was a minor component in excreta. In intact rats, the mean urinary and fecal excretion of radioactivity accounted for 44.20 and 49.80 % of administered radioactivity, respectively. In intact dogs, mean urinary and fecal excretion was 62.00 and 22.30 % of the administered radioactivity, respectively. Rapid oral absorption was observed in rats and dogs when 14 C-enzalutamide was administered as Labrasol solution. Tissue distribution in rats was clarified. The elimination of enzalutamide is mediated primarily by metabolism. Species differences were observed in excretion route.

The Effect of Swimming Experience on Acquisition and Retention of Swimming-Based Taste Aversion Learning in Rats

ERIC Educational Resources Information Center

Masaki, Takahisa; Nakajima, Sadahiko

2010-01-01

Swimming endows rats with an aversion to a taste solution consumed before swimming. The present study explored whether the experience of swimming before or after the taste-swimming trials interferes with swimming-based taste aversion learning. Experiment 1 demonstrated that a single preexposure to 20 min of swimming was as effective as four or…

Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate, High Fat Diet-Fed Rats

PubMed Central

Alam, Md. Ashraful; Kauter, Kathleen; Brown, Lindsay

2013-01-01

Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats. PMID:23446977

Antioxidant effects of melatonin in heart tissue after induction of experimental periodontitis in rats.

PubMed

Özdem, Muhsin; Kırzıoğlu, Fatma Y; Yılmaz, Hacı R; Vural, Hüseyin; Fentoğlu, Özlem; Uz, Efkan; Koçak, Ahmet; Yiğit, Ayşe

2017-01-01

The aim of this study was to evaluate the effects of melatonin on the oxidative stress in heart tissues after induction of experimental periodontitis in rats. Thirty Wistar Albino male rats were divided into four groups as follows: healthy + saline solution (Hs, n = 7), healthy + melatonin (Hm, n = 7), periodontitis + saline solution (Ps, n = 8), and periodontitis + melatonin (Pm, n = 8). Experimental periodontitis was induced using a ligature placed at the gingival margin of the maxillary second molars. Melatonin was applied intraperitoneally (10 mg/kg) every day for 2 weeks. After sacrificing the rats, serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) levels, and melatonin levels were evaluated. The Pm group exhibited lower alveolar bone loss than the Ps group. Melatonin levels increased in the periodontitis groups, and the Pm group had lower MDA levels and higher GSH-Px levels than the Ps group. These findings suggest that melatonin administration reduces MDA and increases GSH-Px levels in heart tissue, and these effects may be due to its antioxidant properties. Further studies are needed to understand the effects of melatonin on the association between periodontitis and cardiovascular disease.

Stevia preferences in Wistar rats.

PubMed

Núñez Martínez, Paula; Argüelles Luis, Juan; Perillán Méndez, Carmen

2016-11-01

The Stevia rebaudiana plant is likely to become a major source of high-potency sweetener for the growing natural-food market. S. rebaudiana is the source of a number of sweet diterpenoid glycosides, but the major sweet constituents are rebaudioside A and stevioside. These two constituents have similar pharmacokinetic and metabolic profiles in rats and humans, and thus, studies carried out with either steviol glycoside are relevant to both. Other studies illustrate the diversity of voluntary sweet intake in mammals. This study was done using a series of two-bottle tests that compared a wide range of sweetener concentrations versus saccharin concentrations and versus water. Wistar rats displayed preferences for stevia extract and pure rebaudioside A solutions over water at a range of concentrations (0.001% to 0.3%), and their intake peak occurred at 0.1% concentration. They also preferred solutions prepared with a commercial rebaudioside A plus erythritol mixture to water, and their peak was at 2% concentration. The present study provides new information about the responses of Wistar rats to stevia compounds and commercial stevia products such as Truvia. These results could help with the appropriate dosage selection for focused behavioral and physiological studies on stevia.

Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats.

PubMed

Rushaidhi, M; Zhang, H; Liu, P

2013-03-27

Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of nicergoline on age-related decrements in radial maze performance and acetylcholine levels.

PubMed

McArthur, R A; Carfagna, N; Banfi, L; Cavanus, S; Cervini, M A; Fariello, R; Post, C

1997-01-01

The effects of chronic oral administration of nicergoline (5.0 mg/kg; bid) on locomotor activity, eight-arm radial maze performance plus striatal, cortical, and hippocampal acetylcholine (ACh) levels were examined in young and aged Wistar rats. Chronic nicergoline administration did not modify either the locomotor activity or radial maze learning in young rats. Young rats learned the radial maze procedure rapidly and improved their performance throughout the successive training sessions. Radial maze performance in young rats was characterised by very few arm reentries. Aged rats were hypoactive and did not explore or enter the radial maze arms, and consequently performed poorly in the radial maze throughout the training sessions. Nicergoline treatment did not significantly modify locomotor activity in aged rats. Aged rats treated with nicergoline also performed poorly initially but improved with repeated training in the radial maze. This improvement was associated with an increasing number of arms being entered and very few arm reentries. Reduced acetylcholine (ACh) levels were also associated with age. Aged rats had significantly reduced levels of ACh in the straitum and cortex, but not the hippocampus as compared to young rats. Nicergoline treatment did not change ACh levels in young rats, but substantially restored the reduced ACh levels in aged rats. These results indicate that nicergoline is an effective cognitive enhancer in a learning model of age-related deficits and that these results may be related to changes in the cholinergic system.

Effect of parenteral glutamine supplementation combined with enteral nutrition on Hsp90 expression and lymphoid organ apoptosis in severely burned rats.

PubMed

Fan, Jun; Wu, Jing; Wu, Li-Dong; Li, Guo-Ping; Xiong, Meng; Chen, Xi; Meng, Qing-Yan

2016-11-01

The aim of this study is to investigate the effects of parenteral glutamine(GLN) supplementation combined with enteral nutrition (EN) on heat shock protein 90(Hsp90) expression, apoptosis of lymphoid organs and circulating lymphocytes, immunological function and survival in severely burned rats. Male SD rats were randomly assigned into 4 groups: a sham burn+EN+GLN-free amino acid (AA) group (n=10), a sham burn+EN+GLN group (n=10), a burn+EN+AA group (n=10), and a burn +EN +GLN group (n=10). Two hours after a 30% total body surface area (TBSA), full-thickness scald burn injury on the back was made, the burned rats in two experimental groups (the burn+EN+AA group and the burn+EN +GLN group) were fed with a conventional enteral nutrition solution by oral gavage for 7 days. Simultaneously, the rats in the burn+EN+GLN group were given 0.35g GLN/kg body weight/day once via a tail vein injection for 7 days, whereas those in the burn+EN+AA group were administered isocaloric/isonitrogenous GLN-free amino acid solution (Tyrosine) for comparison. The rats in two sham burn control groups (the sham burn+EN+AA group and the sham burn+EN +GLN group) were treated in the same procedure as above, except for burn injury. All rats in each of the four groups were given 175kcal/kg body wt/day. There was isonitrogenous, isovolumic and isocaloric intake among four groups. At the end of the 7th day after nutritional programme were finished, all rats were anesthetized and samples were collected for further analysis. Serum immunoglobulin quantification was conducted by ELISA. Circulating lymphocyte numbers were counted by Coulter LH-750 Analyzer. The percentages and apoptotic ratio of CD4 and CD8T lymphocytes in circulation were determined by flow cytometry (FCM). The neutrophil phagocytosis index (NPI) was examined. The GLN concentrations in plasma, thymus, spleen and skeletal muscle were measured by high performance liquid chromatography (HPLC). The organ index evaluation and TUNEL analysis of thymus and spleen were carried out. The expression of Hsp90 in thymus and spleen was analyzed by western blotting. Moreover, the survival in burned rats was observed. The results revealed that parenteral GLN supplementation combined with EN significantly increased the GLN concentrations of plasma and tissues, the serum immunoglobulin content, the circulating lymphocyte number, the CD4/CD8 ratio, the indexes of thymus and spleen, NPI and survival as compared with the burn+EN+AA group (p<0.05). The expression of Hsp90 in thymus and spleen in the burn+EN+GLN group was significantly up-regulated as compared with the burn+EN+AA group (p<0.05). The apoptosis in circulating CD4 and CD8 lymphocytes, thymus and spleen in the burn+EN+GLN group was significantly decreased as compared with the burn+EN+AA group (p<0.05). The results of this study show that parenteral GLN supplementation combined with EN may increase the GLN concentrations of plasma and tissues, up-regulate the expression of Hsp90, attenuate apoptosis in lymphoid organ and circulating lymphocyte, enhance the immunological function and improve survival in severely burned rats. Clinically, therapeutic efforts at the modulation of the immune dysfunction may contribute to a favorable outcome in severely burned patients. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Volume to dissolve applied dose (VDAD) and apparent dissolution rate (ADR): tools to predict in vivo bioavailability from orally applied drug suspensions.

PubMed

Muenster, Uwe; Pelzetter, Christian; Backensfeld, Thomas; Ohm, Andreas; Kuhlmann, Thomas; Mueller, Hartwig; Lustig, Klemens; Keldenich, Jörg; Greschat, Susanne; Göller, Andreas H; Gnoth, Mark Jean

2011-08-01

Low solubility of drug candidates generated in research contributes to their elimination during subsequent development due to insufficient oral bioavailability (BA) of crystalline compound. Therefore, the purpose of the study was to identify critical in vitro solubility and dissolution parameter that would predict critical in vivo dissolution by means of in vitro-in vivo correlation. Thermodynamic solubility and apparent dissolution rate (ADR) were determined using the shake-flask method and mini-flow-through-cell, respectively. Oral BA studies in rats and humans were conducted from drug solution and suspension/tablets. Relative BA was calculated using F(rel) [%]=AUC(suspension)/AUC(solution)*100, representing a measure of in vivo dissolution. Roughly, F(rel) rat >50% translates into F(rel) human of >90%. Both, ADR and log volume to dissolve applied dose (VDAD), when plotted against F(rel) rat, revealed certain threshold levels, (ADR, ∼150-200 μg of compound dissolved under respective assay conditions; VDAD, ∼100-500 ml/kg) which translate into F(rel) in rats of >50%. Thus, assuming that F(rel)>50% in rats is indicative of sufficient in vivo dissolution in humans after oral application, drugs should exhibit a VDAD of ∼100-500 ml/kg or less in aqueous media to avoid insufficient or varying drug absorption. Copyright © 2011 Elsevier B.V. All rights reserved.

Hydroquinone PBPK model refinement and application to dermal exposure.

PubMed

Poet, Torka S; Carlton, Betsy D; Deyo, James A; Hinderliter, Paul M

2010-11-01

A physiologically based pharmacokinetic (PBPK) model for hydroquinone (HQ) was refined to include an expanded description of HQ-glucuronide metabolites and a description of dermal exposures to support route-to-route and cross-species extrapolation. Total urinary excretion of metabolites from in vivo rat dermal exposures was used to estimate a percutaneous permeability coefficient (K(p); 3.6×10(-5) cm/h). The human in vivo K(p) was estimated to be 1.62×10(-4) cm/h, based on in vitro skin permeability data in rats and humans and rat in vivo values. The projected total multi-substituted glutathione (which was used as an internal dose surrogate for the toxic glutathione metabolites) was modeled following an exposure scenario based on submersion of both hands in a 5% aqueous solution of HQ (similar to black and white photographic developing solution) for 2 h, a worst-case exposure scenario. Total multi-substituted glutathione following this human dermal exposure scenario was several orders of magnitude lower than the internal total glutathione conjugates in rats following an oral exposure to the rat NOEL of 20 mg/kg. Thus, under more realistic human dermal exposure conditions, it is unlikely that toxic glutathione conjugates (primarily the di- and, to a lesser degree, the tri-glutathione conjugate) will reach significant levels in target tissues. Copyright © 2010. Published by Elsevier Ltd.

Evaluating the predictability of the in vitro transfer model and in vivo rat studies as a surrogate to investigate the supersaturation and precipitation behaviour of different Albendazole formulations for humans.

PubMed

Ruff, Aaron; Holm, René; Kostewicz, Edmund S

2017-07-15

The present study investigated the ability of the in vitro transfer model and an in vivo pharmacokinetic study in rats to investigate the supersaturation and precipitation behaviour of albendazole (ABZ) relative to data from a human intestinal aspiration study reported in the literature. Two lipid based formulation systems, a hydroxypropyl-β-cyclodextrin (HPβCD) solution and the addition of a crystallization inhibitor (HPMC-E5) on the behaviour of ABZ was investigated. These formulations were investigated to represent differences in their ability to facilitate supersaturation within the small intestine. Overall, both the in vitro transfer model and the in vivo rat study were able to rank order the formulations (as aqueous suspension±HPMC

Curcumin photodynamic effect in the treatment of the induced periodontitis in rats.

PubMed

Theodoro, Letícia Helena; Ferro-Alves, Marcio Luiz; Longo, Mariéllen; Nuernberg, Marta Aparecida Alberton; Ferreira, Renata Pironato; Andreati, Adriele; Ervolino, Edilson; Duque, Cristiane; Garcia, Valdir Gouveia

2017-11-01

This study assessed the effect of curcumin as a photosensitizer in antimicrobial photodynamic therapy (aPDT) for the treatment of induced periodontitis in rats. Periodontitis was induced via a ligature around the mandibular first molar on the left side of 96 rats. The ligature was removed 7 days later, and the animals were randomized into four groups: NT, no local treatment; CUR, irrigation with curcumin solution (40 μM); LED, irradiation with a light-emitting diode (LED, InGaN, 465-485 nm, 200 mW/cm 2 , 60 s); and aPDT, irrigation with curcumin solution (40 μM) followed by irradiation with LED. Eight animals from each group were euthanized at 7, 15, and 30 days post-treatment. Treatments were assessed using alveolar bone loss (ABL) in the furcation region using histological, histometric, and immunohistochemical analyses. Rats treated with aPDT exhibited less ABL at 7 days compared to the NT group, moderate pattern immunolabeling for osteoprotegerin at 30 days, and a pattern of immunolabeling for RANKL from moderate to low. Treatments resulted in smaller numbers of TRAP-positive cells compared to the NT group. aPDT as monotherapy using curcumin as a photosensitizer and LED as the light source was effective in the treatment of induced periodontitis in rats.

Ischemic acute renal failure and antioxidant therapy in the rat. The relation between glomerular and tubular dysfunction.

PubMed Central

Bird, J E; Milhoan, K; Wilson, C B; Young, S G; Mundy, C A; Parthasarathy, S; Blantz, R C

1988-01-01

The effects of antioxidant therapy with probucol were evaluated in rats subjected to 1 h renal ischemia and to 24 h reperfusion. Probucol exerted significant antioxidant effects in renal cortical tubules in vitro when exposed to a catalase-resistant oxidant. At 24 h probucol treatment (IP) improved single nephron glomerular filtration rate (SNGFR) (28.1 +/- 3.3 nl/min) in comparison to untreated ischemic (I) rats (15.2 +/- 3.0), primarily as a result of improving SNGFR in a population of low SNGFR, low flow and/or obstructed nephrons. However, absolute proximal reabsorption remained abnormally low in IP rats at 24 h (5.9 +/- 0.8 nl/min), and cell necrosis was greater than in I rats. Kidney GFR remained low in IP rats due to extensive tubular backleak of inulin measured by microinjection studies. Evaluations after 2 h of reperfusion revealed a higher SNGFR in IP (36 +/- 3.1 nl/min) than I rats (20.8 +/- 2.7 nl/min). Absolute proximal reabsorption was essentially normal (11.6 +/- 1.3 nl/min) in IP rats, which was higher than IP rats at 24 h and the concurrent I rats. Administration of the lipophilic antioxidant, probucol, increased SNGFR and proximal tubular reabsorption within 2 h after ischemic renal failure. Although SNGFR remained higher than I rats at 24 h, absolute reabsorption fell below normal levels and tubular necrosis was more extensive in IP rats. Early improvement in nephron filtration with antioxidants may increase load dependent metabolic demand upon tubules and increase the extent of damage and transport dysfunction. Images PMID:2835399

Pioglitazone enhances the blood pressure-lowering effect of losartan via synergistic attenuation of angiotensin II-induced vasoconstriction.

PubMed

Kong, Xiang; Ma, Ming-Zhe; Qin, Li; Zhang, Yan; Li, Xiao-Yong; Wang, Guo-Dong; Su, Qing; Zhang, Dao-You

2014-09-01

This study was designed to investigate the underlying mechanisms of synergistic antihypertensive effect produced by combination therapy of losartan and pioglitazone in metabolic syndrome (MS) rats. An MS model was induced by feeding rats a high-fat, high-sodium diet and 20% sucrose solution. Losartan (20 mg/kg/day), pioglitazone (10 mg/kg/day), and their combination were orally administered for eight consecutive weeks. Systolic blood pressure (SBP) and mean arterial pressure (MAP) were measured using the tail-cuff method and carotid arterial catheterization, respectively. The aortas were isolated and in vitro vascular reactivity studies were performed. The protein expression of angiotensin type 1 receptor (AT1), endothelial nitric oxide synthase (eNOS), phosphorylated eNOS and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox), level of nitrotyrosine as well as activity of eNOS and NADPH oxidase in aortas of MS rats were detected. After eight weeks of treatment, the SBP and MAP in the losartan (115 ± 5 and 106 ± 6 mmHg), pioglitazone (130 ± 6 and 118 ± 6 mmHg), and combination therapy (105 ± 6 and 98 ± 5 mmHg) groups were lower than those in the model group (150 ± 8 and 136 ± 9 mmHg). Combination therapy of losartan and pioglitazone reduced BP more than either monotherapy, and showed additive effects on improving endothelial dysfunction and abolishing the increased vascular responsiveness to angiotensin II. These synergistic effects were associated with further reductions in protein expression of p47(phox) and AT1, NADPH oxidase activity, and nitrotyrosine level. Our data indicate that combined treatment exerts more beneficial effects on lowering BP and improving vascular lesions. © The Author(s) 2013.

δ opioid receptor antagonist, ICI 174,864, is suitable for the early treatment of uncontrolled hemorrhagic shock in rats.

PubMed

Liu, Liangming; Tian, Kunlun; Zhu, Yu; Ding, Xiaoli; Li, Tao

2013-08-01

Fluid resuscitation is the essential step for early treatment of traumatic hemorrhagic shock. However, its implementation is greatly limited before hospital or during evacuation. The authors investigated whether δ opioid receptor antagonist ICI 174,864 was suitable for the early treatment of traumatic hemorrhagic shock. With uncontrolled hemorrhagic-shock rats, the antishock effects of six dosages of ICI 174,864 (0.1, 0.3, 0.5, 1, 3, and 5 mg/kg) infused with or without a small volume of lactated Ringer's solution (LR) before bleeding controlled or bleeding cessation at different times were observed. ICI 174,864 (0.1-3 mg/kg) with or without 1/4 volume of LR infusion showed dose-dependent increase in the mean arterial blood pressure, and significantly prolonged the survival time and 8-h survival rate, as compared with ICI 174,864 plus 1/2 volume of LR infusion. The best effect was shown with 3 mg/kg of ICI 174,864. Bleeding cessation at 1, 2, or 3 h during infusion of ICI 174,864 (3 mg/kg) plus 1/4 volume of LR improved subsequent treatment (70% 24-h survival rate vs. 50 and 10% 24-h survival rate in hypotensive resuscitation and LR group, respectively). There was significant improvement in hemodynamic parameters, oxygen delivery, and tissue perfusion of hemorrhagic-shock rats with 3 mg/kg of ICI 174,864 plus 1/4 volume of LR infusion. δ Opioid receptor antagonist ICI 174,864 alone or with small volume of fluid infusion has good beneficial effect on uncontrolled hemorrhagic shock. Its early application can "buy" time for subsequent treatment of traumatic shock.

Deposition of ethyl glucuronide in WHP rat hair after chronic ethanol intake.

PubMed

Małkowska, Anna; Szutowski, Mirosław; Dyr, Wanda

2012-01-01

This study investigated the relationship between ethanol intake in rats and the resulting level of ethyl glucuronide (EtG) in rat hair. Rats (n = 50) consumed a 10% ethanol solution for 4 weeks, then EtG was extracted from samples of their hair using a novel extraction procedure involving freezing and thawing. The EtG concentration was measured using gas chromatography and mass spectrometry. The animals voluntarily drank ethanol, with daily consumption in most rats exceeding 5 g/kg b.w. The silylated EtG was stable for at least 28 h. The limit of detection was 0.03 ng/mg, and the limit of quantification was 0.1 ng/mg. Hair samples from rats that consumed ethanol had EtG levels ranging from 0.17-20.72 ng/mg in female rats and 0.15-13.72 ng/mg in males. There was a correlation between the amount of alcohol consumed and the EtG levels in hair from female (p < 0.01), but not male, rats. The method presented allows detection and quantification of EtG in rat hair. We also observed differences in EtG deposition in male and female rats.

The acute effects of different spironolactone doses on cardiac function in streptozotocin-induced diabetic rats.

PubMed

Vranic, Aleksandra; Simovic, Stefan; Ristic, Petar; Nikolic, Tamara; Stojic, Isidora; Srejovic, Ivan; Zivkovic, Vladimir; Jakovljevic, Vladimir; Djuric, Dusan

2017-11-01

Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 μmol/L of spironolactone, diabetic rats treated with 0.1 μmol/L of spironolactone, healthy rats treated with 3 μmol/L of spironolactone, and diabetic rats treated with 3 μmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.

Development of PEG-PLGA based Intravenous Low Molecular Weight Heparin (LMWH) Nanoparticles Intended to Treat Venous Thrombosis.

PubMed

Jogala, Satheesh; Rachamalla, Shyam Sunder; Aukunuru, Jithan

2016-01-01

Anticoagulant therapy is effective in the treatment of DVT. In this regard, LMWH demonstrated significant promise. It is widely used clinically. The goal of this study was to prepare and evaluate intravenous sustained release stealth nanoparticles encapsulating LMWH using PLGA (polylactidecoglycolide) and different grades of PEG (poly ethylene glycols). The nanoparticles were prepared using w/o/w solvent evaporation technique. Prepared nanoparticles were evaluated for particle size, encapsulation efficiency, in-vitro drug release, anti-thrombotic activity in venous thrombosis rat model, estimation of aPTT, tissue bio-distribution studies and stability. Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) studies confirmed the formation of smooth spherical particles. FTIR study reveals successful coating of PEG on the nanoparticles. DSC and XRD results demonstrated that drug changed its physical form in the formulation. The encapsulation efficiency was 63-74%. In vitro drug release was 57-75% for 48 hrs. Macrophage uptake of LMWH with pegylated nanoparticles was less compared to conventional PLGA nanoparticles. In vivo drug release was sustained for 48hrs; Optimized formulation exhibited good enhancement in pharmacokinetic parameters when compared to free drug solution. In vivo sustained release was also demonstrated with antithrombotic activity as well aPTT activity. Optimized formulation demonstrated significant stability, excellent antithrombotic activity in venous thrombosis rat model, improved aPTT levels when compared to free drug solution. An effective stealth LMWH nanoparticle formulation to treat venous thrombosis was successfully developed using w/o/w solvent evaporation technique.

Local tolerance and stability up to 24 months of a new 20% proline-stabilized polyclonal immunoglobulin for subcutaneous administration.

PubMed

Maeder, Werner; Lieby, Patricia; Sebald, Andrea; Spycher, Martin; Pedrussio, Renzo; Bolli, Reinhard

2011-01-01

Subcutaneous administration of human IgG is an alternative to intravenous replacement therapy that is associated with more stable serum IgG levels and fewer systemic adverse events. Highly concentrated IgG solutions are most convenient to minimize infusion volume, but their preparation and stability presents substantial technical difficulties. We report on the stability and local tolerance of IgPro20, an l-proline-stabilized, 20% polyvalent human IgG developed for subcutaneous administration. Stability was tested according to ICH guidelines. Local tolerance and vasoactivity were examined in rabbit and rat models, respectively. The presence of l-proline in IgPro20 reduced viscosity and addition of Polysorbate 80 and inert gassing improved the appearance of the solution. After storage at 25 °C for 24 months, monomer + dimer content, aggregates, and fragments were within specification (≥ 90.0%, ≤ 4.0%, and ≤ 10.0%, respectively), and Fc function and antibody activities were maintained. In rats, intravenous injection of IgPro20 produced mild and transient hypotension comparable to that seen with intravenous IgG products. Local tolerance of IgPro20 in rabbits was comparable to that of a marketed subcutaneous IgG, Beriglobin P. Functionality and quality of IgPro20 are maintained during storage at 25 °C for at least 24 months. The product is well tolerated as assessed in animal models. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

Preliminary evaluation of several disinfection/sterilization techniques for use with microdialysis probes.

PubMed

Huff, Jacquelyn K; Bresnahan, James F; Davies, Malonne I

2003-06-06

This study evaluated the suitability of some disinfection and sterilization methods for use with microdialysis probes. Disinfection or sterilization should minimize the tissue inflammatory reaction and improve the long-term health of rats on study and ensure the quality of data obtained by microdialysis sampling. Furthermore, the treatment should not negatively impact probe integrity or sampling performance. The techniques chosen for evaluation included two disinfection methods (70% ethanol and a commercial contact lens solution) and two sterilization methods (hydrogen peroxide plasma, and e-beam radiation). Linear microdialysis probes treated by these processes were compared to untreated probes removed from the manufacturer's packaging as if sterile (the control group). The probes were aseptically implanted in the livers of rats and monitored for 72 hours. The parameters chosen to evaluate probe performance were relative sample mass recovery and the relative in vivo extraction efficiency of the probe for caffeine. Post mortem bacterial counts and histopathology examination of liver tissue were also conducted. The probes remained intact and functional for the entire study period. The methods tested did not acutely alter the probes although hydrogen peroxide plasma and contact lens solution groups showed reduced extraction efficiencies. Minimal tissue damage was observed surrounding the probes and acute inflammatory reaction was mild to moderate. Low numbers of bacterial colonies from the implantation sites indicates that the health of animals in this study was not impaired. This was also true for the control group (untreated probe).

Protective effects of ethyl pyruvate in cisplatin-induced nephrotoxicity

PubMed Central

Kelle, Ilker; Akkoc, Hasan; Tunik, Selcuk; Nergiz, Yusuf; Erdinc, Meral; Erdinc, Levent

2014-01-01

This study was performed to investigate the effect of ethyl pyruvate on changes in renal functions and oxidative stress related renal injury caused by cisplatin (cis-dichlorodiammine platinum-II; CDDP). Male Wistar albino rats were divided into four groups (n = 8): (1) control group (1 ml Ringer's lactate solution i.p.); (2) ethyl pyruvate (EP) group (50 mg/kg Ringer's EP solution (REPS) i.p.); (3) cisplatin group (a single dose of cisplatin (5 mg/kg, i.p.); and (4) cisplatin + EP group (a single dose of cisplatin (5 mg/kg, i.p.) + REPS 50 mg/kg/day, i.p.) for five days. At the sixth day, kidneys of rats were mounted to a Langendorff apparatus. Renal perfusion pressures were recorded. Blood samples were taken for serum urea, creatinine, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stres index (OSI) evaluations. Kidney tissues were obtained for malondialdehyde (MDA) analyses and histopathological examination. Perfusion pressures, serum urea, creatinine, TOS, OSI and tissue MDA levels were found significantly higher, whereas TAS was notably lower in cisplatin group. Histopathological examination showed apparent renal paranchymal injury in cisplatin group. In cisplatin + REPS group, perfusion pressures, serum urea, creatinine and tissue MDA levels were decreased. Moreover, EP co-administration provided less inflammatory cell infiltration, tubular dilatation, whereas TOS, TAS and OSI improved significantly versus cisplatin group. These findings show that EP has protective effects against cisplatin nephrotoxicity. PMID:26019553

Dipsogenic and feeding influences of intraventricularly infused anionic choline solutions.

PubMed

Mandal, M B; Badgaiyan, R D

1991-10-01

Chloride and bicarbonate solutions of choline were infused into the anteroventral part of the third ventricle of two different groups of rats through chronically implanted stainless steel cannulae. Dipsogenic and feeding responses elicited by these solutions were studied by observations taken at half hour intervals up to two h and then, after 24 h of infusions. Results were compared with the control response evoked by similar infusion of artificial cerebrospinal fluid (aCSF). Food and water intakes were recorded in different groups (n = 18 each) of rats. Dipsogenic response elicited by choline chloride solution in the observation taken 24 h after infusion, however, was higher only as compared to the control. Dipsogenic effect of bicarbonate solution was not significantly different from the control in the first two observations (30 and 60 min), but in the later observations (90, 120 min and 24 h), it was significantly higher. None of the choline solutions significantly alter feeding response within 2 h of infusions. However, in the observation taken 24 h after infusion, the response evoked by choline chloride was greater than that elicited by aCSF. The results support our earlier observation that chloride concentration of third ventricular CSF significantly influences water and food consumption. Intraventricularly administered choline also appears to have positive influence on these behaviors.

Oral bioavailability of ketoprofen in suspension and solution formulations in rats: the influence of poloxamer 188.

PubMed

Fischer, Sarah Maud; Parmentier, Johannes; Buckley, Stephen Timothy; Reimold, Isolde; Brandl, Martin; Fricker, Gert

2012-11-01

The aim of the current study was to investigate the effect of poloxamer 188 (P-188) on the bioavailability of the BCS class 2 drug ketoprofen in vivo. Aqueous suspension and solution formulations of ketoprofen with and without P-188 were orally administered to fasted male Wistar rats. The intrinsic dissolution rate and solubility of ketoprofen in simulated intestinal fluid, in both the presence and absence of P-188, was measured. The AUC and C(max) were found to be significantly enhanced when ketoprofen was administered as suspension and P-188 was present in the formulation (Susp P-188) as compared to the surfactant-free formulation (∼4-fold higher AUC, 7-fold higher C(max) ). While drug solubility appeared to be almost unaffected by P-188, a significantly faster dissolution was observed. In addition, the influence of P-188 on the drug absorption process was investigated by comparison of solution formulations with and without P-188. The in-vivo performance of these solutions, a pure buffer solution and a P-188-containing buffer solution showed no significant difference, suggesting that the increase in bioavailability for Susp P-188 was primarily a consequence of the dissolution rate-enhancing effect. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Pterostilbene improves glycaemic control in rats fed an obesogenic diet: Involvement of skeletal muscle and liver

USDA-ARS?s Scientific Manuscript database

This study aimed to determine whether pterostilbene improved glycaemic control in rats showing insulin resistance induced by an obesogenic diet. Rats were divided into 3 groups: control group and two groups treated with either 15 mg/kg/d (PT15) or 30 mg/kg/d of pterostilbene (PT30). HOMA-IR was decr...

Spermidine-Induced Improvement of Reconsolidation of Memory Involves Calcium-Dependent Protein Kinase in Rats

ERIC Educational Resources Information Center

Girardi, Bruna Amanda; Ribeiro, Daniela Aymone; Signor, Cristiane; Muller, Michele; Gais, Mayara Ana; Mello, Carlos Fernando; Rubin, Maribel Antonello

2016-01-01

In this study, we determined whether the calcium-dependent protein kinase (PKC) signaling pathway is involved in the improvement of fear memory reconsolidation induced by the intrahippocampal administration of spermidine in rats. Male Wistar rats were trained in a fear conditioning apparatus using a 0.4-mA footshock as an unconditioned stimulus.…

Nicotinamide improves sevoflurane-induced cognitive impairment through suppression of inflammation and anti-apoptosis in rat

PubMed Central

Wang, Ying; Zuo, Min

2015-01-01

Nicotinamide is amide form of vitamin B3, participate in oxidation-reduction reaction, and it plays an important role in the maintenance of normal life activities in cells; it has broad application prospects in the treatment of heart blood-vessel disease, respiratory disease, type 1 diabetes and inflammatory autoimmune diseases. Thus the present study aimed to identify whether the nicotinamide improves sevoflurane-induced cognitive impairment and its potential mechanisms in rat. Firstly, Male Sprague-Dawley rats were induced by 2.1% sevoflurane for 6 h. Protective function of nicotinamide on cognitive impairment was evaluated using Morris water maze test in the rats. Next, NF-κB and caspase-3 activities, and p53, Bax and Bcl-2 protein expression was executed using commercial kits and Western blot analysis, respectively. Preconditioning with nicotinamide could improve cognitive impairment in the rats. Administrate of nicotinamide suppressed the activation of NF-κB and caspase-3, reduced the protein expression of Bax, and promoted Bcl-2 protein expression in rats. The present results suggested nicotinamide improves sevoflurane-induced cognitive impairment and has an anti-inflammatory and anti-apoptotic effect against sevoflrane-induced damages. PMID:26884920

The effects of a time-based intervention on experienced middle-aged rats

PubMed Central

Peterson, Jennifer R.; Kirkpatrick, Kimberly

2016-01-01

Impulsive behavior is a common symptom in Attention Deficit Hyperactivity Disorder, schizophrenia, drug abuse, smoking, obesity and compulsive gambling. Stable levels of impulsive choice have been found in humans and rats and a recent study reported significant test-retest reliability of impulsive choice behavior after 1 and 5 months in rats. Time-based behavioral interventions have been successful in decreasing impulsive choices. These interventions led to improvements in the ability to time and respond more appropriately to adventitious choices. The current study examined the use of a time-based intervention in experienced, middle-aged rats. This intervention utilized a variable interval schedule previously found to be successful in improving timing and decreasing impulsive choice. This study found that the intervention led to a decrease in impulsive choices and there was a significant correlation between the improvement in self-control and post-intervention temporal precision in middle-aged rats. Although there were no overall group difference in bisection performance, individual differences were observed, suggesting an improvement in timing. This is an important contribution to the field because previous studies have utilized only young rats and because previous research indicates a decrease in general timing abilities with age. PMID:27826006

Anti-diabetic effects of pumpkin and its components, trigonelline and nicotinic acid, on Goto-Kakizaki rats.

PubMed

Yoshinari, Orie; Sato, Hideyo; Igarashi, Kiharu

2009-05-01

The effects of a pumpkin paste concentrate and its components on oral glucose tolerance and serum lipid levels were determined in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. In the oral glucose tolerance test, the pumpkin paste concentrate-fed group maintained a lower glucose level than the control group between 15 and 60 min. The compounds considered to be effective in improving glucose tolerance and contained in the methanol extract of the pumpkin in relatively abundant amounts were isolated and identified as trigonelline (TRG) and nicotinic acid (NA).Feeding a diet containing TRG and NA respectively improved and tended to improve glucose tolerance. The insulin level increased after 15 min in the TRG-fed GK rats and then gradually decreased over the next 120 min. In contrast, a gradual increase was seen in the insulin level over 120 min in the control GK rats not fed with TRG, suggesting that TRG could improve the insulin resistance. The serum and liver triglyceride (TG) levels in the TRG- and NA-fed GK rats were lower than those in the control GK rats. Lower activity of liver fatty acid synthase (FAS), and higher activity of liver carnitine palmitoyl transferase (CPT) and glucokinase (GLK) in the TRG- and NA-fed GK rats than in the control GK rats were observed. This suggests that the regulation of these enzyme activities by TRG and NA was closely related to the suppression of both TG accumulation and the progression of diabetes.

Enabling technologies for millimeter-wave radio-over-fiber systems in next generation heterogeneous mobile access networks

NASA Astrophysics Data System (ADS)

Zhang, Junwen; Yu, Jianjun; Wang, Jing; Xu, Mu; Cheng, Lin; Lu, Feng; Shen, Shuyi; Yan, Yan; Cho, Hyunwoo; Guidotti, Daniel; Chang, Gee-kung

2017-01-01

Fifth-generation (5G) wireless access network promises to support higher access data rate with more than 1,000 times capacity with respect to current long-term evolution (LTE) systems. New radio-access-technologies (RATs) based on higher carrier frequencies to millimeter-wave (MMW) radio-over-fiber, and carrier-aggregation (CA) using multi-band resources are intensively studied to support the high data rate access and effectively use of frequency resources in heterogeneous mobile network (Het-Net). In this paper, we investigate several enabling technologies for MMW RoF systems in 5G Het-Net. Efficient mobile fronthaul (MFH) solutions for 5G centralized radio access network (C-RAN) and beyond are proposed, analyzed and experimentally demonstrated based on the analog scheme. Digital predistortion based on memory polynomial for analog MFH linearization are presented with improved EVM performances and receiver sensitivity. We also propose and experimentally demonstrate a novel inter-/intra- RAT CA scheme for 5G Het- Net. The real-time standard 4G-LTE signal is carrier-aggregated with three broadband 60GHz MMW signals based on proposed optical-domain band-mapping method. RATs based on new waveforms have also been studied here to achieve higher spectral-efficiency (SE) in asynchronous environments. Full-duplex asynchronous quasi-gapless carrier aggregation scheme for MMW ROF inter-/intra-RAT based on the FBMC is also presented with 4G-LTE signals. Compared with OFDM-based signals with large guard-bands, FBMC achieves higher spectral-efficiency with better EVM performance at less received power and smaller guard-bands.

The role of resistance and aerobic exercise training on insulin sensitivity measures in STZ-induced Type 1 diabetic rodents.

PubMed

Hall, Katharine E; McDonald, Matthew W; Grisé, Kenneth N; Campos, Oscar A; Noble, Earl G; Melling, C W James

2013-10-01

Individuals with Type 1 Diabetes Mellitus (T1DM) can develop insulin resistance. Regular exercise may improve insulin resistance partially through increased expression of skeletal muscle GLUT4 content. To examine if different exercise training modalities can alter glucose tolerance through changes in skeletal muscle GLUT4 content in T1DM rats. Fifty rats were divided into 5 groups; control, diabetic control, diabetic resistance exercised, and diabetic high and low intensity treadmill exercised. Diabetes was induced using multiple low dose Streptozotocin (20 mg/kg/day) injections and blood glucose concentrations were maintained moderately hyperglycemic through subcutaneous insulin pellets. Resistance trained rats climbed a ladder with incremental loads, while treadmill trained rats ran on a treadmill at 27 or 15 m/min, respectively, all for 6 weeks. At weeks 3 and 6, area under the curve measurements following an intravenous glucose tolerance test (AUC-IVGTT) in all diabetic groups were higher than control rats (p<0.05). At 6 weeks, all exercise groups had significantly lower AUC-IVGTT values than diabetic control animals (p<0.05). Treadmill trained rats had the lowest insulin dose requirement of the T1DM rats and the greatest reduction in insulin dosage was evident in high intensity treadmill exercise. Concomitant with improvements in glucose handling improvements, tissue-specific elevations in GLUT4 content were demonstrated in both red and white portions of vastus lateralis and gastrocnemius muscles, suggesting that glucose handling capacity was altered in the skeletal muscle of exercised T1DM rats. These results suggest that, while all exercise modalities can improve glucose tolerance, each mode leads to differential improvements in insulin requirements and protein content alterations. Copyright © 2013 Elsevier Inc. All rights reserved.

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

PubMed Central

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.

2016-01-01

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

Effect of royal jelly on experimental colitis induced by acetic acid and alteration of mast cell distribution in the colon of rats

PubMed Central

Karaca, T.; Bayiroglu, F.; Yoruk, M.; Kaya, M.S.; Uslu, S.; Comba, B.; Mis, L.

2010-01-01

This study investigated the effects of royal jelly (RJ) on acetic acid-induced colitis in rats. Twenty adult female Wistar albino rats were divided into four treatment groups of 5 animals each, including a control group (Group I); Group II was treated orally with RJ (150 mg kg−1 body weight); Group III had acetic acid-induced colitis; and Group IV had acetic acid-induced colitis treated orally with RJ (150 mg kg−1 body weight) for 4 weeks. Colitis was induced by intracolonic instillation of 4% acetic acid; the control group received physiological saline (10 mL kg−1). Colon samples were obtained under deep anaesthesia from animals in all groups. Tissues were fixed in 10% formalin neutral buffer solution for 24 h and embedded in paraffin. Six-micrometre-thick sections were stained with Mallory’s triple stain and toluidine blue in 1% aqueous solution at pH 1.0 for 5 min (for Mast Cells). RJ was shown to protect the colonic mucosa against the injurious effect of acetic acid. Colitis (colonic damage) was confirmed histomorphometrically as significant increases in the number of mast cells (MC) and colonic erosions in rats with acetic acid-induced colitis. The RJ treatment significantly decreased the number of MC and reduced the area of colonic erosion in the colon of RJ-treated rats compared with rats with untreated colitis. The results suggest that oral treatment with RJ could be used to treat colitis. PMID:21263740

Dietary protein affects urea transport across rat urothelia.

PubMed

Spector, David A; Deng, Jie; Stewart, Kerry J

2012-10-01

Recent evidence suggests that regulated solute transport occurs across mammalian lower urinary tract epithelia (urothelia). To study the effects of dietary protein on net urothelial transport of urea, creatinine, and water, we used an in vivo rat bladder model designed to mimic physiological conditions. We placed groups of rats on 3-wk diets differing only by protein content (40, 18, 6, and 2%) and instilled 0.3 ml of collected urine in the isolated bladder of anesthetized rats. After 1 h dwell, retrieved urine volumes were unchanged, but mean urea nitrogen (UN) and creatinine concentrations fell 17 and 4%, respectively, indicating transurothelial urea and creatinine reabsorption. The fall in UN (but not creatinine) concentration was greatest in high protein (40%) rats, 584 mg/dl, and progressively less in rats receiving lower protein content: 18% diet, 224 mg/dl; 6% diet, 135 mg/dl; and 2% diet, 87 mg/dl. The quantity of urea reabsorbed was directly related to a urine factor, likely the concentration of urea in the instilled urine. In contrast, the percentage of instilled urea reabsorbed was greater in the two dietary groups receiving the lowest protein (26 and 23%) than in those receiving higher protein (11 and 9%), suggesting the possibility that a bladder/urothelial factor, also affected by dietary protein, may have altered bladder permeability. These findings demonstrate significant regulated urea transport across the urothelium, resulting in alteration of urine excreted by the kidneys, and add to the growing evidence that the lower urinary tract may play an unappreciated role in mammalian solute homeostasis.

Fructose 1-6 bisphosphate versus University of Wisconsin solution for rat liver preservation: does FBP prevent early mitochondrial injury?

PubMed

de Fraga, R S; Heinen, P E T; Kruel, C R P; Molin, S D; Mota, S M; Cerski, C T S; Gasperin, G; Souto, A A; de Oliveira, J R; Alvares-da-Silva, M R

2011-06-01

Fructose 1,6-biphosphate (FBP) has been shown to exert therapeutic effects in models of ischemia-reperfusion in organs other than the liver. This study compared FBP and University of Wisconsin (UW) solution during cold storage and reperfusion, among mitochondria of adult male Wistar rat livers. Adult male Wistar rats were assigned to two groups according to the preservation solution used; UW or FBP Aspartate transaminase (AST), alanine transferase (ALT); and lactic dehydrogenase (LDH) were measured in samples of the storage solution obtained at 2, 4 and 6 hours of preservation. After 6 hours of cold storage, we reperfused the liver, taking blood samples to measure AST, ALT, LDH, and throbarbituric acid reactive substances (TBARS). Hepatic fragments were processed for histologic analysis; for determinations of TBARS, catalase, and nitric oxide as well as for mitochondrial evaluation by infrared spectroscopy. During cold preservation, levels of AST and LDH in the storage solution were lower among the FBP group, but after reperfusion, serum levels of AST, ALT, and LDH were higher in this group, as was catalase activity. TBARS and nitric oxide were comparable between the groups. In the UW group there was a higher amide I/amide II ratio than in the FBP group, suggesting an abnormal protein structure of the mitochondrial membrane. No signs of preservation injury were observed in any liver biopsy, but sinusoidal congestion was present in livers preserved with FBP. FBP showed a protective effect for preservation during cold storage seeming to protect the mitochondrial membrane although it did not prevent reperfusion injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Self-micelle formation and the incorporation of lipid in the formulation affect the intestinal absorption of Panax notoginseng.

PubMed

Xiong, Jing; Guo, Jianxin; Huang, Luosheng; Meng, Boyu; Ping, Qineng

2008-08-06

The purpose of this research is to evaluate the effect of self-micelle formation and incorporation of lipid in the formulation on absorption of ginsenosides Rg1 and Rb1 from intestinal tract in rats. Ginsenosides Rg1 and Rb1 were extracted from Panax notoginseng saponins (PNS). The critical micellar concentration (CMC) of PNS in deionzied water was determined to be 0.339 mg/ml. At normal physiological ionic strengths, PNS was salted out from the solution above the CMC. The particle size of the micelle grows as PNS concentration increases. By in situ injection to a closed loop of the rat jejunum, AUC0-6h obtained after administration of low concentration solution (12 mg/ml) was 3.61 times for ginsenoside Rg1 and 3.84-folds for ginsenoside Rb1 compared with high concentration solution (120 mg/ml). The release rate of ginsenosides in aqueous medium was too slow to complete in 24h, especially for Rb1. The data suggested that the self-micelle formation tendency in ginsenosides might prevent them from permeation or absorption through the cell membrane of gastrointestinal (GI) tract. To inhibit the formation of micelles, lipid was incorporated in the PNS formulation. The intraduodenal bioavailability in rats showed that the bioavailability was enhanced remarkably relative to the aqueous solution. AUC 0-infinity of ginsenoside Rg1 and Rb1 in the lipid-based formulation were 207.52+/-53.95 and 1961.72+/-686.60 microg ml(-1) h, compared with 7.87+/-2.85 and 148.58+/-36.73 microg ml(-1) h, respectively from its aqueous solution. These findings suggested a new strategy to increase the absorption of amphiphilic saponins.

Characterization of injury in isolated rat proximal tubules during cold incubation and rewarming.

PubMed

Bienholz, Anja; Walter, Björn; Pless-Petig, Gesine; Guberina, Hana; Kribben, Andreas; Witzke, Oliver; Rauen, Ursula

2017-01-01

Organ shortage leads to an increased utilization of marginal organs which are particularly sensitive to storage-associated damage. Cold incubation and rewarming-induced injury is iron-dependent in many cell types. In addition, a chloride-dependent component of injury has been described. This work examines the injury induced by cold incubation and rewarming in isolated rat renal proximal tubules. The tissue storage solution TiProtec® and a chloride-poor modification, each with and without iron chelators, were used for cold incubation. Incubation was performed 4°C for up to 168 h, followed by rewarming in an extracellular buffer (3 h at 37°C). After 48, 120 and 168 h of cold incubation LDH release was lower in solutions containing iron chelators. After rewarming, injury increased especially after cold incubation in chelator-free solutions. Without addition of iron chelators LDH release showed a tendency to be higher in chloride-poor solutions. Following rewarming after 48 h of cold incubation lipid peroxidation was significantly decreased and metabolic activity was tendentially better in tubules incubated with iron chelators. Morphological alterations included mitochondrial swelling and fragmentation being partially reversible during rewarming. ATP content was better preserved in chloride-rich solutions. During rewarming, there was a further decline of ATP content in the so far best conditions and minor alterations under the other conditions, while oxygen consumption was not significantly different compared to non-stored control tubules. Results show an iron-dependent component of preservation injury during cold incubation and rewarming in rat proximal renal tubules and reveal a benefit of chloride for the maintenance of tubular energy state during cold incubation.

Characterization of injury in isolated rat proximal tubules during cold incubation and rewarming

PubMed Central

Bienholz, Anja; Walter, Björn; Pless-Petig, Gesine; Guberina, Hana; Kribben, Andreas; Witzke, Oliver; Rauen, Ursula

2017-01-01

Organ shortage leads to an increased utilization of marginal organs which are particularly sensitive to storage-associated damage. Cold incubation and rewarming-induced injury is iron-dependent in many cell types. In addition, a chloride-dependent component of injury has been described. This work examines the injury induced by cold incubation and rewarming in isolated rat renal proximal tubules. The tissue storage solution TiProtec® and a chloride-poor modification, each with and without iron chelators, were used for cold incubation. Incubation was performed 4°C for up to 168 h, followed by rewarming in an extracellular buffer (3 h at 37°C). After 48, 120 and 168 h of cold incubation LDH release was lower in solutions containing iron chelators. After rewarming, injury increased especially after cold incubation in chelator-free solutions. Without addition of iron chelators LDH release showed a tendency to be higher in chloride-poor solutions. Following rewarming after 48 h of cold incubation lipid peroxidation was significantly decreased and metabolic activity was tendentially better in tubules incubated with iron chelators. Morphological alterations included mitochondrial swelling and fragmentation being partially reversible during rewarming. ATP content was better preserved in chloride-rich solutions. During rewarming, there was a further decline of ATP content in the so far best conditions and minor alterations under the other conditions, while oxygen consumption was not significantly different compared to non-stored control tubules. Results show an iron-dependent component of preservation injury during cold incubation and rewarming in rat proximal renal tubules and reveal a benefit of chloride for the maintenance of tubular energy state during cold incubation. PMID:28672023

The Fine Temporal Structure of the Rat Licking Pattern: What Causes the Variabiliy in the Interlick Intervals and How is it Affected by the Drinking Solution?

PubMed Central

2013-01-01

Licking is a repetitive behavior controlled by a central pattern generator. Even though interlick intervals (ILIs) within bursts of licks are considered fairly regular, the conditions that affect their variability are unknown. We analyzed the licking pattern in rats that licked water, 10% sucrose solution, or 10% ethanol solution, in 90-min recording sessions after 4h of water deprivation. The histograms of ILIs indicate that licking typically occurred at a preferred ILI of about 130−140ms with evidence of bimodal or multimodal distributions due to occasional licking failures. We found that the longer the pause between bursts of licks, the shorter was the first ILI of the burst. When bursts of licks were preceded by a pause >4 s, the ILI was the shortest (~110ms) at the beginning of the burst, and then it increased rapidly in the first few licks and slowly in subsequent licks. Interestingly, the first ILI of a burst of licks was not significantly different when licking any of the 3 solutions, but subsequent licks exhibited a temporal pattern characteristic of each solution. The rapid deceleration in intraburst licking rate was due to an increase from ~27ms to ~56ms in the tongue-spout contact duration while the intercontact interval was only slightly changed (80−90ms). Therefore, the contact duration seems to be the major factor that increases the variability in the ILIs and could be another means for the rat to adjust the amount of fluid ingested in each individual lick. PMID:23902635

Can Urtica dioica supplementation attenuate mercury intoxication in Wistar rats?

PubMed

Siouda, Wafa; Abdennour, Cherif

2015-12-01

The objective of this study was to investigate the possible protective role of nettle Urtica dioica (UD) against Hg-induced toxicity. A total of 28 rats were equally divided into four groups: the control, the Hg (0.8 g HgCl2/kg in the diet), the UD (1.5 ml UD/rat by gavage), and the Hg+UD group. HgCl2 was daily dissolved in distilled water and immediately mixed with the standard diet. A solution of daily infused fresh nettle leaves in boiling water (16 g in 25 ml) was obtained and then it was administrated by gavage. Biochemical and reproductive markers, in addition to glutathione (GSH) level (liver, kidney and testis) and the histological profiles (testis and epididymis) were evaluated after 1 month exposure. Compared to the control, the levels of glucose, triglycerides, urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were significantly raised in the Hg group. In the latter group, the concentrations of Mg, Fe, and Ca were significantly decreased. Besides, Hg+UD group has only showed raised AST activity and reduced Mg level. Concerning the fertility markers, Hg has provoked a significant decrease in the spermatozoa's concentration and motility and in plasma testosterone level as well. Furthermore, hepatic, renal and testicular GSH concentrations have declined significantly in the Hg treated rat compared to the control. A remarkable enhancement of the GSH level was observed in all organs of the UD group. The histological examinations of the Hg group have revealed marked testicular degeneration of the most seminiferous tubules, and showed few sperms in the lumen of epididymis ducts. However, the Hg+UD rats have demonstrated an improved histological structure with the presence of important numbers of sperms in the lumen. In addition, a clear stabilization of organized seminiferous tubules and an increased sperms' numbers were noted in the UD supplemented rats. Nettle leaves have not only played a clear protective role during Hg intoxication, but it also enhanced hepatic, renal and testicular GSH level of Wistar rats.

Can Urtica dioica supplementation attenuate mercury intoxication in Wistar rats?

PubMed Central

Siouda, Wafa; Abdennour, Cherif

2015-01-01

Aim: The objective of this study was to investigate the possible protective role of nettle Urtica dioica (UD) against Hg-induced toxicity. Materials and Methods: A total of 28 rats were equally divided into four groups: the control, the Hg (0.8 g HgCl2/kg in the diet), the UD (1.5 ml UD/rat by gavage), and the Hg+UD group. HgCl2 was daily dissolved in distilled water and immediately mixed with the standard diet. A solution of daily infused fresh nettle leaves in boiling water (16 g in 25 ml) was obtained and then it was administrated by gavage. Biochemical and reproductive markers, in addition to glutathione (GSH) level (liver, kidney and testis) and the histological profiles (testis and epididymis) were evaluated after 1 month exposure. Results: Compared to the control, the levels of glucose, triglycerides, urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were significantly raised in the Hg group. In the latter group, the concentrations of Mg, Fe, and Ca were significantly decreased. Besides, Hg+UD group has only showed raised AST activity and reduced Mg level. Concerning the fertility markers, Hg has provoked a significant decrease in the spermatozoa’s concentration and motility and in plasma testosterone level as well. Furthermore, hepatic, renal and testicular GSH concentrations have declined significantly in the Hg treated rat compared to the control. A remarkable enhancement of the GSH level was observed in all organs of the UD group. The histological examinations of the Hg group have revealed marked testicular degeneration of the most seminiferous tubules, and showed few sperms in the lumen of epididymis ducts. However, the Hg+UD rats have demonstrated an improved histological structure with the presence of important numbers of sperms in the lumen. In addition, a clear stabilization of organized seminiferous tubules and an increased sperms’ numbers were noted in the UD supplemented rats. Conclusion: Nettle leaves have not only played a clear protective role during Hg intoxication, but it also enhanced hepatic, renal and testicular GSH level of Wistar rats. PMID:27047060

Evidence for CGRP re-uptake in rat dura mater encephali

PubMed Central

Gupta, Saurabh; Amrutkar, Dipak Vasantrao; Mataji, Aydin; Salmasi, Hassan; Hay-Schmidt, Anders; Sheykhzade, Majid; Messlinger, Karl; Olesen, Jes; Jansen-Olesen, Inger

2010-01-01

BACKGROUND AND PURPOSE Calcitonin gene-related peptide (CGRP) is widely distributed in the trigeminovascular system and released from sensory fibres of the cranial dura mater upon noxious stimulation. Such release may be a mechanism underlying migraine headache. Based on data from guinea pig basilar artery preparations, we have here studied CGRP release and uptake in an organ preparation of the hemisected rat skull. EXPERIMENTAL APPROACH CGRP release from the cranial dura was quantified by a commercial enzyme-linked immunoassay. CGRP was depleted using repetitive challenges of capsaicin. After incubating the tissue with CGRP for 20 min and extensive washing, another capsaicin challenge was performed. Immunohistochemistry was used to visualize CGRP immunofluorescence in dural nerve fibres. KEY RESULTS Capsaicin-induced CGRP release was attenuated by the transient receptor potential vanilloid receptor type I antagonist capsazepine or by Ca2+-free solutions. After the CGRP-depleted preparation had been exposed to exogenous CGRP, capsaicin-induced CGRP release was increased compared to the challenge just prior to incubation. CGRP uptake was not influenced by Ca2+-free solutions. Olcegepant and CGRP8–37 (CGRP receptor antagonists) did not affect uptake of CGRP. However, a monoclonal CGRP-binding antibody decreased CGRP uptake significantly. Release of CGRP after incubation was attenuated by Ca2+-free solutions and by capsazepine. Immunohistochemical assays indicated a weak trend towards CGRP uptake in rat dura mater. CONCLUSION AND IMPLICATIONS We have presented evidence for CGRP uptake in nerves and its re-release in rat dura mater. This may have implications for the pathophysiology and treatment of migraine. PMID:20804493

Machine perfusion preservation of the non-heart-beating donor rat livers using polysol, a new preservation solution.

PubMed

Bessems, M; Doorschodt, B M; van Vliet, A K; van Gulik, T M

2005-01-01

The increasing shortage of donor organs has led to a focus on extended criteria donors, including the non-heart-beating donor (NHBD). An optimal preservation method is required to facilitate successful transplantation of these ischemically damaged organs. The recent literature has shown clear advantages of hypothermic machine perfusion (MP) over cold storage (CS). For MP, modified University of Wisconsin perfusion solution (UW-G) is often used, which, however, is known to cause microcirculatory obstruction, is difficult to obtain, and is expensive. Therefore, Polysol was developed as a MP preservation solution that contains specific nutrients for the liver, such as amino acids, energy substrates, and vitamins. The aim of this study was to compare Polysol with UW-G in a NHBD rat liver model. After 24 hours hypothermic MP of NHBD rat livers using UW-G or Polysol, liver damage and function parameters were assessed during 60 minutes of reperfusion with Krebs-Henseleit buffer. Control livers were reperfused after 24 hours CS in UW. Liver enzyme release was significantly higher among the CS-UW group compared to MP using UW-G or Polysol. Flow during reperfusion was significantly higher when using Polysol compared to UW-G. Bile production and ammonia clearance were highest when using Polysol compared to UW-G. There was less cellular edema after preservation with Polysol compared to UW-G. MP of NHBD rat livers for 24 hours using UW-G or Polysol resulted in less hepatocellular damage than CS in UW. MP of NHBD livers for 24 hours using Polysol is superior to MP using UW-G.

Neural Basis of Ventromedial Hypothalamic Oxytocin-Driven Decrease in Appetite.

PubMed

Klockars, Oscar A; Waas, Joseph R; Klockars, Anica; Levine, Allen S; Olszewski, Pawel K

2017-12-16

Oxytocin (OT) administration in the ventromedial hypothalamic nucleus (VMH) reduces chow intake. The nature of VMH OT's anorexigenic action remains unclear. Here we provide insight into neural mechanisms underlying VMH OT-driven anorexia by (a) identifying feeding-related brain sites activated by VMH OT injection; (b) measuring VMH OT receptor (OTr) mRNA changes in response to hunger and palatability; and (c) examining how VMH OT affects episodic sweet solution intake in sated and hungry rats. We established effective doses of VMH OT in deprivation-induced and scheduled feeding and determined whether an OT antagonist blocks the effect. Then, OT (or antagonist) was injected in the VMH of sated rats given episodically sucrose and saccharin solutions. OT was also injected in hungry animals offered simultaneously chow and sugar water. Brain activation after VMH OT was determined by Fos immunoreactivity (IR). OTr expression was established with rtPCR after chow deprivation or saccharin exposure. VMH OT decreased intake of chow and the effect was reversed by the antagonist, though the antagonist alone was not orexigenic. OT did not affect intakes of energy-dilute saccharin and sucrose solutions in sated or hungry rats. Fos IR was elevated in the VMH and energy balance-related paraventricular and arcuate nuclei, but not reward areas. VMH OTr expression was higher in hungry rats than in sated controls; saccharin intake had no effect. OT acting in the VMH decreases intake driven by energy not by palatability, and it stimulates activity of hypothalamic sites controlling energy balance. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Magnetic resonance imaging of rodent spinal cord with an improved performance coil at 7 Tesla

NASA Astrophysics Data System (ADS)

Solis-Najera, S. E.; Rodriguez, A. O.

2014-11-01

Magnetic Resonance Imaging of animal models provide reliable means to study human diseases. The image acquisition particularly determined by the radio frequency coil to detect the signal emanated from a particular region of interest. A scaled-down version of the slotted surface coil was built based on the previous results of a magnetron-type surface coil for human applications. Our coil prototype had a 2 cm total diameter and six circular slots and was developed for murine spinal cord at 7 T. Electromagnetic simulations of the slotted and circular coils were also performed to compute the spatially dependent magnetic and electric fields using a simulated saline-solution sphere. The quality factor of both coils was experimentally measured giving a lower noise figure and a higher quality factor for the slotted coil outperforming the circular coil. Images of the spinal cord of a rat were acquired using standard pulse sequences. The slotted surface coil can be a good tool for spinal cord rat imaging using conventional pulse sequences at 7 T.

Iron chelated cyclic peptide, ferrichrysin, for oral treatment of iron deficiency: solution properties and efficacy in anemic rats.

PubMed

Suzuki, Sachiko; Fukuda, Katsuharu; Irie, Motoko; Hata, Yoji

2007-01-01

Ferrichrysin (Fcy), which is produced by Aspergillus oryzae and is present in foods used for human consumption, belongs to a group of hydroxamate siderophore ferric iron chelators. Fcy (100 mg/mL) dissolves completely at both pH 2.0 and 7.0, being very stable at a wide range of pH, high temperatures and pressures, with little reactivity to dietary iron absorption inhibitors, phytic acid, tannic acid, and catechin. We studied the effect of Fcy in male Sprague-Dawley rats with iron-deficiency anemia, which were separated into three different dietary groups (n=5) and supplementing diets as follows: (i) ferric citrate, (ii) heme iron concentrate, and (iii) Fcy (35 mg Fe/kg diet) for three weeks. Fcy exhibited the same beneficial effect in improving iron deficiency anemia as ferric citrate, being significantly greater than the effect of heme iron. The iron concentration of liver in the Fcy group was 35% greater than that in the ferric citrate group. These findings indicate that Fcy could be an efficient oral iron supplement to prevent or treat iron deficiency.

Impairment of α(2)-macroglobulin synthesis in experimental hepatopathic rats treated with turpentine oil.

PubMed

Kuribayashi, Takashi; Seita, Testuro; Honjo, Toshio; Yamazaki, Shunsuke; Momotani, Eiichi; Yamamoto, Shizuo

2012-01-01

The aim of this study was to investigate the synthesis of α(2)-macroglobulin (α2M) in hepatopathic rats injected with turpentine oil to induce acute inflammation. Hepatopathy was induced by oral administration of acetaminophen at a dose of 1 g/kg daily for 2 weeks or a 25% solution of carbon tetrachloride (CCl(4)) at 2 ml/kg body weight three times per week for 7 weeks. Acute inflammation was induced by intramuscular injection of turpentine oil at a dose of 1.0 ml/kg body weight. Serum concentrations of α2M were measured by enzyme-linked immunosorbent assay. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total protein differed significantly between acetaminophen or CCl(4)-induced hepatopathic rats and acetaminophen control (AA-control) or CCl(4) control (CC-control) rats. Furthermore, pathological examination confirmed hepatopathy in rat livers. Peak serum concentrations and area under the time-concentration curve for α2M showed significant differences between hepatopathic rats and AA-control or CC-control rats. Thus, serum concentrations of α2M did not increase when compared with nontreated rats.

Comparison of microdialysis sampling perfusion fluid components on the foreign body reaction in rat subcutaneous tissue.

PubMed

Keeler, Geoffrey D; Durdik, Jeannine M; Stenken, Julie A

2014-06-16

Microdialysis sampling is a commonly used technique for collecting solutes from the extracellular space of tissues in laboratory animals and humans. Large molecular weight solutes can be collected using high molecular weight cutoff (MWCO) membranes (100kDa or greater). High MWCO membranes require addition of high molecular weight dextrans or albumin to the perfusion fluid to prevent fluid loss via ultrafiltration. While these perfusion fluid additives are commonly used during microdialysis sampling, the tissue response to the loss of these compounds across the membrane is poorly understood. Tissue reactions to implanted microdialysis sampling probes containing different microdialysis perfusion fluids were compared over a 7-day time period in rats. The base perfusion fluid was Ringer's solution supplemented with either bovine serum albumin (BSA), rat serum albumin (RSA), Dextran-70, or Dextran-500. A significant inflammatory response to Dextran-70 was observed. No differences in the tissue response between BSA and RSA were observed. Among these agents, the BSA, RSA, and Dextran-500 produced a significantly reduced inflammatory response compared to the Dextran-70. This work demonstrates that use of Dextran-70 in microdialysis sampling perfusion fluids should be eliminated and replaced with Dextran-500 or other alternatives. Copyright © 2013 Elsevier B.V. All rights reserved.

Dissolved molecular hydrogen (H2) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity.

PubMed

Nakayama, Masaaki; Zhu, Wan-Jun; Watanabe, Kimio; Gibo, Ayano; Sherif, Ali M; Kabayama, Shigeru; Ito, Sadayoshi

2017-10-31

Peritoneal dialysis (PD) is used as renal replacement therapy in patients with end-stage kidney disease. However, peritoneal membrane failure remains problematic and constitutes a critical cause of PD discontinuation. Recent studies have revealed the unique biological action of molecular hydrogen (H 2 ) as an anti-oxidant, which ameliorates tissue injury. In the present study, we aimed to examine the effects of H 2 on the peritoneal membrane of experimental PD rats. Eight-week-old male Sprague-Dawley rats were divided into the following groups (n = 8-11 each) receiving different test solutions: control group (no treatment), PD group (commercially available lactate-based neutral 2.5% glucose PD solution), and H 2 PD group (PD solution with dissolved H 2 at 400 ppb). Furthermore, the influence of iron (FeCl 3 : 5 μM: inducer of oxidative cellular injury) in the respective PD solutions was also examined (Fe-PD and Fe-H 2 PD groups). The H 2 PD solution was manufactured by bathing a PD bag in H 2 -oversaturated water created by electrolysis of the water. Twenty mL of the test solutions were intraperitoneally injected once a day for 10 days. Parietal peritoneum samples and cells collected from the peritoneal surface following treatment with trypsin were subjected to analysis. In the PD group as compared to controls, a mild but significant sub-mesothelial thickening was observed, with increase in the number of cells in the peritoneal surface tissue that were positive for apoptosis, proliferation and vimentin, as seen by immunostaining. There were significantly fewer of such changes in the H 2 PD group, in which there was a dominant presence of M2 (CD163+) macrophages in the peritoneum. The Fe-PD group showed a significant loss of mesothelial cells with sub-mesothelial thickening, these changes being ameliorated in the Fe-H 2 PD group. H 2 -dissolved PD solutions could preserve mesothelial cells and peritoneal membrane integrity in PD rats. Clinical application of H 2 in PD could be a novel strategy for protection of peritoneal tissue during PD treatment.

Long-term myocardial preservation: beneficial and additive effects of polarized arrest (Na+-channel blockade), Na+/H+-exchange inhibition, and Na+/K+/2Cl- -cotransport inhibition combined with calcium desensitization.

PubMed

Snabaitis, A K; Chambers, D

1999-11-27

Polarized arrest, induced by tetrodotoxin (TTX) at an optimal concentration of 22 micromol/L, has been shown to reduce ionic imbalance and improve myocardial preservation compared with hyperkalemic (depolarized) arrest. Additional pharmacologic manipulation of ionic changes (involving inhibition of Na+ influx by the Na+/H+ exchanger [HOE694] and Na+/K+/2Cl- cotransporter [furosemide], and calcium desensitization [BDM]) may further improve long-term preservation. In this study, we (i) established optimal concentrations of each drug, (ii) determined additive effects of optimal concentrations of each drug and (iii) compared our optimal preservation solution to an established depolarizing cardioplegia (St Thomas' Hospital solution No 2: STH2) used during long-term hypothermic storage for clinical transplantation. The isolated working rat heart, perfused with Krebs Henseleit (KH) buffer was used; cardiac function was measured after 20 min aerobic working mode perfusion. The hearts (n=6/group) were arrested with a 2 ml infusion (for 30 sec) of the polarizing (control) solution (22 micromol/L TTX in KH) or control+drug and subjected to 5 hr or 8 hr of storage at 7.5 degrees C in the arresting solution. Postischemic function during reperfusion was measured (expressed as percentage of preischemic function). Dose-response studies established optimal concentrations of HOE694 (10 micromol/L), furosemide (1.0 micromol/L) and BDM (30 mmol/L) in the polarizing (control) solution. Sequential addition to the control solution (Group I) of optimal concentrations of HOE694 (Group II), furosemide (Group III), and BDM (Group IV) were compared with STH2 (Group V); postischemic recovery of aortic flow was 29+/-7%, 49+/-6%*, 56+/-2%*, 76+/-3%*, and 25+/-6%, respectively (*P<0.05 vs. I and V). Creatine kinase leakage was lowest, and myocardial ATP content was highest in Group IV. A polarizing preservation solution (KH+TTX) containing HOE694, furosemide, and BDM significantly enhanced long-term preservation compared with an optimized depolarizing solution (STH2) used clinically for long-term donor heart preservation.

A combined solenoid-surface RF coil for high-resolution whole-brain rat imaging on a 3.0 Tesla clinical MR scanner.

PubMed

Underhill, Hunter R; Yuan, Chun; Hayes, Cecil E

2010-09-01

Rat brain models effectively simulate a multitude of human neurological disorders. Improvements in coil design have facilitated the wider utilization of rat brain models by enabling the utilization of clinical MR scanners for image acquisition. In this study, a novel coil design, subsequently referred to as the rat brain coil, is described that exploits and combines the strengths of both solenoids and surface coils into a simple, multichannel, receive-only coil dedicated to whole-brain rat imaging on a 3.0 T clinical MR scanner. Compared with a multiturn solenoid mouse body coil, a 3-cm surface coil, a modified Helmholtz coil, and a phased-array surface coil, the rat brain coil improved signal-to-noise ratio by approximately 72, 61, 78, and 242%, respectively. Effects of the rat brain coil on amplitudes of static field and radiofrequency field uniformity were similar to each of the other coils. In vivo, whole-brain images of an adult male rat were acquired with a T(2)-weighted spin-echo sequence using an isotropic acquisition resolution of 0.25 x 0.25 x 0.25 mm(3) in 60.6 min. Multiplanar images of the in vivo rat brain with identification of anatomic structures are presented. Improvement in signal-to-noise ratio afforded by the rat brain coil may broaden experiments that utilize clinical MR scanners for in vivo image acquisition. 2010 Wiley-Liss, Inc.

Nutritional support contributes to recuperation in a rat model of aplastic anemia by enhancing mitochondrial function.

PubMed

Yang, Guang; Zhao, Lifen; Liu, Bing; Shan, Yujia; Li, Yang; Zhou, Huimin; Jia, Li

2018-02-01

Acquired aplastic anemia (AA) is a hematopoietic stem cell disease that leads to hematopoietic disorder and peripheral blood pancytopenia. We investigated whether nutritional support is helpful to AA recovery. We established a rat model with AA. A nutrient mixture was administered to rats with AA through different dose gavage once per day for 55 d. Animals in this study were assigned to one of five groups: normal control (NC; group includes normal rats); AA (rats with AA); high dose (AA + nutritional mixture, 2266.95 mg/kg/d); medium dose (1511.3 mg/kg/d); and low dose (1057.91 mg/kg/d). The effects of nutrition administration on general status and mitochondrial function of rats with AA were evaluated. The nutrient mixture with which the rats were supplemented significantly improved weight, peripheral blood parameters, and histologic parameters of rats with AA in a dose-dependent manner. Furthermore, we observed that the number of mitochondria in the liver, spleen, kidney, and brain was increased after supplementation by transmission electron microscopy analysis. Nutrient administration also improved mitochondrial DNA content, adenosine triphosphate content, and membrane potential but inhibited oxidative stress, thus, repairing the mitochondrial dysfunction of the rats with AA. Taken together, nutrition supplements may contribute to the improvement of mitochondrial function and play an important role in the recuperation of rats with AA. Copyright © 2017 Elsevier Inc. All rights reserved.

Dietary supplementation with the polyphenol-rich açaí pulps (Euterpe oleracea Mart. and Euterpe precatoria Mart.) improves cognition in aged rats and attenuates inflammatory signaling in BV-2 microglial cells.

PubMed

Carey, Amanda N; Miller, Marshall G; Fisher, Derek R; Bielinski, Donna F; Gilman, Casey K; Poulose, Shibu M; Shukitt-Hale, Barbara

2017-05-01

The present study was carried out to determine if lyophilized açaí fruit pulp (genus, Euterpe), rich in polyphenols and other bioactive antioxidant and anti-inflammatory phytochemicals, is efficacious in reversing age-related cognitive deficits in aged rats. The diets of 19-month-old Fischer 344 rats were supplemented for 8 weeks with 2% Euterpe oleracea (EO), Euterpe precatoria (EP), or a control diet. Rats were tested in the Morris water maze and then blood serum from the rats was used to assess inflammatory responses of BV-2 microglial cells. After 8 weeks of dietary supplementation with 2% EO or EP, rats demonstrated improved working memory in the Morris water maze, relative to controls; however, only the EO diet improved reference memory. BV-2 microglial cells treated with blood serum collected from EO-fed rats produced less nitric oxide (NO) than control-fed rats. Serum from both EO- and EP-fed rats reduced tumor necrosis factor-alpha (TNF-α). There is a relationship between performance in the water maze and the production of NO and TNF-α by serum-treated BV-2 cells, such that serum from rats with better performance was more protective against inflammatory signaling. Protection of memory during aging by supplementation of lyophilized açaí fruit pulp added to the diet may result from its ability to influence antioxidant and anti-inflammatory signaling.

THERMAL TRANSITIONS IN NORMAL AND DEUTERATED RAT-TAIL TENDON, HUMAN SKIN, AND TUNA-FISH SKIN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rigby, B.J.

1962-07-30

The transition temperature and shrinkage temperature of collogens were determined in normal and deuterated rat-tail tendon, human skin, and tuna-fish skin. Increases were observed in the deuterated samples. Results, obtained with solid collagen, are compared with those obtained with collagen in solution. It is concluded that hydrogen bonds are involved in both reactions. (C.H.)

[Establishment of biological assess for quality control of Fuzi based on determination of premature ventricular contractions in rats].

PubMed

Zhao, Zhi-Hao; Zhang, Ding-Kun; Wu, Ming-Quan; Li, Chun-Yu; Cao, Li-Juan; Zhang, Ping; Liu, Cui-Zhe; Wang, Jia-Bo; Xiao, Xiao-He

2016-10-01

Aconiti Lateralis Radix (Fuzi) is a toxic traditional Chinese medicine with definite efficacy. In order to improve the quality control of its different prepared products and ensure the security in clinic, it is significant to establish a method of quality evaluation related to clinic adverse effects. Aiming at the important biological marker of early cardiac toxicity reaction, there was no method to detect it. In this manuscript, a novel approach for measuring the minimal toxic dose (MTD) of premature ventricular contractions (PVC) poisoning of rats was established. Then, the determination methodology and conditions were optimized to meet the needs of the quality and biological assessment, including animal sex, weight, stability of standards and test solutions. Using this method, the MTD value of different Fuzi products were determined, such as Heishunpian, Baifupian, Zhengfupian, Baofupian, and Paotianxiong. The results showed that the MTD of Fuzi was significantly decreased after detoxification processed (P<0.05) and the MTD of Heishunpian, Zhengfupian, Baofupian and Baifupian was as much as 15.76, 22.36, 19.65 and 20.97 times to that of unprocessed Shengfuzi. In addition, Paotianxiong could not induce PVC in rats, which indicated that Paotianxiong was nontoxic and safe.This method could appropriately reflects the cardiotoxity of Fuzi and its prepared samples. Together with the chemical composition analysis, the contents of diester alkaloids were explored including aconitine, mesaconitine and hypaconitine as well as monoester alkaloids in Fuzi and its prepared products were significantly associated with PVC. Furthermore, there may be some components undetermined facilitating arrhythmia to be worth exploring. This research provides an overall and comprehensive approach to diagnose early clinical cardiotoxity and control the quality of Fuzi, which could not only be a complementary solution for the chemical evaluation, but a new method to ensure its efficacy and security of clinical application. Copyright© by the Chinese Pharmaceutical Association.

Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model.

PubMed

Dai, Bingyang; Li, Lan; Li, Qiangqiang; Song, Xiaoxiao; Chen, Dongyang; Dai, Jin; Yao, Yao; Yan, Wenjin; Teng, Huajian; Yang, Fang; Xu, Zhihong; Jiang, Qing

2017-07-01

: L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel-Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis.

Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model

PubMed Central

Dai, Bingyang; Li, Lan; Li, Qiangqiang; Song, Xiaoxiao; Chen, Dongyang; Dai, Jin; Yao, Yao; Yan, Wenjin; Teng, Huajian; Yang, Fang; Xu, Zhihong; Jiang, Qing

2017-01-01

L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel–Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis. PMID:28306627

Hyperbranched polyglycerol is superior to glucose for long-term preservation of peritoneal membrane in a rat model of chronic peritoneal dialysis.

PubMed

Du, Caigan; Mendelson, Asher A; Guan, Qiunong; Dairi, Ghida; Chafeeva, Irina; da Roza, Gerald; Kizhakkedathu, Jayachandran N

2016-12-13

Replacing glucose with a better biocompatible osmotic agent in peritoneal dialysis (PD) solutions is needed in PD clinic. We previously demonstrated the potential of hyperbranched polyglycerol (HPG) as a replacement for glucose. This study further investigated the long-term effects of chronic exposure to HPG as compared to a glucose-based conventional PD solution on peritoneal membrane (PM) structure and function in rats. Adult male Wistar rats received once-daily intraperitoneal injection of 10 mL of HPG solution (1 kDa, HPG 6%) compared to Physioneal™ 40 (PYS, glucose 2.27%) or electrolyte solution (Control) for 3 months. The overall health conditions were determined by blood chemistry analysis. The PM function was determined by ultrafiltration, and its injury by histological and transcriptome-based pathway analyses. Here, we showed that there was no difference in the blood chemistry between rats receiving the HPG and the Control, while PYS increased serum alkaline phosphatase, globulin and creatinine and decreased serum albumin. Unlike PYS, HPG did not significantly attenuate PM function, which was associated with smaller change in both the structure and the angiogenesis of the PM and less cells expressing vascular endothelial growth factor, α-smooth muscle actin and MAC387 (macrophage marker). The pathway analysis revealed that there were more inflammatory signaling pathways functioning in the PM of PYS group than those of HPG or Control, which included the signaling for cytokine production in both macrophages and T cells, interleukin (IL)-6, IL-10, Toll-like receptors, triggering receptor expressed on myeloid cells 1 and high mobility group box 1. The results from this experimental study indicate the superiority of HPG to glucose in the preservation of the peritoneum function and structure during the long-term PD treatment, suggesting the potential of HPG as a novel osmotic agent for PD.

Extinction, Spontaneous Recovery and Renewal of Flavor Preferences Based on Taste-Taste Learning

ERIC Educational Resources Information Center

Diaz, Estrella; De la Casa, L. G.

2011-01-01

This paper presents evidence of extinction, spontaneous recovery and renewal in a conditioned preferences paradigm based on taste-taste associations. More specifically, in three experiments rats exposed to a simultaneous compound of citric acid-saccharin solution showed a preference for the citric solution when the preference was measured with a…

Adiponectin improves coronary no-reflow injury by protecting the endothelium in rats with type 2 diabetes mellitus.

PubMed

Han, Xue; Wu, Ye; Liu, Xin; Ma, Lu; Lv, Tingting; Sun, Qi; Xu, Wenli; Zhang, Suli; Wang, Ke; Wang, Wen; Ma, Xinliang; Liu, Huirong

2017-08-31

To determine the effect of adiponectin (APN) on the coronary no-reflow (NR) injury in rats with Type 2 diabetes mellitus (T2DM), 80 male Sprague-Dawley rats were fed with a high-sugar-high-fat diet to build a T2DM model. Rats received vehicle or APN in the last week and then were subjected to myocardial ischemia reperfusion (MI/R) injury. Endothelium-dependent vasorelaxation of the thoracic aorta was significantly decreased and serum levels of endothelin-1 (ET-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were noticably increased in T2DM rats compared with rats without T2DM. Serum APN was positively correlated with the endothelium-dependent vasorelaxation, but negatively correlated with the serum level of ET-1. Treatment with APN improved T2DM-induced endothelium-dependent vasorelaxation, recovered cardiac function, and decreased both NR size and the levels of ET-1, ICAM-1 and VCAM-1. Hypoadiponectinemia was associated with the aggravation of coronary NR in T2DM rats. APN could alleviate coronary NR injury in T2DM rats by protecting the endothelium and improving microcirculation. © 2017 The Author(s).

Beneficial effects of exercise training in heart failure are lost in male diabetic rats.

PubMed

Boudia, Dalila; Domergue, Valérie; Mateo, Philippe; Fazal, Loubina; Prud'homme, Mathilde; Prigent, Héloïse; Delcayre, Claude; Cohen-Solal, Alain; Garnier, Anne; Ventura-Clapier, Renée; Samuel, Jane-Lise

2017-12-01

Exercise training has been demonstrated to have beneficial effects in patients with heart failure (HF) or diabetes. However, it is unknown whether diabetic patients with HF will benefit from exercise training. Male Wistar rats were fed either a standard (Sham, n = 53) or high-fat, high-sucrose diet ( n = 66) for 6 mo. After 2 mo of diet, the rats were already diabetic. Rats were then randomly subjected to either myocardial infarction by coronary artery ligation (MI) or sham operation. Two months later, heart failure was documented by echocardiography and animals were randomly subjected to exercise training with treadmill for an additional 8 wk or remained sedentary. At the end, rats were euthanized and tissues were assayed by RT-PCR, immunoblotting, spectrophotometry, and immunohistology. MI induced a similar decrease in ejection fraction in diabetic and lean animals but a higher premature mortality in the diabetic group. Exercise for 8 wk resulted in a higher working power developed by MI animals with diabetes and improved glycaemia but not ejection fraction or pathological phenotype. In contrast, exercise improved the ejection fraction and increased adaptive hypertrophy after MI in the lean group. Trained diabetic rats with MI were nevertheless able to develop cardiomyocyte hypertrophy but without angiogenic responses. Exercise improved stress markers and cardiac energy metabolism in lean but not diabetic-MI rats. Hence, following HF, the benefits of exercise training on cardiac function are blunted in diabetic animals. In conclusion, exercise training only improved the myocardial profile of infarcted lean rats fed the standard diet. NEW & NOTEWORTHY Exercise training is beneficial in patients with heart failure (HF) or diabetes. However, less is known of the possible benefit of exercise training for HF patients with diabetes. Using a rat model where both diabetes and MI had been induced, we showed that 2 mo after MI, 8 wk of exercise training failed to improve cardiac function and metabolism in diabetic animals in contrast to lean animals.

Epoetin beta pegol ameliorates flow-mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic rats.

PubMed

Serizawa, Kenichi; Yogo, Kenji; Tashiro, Yoshihito; Kawasaki, Ryohei; Endo, Koichi; Shimonaka, Yasushi; Hirata, Michinori

2017-04-01

Patients with diabetic nephropathy have a high cardiovascular mortality. Epoetin beta pegol (continuous erythropoietin receptor activator, C.E.R.A.) is a drug for the treatment of renal anemia. In this study, we investigated the effect of C.E.R.A. on vascular endothelial function as evaluated by flow-mediated dilation (FMD) and the relationship between hematopoiesis and FMD in diabetic nephropathy rats. Male Spontaneously Diabetic Torii rats (SDT, 22 weeks old) were used. C.E.R.A. (0.6, 1.2 μg/kg) was administered subcutaneously once every 2 weeks for 8 weeks. At 1 week after last administration (31 weeks old), we assessed FMD in the femoral arteries of anesthetized rats using a high-resolution ultrasound system. FMD was also measured 1 week after single C.E.R.A. treatment (5.0 μg/kg) to examine the influence of hematopoiesis. Flow-mediated dilation was significantly decreased in SDT rats before the start of C.E.R.A. treatment (22 weeks old). Repeated administration of C.E.R.A. dose-dependently improved FMD in SDT rats (31 weeks old) without changing blood glucose, nitroglycerin-induced vasodilation, or kidney function. Long-term administration of C.E.R.A. improved the state of endothelial nitric oxide synthase uncoupling in the femoral arteries of SDT rats, which showed a positive correlation with FMD. On the other hand, there was no correlation between FMD and Hb or Hct in SDT rats. Furthermore, at 1 week after single administration of C.E.R.A., FMD was not significantly improved although hemoglobin levels were comparable with levels following long-term C.E.R.A. Long-term treatment with C.E.R.A. improved FMD in SDT rats even after onset of endothelial dysfunction. © 2017 The Authors. Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

Assessment of formulated amodiaquine microparticles in Leishmania donovani infected rats.

PubMed

Nettey, Henry; Allotey-Babington, Grace Lovia; Somuah, Isaac; Banga, N'guessan Benoit; Afrane, Barima; Amponsah, Seth Kwabena; Annor, Henrietta; Darko, Henry; Hanson, Kwame; Aidoo, Anoa; Broni, Marisa Nyarkoa; Sasu, Clement; Nyarko, Alexander

2017-02-01

The aim of this study was to formulate, characterise and evaluate the activity of amodiaquine microparticles against Leishmania donovani. Microparticles were formulated by encapsulating the drug in bovine serum albumin using the spray-dryer method. The microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency and in vitro release profile. The size range of the microparticles formulated was between 1.9 and 10 μm with an average zeta potential of -25.5 mV. Of the expected 20% drug loading, an average of 18.27% was obtained giving an encapsulation efficiency of 91.35%. Pharmacokinetic profile of amodiaquine improved with microencapsulation of the drug with C max , AUC 0→48 and t 1//2 all significantly higher than amodiaquine solution. Amodiaquine microparticles showed an overall higher bioavailability and hence were more effective in eliminating intra-tissue parasites than the drug solution. It would therefore be expected that the formulated microparticles will be more effective in treating visceral leishmaniasis.

Evaluation of Heavy-Chain C-Terminal Deletion on Product Quality and Pharmacokinetics of Monoclonal Antibodies.

PubMed

Jiang, Guoying; Yu, Christopher; Yadav, Daniela B; Hu, Zhilan; Amurao, Annamarie; Duenas, Eileen; Wong, Marc; Iverson, Mark; Zheng, Kai; Lam, Xanthe; Chen, Jia; Vega, Roxanne; Ulufatu, Sheila; Leddy, Cecilia; Davis, Helen; Shen, Amy; Wong, Pin Y; Harris, Reed; Wang, Y John; Li, Dongwei

2016-07-01

Due to their potential influence on stability, pharmacokinetics, and product consistency, antibody charge variants have attracted considerable attention in the biotechnology industry. Subtle to significant differences in the level of charge variants and new charge variants under various cell culture conditions are often observed during routine manufacturing or process changes and pose a challenge when demonstrating product comparability. To explore potential solutions to control charge heterogeneity, monoclonal antibodies (mAbs) with native, wild-type C-termini, and mutants with C-terminal deletions of either lysine or lysine and glycine were constructed, expressed, purified, and characterized in vitro and in vivo. Analytical and physiological characterization demonstrated that the mAb mutants had greatly reduced levels of basic variants without decreasing antibody biologic activity, structural stability, pharmacokinetics, or subcutaneous bioavailability in rats. This study provides a possible solution to mitigate mAb heterogeneity in C-terminal processing, improve batch-to-batch consistency, and facilitate the comparability study during process changes. Published by Elsevier Inc.

Probing the functional impact of sub-retinal prosthesis

PubMed Central

Roux, Sébastien; Matonti, Frédéric; Dupont, Florent; Hoffart, Louis; Takerkart, Sylvain; Picaud, Serge; Pham, Pascale; Chavane, Frédéric

2016-01-01

Retinal prostheses are promising tools for recovering visual functions in blind patients but, unfortunately, with still poor gains in visual acuity. Improving their resolution is thus a key challenge that warrants understanding its origin through appropriate animal models. Here, we provide a systematic comparison between visual and prosthetic activations of the rat primary visual cortex (V1). We established a precise V1 mapping as a functional benchmark to demonstrate that sub-retinal implants activate V1 at the appropriate position, scalable to a wide range of visual luminance, but with an aspect-ratio and an extent much larger than expected. Such distorted activation profile can be accounted for by the existence of two sources of diffusion, passive diffusion and activation of ganglion cells’ axons en passant. Reverse-engineered electrical pulses based on impedance spectroscopy is the only solution we tested that decreases the extent and aspect-ratio, providing a promising solution for clinical applications. DOI: http://dx.doi.org/10.7554/eLife.12687.001 PMID:27549126

Evaluation of hydrogels for soft tissue adhesives in vitro and in vivo analyses

NASA Astrophysics Data System (ADS)

Yuan, Liu; Fan, Wenshuai; Han, Linyingjun; Guo, Changan; Yan, Zuoqin; Zhu, Meifang; Mo, Xiumei

2018-03-01

In this study, natural materials (sodium alginate, dextran, gelatin and carboxymethyl chitosan) were modified to get aldehyde components and amino components. Upon mixing the two-component solutions together, four kinds of Schiff base hydrogels formed successfully within 5-300 s and could seal the wound tissue. The cytotoxicity tests of hydrogel extraction solution confirmed that the hydrogels are nontoxic materials. The adhesive ability was evaluated in vivo by measuring the adhesive strength after sealing the skin incisions on the back of rats. All the hydrogels showed higher adhesive strength than that of commercial fibrin glue and the blank control. The histological staining observation by hematoxylin and eosin staining (HE) and Masson's trichrome staining (MTC) methods suggested that the hydrogels had good biocompatibility and biodegradation in vivo. They have only normal initial inflammation to skin tissue and could improve the formation of new collagen in the incision section. So, the prepared hydrogels were both safe and effective tissue adhesive, which had the great potentials to be used as skin tissue adhesive.

Diet-Induced Ketosis Improves Cognitive Performance in Aged Rats

PubMed Central

Xu, Kui; Sun, Xiaoyan; Eroku, Bernadette O.; Tsipis, Constantinos P.; Puchowicz, Michelle A.; LaManna, Joseph C.

2010-01-01

Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1α levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions. PMID:20204773

[Effect of Electroacupuncture on Cerebro-cortex Caspase-3 Expression and Blood Lipid Levels in Hyperlipemia Rats with Cerebral Ischemia].

PubMed

Wang, Zhuo-Yu; Ma, Jia-Jia; Guan, Han-Yu; Tian, Yao; Ren, Xiu-Jun; Ma, Hui-Fang

2017-04-25

To observe the effect of electroacupuncture (EA) stimulation of "Fenglong" (ST 40), "Sanyinjiao" (SP 6) plus manual acupuncture (MA) stimulation of "Shuigou" (GV 26) and "Baihui" (GV 20) on Caspase-3 protein expression in the cerebral cortex of rats with hyperlipemia and cerebral ischemia(HL-CI),so as to reveal its mechanisms underlying improvement of HL-CI. Forty-five rats were randomly divided into normal control,sham operation,model,EA group I(EA+MA was given for 14 days, i.e., 7 days before CI, and 7 days more after HL-CI)and EA group Ⅱ (EA+MA was given for only 7 days after HL-CI),with 9 rats being in each group. The HL-CI model was established by feeding the animals with high fat forage for 6 weeks and then making an occlusion of the unilateral middle cerebral artery by regional application of quantitative paper adsorbing 50% FeCl 3 solution (10 μL). Rats of the sham operation group were treated with the same procedures only without application of FeCl 3 solution. For rats of the EA group I,EA (1-3 mA, 2 Hz/100 Hz) was applied to bilateral acupoints SP 6 and ST 40 (for 20 min),and MA stimulation applied to GV 26 and GV 20. EA was conducted once daily for 7 days after 6 weeks' high fat fo-rage feeding, and EA+MA intervention was conducted once daily for 7 days after CI modeling. For rats in the EA group Ⅱ, EA+MA was applied to the same 4 acupoints once a day for 7 days only after CI modeling. The neurological impairment was assessed by Zea Longa's scoring. The blood sample was taken from the abdominal aorta for measuring the contents of serum cholesterol (CHO),triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Pathological changes of the cerebral cortex were observed after H.E. staining, and the expression of cerebro-cortex Caspase-3 was analyzed by immunohistochemistry. Following modeling,the neurological score,CHO, TG and LDL-C contents, and the number of Caspase-3 positive cells as well as Caspase-3 immunoactivity level were significantly increased in the model group( P <0.05), while serum HDL-C level was obviously decreased( P <0.05). After the treatment,the increased neurological score, CHO, TG and LDL-C contents, and the number of Caspase-3 positive cells and Caspase-3 immunoactivity level were considerably decreased in the EA group I and Ⅱ( P <0.05)while the decreased HDL-C level was notably increased relevant to the model group( P <0.05). The effects of the EA group I were notably superior to those of EA group Ⅱ in down-regulating the neurological score,CHO, TG and LDL-C levels and the expression of Caspase-3 protein( P <0.05). No significant differences were found between the normal control and sham operation groups in the neurological scores 20 min and 7 days after modeling and Caspase-3 expression levels ( P >0.05). H.E. staining showed a reduction of the apoptotic cells and inflammatory cells in both EA group I and Ⅱ. Both EA and EA+MA interventions can improve neurological function in HL-CI rats,which may be related to their effects in adjusting the levels of serum lipids and down-regulating the expression of cell apoptosis-related Caspase-3 protein in the ischemic cortex. Moreover, the cerebral ischemia injury may be lightened by EA-lowering hyperlipemia first.

Exploring the Urtica dioica Leaves Hemostatic and Wound-Healing Potential.

PubMed

Zouari Bouassida, Karama; Bardaa, Sana; Khimiri, Meriem; Rebaii, Tarek; Tounsi, Slim; Jlaiel, Lobna; Trigui, Mohamed

2017-01-01

The present paper investigated the efficiency of Urtica dioica (U. dioica) on hemostatic and wound healing activities. U. dioica leaf extracts were evaluated for their antibacterial and antioxidant effects as well as their flavonoid and polyphenol content. The hydroethanolic extract (EtOH-H 2 OE), showing the most potent antibacterial and antioxidant activities in vitro , thanks to its flavonoid and polyphenol richness, was selected for hemostatic and wound healing evaluation. Twenty-four rats completing full-thickness wounds were split into four groups. The wounds were topically treated with saline solution, glycerol, "CICAFLORA," and U. dioica EtOH-H 2 OE (50  µ L/mm 2 ) until day 11. The wound healing effect was assessed by macroscopic, histological, and biochemical parameters. Rats treated with EtOH-H 2 OE showed fast wound closure (92.39%) compared to the control animals (60.91%) on the 11th day of wounding ( P < 0.01). Histopathological and biochemical explorations showed full epidermal regeneration and an improvement of the hydroxyproline content in the U. dioica EtOH-H 2 OE treated rats. Analysis of fatty acids and sterols by GC-MS showed the presence of unsaturated fatty acids and a high concentration of lupeol known for their involvement in reepithelialization. These results prove the efficiency of U. dioica EtOH-H 2 OE in wound healing and supported its traditional use.

Egg white-derived peptides prevent male reproductive dysfunction induced by mercury in rats.

PubMed

Rizzetti, Danize Aparecida; Martinez, Caroline Silveira; Escobar, Alyne Goulart; da Silva, Taiz Martins; Uranga-Ocio, José Antonio; Peçanha, Franck Maciel; Vassallo, Dalton Valentim; Castro, Marta Miguel; Wiggers, Giulia Alessandra

2017-02-01

Oxidative stress in known to contribute to the male reproductive dysfunction induced by mercury (Hg). Our study tested the hypothesis that the egg white hydrolysate (EWH), a potent antioxidant in vitro, is able to prevent the effects of prolonged Hg exposure on male reproductive system in rats. For this, rats were treated for 60 days with: a) Untreated - saline solution (i.m.); b) Hydrolysate - EWH (1 g/kg/day, gavage); c) Mercury - HgCl 2 (1st dose 4.6 μg/kg, subsequent doses 0.07 μg/kg/day, i.m.); d) Hydrolysate-Mercury. At the end of the treatment, sperm motility, count and morphological studies were performed; Reactive Oxygen Species (ROS) levels, lipid peroxidation, antioxidant capacity, histological and immunohistochemical assays on testis and epididymis were also carried out. As results, HgCl 2 -treatment decreased sperm number, increased sperm transit time in epididymis and impaired sperm morphology. However, these harmful effects were prevented by EWH. HgCl 2 -treatment also increased ROS levels, lipid peroxidation and antioxidant capacity in testis and epididymis as well as promoted testicular inflammation and histological changes in epididymis. EWH improved histological and immunohistochemical alterations, probably due to its antioxidant property. In conclusion, the EWH could represent a powerful natural alternative to protect the male reproductive system against Hg-induced sperm toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploring the Urtica dioica Leaves Hemostatic and Wound-Healing Potential

PubMed Central

Bardaa, Sana; Khimiri, Meriem; Rebaii, Tarek; Jlaiel, Lobna

2017-01-01

The present paper investigated the efficiency of Urtica dioica (U. dioica) on hemostatic and wound healing activities. U. dioica leaf extracts were evaluated for their antibacterial and antioxidant effects as well as their flavonoid and polyphenol content. The hydroethanolic extract (EtOH-H2OE), showing the most potent antibacterial and antioxidant activities in vitro, thanks to its flavonoid and polyphenol richness, was selected for hemostatic and wound healing evaluation. Twenty-four rats completing full-thickness wounds were split into four groups. The wounds were topically treated with saline solution, glycerol, “CICAFLORA,” and U. dioica EtOH-H2OE (50 µL/mm2) until day 11. The wound healing effect was assessed by macroscopic, histological, and biochemical parameters. Rats treated with EtOH-H2OE showed fast wound closure (92.39%) compared to the control animals (60.91%) on the 11th day of wounding (P < 0.01). Histopathological and biochemical explorations showed full epidermal regeneration and an improvement of the hydroxyproline content in the U. dioica EtOH-H2OE treated rats. Analysis of fatty acids and sterols by GC-MS showed the presence of unsaturated fatty acids and a high concentration of lupeol known for their involvement in reepithelialization. These results prove the efficiency of U. dioica EtOH-H2OE in wound healing and supported its traditional use. PMID:29201895

Resident intruder paradigm-induced aggression relieves depressive-like behaviors in male rats subjected to chronic mild stress

PubMed Central

Wei, Sheng; Ji, Xiao-wei; Wu, Chun-ling; Li, Zi-fa; Sun, Peng; Wang, Jie-qiong; Zhao, Qi-tao; Gao, Jie; Guo, Ying-hui; Sun, Shi-guang; Qiao, Ming-qi

2014-01-01

Background Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that the resident intruder paradigm (RIP) results in aggressive behavior in male rats. However, it is not known how resident intruder paradigm-induced aggression affects depressive-like behavior in isolated male rats subjected to chronic mild stress (CMS), which is an animal model of depression. Material/Methods Male Wistar rats were divided into 3 groups: non-stressed controls, isolated rats subjected to the CMS protocol, and resident intruder paradigm-exposed rats subjected to the CMS protocol. Results In the sucrose intake test, ingestion of a 1% sucrose solution by rats in the CMS group was significantly lower than in control and CMS+RIP rats after 3 weeks of stress. In the open-field test, CMS rats had significantly lower open-field scores compared to control rats. Furthermore, the total scores given the CMS group were significantly lower than in the CMS+RIP rats. In the forced swimming test (FST), the immobility times of CMS rats were significantly longer than those of the control or CMS+RIP rats. However, no differences were observed between controls and CMS+RIP rats. Conclusions Our data show that aggressive behavior evoked by the resident intruder paradigm could relieve broad-spectrum depressive-like behaviors in isolated adult male rats subjected to CMS. PMID:24911067

Serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) improves voiding efficiency in the diabetic rat.

PubMed

Tu, Hongjian; Cao, Nailong; Gu, Baojun; Si, Jiemin; Chen, Zhong; Andersson, Karl-Erik

2015-07-01

To examine the effects of the serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) on micturition in rats with diabetes mellitus (DM). Female Sprague-Dawley rats (n = 16) were divided into two groups: rats with Type 1 DM and age-matched control rats. DM was induced by i.p. injection of streptozotocin (65 mg/kg) and detailed cystometrogram (CMG) studies were performed 8 weeks post-injection in all rats under urethane anaesthesia. The selective 5-HT2A antagonist ketanserin was administered after each DOI dose-response curve was plotted. All drugs were administered i.v. Compared with controls, comprehensive urodynamic studies showed that DM rats had a higher bladder capacity and post-void residual urine volume (PVR), and a markedly lower voiding efficiency. In DM rats, DOI (0.01-0.3 mg/kg) induced significant dose-dependent increases in micturition volume and reductions in PVR, resulting in greater voiding efficiency. CMG measurements showed a dose-dependent increase in high-frequency oscillation (HFO) activity, evidenced by an increased duration of HFOs per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI-induced changes. The HFOs observed in the present study seem to correlate with external urethral sphincter bursting activity during voiding. Bladder voiding efficiency was reduced in DM rats. The 5-HT2A receptor agonist can enhance HFO activity and improves voiding efficiency, and so may represent a new strategy to improve voiding efficiency after DM in experimental studies. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation.

PubMed

Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

2015-03-01

Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured spatial learning and memory, the time of normal rats was shortened by GEN treatment compared to the vehicle group, but only in the early stages of testing. In the glucose-loaded group, GEN treatment improved performance as mazes were advanced. In the open-field test, GEN treatment delayed habituation to the new environment in normal rats, and increased the exploratory behaviors of glucose-loaded rats. There were no significant differences observed for emotionality or fear-motivated learning and memory. Together, these results indicate that GEN treatment improved spatial learning and memory only in the early stages of testing in the normal state, but improved spatial learning and memory when glucose levels increased during memory consolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic treadmill exercise in rats delicately alters the Purkinje cell structure to improve motor performance and toxin resistance in the cerebellum.

PubMed

Huang, Tung-Yi; Lin, Lung-Sheng; Cho, Keng-Chi; Chen, Shean-Jen; Kuo, Yu-Min; Yu, Lung; Wu, Fong-Sen; Chuang, Jih-Ing; Chen, Hsiun-Ing; Jen, Chauying J

2012-09-01

Although exercise usually improves motor performance, the underlying cellular changes in the cerebellum remain to be elucidated. This study aimed to investigate whether and how chronic treadmill exercise in young rats induced Purkinje cell changes to improve motor performance and rendered the cerebellum less vulnerable to toxin insults. After 1-wk familiarization of treadmill running, 6-wk-old male Wistar rats were divided into exercise and sedentary groups. The exercise group was then subjected to 8 wk of exercise training at moderate intensity. The rotarod test was carried out to evaluate motor performance. Purkinje cells in cerebellar slices were visualized by lucifer yellow labeling in single neurons and by calbindin immunostaining in groups of neurons. Compared with sedentary control rats, exercised rats not only performed better in the rotarod task, but also showed finer Purkinje cell structure (higher dendritic volume and spine density with the same dendritic field). The exercise-improved cerebellar functions were further evaluated by monitoring the long-lasting effects of intraventricular application of OX7-saporin. In the sedentary group, OX7-saporin treatment retarded the rotarod performance and induced ∼60% Purkinje cell loss in 3 wk. As a comparison, the exercise group showed much milder injuries in the cerebellum by the same toxin treatment. In conclusion, exercise training in young rats increased the dendritic density of Purkinje cells, which might play an important role in improving the motor performance. Furthermore, as Purkinje cells in the exercise group were relatively toxin resistant, the exercised rats showed good motor performance, even under toxin-treated conditions.

MitoQ blunts mitochondrial and renal damage during cold preservation of porcine kidneys.

PubMed

Parajuli, Nirmala; Campbell, Lia H; Marine, Akira; Brockbank, Kelvin G M; Macmillan-Crow, Lee Ann

2012-01-01

Cold preservation has greatly facilitated the use of cadaveric kidneys for transplantation but damage occurs during the preservation episode. It is well established that oxidant production increases during cold renal preservation and mitochondria are a key target for injury. Our laboratory has demonstrated that cold storage of renal cells and rat kidneys leads to increased mitochondrial superoxide levels and mitochondrial electron transport chain damage, and that addition of Mitoquinone (MitoQ) to the preservation solutions blunted this injury. In order to better translate animal studies, the inclusion of large animal models is necessary to develop safe preclinical protocols. Therefore, we tested the hypothesis that addition of MitoQ to cold storage solution preserves mitochondrial function by decreasing oxidative stress, leading to less renal tubular damage during cold preservation of porcine kidneys employing a standard criteria donor model. Results showed that cold storage significantly induced oxidative stress (nitrotyrosine), renal tubular damage, and cell death. Using High Resolution Respirometry and fresh porcine kidney biopsies to assess mitochondrial function we showed that MitoQ significantly improved complex II/III respiration of the electron transport chain following 24 hours of cold storage. In addition, MitoQ blunted oxidative stress, renal tubular damage, and cell death after 48 hours. These results suggested that MitoQ decreased oxidative stress, tubular damage and cell death by improving mitochondrial function during cold storage. Therefore this compound should be considered as an integral part of organ preservation solution prior to transplantation.

MitoQ Blunts Mitochondrial and Renal Damage during Cold Preservation of Porcine Kidneys

PubMed Central

Parajuli, Nirmala; Campbell, Lia H.; Marine, Akira; Brockbank, Kelvin G. M.; MacMillan-Crow, Lee Ann

2012-01-01

Cold preservation has greatly facilitated the use of cadaveric kidneys for transplantation but damage occurs during the preservation episode. It is well established that oxidant production increases during cold renal preservation and mitochondria are a key target for injury. Our laboratory has demonstrated that cold storage of renal cells and rat kidneys leads to increased mitochondrial superoxide levels and mitochondrial electron transport chain damage, and that addition of Mitoquinone (MitoQ) to the preservation solutions blunted this injury. In order to better translate animal studies, the inclusion of large animal models is necessary to develop safe preclinical protocols. Therefore, we tested the hypothesis that addition of MitoQ to cold storage solution preserves mitochondrial function by decreasing oxidative stress, leading to less renal tubular damage during cold preservation of porcine kidneys employing a standard criteria donor model. Results showed that cold storage significantly induced oxidative stress (nitrotyrosine), renal tubular damage, and cell death. Using High Resolution Respirometry and fresh porcine kidney biopsies to assess mitochondrial function we showed that MitoQ significantly improved complex II/III respiration of the electron transport chain following 24 hours of cold storage. In addition, MitoQ blunted oxidative stress, renal tubular damage, and cell death after 48 hours. These results suggested that MitoQ decreased oxidative stress, tubular damage and cell death by improving mitochondrial function during cold storage. Therefore this compound should be considered as an integral part of organ preservation solution prior to transplantation. PMID:23139796

Effect of Surface Alloying by Silicon on the Corrosion Resistance and Biocompatibility of the Binary NiTi

NASA Astrophysics Data System (ADS)

Psakhie, S. G.; Meisner, S. N.; Lotkov, A. I.; Meisner, L. L.; Tverdokhlebova, A. V.

2014-07-01

This paper presents the study on changes in element and phase compositions in the near-surface layer and on surface topography of the NiTi specimens after the silicon ion-beam treatment. The effect of these parameters of the near-surface layer on corrosion properties in biochemical solutions and biocompatibility with mesenchymal stem cells of rat marrow is studied. Ion-beam surface modification of the specimens was performed by a DIANA-3 implanter (Tomsk, Russia), using single-ion-beam pulses under oil-free pumping and high vacuum (10-4 Pa) conditions in a high-dose ion implantation regime. The fluence made 2 × 1017 cm-2, at an average accelerating voltage of 60 kV, and pulse repetition frequency of 50 Hz. The silicon ion-beam treatment of specimen surfaces is shown to bring about a nearly twofold improvement in the corrosion resistance of the material to attack by aqueous solutions of NaCl (artificial body fluid) and human plasma and a drastic decrease in the nickel concentration after immersion of the specimens into the solutions for ~3400 and ~6000 h, respectively (for the artificial plasma solution, a nearly 20-fold decrease in the Ni concentration is observed). It is shown that improvement of NiTi corrosion resistance after treatment by Si ions occurs mainly due to the formation of two-layer composite coating based on Ti oxides (outer layer) on the NiTi surface and adjacent inner layer of oxides, carbides, and silicides of the NiTi alloy components. Inner layer with high silicon concentration serves as a barrier layer preventing nickel penetration into biomedium. This, in our opinion, is the main reason why the NiTi alloy exhibits no cytotoxic properties after ion modification of its surface and leads to the biocompatibility improvement at the cellular level, respectively.

Biocompatibility of peritoneal dialysis fluids: long-term exposure of nonuremic rats.

PubMed

Musi, Barbara; Braide, Magnus; Carlsson, Ola; Wieslander, Anders; Albrektsson, Ann; Ketteler, Markus; Westenfeld, Ralf; Floege, Jürgen; Rippe, Bengt

2004-01-01

Long-term peritoneal dialysis (PD) leads to structural and functional changes in the peritoneum. The aim of the present study was to investigate the long-term effects of PD fluid components, glucose and glucose degradation products (GDP), and lactate-buffered solution on morphology and transport characteristics in a nonuremic rat model. Rats were subjected to two daily intraperitoneal injections (20 mL/day) during 12 weeks of one of the following: commercial PD fluid (Gambrosol, 4%; Gambro AB, Lund, Sweden), commercial PD fluid with low GDP levels (Gambrosol trio, 4%; Gambro AB), sterile-filtered PD fluid (4%) without GDP, or a glucose-free lactate-buffered PD fluid. Punctured and untreated controls were used. Following exposure, the rats underwent a single 4-hour PD dwell (30 mL, 4% glucose) to determine peritoneal function. Additionally, submesothelial tissue thickness, percentage of high mesothelial cells (perpendicular diameter > 2 microm), vascular density, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF) beta1 mRNA expression were determined. Submesothelial collagen concentration was estimated by van Gieson staining. Submesothelial tissue thickness and vascular density, mediated by VEGF and TGFbeta production, in the diaphragmatic peritoneum increased significantly in rats exposed to any PD fluid. Gambrosol induced a marked increased fibrosis of the hepatic peritoneum. A significant increase in high mesothelial cells was observed in the Gambrosol group only. Net ultrafiltration was reduced in the Gambrosol and in the glucose-free groups compared to untreated controls. Small solute transport was unchanged, but all groups exposed to fluids showed significantly increased lymph flow. Our results show that long-term exposure to different components of PD fluids leads to mesothelial cell damage, submesothelial fibrosis, and neoangiogenesis. Mesothelial cell damage could be connected to the presence of GDP; the other changes were similar for all fluids. Peritoneal transport characteristics did not change in any consistent way and the neoangiogenesis observed was not paralleled by increased solute transport.

[Resistance of the functional systems of the smooth muscle cells of isolated myometrium to long-term incubation in Ringer-Locke solution at 4 degrees C].

PubMed

Peshikov, V L; Tsirkin, V I; Burmistrova, T D; Bordunovskaia, V P

1977-09-01

Contractile effects of adrenaline, acethylcholine and hyperpotassium solution on the isolated myometrium strips (non-pregnent rats, and women; pregnant rabbits, cats, and women) are studied. The amplitudes of these contractile effects were seen decreasing if the strips were previously immersed in the Ringer-Lokk solution at 4 degrees C 5--9 days prior to observation.

Parenteral nanoemulsions of risperidone for enhanced brain delivery in acute psychosis: Physicochemical and in vivo performances.

PubMed

Đorđević, Sanela M; Santrač, Anja; Cekić, Nebojša D; Marković, Bojan D; Divović, Branka; Ilić, Tanja M; Savić, Miroslav M; Savić, Snežana D

2017-11-30

This work aimed to deepen the lately acquired knowledge about parenteral nanoemulsions as carriers for brain delivery of risperidone, a poorly water-soluble antipsychotic drug, through establishing the prospective relationship between their physicochemical, pharmacokinetic, biodistribution, and behavioral performances. For this purpose, two optimized risperidone-loaded nanoemulsions, stabilized by lecithin or lecithin/polysorbate 80 mixture, and costabilized by sodium oleate, were produced by high-pressure homogenization. The characterization revealed the favorable droplet size, narrow size distribution, high surface charge, with proven stability to autoclaving and long-term stability for at least one year at 25±2°C. Pharmacokinetic and tissue distribution results demonstrated improved plasma, liver, and brain pharmacokinetic parameters, resulting in 1.2-1.5-fold increased relative bioavailability, 1.1-1.8-fold decreased liver distribution, and about 1.3-fold improved brain uptake of risperidone active moiety following intraperitoneal administration of nanoemulsions relative to solution in rats. In behavioral study, investigated nanoemulsions showed pronounced reduction in basal and, more pertinently, amphetamine-induced locomotor activity in rats, with an early onset of antipsychotic action, and this effect lasted at least 90min after drug injection. Together, these findings corroborate the applicability of parenteral nanoemulsions as carriers for enhanced brain delivery of risperidone, further suggesting their promise in acute psychosis treatment or other emergency situations. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and characterization of Tripterygium wilfordii multi-glycoside nanoparticle using supercritical anti-solvent process.

PubMed

Chen, Fengli; Li, Tong; Li, Shuangyang; Hou, Kexin; Liu, Zaizhi; Li, Lili; Cui, Guoqiang; Zu, Yuangang; Yang, Lei

2014-02-17

The aim of this study was to prepare nanosized Tripterygium wilfordii multi-glycoside (GTW) powders by the supercritical antisolvent precipitation process (SAS), and to evaluate the anti-inflammatory effects. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of process parameters such as precipitation pressure (15-35 MPa), precipitation temperature (45-65 °C), drug solution flow rates (3-7 mL/min) and drug concentrations (10-30 mg/mL) were investigated. The nanospheres obtained with mean diameters ranged from 77.5 to 131.8 nm. The processed and unprocessed GTW were characterized by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy and thermal gravimetric analysis. The present study was designed to investigate the beneficial effect of the GTW nanoparticles on adjuvant-induced arthritis in albino rats. The processed and unprocessed GTW were tested against Freund's complete adjuvant-induced arthritis in rats. Blood samples were collected for the estimation of interleukins (IL-1α, IL-1β) and tumor necrosis factor-α (TNF-α). It was concluded that physicochemical properties and anti-inflammatory activity of GTW nanoparticles could be improved by physical modification, such as particle size reduction using supercritical antisolvent (SAS) process. Further, SAS process was a powerful methodology for improving the physicochemical properties and anti-inflammatory activity of GTW.

Preparation and Characterization of Tripterygium wilfordii Multi-Glycoside Nanoparticle Using Supercritical Anti-Solvent Process

PubMed Central

Chen, Fengli; Li, Tong; Li, Shuangyang; Hou, Kexin; Liu, Zaizhi; Li, Lili; Cui, Guoqiang; Zu, Yuangang; Yang, Lei

2014-01-01

The aim of this study was to prepare nanosized Tripterygium wilfordii multi-glycoside (GTW) powders by the supercritical antisolvent precipitation process (SAS), and to evaluate the anti-inflammatory effects. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of process parameters such as precipitation pressure (15–35 MPa), precipitation temperature (45–65 °C), drug solution flow rates (3–7 mL/min) and drug concentrations (10–30 mg/mL) were investigated. The nanospheres obtained with mean diameters ranged from 77.5 to 131.8 nm. The processed and unprocessed GTW were characterized by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy and thermal gravimetric analysis. The present study was designed to investigate the beneficial effect of the GTW nanoparticles on adjuvant-induced arthritis in albino rats. The processed and unprocessed GTW were tested against Freund’s complete adjuvant-induced arthritis in rats. Blood samples were collected for the estimation of interleukins (IL-1α, IL-1β) and tumor necrosis factor-α (TNF-α). It was concluded that physicochemical properties and anti-inflammatory activity of GTW nanoparticles could be improved by physical modification, such as particle size reduction using supercritical antisolvent (SAS) process. Further, SAS process was a powerful methodology for improving the physicochemical properties and anti-inflammatory activity of GTW. PMID:24549173

Rosiglitazone Improves Insulin Sensitivity and Baroreflex Gain in Rats with Diet-Induced Obesity

PubMed Central

Zhao, Ding; McCully, Belinda H.

2012-01-01

Obesity decreases baroreflex gain (BRG); however, the mechanisms are unknown. We tested the hypothesis that impaired BRG is related to the concurrent insulin resistance, and, therefore, BRG would be improved after treatment with the insulin-sensitizing drug rosiglitazone. Male rats fed a high-fat diet diverged into obesity-prone (OP) and obesity-resistant (OR) groups after 2 weeks. Then, OP and OR rats, as well as control (CON) rats fed a standard diet, were treated daily for 2 to 3 weeks with rosiglitazone (3 or 6 mg/kg) or its vehicle by gavage. Compared with OR and CON rats, conscious OP rats exhibited reductions in BRG (OP, 2.9 ± 0.1 bpm/mm Hg; OR, 4.0 ± 0.2 bpm/mm Hg; CON, 3.9 ± 0.2 bpm/mm Hg; P < 0.05) and insulin sensitivity (hyperinsulinemic euglycemic clamp; OP, 6.8 ± 0.9 mg/kg · min; OR, 22.2 ± 1.2 mg/kg · min; CON, 17.7 ± 0.8 mg/kg · min; P < 0.05), which were well correlated (r2 = 0.49; P < 0.01). In OP rats, rosiglitazone dose-dependently improved (P < 0.05) insulin sensitivity (12.8 ± 0.6 mg/kg · min at 3 mg/kg; 16.0 ± 1.5 mg/kg · min at 6 mg/kg) and BRG (3.8 ± 0.4 bpm/mm Hg at 3 mg/kg; 5.3 ± 0.7 bpm/mm Hg at 6 mg/kg). However, 6 mg/kg rosiglitazone also increased BRG in OR rats without increasing insulin sensitivity, disrupted the correlation between BRG and insulin sensitivity (r2 = 0.08), and, in OP and OR rats, elevated BRG relative to insulin sensitivity (analysis of covariance; P < 0.05). Moreover, in OP rats, stimulation of the aortic depressor nerve, to activate central baroreflex pathways, elicited markedly reduced decreases in heart rate and arterial pressure, but these responses were not improved by rosiglitazone. In conclusion, diet-induced obesity impairs BRG via a central mechanism that is related to the concurrent insulin resistance. Rosiglitazone normalizes BRG, but not by improving brain baroreflex processing or insulin sensitivity. PMID:22815534

Exercise training improves the defective centrally mediated erectile responses in rats with type I diabetes.

PubMed

Zheng, Hong; Mayhan, William G; Patel, Kaushik P

2011-11-01

Erectile dysfunction is a serious and common complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for the penile erection. The goal of the present study was to determine the impact of exercise training (ExT) on the centrally mediated erectile dysfunction in streptozotocin (STZ)-induced type I diabetic (T1D) rats. Male Sprague-Dawley rats were injected with STZ to induce diabetes mellitus. Three weeks after STZ or vehicle injections, rats were assigned to either ExT (treadmill running for 3-4 weeks) or sedentary groups to produce four experimental groups: control + sedentary, T1D + sedentary, control + ExT, and T1D + ExT. After 3-4 weeks ExT, central N-methyl-D-aspartic acid (NMDA) or sodium nitroprusside (SNP)-induced penile erectile responses were measured. Neuronal nitric oxide synthase (nNOS) expression in the paraventricular nucleus (PVN) of the hypothalamus was measured by using histochemistry, real time polymerase chain reaction (PCR) and Western blot approaches. In rats with T1D, ExT significantly improved the blunted erectile response, and the intracavernous pressure changes to NMDA (50 ng) microinjection within the PVN (T1D + ExT: 3.0 ± 0.6 penile erection/rat; T1D + sedentary: 0.5 ± 0.3 penile erection/rat within 20 minutes, P < 0.05). ExT improved erectile dysfunction induced by central administration of exogenous nitric oxide (NO) donor, SNP in T1D rats. Other behavior responses including yawning and stretching, induced by central NMDA and SNP microinjection were also significantly increased in T1D rats after ExT. Furthermore, we found that ExT restored the nNOS mRNA and protein expression in the PVN in T1D rats. These results suggest that ExT may have beneficial effects on the erectile dysfunction in diabetes through improvement of NO bioavailability within the PVN. Thus, ExT may be used as therapeutic modality to up-regulate nNOS within the PVN and improve the central component of the erectile dysfunction in diabetes mellitus. © 2011 International Society for Sexual Medicine.

Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide.

PubMed

Nurliyani; Harmayani, Eni; Sunarti

2015-01-01

The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (p<0.05) triglyceride than the rats fed goat milk or soy milk kefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (p<0.05) than rats fed goat millk kefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (p<0.01) than untreated diabetic rats. The average number of Langerhans and β-cells in diabetic rats fed kefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells.

[Study on the oxidative stress in the ovaries of a rat model of polycystic ovary].

PubMed

Gong, Jin; Wu, Dong-bo; Zhang, Lan-lan; Li, Jia; Zhao, Xing; Zhang, Dan

2015-03-01

To establish a pathological animal model of polycystic ovary (PCO) by letrozole in rats. Investigate whether PCO were mediated by the effect of oxidative stress by measuring oxidative stress levels in this cohort of rats with PCO, and proceed a new way of treatment for polycystic ovary syndrom (PCOS). 90 SD female rats aged 6 weeks were randomly divided into two groups, including a control group of 45 rats that received vehicle only [19% aqueous solution of carboxmethlycellulose (CMC), 1 mL/d] once daily orally (p.o.), and an experimental group of 45 rats, which were administered letrozole at concentrations of 1 mg/kg p.o. dissolved in 1% CMC (1 mL/d) once daily. The treatment period was 28 d. During this period, vaginal smears were collected daily for estrus cycle determination and body masses were measured every 7 d. On the day subsequent to the last letrozole dose administration, rats were killed; Uteri and ovaries were then excised and weighed for the calculation of organ indexes. Serum hormone levels, SHBG and histologic changes in the ovaries were examined. Then testosterone free index (FAD) was calculated. Oxidant status was evaluated by determination of ovarian total oxidant status (TOS), malondialdehyde (MDA) concentration and intracellular reactive oxygen species (ROS) level, while antioxidant status was evaluated by determination of total antioxidant status (TAS) and superoxide dismutase (SOD) concentration. Vaginal smear test showed the estrus cycle began to disappear from day 12 to day 15. A statistically significant difference in growth curves, ovarian weights, uterine weights and organ indexes between the groups were also observed. In rats with PCO serum testosterone (T), follicle-stimulating hormone (FSH) concentrations and free androgen index (FADI) were significantly increased compared with the control group (rats without PCO). However, rats with PCO had decreased levels of estrogen (E2), luteinizing hormone (LH), and progesterone (P) compared with the control group. In a rat model of PCO achieved via letrozole, it was found that the levels of TOS, MDA, oxidative stress index (OSI) and intracellular ROS were significantly increased, while the TAS level, SOD content were significantly decreased in the ovary homogenates (P<0.05). The results indicated that the PCOS pathological process significantly increased the oxidative stress production. PCO rat model successfully induced via letrozole, and it is a suitable model for study of ovarian lesions. Oxidative stress also contributes to the PCO rat model, the protective effect of antioxidant might provide a new insight into the potential therapeutic solution to PCOS.

[The role of delta-1 opiate receptors in regulation of contractility in isolated rat heart during normal oxygenation and ischemia-reperfusion].

PubMed

Lasukova, T V; Maslov, L N; Lishmanov, Iu B; Gross, G J

2004-01-01

The experiments on isolated rat heart demonstrated significant decrease in reperfusion-induced damage of cardiomyocytes by addition of selective delta 1 receptor agonist DPDPE (0.1 mg/l) to the perfusion solution. On the contrary, no cardioprotective effect was observed for 0.5 mg/l concentration of the peptide or after its intravenous injection. Stimulation of the cardiac delta 1 opioid receptors by intravenous injection of 0.5 mg/kg DPDPE or its addition to the perfusion solution decreased myocardial contractility both in conditions of normal oxygenation and during reperfusion. Thus, the cardioprotective and negative inotropic effect of DPDPE is mediated by activation of the cardiac delta 1 opioid receptors.

Thiolated chitosan nanoparticles for the nasal administration of leuprolide: bioavailability and pharmacokinetic characterization.

PubMed

Shahnaz, Gul; Vetter, Anja; Barthelmes, Jan; Rahmat, Deni; Laffleur, Flavia; Iqbal, Javed; Perera, Glen; Schlocker, Wolfgang; Dünnhaput, Sarah; Augustijns, Patrick; Bernkop-Schnürch, Andreas

2012-05-30

The purpose of this study was to develop thiolated nanoparticles to enhance the bioavailability for the nasal application of leuprolide. Thiolated chitosan-thioglycolic acid (chitosan-TGA) and unmodified chitosan nanoparticles (NPs) were developed via ionic gelation with tripolyphosphate (TPP). Leuprolide was incorporated during the formulation process of NPs. The thiolated (chitosan-TGA) NPs had a mean size of 252 ± 82 nm, a zeta potential of +10.9 ± 4 mV, and payload of leuprolide was 12 ± 2.8. Sustained release of leuprolide from thiolated NPs was demonstrated over 6h, which might be attributed to inter- and/or intramolecular disulfide formation within the NPs network. Ciliary beat frequency (CBF) study demonstrated that thiolated NPs can be considered as suitable additives for nasal drug delivery systems. Compared to leuprolide solution, unmodified NPs and thiolated NPs provoked increased leuprolide transport through porcine nasal mucosa by 2.0 and 5.2 folds, respectively. The results of a pharmacokinetic study in male Sprague-Dawley rats showed improved transport of leuprolide from thiolated NPs as compared to leuprolide solution. Thiolated NPs had a 6.9-fold increase in area under the curve, more than 4-fold increase in elimination half-life, and a ∼3.8-fold increase in maximum plasma concentration compared to nasal solution alone. The relative nasal bioavailability (versus s.c. injection) of leuprolide thiolated NPs calculated on the basis of AUC((0-6)) was about 19.6% as compared to leuprolide solution 2.8%. The enhanced bioavailability of leuprolide is likely due to facilitated transport by thiolated NPs rather than improved release. Copyright © 2012. Published by Elsevier B.V.

Recombinant Dendroides canadensis antifreeze proteins as potential ingredients in cryopreservation solutions.

PubMed

Halwani, Dina O; Brockbank, Kelvin G M; Duman, John G; Campbell, Lia H

2014-06-01

Expanding cryopreservation methods to include a wider range of cell types, such as those sensitive to freezing, is needed for maintaining the viability of cell-based regenerative medicine products. Conventional cryopreservation protocols, which include use of cryoprotectants such as dimethylsulfoxide (Me2SO), have not prevented ice-induced damage to cell and tissue matrices during freezing. A family of antifreeze proteins (AFPs) produced in the larvae of the beetle, Dendroides canadensis allow this insect to survive subzero temperatures as low as -26°C. This study is an assessment of the effect of the four hemolymph D. canadensis AFPs (DAFPs) on the supercooling (nucleating) temperature, ice structure patterns and viability of the A10 cell line derived from the thoracic aorta of embryonic rat. Cryoprotectant solution cocktails containing combinations of DAFPs in concentrations ranging from 0 to 3mg/mL in Unisol base mixed with 1M Me2SO were first evaluated by cryomicroscopy. Combining multiple DAFPs demonstrated significant supercooling point depressing activity (∼9°C) when compared to single DAFPs and/or conventional 1M Me2SO control solutions. Concentrations of DAFPs as low as 1 μg/mL were sufficient to trigger this effect. In addition, significantly improved A10 smooth muscle cell viability was observed in cryopreservation experiments with low DAFP-6 and DAFP-2 concentrations in combination with Me2SO. No significant improvement in viability was observed with either DAFP-1 or DAFP-4. Low and effective DAFP concentrations are advantageous because they minimize concerns regarding cell cytotoxicity and manufacturing cost. These findings support the potential of incorporating DAFPs in solutions used to cryopreserve cells and tissues. Copyright © 2014 Elsevier Inc. All rights reserved.

Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).

PubMed

Dain, Alejandro; Repossi, Gaston; Diaz-Gerevini, Gustavo T; Vanamala, Jairam; Das, Undurti N; Eynard, Aldo R

2016-11-25

Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM. After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls. Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups. eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory indices. ω-3 + NDGA supplementation, at the doses tested, ameliorated inflammatory, metabolic and oxidative stress markers studied.

Increased sucrose intake and corresponding c-Fos in amygdala and parabrachial nucleus of dietary obese rats.

PubMed

Li, Jinrong; Chen, Ke; Yan, Jianqun; Wang, Qian; Zhao, Xiaolin; Yang, Xuejuan; Yang, Dejun; Zhao, Shiru; Zhu, Guangjing; Sun, Bo

2012-09-13

The intake-excitatory effects of caloric foods are mainly due to the palatable taste and the ensuing positive postingestive effects. Dietary obese individuals are inclined to overeat high caloric foods. However, it is still unclear whether the taste or postingestive reinforcement mainly contributes to the excessive intake by obese individuals. In the present study, we measured 10- or 120-min sucrose solution drunk by dietary obese rats and measured c-Fos expression following 120-min tests in the central nucleus of amygdala (CeA), a forebrain nucleus involved in the hedonic reward and craving, and the parabrachial nucleus (PBN), a taste relay area responsive to positive postingestive effects. Dietary obese rats, compared with those fed normal chow, ingested larger amounts of sucrose solution (0.25 M) in the 120-min test, but not in the 10-min test. In addition, significantly more sucrose-induced c-Fos positive cells were found in the CeA, but much less in the external lateral subnucleus of the PBN of dietary obese rats. Our results demonstrate that increased sucrose intake in dietary obese rats is mainly due to the alteration of postingestive effects. The differences in these postingestive effects in obesity may involve greater positive/excitatory signals in which the CeA may play a role, and less negative/inhibitory signals in which the el-PBN may be involved. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baiden, H.N.; Ercanli-Huffman, F.G.

Bioavailability of zinc from sweet potato (SP) roots and leaves were determined, by extrinsic labeling technique, in rats fed control and zinc deficient diets. Weanling male Sprague Dawley (SD) rats (60-75g) were divided into 4 groups, and fed laboratory chow, a control diet (ad libitum and pair fed) and a zinc deficient diet, for 4 weeks. Each group then was divided into at least 2 sub groups, containing 6 rats, which were intubated with one of 3 tubing solutions extrinsically labeled with /sup 65/Zn; baked sweet potato roots (BSPR), raw sweet potato leaves (RSPL) and cooked sweet potato leaves (CSPL).more » Five hours after intubation the rats were sacrificed, blood, liver, testes, spleen, heart, brain, thymus and lungs were removed. Feces, urine, and GI tract contents were collected and their /sup 65/Zn activity was determined in a gamma counter. In all treatment groups zinc bioavailability from BSPR, RSPL or CSPL were not significantly different. Zinc deficient rats absorbed significantly more (P < 0.01) /sup 65/Zn (86-90% of the dose), regardless of type of tubing solution than the pairfed or control animals (35-58% of the dose). The highest retention of /sup 65/Zn was found in the liver (12-20% of absorbed dose), GI tract (6-17% of absorbed dose), kidney (2-8% of absorbed dose), and blood (1-5% of absorbed dose). The lowest retention was found in the brain, heart, thymus and testes. (< 1% of absorbed dose).« less

[Effect of Aβ1-42 injection on hippocampus cells in rats and protective role of polygona-polysaccharose for Alzheimer's disease].

PubMed

Yi, Yuxin; Wu, Shixing; Ye, Maosheng; Zeng, Yi; Zhang, Ping; Xie, Yiqun

2014-04-01

To determine the effect of polygona-polysaccharose (PP) on learning and memory ability in rats with Alzheimer's disease (AD). Forty five Sprague-Dawley rats were assigned into 3 groups. Rats in the sham-operated group were injected with normal saline. Rats in the Aβ group were injected with Aβ1-42. Rats in the PP group were injected with 16% PP solution for 45 days consecutively. The Morris water maze was used to investigate the ability of learning and memory in the rats. The effect of Aβ and PP on the hippocampus cells was observed by HE and Congo red staining of methanol. Rats in the sham-operated group had no obvious morphological change; and morphology of rats in the PP group was basicaly normal. The layer of pyramidal cells in the Aβ group was decreased. The cells appeared sparse and irregular and became smaller. Karyopyknosis and vacuolar degeneration cells were also found. More positive staining materials aggradated in the Aβ group compared with the PP group by Congo red staining (P<0.05). Aβ infusion into the hippocampus results in the impairment of the neuronal degeneration in the rats, which shows similar characterizations of AD. PP can reduce the deposition of Aβ in the hippocampus.

Intrauterine Growth Restricted Rats Exercised at Pregnancy: Maternal-Fetal Repercussions.

PubMed

Corvino, S B; Netto, A O; Sinzato, Y K; Campos, K E; Calderon, I M P; Rudge, M V C; Volpato, G T; Zambrano, E; Damasceno, D C

2015-08-01

To evaluate the effect of swimming in pregnant rats born with intrauterine growth restriction (IUGR) and their offspring, IUGR rats were obtained using the streptozotocin-induced severe diabetic (SD) rats. In this study, the nondiabetic parental generation presented 10 rats and diabetic parental generation presented 116 rats. Of these, the mated nondiabetic female rats were 10 and the number of diabetic rats was 45. In relation to term pregnancy, there were 10 animals in the nondiabetic group and 15 rats in the diabetic group. In the offspring of SD rats (IUGR group), 43 females were classified as small for pregnancy age, 19 rats were classified as appropriate for pregnancy age, and 0 female was classified as large for pregnancy age. The nondiabetic and SD pregnant rats generated offspring with appropriate (control [C]) and small (IUGR) weight for pregnancy age, respectively. At adult life, the C group was maintained as nonexercised C group and IUGR rats were distributed into 2 subgroups, namely, nonexercised (IUGR) and exercised (IUGRex). The rate of mated rats in the IUGR group was reduced compared to the C group. During pregnancy, the IUGR rats presented hyperinsulinemia, impaired reproductive outcomes, decreased body weight, hypertriglyceridemia, and hyperlactacidemia. The IUGRex presented reduced insulin and triglyceride levels. Thus, swimming improved lipid metabolism and increased insulin sensitivity. However, the offspring showed retarded growth, reinforcing the need to stimulate the exercise practice in women under supervision with different professional expertise to promote appropriate gestational conditions and improve perinatal outcomes. © The Author(s) 2015.

EFFECT OF PHOSPHORYLATED HESPERIDIN AND HYALURONIDASE ON THE RATE OF ERYTHROCYTE REMOVAL FROM THE PERITONEAL CAVITY OF RATS

DTIC Science & Technology

Previously reported studies reveal that phosphorylated hesperidin interferes with absorption of 0.9% NaCl solution from the peritoneal cavity of rats...while hyaluronidase facilitzvates this process. In the present study the effect of phosphorylated hesperidin and hyaluronidase on absorption of...suspension. Treatment with phosphorylated hesperidin significantly interfered with the absorption, only 12% of the originally administered erythrocytes being

Defining the Dormant Tumor Microenvironment for Breast Cancer Prevention and Treatment

DTIC Science & Technology

2011-09-01

USAMRMC a. REPORT U b . ABSTRACT U c. THIS PAGE U UU 36 19b. TELEPHONE NUMBER (include area code) 2 TABLE OF CONTENTS...Each group will include 12 rats. b ) Breed rats in the parous group. After parturition, normalize the number of pups to eight. Ten days after...solution ultrasonication assisted tryptic digestion (UATD) method. Parity arm completed. b ) Analyzed the digested mammary ECM samples from

Polyphenol-Rich Extract of Syzygium cumini Leaf Dually Improves Peripheral Insulin Sensitivity and Pancreatic Islet Function in Monosodium L-Glutamate-Induced Obese Rats

PubMed Central

Sanches, Jonas R.; França, Lucas M.; Chagas, Vinicyus T.; Gaspar, Renato S.; dos Santos, Kayque A.; Gonçalves, Luciana M.; Sloboda, Deborah M.; Holloway, Alison C.; Dutra, Richard P.; Carneiro, Everardo M.; Cappelli, Ana Paula G.; Paes, Antonio Marcus de A.

2016-01-01

Syzygium cumini (L.) Skeels (Myrtaceae) has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed, and pulp-fruit, however. there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc) on lean and monosodium L-glutamate (MSG)-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg) or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a twofold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10–1000 μg/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E β-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating β-cell insulin release, which was associated with improvements in metabolic outcomes in MSG-induced obese rats. PMID:27014062

Polyphenol-Rich Extract of Syzygium cumini Leaf Dually Improves Peripheral Insulin Sensitivity and Pancreatic Islet Function in Monosodium L-Glutamate-Induced Obese Rats.

PubMed

Sanches, Jonas R; França, Lucas M; Chagas, Vinicyus T; Gaspar, Renato S; Dos Santos, Kayque A; Gonçalves, Luciana M; Sloboda, Deborah M; Holloway, Alison C; Dutra, Richard P; Carneiro, Everardo M; Cappelli, Ana Paula G; Paes, Antonio Marcus de A

2016-01-01

Syzygium cumini (L.) Skeels (Myrtaceae) has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed, and pulp-fruit, however. there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc) on lean and monosodium L-glutamate (MSG)-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg) or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a twofold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10-1000 μg/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E β-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating β-cell insulin release, which was associated with improvements in metabolic outcomes in MSG-induced obese rats.

Disposition and pharmacokinetics in rats of McN-5707, a potential antidepressant drug

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, K.T.; Holland, M.L.; Hills, J.F.

1986-03-01

A single 80 mg/kg oral solution dose of McN-5707-/sup 14/C x HBr (trans-6-(2-chlorophenyl)-1,2,3,5,6,10b-hexahydropyrrolo(2,1-a)isoquinoline hydrobromide (1:1)) was administered orally to 40 Wistar rats. Total /sup 14/C concentrations in plasma were high (> 4.5 ..mu..g x equiv/mL) for at least 24 hours after dosing. Unchanged McN-5707 represented < 10% of the total /sup 14/C concs in plasma at 45 min and < 1% at 24 hours after dosing. In the 8 days following dose administration, 23% of the dose was excreted in urine and 70% of the dose was excreted in feces. Analysis (HPLC and TLC) of glusulase treated urine, plasma andmore » fecal samples revealed the presence of multiple metabolites of McN-5707. Unchanged McN-5707 was found only in fecal extracts (2-7% of dose). Single solution doses of McN-5707 x HBr were administered p.o. (20 mg/kg) and i.v. (4 mg/kg) to 39 Wistar rats. Plasma samples were analyzed for McN-5707 using a capillary GC assay. These studies indicated that McN-5707 was well absorbed and extensively metabolized in rats following oral doses.« less

Effects of pinealectomy and melatonin supplementation on endometrial explants in a rat model.

PubMed

Koc, Onder; Gunduz, Bülent; Topcuoglu, Ata; Bugdayci, Güler; Yilmaz, Fahri; Duran, Bülent

2010-11-01

To determine the effects of pinealectomy on endometrial explants in rats and evaluate the activity of superoxide dismutase (SOD) and catalase (CAT) and the levels of malondialdehyde (MDA) in the rat endometriosis model. Rats with experimentally induced endometriosis were randomly divided into three groups after second-look laparotomies. Group 1 (pinealectomy, n = 8) and Group 2 (pinealectomy+melatonin, n = 8) underwent pinealectomies after the second-look laparotomies. Group 3 was presented as control group (vehicle solution+without pinealectomy (n = 6)). Melatonin was administered intraperitoneally for 4 weeks in Group 2, whereas an equal volume of vehicle solution was given to Groups 1 and 3. Evaluation of the volume of the endometrial explants, histopathological examination and preservation of explant epitheliums according to the scoring system were undertaken. There was a statistically significant increase in spherical explant volumes of Group 1 compared to Groups 2 and 3. In Group 1, the level of MDA was significantly higher and SOD and CAT activity was significantly lower compared to Groups 2 and 3. A statistically significant increase in the epithelial lining scores of explants was noted in Group 1 compared to Groups 2 and 3. The effects of pinealectomy on the progression of endometriosis explants were reversed by melatonin. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

New High-performance Liquid Chromatography-DAD Method for Analytical Determination of Arbutin and Hydroquinone in Rat Plasma.

PubMed

Gallo, F R; Pagliuca, G; Multari, G; Panzini, G; D'amore, E; Altieri, I

2015-01-01

Natural substances present in herbal preparations should be carefully used because they can give toxic or therapeutic effects despite of their amount or the way of administration. The safety of products of vegetable origin must be assessed before commercialisation by monitoring the active ingredients and their metabolites. This study was therefore designed to identify and quantify arbutin and its metabolite hydroquinone, naturally present in Arctostaphylos uva-ursi (L.) Spreng plant in rat plasma, after an acute and subacute administration of aqueous arbutin solution in Wistar rats. For this purpose a reversed-phase high-performance liquid chromatography coupled with photodiode array detection was developed to assess the pharmacokinetic of arbutin and hydroquinone in plasma of female rats treated with aqueous arbutin solutions. The detection (arbutin: 0.0617 µg/ml and hydroquinone 0.0120 µg/ml) and quantification (arbutin: 0.2060 µg/ml and hydroquinone: 0.0400 µg/ml) limits were determined. At the arbutin concentration level of 10.7 µg/ml repeatability was 13.33% and its recovery 93.4±6.93%, while at the hydroquinone concentration level of 10.6 µg/ml repeatability was 11.66% and its recovery 92.9±7.75%. Furthermore the method was fully validated and the obtained data indicate that the new method provides good performances.

A loop resonator for slice-selective in vivo EPR imaging in rats

PubMed Central

Hirata, Hiroshi; He, Guanglong; Deng, Yuanmu; Salikhov, Ildar; Petryakov, Sergey; Zweier, Jay L.

2008-01-01

A loop resonator was developed for 300-MHz continuous-wave electron paramagnetic resonance (CW-EPR) spectroscopy and imaging in live rats. A single-turn loop (55 mm in diameter) was used to provide sufficient space for the rat body. Efficiency for generating a radiofrequency magnetic field of 38 µT/W1/2 was achieved at the center of the loop. For the resonator itself, an unloaded quality factor of 430 was obtained. When a 350 g rat was placed in the resonator at the level of the lower abdomen, the quality factor decreased to 18. The sensitive volume in the loop was visualized with a bottle filled with an aqueous solution of the nitroxide spin probe 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrrolin-1-yloxy (3-CP). The resonator was shown to enable EPR imaging in live rats. Imaging was performed for 3-CP that had been infused intravenously into the rat and its distribution was visualized within the lower abdomen. PMID:18006343

Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion.

PubMed

Bambakidis, Nicholas C; Miller, Robert H

2004-01-01

A substantial cause of neurological disability in spinal cord injury is oligodendrocyte death leading to demyelination and axonal degeneration. Rescuing oligodendrocytes and preserving myelin is expected to result in significant improvement in functional outcome after spinal cord injury. Although previous investigators have used cellular transplantation of xenografted pluripotent embryonic stem cells and observed improved functional outcome, these transplants have required steroid administration and only a minority of these cells develop into oligodendrocytes. The objective of the present study was to determine whether allografts of oligodendrocyte precursors transplanted into an area of incomplete spinal cord contusion would improve behavioral and electrophysiological measures of spinal cord function. Additional treatment incorporated the use of the glycoprotein molecule Sonic hedgehog (Shh), which has been shown to play a critical role in oligodendroglial development and induce proliferation of endogenous neural precursors after spinal cord injury. Laboratory study. Moderate spinal cord contusion injury was produced in 39 adult rats at T9-T10. Ten animals died during the course of the study. Nine rats served as contusion controls (Group 1). Six rats were treated with oligodendrocyte precursor transplantation 5 days after injury (Group 2). The transplanted cells were isolated from newborn rat pups using immunopanning techniques. Another eight rats received an injection of recombinant Shh along with the oligodendrocyte precursors (Group 3), while six more rats were treated with Shh alone (Group 4). Eight additional rats received only T9 laminectomies to serve as noninjured controls (Group 0). Animals were followed for 28 days. After an initial complete hindlimb paralysis, rats of all groups receiving a contusive injury recovered substantial function within 1 week. By 28 days, rats in Groups 2 and 3 scored 4.7 and 5.8 points better on the Basso, Beattie, Bresnahan (BBB) open field locomotor score than rats in group 1 (Groups 2 and 3=18.2 and 19.4 points, respectively, after 28 days vs. Group 1=13.6 points; p=.015). Rats in Group 4 scored no better than those in Group 1 (BBB=16.4). Motor evoked potential (MEP) recordings revealed a strong trend towards significant improvement in latency measurements in all treatment groups compared with controls at 28 days, although three animals in Group 1 and two animals in Group 3 were not recordable. Histological examination demonstrated significantly more spared white matter in the same groups that correlated with the improvements in BBB scores and MEP latencies. Immunohistochemical analysis showed the survival, proliferation and migration of the transplanted cells, as well as the induction of proliferating endogenous neural precursor cells in animals treated with Shh. These findings suggest that the transplantation of oligodendrocyte precursors may improve axonal conduction and spinal cord function in the injured spinal cord. The benefits seem more pronounced with the addition of Shh, and the addition of Shh alone results in the proliferation of an endogenous population of neural precursor cells.

Nebulization of Cyclic Arginine-Glycine-(D)-Aspartic Acid-Peptide Grafted and Drug Encapsulated Liposomes for Inhibition of Acute Lung Injury.

PubMed

Desu, Hari R; Thoma, Laura A; Wood, George C

2018-03-13

Acute lung injury (ALI) is a fatal syndrome in critically ill patients. It is characterized by lung edema and inflammation. Numerous pro-inflammatory mediators are released into alveoli. Among them, interleukin-1beta (IL-1β) causes an increase in solute permeability across the alveolar-capillary barrier leading to edema. It activates key effector cells (alveolar epithelial and endothelial cells) releasing inflammatory chemokines and cytokines. The purpose of the study was to demonstrate that nebulized liposomes inhibit ALI in vivo. In vivo ALI model was simulated through intra-tracheal instillation of IL-1β solution (100 μg/mL in PBS, pH 7.2, 200 μL) in male Sprague-Dawley rats. Various formulations were tested in ALI induced rats. These formulations include plain liposomes (PL), methylprednisolone sodium succinate solution (MPS solution), cRGD-peptide grafted liposomes (L cRGD ) and methylprednisolone sodium succinate encapsulated and cRGD-peptide grafted liposomes (MPS-L cRGD ). Formulations were nebulized in vivo in rats using micro-pump nebulizer. Liposome formulations exhibited higher levels of drug concentration in lungs. The physicochemical parameters demonstrated that the liposome formulations were stable. On the basis of aerodynamic droplet-size, nebulized formulations were estimated to deposit in different regions of respiratory tract, especially alveolar region, Among the formulations, MPS-L cRGD caused significant reduction of edema, neutrophil infiltration and inflammation biochemical marker levels. From the results, it can be inferred that nebulization of targeted liposomes had facilitated spatial and temporal modulation of drug delivery resulting in alleviation of ALI.

Effect of K+ and Na+ on calcium-dependent electron-dense particles in the monoaminergic synaptic vesicles of rat pineal nerves fixed in Ca2+-containing solutions.

PubMed

Pellegrino de Iraldi, A; Corazza, J P

1983-01-01

The effect of K+ and Na+ on the Ca2+ binding site in the dense core of monoaminergic vesicles of pineal nerves was investigated in the rat. Rat pineal glands, bisected immediately after decapitation, were incubated at room temperature in solutions containing high K+ or high Na+ in the presence or absence of Ca2+. Fixation was performed in glutaraldehyde-osmium tetroxide in collidine buffer, with and without CaCl2. It was confirmed that, after fixation in Ca2+-containing solutions, an electron-dense particle, located in the vesicle core, which can be considered a calcium deposit, appears within the synaptic vesicles. It was observed that this Ca2+ deposit may be modified by incubation in a high K+ or high Na+ milieu before fixation in Ca2+ containing solutions. When the incubation was carried out with high K+ and high Ca2+ simultaneously, Ca2+ deposits were considerably increased. With K+ alone, no Ca2+ deposits were apparent, as when electrical stimulation is applied before fixation. This effect was not observed when the incubation was done in high Na+. Consecutive incubations in high K+ and high Na+, respectively, restored the capability of the vesicle cores to bind Ca2+. Prolonged incubation in high Na+ before fixation increased Ca2+ deposits within the vesicles. These findings are in line with data on the effect of these ions upon the storage and release of biogenic amines and suggest that these ions modify the capability of synaptic vesicles to bind Ca2+.

Preclinical safety evaluation of submicronized sildenafil citrate nebulization solution in small experimental animals.

PubMed

Agrawal, Priyanka; Soni, Sandeep; Mittal, Gaurav; Bhatnagar, Aseem

2015-01-01

Sildenafil citrate (SC) nebulization solution has the potential to treat pulmonary hypertension by delivering high concentration directly to the respiratory system while minimizing systemic drug exposure and associated toxicity. The objective of the present study was to evaluate the potential toxicity of aerosolized SC (inhaled) in Sprague dawley rats for 28 days. The rats were randomly divided into five groups (n = 6). Placebo (normal saline) was inhaled to group I (control). Group II was exposed to therapeutic dose (TD): 20 mg/kg, while group 3 and group 4 were exposed to 3 TD and 6 TD, respectively, till 28 days and toxicokinetic parameters were evaluated in group V. The particle size of the nebulized solution of SC (1%) was measured by using Anderson Cascade Impactor. At the end of experiment, all animals were sacrificed. Endpoints used to evaluate potential toxicity of inhaled sildenafil citrate were clinical observations, body weight, and clinical pathology along with broncho-alveolar lavage (BAL) Fluid investigation. ACI study has shown that more than 70% aerosolized drug particles were in submicron range (0.3-0.5 μm). There was no systemic toxicity or clinically limiting local respiratory toxicity associated with inhalation exposure to SC nebulization solution at 6 TD. No significant changes were observed in the level of different blood and BALF parameters in treated groups in comparison to control. Histopathological examination revealed no abnormal findings in the animals of treated group. The data demonstrate that aerosolized sildenafil citrate is well tolerated in rats and suggest its use in humans.

Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats.

PubMed

Kawamura, Tomohiro; Huang, Chien-Sheng; Tochigi, Naobumi; Lee, Sungsoo; Shigemura, Norihisa; Billiar, Timothy R; Okumura, Meinoshin; Nakao, Atsunori; Toyoda, Yoshiya

2010-12-27

Successful abrogation of ischemia/reperfusion (I/R) injury of lung grafts could significantly improve short- and long-term outcomes for lung transplant (LTx) recipients. Hydrogen gas has potent antioxidant and antiapoptotic properties and has been recently used in number of experimental and clinical studies. The purpose of this research was to investigate whether inhaled hydrogen gas could reduce graft I/R injury during lung transplantation. Orthotopic left LTxs were performed in syngenic Lewis rats. Grafts were perfused with and stored in low potassium dextran solution at 4°C for 6 hr. The recipients received 100% O2 or 98% O2 with 2% N2, 2% He, or 2% H2 during surgery and 1 hr after reperfusion. The effects of hydrogen were assessed by functional, pathologic, and molecular analysis. Gas exchange was markedly impaired in animals exposed to 100% O2, 2% N2, or 2% He. Hydrogen inhalation attenuated graft injury as indicated by significantly improved gas exchange 2 hr after reperfusion. Graft lipid peroxidation was significantly reduced in the presence of hydrogen, demonstrating antioxidant effects of hydrogen in the transplanted lungs. Lung cold I/R injury causes the rapid production and release of several proinflammatory mediators and epithelial apoptosis. Exposure to 2% H2 significantly blocked the production of several proinflammatory mediators and reduced apoptosis with induction of the antiapoptotic molecules B-cell lymphoma-2 and B-cell lymphoma-extra large. Treatment of LTx recipients with inhaled hydrogen can prevent lung I/R injury and significantly improve the function of lung grafts after extended cold preservation, transplant, and reperfusion.

The effects of changes of water balance on the renal pelvic epithelium of the rat.

PubMed

Khorshid, M R; Moffat, D B

1975-01-01

The effects of changes of water balance on the renal pelvic epithelium of the rat. The fine structure of the various epithelia which line the renal pelvis was investigated in five hydropenic rats and five rats undergoing a water diuresis. In the former, the thin epithelium which covers the outer medulla showed dilated intercellular spaces and an increased number of cytoplasmic vacuoles whereas the intercellular spaces were tightly closed and there were few vacuoles in the diuretic rats. It was considered that these changes indicate an exchange of water and solute between pelvic urine and the outer since medulla they are similar to those occurring in epithelia elsewhere which are engaged in transport of salt or water. Similar but less marked changes were found in the papillary epithelium. Changes in the transitional epithelium were similar to those which have previously been described elsewhere in the urinary tract.

The Effect of Lactic Acid Bacteria-fermented Soybean Milk Products on Carrageenan-induced Tail Thrombosis in Rats

PubMed Central

KAMIYA, Seitaro; OGASAWARA, Masayoshi; ARAKAWA, Masayuki; HAGIMORI, Masayori

2013-01-01

Thrombosis is characterized by congenital and acquired procatarxis. Lactic acid bacteria-fermented soybean milk products (FS-LAB) inhibit hepatic lipid accumulation and prevent atherosclerotic plaque formation. However, the therapeutic efficacy of FS-LAB against thrombosis has yet to be investigated. In this study, FS-LAB were administered subcutaneously into the tails of rats, with the subsequent intravenous administration of κ-carrageenan 12 hr after the initial injection. In general, administration of κ-carrageenan induces thrombosis. The length of the infarcted tail regions was significantly shorter in the rats administered a single-fold or double-fold concentration of the FS-LAB solution compared with the region in control rats. Therefore, FS-LAB exhibited significant antithrombotic effects. Our study is the first to characterize the properties of FS-LAB and, by testing their efficacy on an in vivo rat model of thrombosis, demonstrate the potency of their antithrombotic effect. PMID:24936368

Choline Alleviates Parenteral Nutrition-Associated Duodenal Motility Disorder in Infant Rats.

PubMed

Zhu, Jie; Wu, Yang; Guo, Yonggao; Tang, Qingya; Lu, Ting; Cai, Wei; Huang, Haiyan

2016-09-01

Parenteral nutrition (PN) has been found to influence duodenal motility in animals. Choline is an essential nutrient, and its deficiency is related to PN-associated organ diseases. Therefore, this study was aimed to investigate the role of choline supplementation in an infant rat model of PN-associated duodenal motility disorder. Three-week-old Sprague-Dawley male rats were fed chow and water (controls), PN solution (PN), or PN plus intravenous choline (600 mg/kg) (PN + choline). Rats underwent jugular vein cannulation for infusion of PN solution or 0.9% saline (controls) for 7 days. Duodenal oxidative stress status, concentrations of plasma choline, phosphocholine, and betaine and serum tumor necrosis factor (TNF)-α were assayed. The messenger RNA (mRNA) and protein expression of c-Kit proto-oncogene protein (c-Kit) and membrane-bound stem cell factor (mSCF) together with the electrophysiological features of slow waves in the duodenum were also evaluated. Rats on PN showed increased reactive oxygen species; decreased total antioxidant capacity in the duodenum; reduced plasma choline, phosphocholine, and betaine; and enhanced serum TNF-α concentrations, which were reversed by choline intervention. In addition, PN reduced mRNA and protein expression of mSCF and c-Kit, which were inversed under choline administration. Moreover, choline attenuated depolarized resting membrane potential and declined the frequency and amplitude of slow waves in duodenal smooth muscles of infant rats induced by PN, respectively. The addition of choline to PN may alleviate the progression of duodenal motor disorder through protecting smooth muscle cells from injury, promoting mSCF/c-Kit signaling, and attenuating impairment of interstitial cells of Cajal in the duodenum during PN feeding. © 2015 American Society for Parenteral and Enteral Nutrition.

High ambient temperature increases intravenous methamphetamine self-administration on fixed and progressive ratio schedules in rats.

PubMed

Cornish, Jennifer L; Clemens, Kelly J; Thompson, Murray R; Callaghan, Paul D; Dawson, Bronwyn; McGregor, Iain S

2008-01-01

Methamphetamine is a drug that is often consumed at dance parties or nightclubs where the ambient temperature is high. The present study determined whether such high ambient temperatures alter intravenous methamphetamine self-administration in the rat. Male Hooded Wistar rats were trained to self-administer intravenous methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 1 (FR1) or progressive ratio (PR) schedule of reinforcement at an ambient temperature of 23 +/- 1 degrees C. They were then given their daily self-administration session at a raised ambient temperature of 30 +/- 1 degrees C. Methamphetamine self-administration was increased at 30 degrees C under both FR1 and PR reinforcement schedules, with the latter effect indicating that heat enhances the motivation to obtain methamphetamine. High temperatures did not alter self-administration of the D1 receptor agonist SKF 82958 in methamphetamine-experienced rats suggesting some specificity in the methamphetamine effect. When rats were given access to drink isotonic saline solution during methamphetamine self-administration sessions they drank much more solution at 30 degrees C than 23 degrees C. However, availability of isotonic saline to drink did not alter the heat-induced facilitation of methamphetamine self-administration (PR schedule) indicating that the heat effect does not simply reflect increased motivation for intravenous fluids. Hyperthermia was evident in rats self-administering methamphetamine at high ambient temperatures and fluid consumption did not prevent this effect. Heat did not affect blood levels of methamphetamine, or its principal metabolite amphetamine indicating that the facilitatory effect of heat did not reflect altered methamphetamine pharmacokinetics. Overall, these results show that high ambient temperatures increase the reinforcing efficacy of methamphetamine and encourage higher levels of drug intake.

Evidence for hydroxyl radical scavenging action of nitric oxide donors in the protection against 1-methyl-4-phenylpyridinium-induced neurotoxicity in rats.

PubMed

Banerjee, Rebecca; Saravanan, Karuppagounder S; Thomas, Bobby; Sindhu, Kizhake M; Mohanakumar, Kochupurackal P

2008-06-01

In the present study we provide evidence for hydroxyl radical (*OH) scavenging action of nitric oxide (NO*), and subsequent dopaminergic neuroprotection in a hemiparkinsonian rat model. Reactive oxygen species are strongly implicated in the nigrostriatal dopaminergic neurotoxicity caused by the parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). Since the role of this free radical as a neurotoxicant or neuroprotectant is debatable, we investigated the effects of some of the NO* donors such as S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine hydrochloride (SIN-1), sodium nitroprusside (SNP) and nitroglycerin (NG) on in vitro *OH generation in a Fenton-like reaction involving ferrous citrate, as well as in MPP+-induced *OH production in the mitochondria. We also tested whether co-administration of NO* donor and MPP+ could protect against MPP+-induced dopaminergic neurotoxicity in rats. While NG, SNAP and SIN-1 attenuated MPP+-induced *OH generation in the mitochondria, and in a Fenton-like reaction, SNP caused up to 18-fold increase in *OH production in the latter reaction. Striatal dopaminergic depletion following intranigral infusion of MPP+ in rats was significantly attenuated by NG, SNAP and SIN-1, but not by SNP. Solutions of NG, SNAP and SIN-1, exposed to air for 48 h to remove NO*, when administered similarly failed to attenuate MPP+-induced neurotoxicity in vivo. Conversely, long-time air-exposed SNP solution when administered in rats intranigrally, caused a dose-dependent depletion of the striatal dopamine. These results confirm the involvement of *OH in the nigrostriatal degeneration caused by MPP+, indicate the *OH scavenging ability of NO*, and demonstrate protection by NO* donors against MPP+-induced dopaminergic neurotoxicity in rats.

Estradiol enhances the acquisition of lithium chloride-induced conditioned taste aversion in castrated male rats

NASA Astrophysics Data System (ADS)

Lin, Shih-Fan; Tsai, Yuan-Feen; Tai, Mei-Yun; Yeh, Kuei-Ying

2015-10-01

The present study examined the effects of short-term treatment with ovarian hormones on the acquisition of conditioned taste aversion (CTA). Adult male rats were castrated and randomly divided into LiCl- and saline-treated groups. Nineteen days after castration, all of the animals were subjected to 23.5-h daily water deprivation for seven successive days (day 1 to day 7). On the conditioning day (day 8), the rats received either a 4 ml/kg of 0.15 M LiCl or the same dose of saline injection immediately after administration of a 2 % sucrose solution during the 30-min water session. Starting from day 6, rats in both groups received one of the following treatments: daily subcutaneous injection of (1) estradiol alone (30 μg/kg; estradiol benzoate (E) group), (2) estradiol plus progesterone (500 μg; E + progesterone (P) group), or (3) olive oil. From day 9 to day 11, all of the rats were given daily two-bottle preference tests during the 30-min fluid session. The estradiol and estradiol plus progesterone treatments in the LiCl groups resulted in significantly lower preference scores for the sucrose solution compared with the olive oil treatment groups, but no difference in preference score was seen between these two groups. These results indicate that both the estradiol and estradiol plus progesterone treatments in the LiCl groups enhanced the acquisition of CTA learning and suggest that estradiol affects the acquisition of CTA mediated by an activational effect in male rats, whereas progesterone treatment does not influence the effects of estradiol on the acquisition of CTA.

Vagus Nerve Stimulation Delivered During Motor Rehabilitation Improves Recovery in a Rat Model of Stroke

PubMed Central

Khodaparast, Navid; Hays, Seth A.; Sloan, Andrew M.; Fayyaz, Tabbassum; Hulsey, Daniel R.; Rennaker, Robert L.; Kilgard, Michael P.

2014-01-01

Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into three groups: vagus nerve stimulation during rehab, vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), pre-lesion training, post-lesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed one week of recovery before post-lesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All seventeen trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to pre-lesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to pre-lesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared to rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. PMID:24553102

Osmolality- and Na+ -dependent effects of hyperosmotic NaCl solution on contractile activity and Ca2+ cycling in rat ventricular myocytes.

PubMed

Ricardo, Rafael A; Bassani, Rosana A; Bassani, José W M

2008-01-01

Hypertonic NaCl solutions have been used for small-volume resuscitation from hypovolemic shock. We sought to identify osmolality- and Na(+)-dependent components of the effects of the hyperosmotic NaCl solution (85 mOsm/kg increment) on contraction and cytosolic Ca(2+) concentration ([Ca(2+)](i)) in isolated rat ventricular myocytes. The biphasic change in contraction and Ca(2+) transient amplitude (decrease followed by recovery) was accompanied by qualitatively similar changes in sarcoplasmic reticulum (SR) Ca(2+) content and fractional release and was mimicked by isosmotic, equimolar increase in extracellular [Na(+)] ([Na(+)](o)). Raising osmolality with sucrose, however, augmented systolic [Ca(2+)](i) monotonically without change in SR parameters and markedly decreased contraction amplitude and diastolic cell length. Functional SR inhibition with thapsigargin abolished hyperosmolality effects on [Ca(2+)](i). After 15-min perfusion, both hyperosmotic solutions slowed mechanical relaxation during twitches and [Ca(2+)](i) decline during caffeine-evoked transients, raised diastolic and systolic [Ca(2+)](i), and depressed systolic contractile activity. These effects were greater with sucrose solution, and were not observed after isosmotic [Na(+)](o) increase. We conclude that under the present experimental conditions, transmembrane Na(+) redistribution apparently plays an important role in determining changes in SR Ca(2+) mobilization, which markedly affect contractile response to hyperosmotic NaCl solutions and attenuate the osmotically induced depression of contractile activity.

The structure and dynamics of rat apo-cellular retinol-binding protein II in solution: comparison with the X-ray structure.

PubMed

Lu, J; Lin, C L; Tang, C; Ponder, J W; Kao, J L; Cistola, D P; Li, E

1999-03-05

The structure and dynamics of rat apo-cellular retinol binding protein II (apo-CRBP II) in solution has been determined by multidimensional NMR analysis of uniformly enriched recombinant rat 13C, 15N-apo-CRBP II and 15N-apo-CRBP II. The final ensemble of 24 NMR structures has been calculated from 3274 conformational restraints or 24.4 restraints/residue. The average root-mean-square deviation of the backbone atoms for the final 24 structures relative to their mean structure is 1.06 A. Although the average solution structure is very similar to the crystal structure, it differs at the putative entrance to the binding cavity, which is formed by the helix-turn-helix motif, the betaC-betaD turn and the betaE-betaF turn. The mean coordinates of the main-chain atoms of amino acid residues 28-38 are displaced in the solution structure relative to the crystal structure. The side-chain of F58, located on the betaC-betaD turn, is reoriented such that it interacts with L37 and no longer blocks entry into the ligand-binding pocket. Residues 28-35, which form the second helix of the helix-turn-helix motif in the crystal structure, do not exhibit a helical conformation in the solution structure. The solution structure of apo-CRBP II exhibits discrete regions of backbone disorder which are most pronounced at residues 28-32, 37-38 and 73-76 in the betaE-betaF turn as evaluated by the consensus chemical shift index, the root-mean-square deviation, amide 1H exchange rates and 15N relaxation studies. These studies indicate that fluctuations in protein conformation occur on the microseconds to ms time-scale in these regions of the protein. Some of these exchange processes can be directly observed in the three-dimensional 15N-resolved NOESY spectrum. These results suggest that in solution, apo-CRBP II undergoes conformational changes on the microseconds to ms time-scale which result in increased access to the binding cavity. Copyright 1999 Academic Press.

Mechanisms underlying the neurokinin A-induced contraction of the pregnant rat myometrium

PubMed Central

Shintani, Yoshinobu; Nishimura, Junji; Niiro, Naohisa; Hirano, Katsuya; Nakano, Hitoo; Kanaide, Hideo

2000-01-01

Using fura-PE3 fluorimetry and α-toxin permeabilization, the characteristics of the contractile responses to neurokinin A (NKA) were determined in the pregnant rat myometrium. NKA induced contractions in rat myometrium in a concentration-dependent manner. There were no significant differences in the maximum contractions and EC50 values between the pregnant and non-pregnant myometrium, however, the contraction of only the former was greatly enhanced in the presence of phosphoramidon (PPAD), an endopeptidase inhibitor. In the pregnant myometrium, NKA induced sustained increases in [Ca2+]i and tension in normal physiological saline solution, while only small transient increases in [Ca2+]i and tension were observed in Ca2+-free solution. Both diltiazem (10 μM) and SK-F 96365 (10 μM) significantly inhibited the NKA-induced elevations of [Ca2+]i and tension. The effects were additive when these drugs were used together. NKA induced a significant leftward shift of the [Ca2+]i-tension curve obtained by changing the external Ca2+ (0–2.5 mM) during depolarization with high K+ solution. This Ca2+-sensitizing effect by NKA was also observed in the α-toxin permeabilized myometrium. These results indicated that in the pregnant rat myometrium: (1) the responsiveness to NKA increased, although it was masked by the increase in the endopeptidase activity; (2) NKA induced contractions of the myometrium by increasing both [Ca2+]i and the myofilament Ca2+ sensitivity and (3) The NKA-induced [Ca2+]i elevation was partly due to the intracellular Ca2+ release and mainly due to the Ca2+ influx, which was thought to be through both voltage dependent calcium channels and non-specification channels. PMID:10882403

Lychee seed extract protects against neuronal injury and improves cognitive function in rats with type II diabetes mellitus with cognitive impairment

PubMed Central

Wu, Jianming; Chen, Haixia; Zeng, Yuan; Wang, Xiuling; Yang, Le; Mei, Qibing; Cao, Shousong; Qin, Dalian

2018-01-01

Lychee seed is a traditional Chinese medicine and has many beneficial effects such as modulation of blood sugar and lipids, antioxidation, antivirus and antitumor. Studies have indicated that type II diabetes mellitus (T2DM) and Alzheimer's disease (AD) share common biological mechanisms including insulin resistance, impaired glucose metabolism, β-amyloid (Aβ) formation, oxidative stress and presence of advanced glycation end products (AGEs). The present study investigated the effects of lychee seed extract (LSE) on neuroprotection, cognitive function improvement and possible underlying mechanisms in a rat model of T2DM with cognitive impairment. We analyzed the chemical profile of LSE using a UHPLC-SPD chromatogram and evaluated its effect on the improvement of spatial learning and memory of rats by a Morris water maze. The levels of glucose, insulin, Aβ, AGEs, Tau protein and acetylcholinesterase in the blood and/or hippocampus of rats were determined by blood-glucose meter, radioimmunoassay, chemical chromatometry, enzyme-linked immunosorbent assay (ELISA) and immunohistochemical analysis, respectively. Results demonstrated that LSE consists of eight major and around 20 minor ingredients, and it remarkably prevents neuronal injury and improves cognitive functions in T2DM rats. The levels of glucose, insulin, Aβ, AGEs and Tau protein were significantly increased in the blood and/or hippocampus of T2DM rats, while LSE remarkably decreased their levels compared to vehicle treatment (P<0.01). The possible mechanisms may be associated with IR improvement and decreased formations of Aβ, AGEs and Tau protein in the hippocampus of T2DM rats. LSE may be developed as the agent for the treatment of T2DM and/or AD clinically. PMID:29138799

Alcohol and acute pancreatitis. An experimental study in the rat.

PubMed

Jalovaara, P; Apaja, M

1978-01-01

The effect of chronic alcohol pretreatment and various pancreatobiliary secretions on the severity of experimental pancreatitis was studied in the rat. 95 rats were pretreated with ethanol (20% w/v, 1.1 ml/100 g body weight) five times weekly for 10 to 12 weeks by gastric intubation. 88 rats served as controls. Pancreatic lesions were produced by retograde injection of different pancreatobiliary secretions into the pancreatic ducts. The secretions were collected from both normal and chronically alcohol-fed rats, and each was used for induction of experimental pancreatitis in the control and alcohol pretreated rats. Bile obtained from normal rats was no more toxic to the pancreas than 0.9% saline solution, while bile obtained from the chronically alcohol-fed rats caused significantly more serious lesions to the pancreas than did normal rat bile. Bile-pancreatic juice (mixture of secretions at papilla of Vater) of normal and chronically alcohol-fed rats was as toxic as the bile of the alcohol-fed rats. Alcohol pretreatment had no significant effect on the severity of pancreatitis when control and alcohol-fed groups separately or the whole material according to pretreatment was examined. These results suggest that the metabolic effects of ethanol on the pancreas as such do not sensitize the pancreas to acute pancreatitis. An exogenous mechanism is required. The reflux of toxic alcoholic bile into the pancreas might act as an induction factor in acute alcohol pancreatitis.

Long term dietary methoxychlor exposure in rats increases sodium solution consumption but has few effects on other sexually dimorphic behaviors.

PubMed

Flynn, K M; Delclos, K B; Newbold, R R; Ferguson, S A

2005-09-01

Methoxychlor is an insecticide with estrogen-like activity, thus exposure during development might cause sexually dimorphic behavioral alterations. To evaluate this, pregnant rats consumed diets containing 0, 10, 100 or 1000 ppm methoxychlor from gestational day 7, and offspring continued on these diets until postnatal day (PND) 77. Assessments of sexually dimorphic behaviors in offspring indicated that intake of a 3.0% sodium chloride solution was significantly increased (41%) in males and females of the 1000 ppm group. No treatment group differed from controls in open field nor running wheel activity, play behavior, nor 0.3% saccharin solution intake. Offspring of the 1000 ppm group showed significantly decreased body weight, reaching 17% less than controls at PND 77, but not clearly related to their salt solution intake. During pregnancy, 1000 ppm dams consumed 23% less food and weighed 10% less than controls, but this did not affect litter outcomes. These results indicate that in rodents, developmental and chronic exposure to dietary methoxychlor alters the sexually dimorphic behavior of salt-solution intake in young adults of both sexes. Similar behavioral alterations with other xenoestrogens, and the potential for interactions among xenoestrogens, suggest that this report may minimize the true effects of dietary methoxychlor exposure.

Preliminary study of coconut water for graft tissues preservation in transplantation.

PubMed

César, Jorge Miguel Schettino; Petroianu, Andy; Vasconcelos, Leonardo de Souza; Cardoso, Valbert Nascimento; Mota, Luciene das Graças; Barbosa, Alfredo José Afonso; Soares, Cristina Duarte Vianna; de Oliveira, Amanda Lima

2015-01-01

to verify the effectiveness of coconut water in preserving tissues for transplant. Fifty male Wistar rats were randomly distributed in five groups, according to the following preservation solutions for tissue grafts: Group 1: Lactated Ringer; Group 2: Belzer solution; Group 3: mature coconut water; Group 4: green coconut water; Group 5: modified coconut water. In Group 5, the green coconut water has been modified like the Belzer solution. From each animal we harvested the spleen, ovaries and skin of the back segment. These tissues were preserved for six hours in one of the solutions. Then, the grafts were reimplanted. The recovery of the function of the implanted tissues was assessed 90 days after surgery, by splenic scintigraphy and blood exam. The implanted tissues were collected for histopathological examination. The serum levels did not differ among groups, except for the animals in Group 5, which showed higher levels of IgG than Group 1, and differences in relation to FSH between groups 1 and 2 (p <0.001), 4 and 2 (p = 0.03) and 5 and 2 (p = 0.01). The splenic scintigraphy was not different between groups. The ovarian tissue was better preserved in mature coconut water (p <0.007). the coconut water-based solutions preserves spleen, ovary, and rat skin for six hours, maintaining their normal function.

Effects of saliva from chronically reserpinized rat on Na and K transport in perfused main excretory duct of submandibular gland of normal rat.

PubMed

Jirakulsomchok, D; Schneyer, C A

1987-09-01

Reserpine (RES) (0.5 mg/kg body wt, ip) was administered to rats for 7 days. On Day 8 saliva was evoked from these animals by intraperitoneal injection of pilocarpine nitrate (10 mg/kg body wt) and saliva from submandibular and parotid glands was collected separately. These collected salivas were used to perfuse through the main ducts of the submandibular glands of normal rats. After a control period of perfusion of the main duct with bicarbonate saline solution, parotid saliva from RES rats was perfused through the duct followed by regular perfusion. There was inhibition of Na absorption (22%) and K secretion (23%). Moreover, when submandibular saliva from treated rat was perfused through the main duct prior to regular perfusion, there was a decrease in Na absorption (31%) and K secretion (28%). In contrast, perfusion of the main duct with either parotid or submandibular saliva from normal rats caused no significant changes in Na and K transport. The present experiments confirm previous studies that there is some Na-inhibitory factor(s) present in saliva of the chronically RES-treated rat.

Bone marrow mesenchymal stem cells combined with minocycline improve spinal cord injury in a rat model

PubMed Central

Chen, Dayong; Zeng, Wei; Fu, Yunfeng; Gao, Meng; Lv, Guohua

2015-01-01

The aims of this study were to assess that the effects of bone marrow mesenchymal stem cells (BMSCs) combination with minocycline improve spinal cord injury (SCI) in rat model. In the present study, the Wistar rats were randomly divided into five groups: control group, SCI group, BMSCs group, Minocycline group and BMSCs + minocycline group. Basso, Beattie and Bresnahan (BBB) test and MPO activity were used to assess the effect of combination therapy on locomotion and neutrophil infiltration. Inflammation factors, VEGF and BDNF expression, caspase-3 activation, phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions were estimated using commercial kits or western blot, respectively. BBB scores were significantly increased and MPO activity was significantly undermined by combination therapy. In addition, combination therapy significantly decreased inflammation factors in SCI rats. Results from western blot showed that combination therapy significantly up-regulated the protein of VEGF and BDNF expression and down-regulated the protein of phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions in SCI rats. Combination therapy stimulation also suppressed the caspase-3 activation in SCI rats. These results demonstrated that the effects of bone marrow mesenchymal stem cells combination with minocycline improve SCI in rat model. PMID:26722382

Adult rats are more sensitive to the vascular effects induced by hyperhomocysteinemia than young rats.

PubMed

de Andrade, Claudia Roberta; de Campos, Glenda Andréa Déstro; Tirapelli, Carlos Renato; Laurindo, Francisco R M; Haddad, Renato; Eberlin, Marcos N; de Oliveira, Ana Maria

2010-01-01

We aimed to investigate the vascular effects of hyperhomocysteinemia (HHcy) on carotid arteries from young and adult rats. With this purpose young and adult rats received a solution of DL-homocysteine-thiolactone (1 g/kg body weight/day) in the drinking water for 7, 14 and 28 days. Increase on plasma homocysteine occurred in young and adult rats treated with DL-homocysteine-thiolactone in all periods. Vascular reactivity experiments using standard muscle bath procedures showed that HHcy enhanced the contractile response of endothelium-intact, carotid rings to phenylephrine in both young and adult rats. However, in young rats, the increased phenylephrine-induced contraction was observed after hyperhomocysteinemia for 14 and 28 days, whereas in adult rats this response was already apparent after 7 day treatment. HHcy impaired acetylcholine-induced relaxation in arteries from adult but not young rats. The contraction induced by phenylephrine in carotid arteries in the presence of Y-27632 was reversed to control values in arteries from young but not adult rats with hyperhomocysteinemia. HHcy did not alter the contraction induced by CaCl(2) in carotid arteries from young rats, but enhanced CaCl(2)-induced contraction in the arteries from adult rats. HHcy increased the basal levels of superoxide anion in arteries from both groups. Finally, HHcy decreased the basal levels of nitrite in arteries from adult but not young rats. The major new finding of the present work is that arteries from young rats are more resistant to vascular changes evoked by HHcy than arteries from adult rats. Also, we verified that the enhanced vascular response to phenylephrine observed in carotid arteries of DL-homocysteine thiolactone-treated rats is mediated by different mechanisms in young and adult rats. Copyright 2010. Published by Elsevier Inc.

Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide

PubMed Central

Harmayani, Eni; Sunarti

2015-01-01

The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (p<0.05) triglyceride than the rats fed goat milk or soy milk kefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (p<0.05) than rats fed goat millk kefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (p<0.01) than untreated diabetic rats. The average number of Langerhans and β-cells in diabetic rats fed kefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells. PMID:26877646

A study of the intrarenal recycling of urea in the rat with chronic experimental pyelonephritis.

PubMed Central

Gilbert, R M; Weber, H; Turchin, L; Fine, L G; Bourgoignie, J J; Bricker, N S

1976-01-01

The concentrating ability of the kidney was studied by clearance and micropuncture techniques and tissue slice analyses in normal rats with two intact kidneys (intact controls), normal rats with a solitary kidney (uninephrectomized controls), and uremic rats with a single pyelonephritic kidney. Urinary osmolality after water deprivation for 24 h and administration of antidiuretic hormone was 2,501+/-217 and 2,874+/-392 mosmol/kg H2O in intact and uninephrectomized control rats, respectively, and 929+/-130 mosmol/kg H2O in pyelonephritic rats (P less than 0.001 compared to each control group). Fractional water reabsorption and concentrating ability were significantly decreased in the pyelonephritic group, and, to achieve an equivalent fractional excretion of urea, a greater fractional excretion of water was required in the pyelonephritic rats than in the control rats. Whole animal glomerular filtration rate was 1.57+/-0.19 ml/min and 1.39+/-0.18 ml/min in intact and in uninephrectomized controls, respectively, and 0.30+/-0.07 ml/min in pyelonephritic rats (P less than 0.001 compared to each control group). Single nephron glomerular filtration rate was 35.6+/-3.8 nl/min in intact control rats and was significantly increased (P less than 0.05) in both uninephrectomized (88.0+/-10.8 nl/min) and pyelonephritic rats (71.5+/-14.4 nl/min). In all groups fractional water delivery and fractional sodium delivery were closely comparable at the end of the proximal convoluted tubule and at the beginning of the distal convoluted tubule. In contrast, fractional urea delivery out of the proximal tubule was greater in the intact control group (73+/-8%) than in either the uninephrectomized (52+/-2%) or the pyelonephritic group (53+/-3%) (P less than 0.005). Fractional urea delivery at the early part of the distal tubule increased significantly to 137+/-11% and 93+/-6% of the filtered load in intact control and uninephrectomized control rats, respectively (P less than 0.001 compared to the late proximal values of each group), but failed to increase significantly in pyelonephritic rats (65+/-13%), indicating interruption of the normal recycling of urea in the latter group. Analysis of tissue slices demonstrated a rising corticopapillary gradient for total tissue water solute concentration as well as for tissue water urea concentration in both groups of control rats. In contrast, the pyelonephritic animals exhibited no similar gradients from cortex to papilla. These data indicate that the pyelonephritic kidney fails to recycle urea and accumulate interstitial solute. The latter must inevitably lead to a concentrating defect. Images PMID:993348

Effect of a pharmacologically induced decrease in core temperature in rats resuscitated from cardiac arrest.

PubMed

Katz, Laurence M; Frank, Jonathan E; Glickman, Lawrence T; McGwin, Gerald; Lambert, Brice H; Gordon, Christopher J

2015-07-01

Hypothermia is recommended by international guidelines for treatment of unconscious survivors of cardiac arrest to improve neurologic outcomes. However, temperature management is often underutilized because it may be difficult to implement. The present study evaluated the efficacy of pharmacologically induced hypothermia on survival and neurological outcome in rats resuscitated from cardiac arrest. Cardiac arrest was induced for 10 min in 120 rats. Sixty-one rats were resuscitated and randomized to normothermia, physical cooling or pharmacological hypothermia 5 min after resuscitation. Pharmacological hypothermia rats received a combination of ethanol, vasopressin and lidocaine (HBN-1). Physical hypothermia rats were cooled with intravenous iced saline and cooling pads. Rats in the pharmacological hypothermia group received HBN-1 at ambient temperature (20 °C). Normothermic rats were maintained at 37.3 ± 0.2 °C. HBN-1 (p < 0.0001) shortened the time (85 ± 71 min) to target temperature (33.5 °C) versus physical hypothermia (247 ± 142 min). The duration of hypothermia was 17.0 ± 6.8h in the HBN-1 group and 17.3 ± 7.5h in the physical hypothermia group (p = 0.918). Survival (p = 0.034), neurological deficit scores (p < 0.0001) and Morris Water Maze performance after resuscitation (p = 0.041) was improved in the HBN-1 versus the normothermic group. HBN-1 improved survival and early neurological outcome compared to the physical hypothermia group while there was no significant difference in performance in the Morris water maze. HBN-1 induced rapid and prolonged hypothermia improved survival with good neurological outcomes after cardiac arrest suggesting that pharmacologically induced regulated hypothermia may provide a practical alternative to physical cooling. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Vildagliptin and caloric restriction for cardioprotection in pre-diabetic rats.

PubMed

Tanajak, Pongpan; Pintana, Hiranya; Siri-Angkul, Natthaphat; Khamseekaew, Juthamas; Apaijai, Nattayaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2017-02-01

Long-term high-fat diet (HFD) consumption causes cardiac dysfunction. Although calorie restriction (CR) has been shown to be useful in obesity, we hypothesized that combined CR with dipeptidyl peptidase-4 (DPP-4) inhibitor provides greater efficacy than monotherapy in attenuating cardiac dysfunction and metabolic impairment in HFD-induced obese-insulin resistant rats. Thirty male Wistar rats were divided into 2 groups to be fed on either a normal diet (ND, n = 6) or a HFD (n = 24) for 12 weeks. Then, HFD rats were divided into 4 subgroups (n = 6/subgroup) to receive just the vehicle, CR diet (60% of mean energy intake and changed to ND), vildagliptin (3 mg/kg/day) or combined CR and vildagliptin for 4 weeks. Metabolic parameters, heart rate variability (HRV), cardiac mitochondrial function, left ventricular (LV) and fibroblast growth factor (FGF) 21 signaling pathway were determined. Rats on a HFD developed insulin and FGF21 resistance, oxidative stress, cardiac mitochondrial dysfunction and impaired LV function. Rats on CR alone showed both decreased body weight and visceral fat accumulation, whereas vildagliptin did not alter these parameters. Rats in CR, vildagliptin and CR plus vildagliptin subgroups had improved insulin sensitivity and oxidative stress. However, vildagliptin improved heart rate variability (HRV), cardiac mitochondrial function and LV function better than the CR. Chronic HFD consumption leads to obese-insulin resistance and FGF21 resistance. Although CR is effective in improving metabolic regulation, vildagliptin provides greater efficacy in preventing cardiac dysfunction by improving anti-apoptosis and FGF21 signaling pathways and attenuating cardiac mitochondrial dysfunction in obese-insulin-resistant rats. © 2017 Society for Endocrinology.

Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats.

PubMed

De Bruin, N M W J; Kiliaan, A J; De Wilde, M C; Broersen, L M

2003-07-01

Rationale. Hypertension is considered a risk factor for the development of cognitive disorders, because of its negative effects on cerebral vasculature and blood flow. Genetically induced hypertension in rats has been associated with a range of cognitive impairments. Therefore, spontaneously hypertensive rats (SHR) can potentially be used as a model for cognitive deficits in human subjects. Consecutively, it can be determined whether certain food components can improve cognition in these rats. Objective. The present study aimed to determine whether SHR display specific deficits in attention, learning, and memory function. Additionally, effects of chronic uridine and choline administration were studied. Methods. 5-7 months old SHR were compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. (a) The operant delayed non-matching-to-position (DNMTP) test was used to study short-term memory function. (b) The five-choice serial reaction time (5-CSRT) task was used to assess selective visual attention processes. (c) Finally, the Morris water maze (MWM) acquisition was used as a measure for spatial learning and mnemonic capabilities. Results. (1) SHR exhibited significantly impaired performance in the 5-CSRT test in comparison with the two other rat strains. Both the SHR and WKY showed deficits in spatial learning when compared with the SD rats. (2) Uridine and choline supplementation normalized performance of SHR in the 5-CSRT test. (3) In addition, uridine and choline treatment improved MWM acquisition in both WKY and SHR rats. Conclusion. The present results show that the SHR have a deficiency in visual selective attention and spatial learning. Therefore, the SHR may provide an interesting model in the screening of substances with therapeutic potential for treatment of cognitive disorders. A combination of uridine and choline administration improved selective attention and spatial learning in SHR.

Determination of aesculin in rat plasma by high performance liquid chromatography method and its application to pharmacokinetics studies.

PubMed

Chen, QiuHong; Hou, ShiXiang; Zheng, Jia; Bi, YueQi; Li, YuanBo; Yang, XiaoJiao; Cai, Zheng; Song, XiangRong

2007-10-15

A sensitive and reproducible high performance liquid chromatography method with UV detection was described for the determination of aesculin in rat plasma. After deproteinization by methanol using metronidazole as internal standard (I.S.), solutes were evaporated to dryness at 40 degrees C under a gentle stream of nitrogen. The residue was reconstituted in 100 microl of mobile phase and a volume of 20 microl was injected into the HPLC for analysis. Solutes were separated on a Diamonsil C18 column (250 mm x 4.6 mm i.d., 5 microm particle size, Dikma) protected by a ODS guard column (10 mm x 4.0 mm i.d., 5 microm particle size), using acetonitrile-0.1% triethylamine solution (adjusted to pH 3.0 using phosphoric acid) (10:90, v/v) as mobile phase (flow-rate 1.0 ml/min), and wavelength of the UV detector was set at 338 nm. No interference from any endogenous substances was observed during the elution of aesculin and internal standard (I.S., metronidazole). The retention times for I.S and aesculin were 10.4 and 12.4 min, respectively. The limit of quantification was evaluated to be 57.4 ng/ml and the limit of detection was 24.0 ng/ml. The method was used in the study of pharmacokinetics of aesculin after intraperitoneal injection (i.p.) administration in rats.

Efficacy of Poly(D,L-Lactic Acid-co-Glycolic acid)-Poly(Ethylene Glycol)-Poly(D,L-Lactic Acid-co-Glycolic Acid) Thermogel As a Barrier to Prevent Spinal Epidural Fibrosis in a Postlaminectomy Rat Model.

PubMed

Li, Xiangqian; Chen, Lin; Lin, Hong; Cao, Luping; Cheng, Ji'an; Dong, Jian; Yu, Lin; Ding, Jiandong

2017-04-01

Experimental animal study. The authors conducted a study to determine the efficacy and safety of the poly(D,L-lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) thermogel to prevent peridural fibrosis in an adult rat laminectomy model. Peridural fibrosis often occurs after spinal laminectomy. It might cause persistent back and/or leg pain postoperatively and make a reoperation more difficult and dangerous. Various materials have been used to prevent epidural fibrosis, but only limited success has been achieved. The PLGA-PEG-PLGA thermogel was synthesized by us. Total L3 laminectomies were performed on 24 rats. The PLGA-PEG-PLGA thermogel or chitosan (CHS) gel (a positive control group) was applied to the operative sites in a blinded manner. In the control group, the L3 laminectomy was performed and the defect was irrigated with the NS solution 3 times. All the rats were killed 4 weeks after the surgery. The cytotoxicity of this thermogel was evaluated in vitro and the result demonstrated that no evidence of cytotoxicity was observed. The extent of epidural fibrosis, the area of epidural fibrosis, and the density of the fibroblasts and blood vessel were evaluated histologically. There were statistical differences among the PLGA-PEG-PLGA thermogel or CHS gel group compared with the control group. Although there was no difference between the PLGA-PEG-PLGA thermogel and CHS gel, the efficiency of the PLGA-PEG-PLGA thermogel was shown to be slightly improved compared with the CHS gel. The biocompatibility of the PLGA-PEG-PLGA thermogel was proven well. The application of this thermogel effectively reduced epidural scarring and prevented the subsequent adhesion to the dura mater. No side effects were noted in the rats.

Preventive strategy for Candida gut translocation during ischemia-reperfusion injury supervening on protein-calorie malnutrition.

PubMed

Marotta, F; Barreto, R; Kawakita, S; Minelli, E; Pavasuthipaisit, K; Lorenzetti, A; Nishiwaki, M; Gelosa, F; Fesce, E; Okura, R

2006-01-01

The aim of the present study was to test the hypothesis that protein-calorie malnutrition aggravates the gut translocation of Candida albicans triggered by mesenteric ischemia-reperfusion (IR) injury in an experimental model while testing a natural product containing the antifungal anethole/polygodial mixture (Kolorex). MFI strain white mice (n = 90) were randomly allocated to a 4-week dietary regimen: (1) standard pellet diet containing 25% casein; (2) low-protein (2.5%) casein diet; (3) as group 2 plus oral supplementation with 20 microL of a 5% solution of Kolorex during the last 4 days. Twenty rats from each of these groups (termed 1a, 2a and 3a) were orally inoculated with Candida suspension 6 h prior to mesenteric IR injury. Animals of each group but without Candida inoculation (termed 1b, 2b and 3b) served as control. A colon permeability study was carried out as well. Rats were killed prior to the IR injury and 3 h afterwards. Control rats were killed at the same time. Over 60% of the mesenteric lymph nodes and 30% of kidney samples were positive for C. albicans in the low-protein-fed rats after IR injury. Kolorex significantly decreased that rate of positivity and also significantly reduced the concentration of C. albicans per gram of each positive tissue sample examined. Protein-calorie malnourished animals showed a statistically significant increase in colon permeability and this phenomenon further increased after IR injury. The groups of rats treated with Kolorex compound showed a partial, although significant, improvement of this parameter. These results suggest that Kolorex might exert a competitive effect against with C. albicans colonization. The present study represents the first experimental in vivo investigation of the anethole/polygodial-containing compound under the specific conditions of calorie-protein malnutrition and the results have potential clinical interest.

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease.

PubMed

Ismail, Manal Fouad; Elmeshad, Aliaa Nabil; Salem, Neveen Abdel-Hameed

2013-01-01

To sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs) in comparison to rivastigmine solution (RS) was assessed in an aluminium chloride (AlCl(3))-induced Alzheimer's model. Liposomes were prepared by lipid hydration (F1) and heating (F2) methods. Rats were treated with either RS or RLs (1 mg/kg/day) concomitantly with AlCl(3) (50 mg/kg/day). The study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm) than F2 (528.7 ± 15.5 nm), but both entrapped the same amount of the drug (92.1% ± 1.4%). After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl(3), with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethy-larginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na(+)/K(+)-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl(3)-treated animals; however, RLs succeeded in normalization of AChE and Na(+)/K(+) ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl(3)-treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl(3)-treated rats. The profound therapeutic effect of RLs over RS was evidenced by nearly preventing amyloid plaque formation, as shown in the histopathological examination of rat brain. RLs could be a potential drug-delivery system for ameliorating Alzheimer's disease.

Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer’s disease

PubMed Central

Ismail, Manal Fouad; ElMeshad, Aliaa Nabil; Salem, Neveen Abdel-Hameed

2013-01-01

Background To sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs) in comparison to rivastigmine solution (RS) was assessed in an aluminium chloride (AlCl3)-induced Alzheimer’s model. Methods Liposomes were prepared by lipid hydration (F1) and heating (F2) methods. Rats were treated with either RS or RLs (1 mg/kg/day) concomitantly with AlCl3 (50 mg/kg/day). Results The study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm) than F2 (528.7 ± 15.5 nm), but both entrapped the same amount of the drug (92.1% ± 1.4%). After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl3, with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethy-larginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na+/K+-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl3-treated animals; however, RLs succeeded in normalization of AChE and Na+/K+ ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl3-treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl3-treated rats. The profound therapeutic effect of RLs over RS was evidenced by nearly preventing amyloid plaque formation, as shown in the histopathological examination of rat brain. Conclusion RLs could be a potential drug-delivery system for ameliorating Alzheimer’s disease. PMID:23378761

Treating chronic arsenic toxicity with high selenium lentil diets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sah, Shweta; Vandenberg, Albert; Smits, Judit, E-mail: judit.smits@ucalgary.ca

2013-10-01

Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we comparemore » diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell response.« less

Effects of modified Sanhuang decoction () enema on serum tumor necrosis factor-α and colonic mucosa interleukin-1β, interleukin-6 levels in ulcerative colitis rats.

PubMed

Wang, Shuai; Zhou, Tao; Zhai, Jun-Peng; Wang, Li-Hua; Chen, Jing

2014-11-01

To investigate the effects of Modified Sanhuang Decoction (, MSD) enema on the serum tumor necrosis factor alpha (TNF-α) and colonic mucosa interleukin-1β (IL-1β), interleukin-6 (IL-6) levels in experimental ulcerative colitis (UC) rats. Forty-five male Wistar rats were randomly divided into 4 groups: normal group (n=12), model group (n=11), salazosulfapyridine (SASP) group (n=11) and MSD group (n=11). The UC model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Rats in the normal group and model group were clystered with 0.9% normal saline, while in the SASP group and MSD group were clystered with SASP and MSD enema, respectively. After drug administration (10 mL/kg body weight, for 7 days), colonic gross changes and colonic mucosa histology were observed, serum TNF-α and colonic mucosa IL-1β, IL-6 levels were tested by enzyme linked immunosorbent assay and radioimmunoassay, respectively. As compared with the normal group, the experimental UC rats, the colonic mucosal damage index scores (CMDIs), histopathological scores (HS) and the serum TNF-α and colonic mucosa IL-1β, IL-6 levels significantly increased (P<0.05 or P<0.01). In the MSD and SASP groups, the ulcer area significantly reduced, and edema disappeared. The CMDIs, HS, the serum TNF-α and colonic mucosa IL-1β, IL-6 levels in the MSD and SASP groups significantly decreased (P<0.05 or P<0.01) compared with the model group. The CMDIs in the MSD group were lower than that in the SASP group (P<0.05), but there were no significant differences in HS, serum TNF-α or colonic mucosa IL-1β, IL-6 levels between the MSD and SASP groups. MSD enema can improve colonic mucosa impairment and decrease serum TNF-α and colonic mucosa IL-1β, IL-6 levels in experimental UC.

l-glutamine and l-alanine supplementation increase glutamine-glutathione axis and muscle HSP-27 in rats trained using a progressive high-intensity resistance exercise.

PubMed

Leite, Jaqueline Santos Moreira; Raizel, Raquel; Hypólito, Thaís Menezes; Rosa, Thiago Dos Santos; Cruzat, Vinicius Fernandes; Tirapegui, Julio

2016-08-01

In this study we investigated the chronic effects of oral l-glutamine and l-alanine supplementation, either in their free or dipeptide form, on glutamine-glutathione (GLN-GSH) axis and cytoprotection mediated by HSP-27 in rats submitted to resistance exercise (RE). Forty Wistar rats were distributed into 5 groups: sedentary; trained (CTRL); and trained supplemented with l-alanyl-l-glutamine, l-glutamine and l-alanine in their free form (GLN+ALA), or free l-alanine (ALA). All trained animals were submitted to a 6-week ladder-climbing protocol. Supplementations were offered in a 4% drinking water solution for 21 days prior to euthanasia. Plasma glutamine, creatine kinase (CK), myoglobin (MYO), and erythrocyte concentration of reduced GSH and glutathione disulfide (GSSG) were measured. In tibialis anterior skeletal muscle, GLN-GSH axis, thiobarbituric acid reactive substances (TBARS), and the expression of heat shock factor 1 (HSF-1), 27-kDa heat shock protein (HSP-27), and glutamine synthetase were determined. In CRTL animals, high-intensity RE reduced muscle glutamine levels and increased GSSG/GSH rate and TBARS, as well as augmented plasma CK and MYO levels. Conversely, l-glutamine-supplemented animals showed an increase in plasma and muscle levels of glutamine, with a reduction in GSSG/GSH rate, TBARS, and CK. Free l-alanine administration increased plasma glutamine concentration and lowered muscle TBARS. HSF-1 and HSP-27 were high in all supplemented groups when compared with CTRL (p < 0.05). The results presented herein demonstrate that l-glutamine supplemented with l-alanine, in both a free or dipeptide form, improve the GLN-GSH axis and promote cytoprotective effects in rats submitted to high-intensity RE training.

[Evaluation of grip strength in normal and obese Wistar rats submitted to swimming with overload after median nerve compression].

PubMed

Coradinia, Josinéia Gresele; Kakihata, Camila Mayumi Martin; Kunz, Regina Inês; Errero, Tatiane Kamada; Bonfleur, Maria Lúcia; Bertolini, Gladson Ricardo Flor

2015-01-01

To verify the functionality through muscle grip strength in animals with obesity induced by monosodium glutamate (MSG) and in control animals, which suffered compression of the right median nerve, and treated with swimming with overload. During the first five days of life, neonatal Wistar rats received subcutaneous injections of MSG. The control group received a hypertonic saline solution. Forty-eight rats were divided into six groups: G1 (control); G2 (control + injury); G3 (control + injury + swimming); G4 (obese); G5 (obese + injury); G6 (obese + injury + swimming). The animals in groups G2, G3, G5 and G6 were submitted to compression of the median nerve and G3 and G6 groups were treated, after injury, with swimming exercise with load for three weeks. The swimming exercise had a progressive duration, according to the week, of 20, 30 and 40minutes. Muscle strength was assessed using a grip strength meter preoperatively and on the 3rd, 7th, 14th and 21st days after surgery. The results were expressed and analyzed using descriptive and inferential statistics. When the grip strength was compared among assessments regardless of group, in the second assessment the animals exhibited lower grip strength. G1 and G4 groups had greater grip strength, compared to G2, G3, G4 and G6. The swimming exercise with overload has not been effective in promoting improvement in muscle grip strength after compression injury of the right median nerve in control and in obese-MSG rats. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Sex differences in hepatic and intestinal contributions to nevirapine biotransformation in rats.

PubMed

Pinheiro, P F; Marinho, A T; Antunes, A M M; Marques, M M; Pereira, S A; Miranda, J P

2015-05-25

The understanding of the intestine contribution to drug biotransformation improved significantly in recent years. However, the sources of inter-individual variability in intestinal drug biotransformation, namely sex-differences, are still elusive. Nevirapine (NVP) is an orally taken anti-HIV drug associated with severe idiosyncratic reactions elicited by toxic metabolites, with women at increased risk. As such, NVP is a good model to assess sex-dimorphic metabolism. The aim of this study was to perform a comparative profiling of NVP biotransformation in rat intestine and liver and evaluate whether or not it is organ- and sex-dependent. Therefore, nevirapine-containing solutions were perfused through the intestine, in a specially designed chamber, or incubated with liver slices, from male and female Wistar rats. The levels of NVP and its Phase I metabolites were quantified by HPLC-UV. Liver incubation experiments yielded the metabolites 2-, 3-, 8-, and 12-OH-NVP, being 12-OH-NVP and 2-OH-NVP the major metabolites in males and females, respectively. Inter-sex differences in the metabolic profile were also detected in the intestine perfusion experiments. Herein, the metabolites 3- and 12-OH-NVP were only found in male rats, whereas 2-OH-NVP levels were higher in females, both in extraluminal (p<0.01) and intraluminal media. The metabolite 8-OH-NVP was not detected in the intraluminal media from either males or females. In this study, important inter-sex differences were detected in both organs, providing further clues to the sex-dimorphic profile of NVP toxicity. Moreover, an extra-hepatic contribution to NVP biotransformation was observed, strengthening the relevance of the intestinal contribution in the biotransformation of orally taken-drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

PubMed Central

Reichert, Karla; Pereira do Carmo, Helison Rafael; Galluce Torina, Anali; Diógenes de Carvalho, Daniela; Carvalho Sposito, Andrei; de Souza Vilarinho, Karlos Alexandre; da Mota Silveira-Filho, Lindemberg; Martins de Oliveira, Pedro Paulo

2016-01-01

Purpose Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Methods Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. Results End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Conclusion Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events. PMID:27880844

Suppressing effect of COR659 on alcohol, sucrose, and chocolate self-administration in rats: involvement of the GABAB and cannabinoid CB1 receptors.

PubMed

Maccioni, Paola; Colombo, Giancarlo; Lorrai, Irene; Zaru, Alessandro; Carai, Mauro A M; Gessa, Gian Luigi; Brizzi, Antonella; Mugnaini, Claudia; Corelli, Federico

2017-09-01

COR659 [methyl2-(4-chlorophenylcarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate] is a new, positive allosteric modulator (PAM) of the GABA B receptor. This study evaluated whether COR659 shared with previously tested GABA B PAMs the capacity to reduce alcohol self-administration in rats. Treatment with non-sedative doses of COR659 (2.5, 5, and 10 mg/kg; i.p.) suppressed lever-responding for alcohol (15% v/v) in Sardinian alcohol-preferring (sP) rats under the fixed ratio (FR) 4 (FR4) and progressive ratio (PR) schedules of reinforcement; COR659 was more potent and effective than the reference GABA B PAM, GS39783. Treatment with COR659, but not GS39783, suppressed (a) lever-responding for a sucrose solution (1-3% w/v) in sP rats under the FR4 and PR schedules, (b) lever-responding for a chocolate solution [5% (w/v) Nesquik®] in Wistar rats under the FR10 and PR schedules, and (c) cue-induced reinstatement of chocolate seeking in Wistar rats. Treatment with COR659 was completely ineffective on lever-responding (FR10) for regular food pellets in food-deprived Wistar rats. Pretreatment with the GABA B receptor antagonist, SCH50911, partially blocked COR659-induced reduction of alcohol self-administration, being ineffective on reduction of chocolate self-administration. Pretreatment with the cannabinoid CB 1 receptor antagonist, AM4113, fully blocked COR659-induced reduction of chocolate self-administration, being ineffective on reduction of alcohol self-administration. COR659 might exert its behavioral effects via a composite mechanism: (i) positive allosteric modulation of the GABA B receptor, responsible for a large proportion of reduction of alcohol self-administration; (ii) an action at other receptor system(s), including the cannabinoid CB 1 receptor, through which COR659 affects seeking and consumption of highly palatable foods.

Fibrinolytic preflush upon liver retrieval from non-heart beating donors to enhance postpreservation viability and energetic recovery upon reperfusion.

PubMed

Minor, T; Hachenberg, A; Tolba, R; Pauleit, D; Akbar, S

2001-06-27

Our objective was to evaluate graft equilibration with high viscosity (University of Wisconsin solution [UW]) or low viscosity (Bretschneider's histidine-tryptophan-ketoglutarate [HTK]) during liver procurement from non-heart beating donors (NHBD) and the potential impact of a preceding fibrinolysis with streptokinase on postpreservation viability. After 60 min of cardiac arrest, rat livers were perfused by gravity (60 cm H2O) via the portal vein with either 60 ml of HTK, 20 ml of UW, or 20 ml of Ringer's solution (22 degrees C including 7500U of streptokinase) and, subsequently, 20 ml of UW. After 24 h of storage at 4 degrees C, viability of the livers was assessed upon isolated reperfusion in vitro. Magnetic resonance imaging revealed severe perfusion deficits, which were mildly attenuated with HTK, upon flush-out with UW. After preflush with streptokinase, a mostly homogenous distribution of the preservation solution was observed throughout the liver tissue. The choice of the flush-out solution (UW or HTK) had no influence on parenchymal enzyme leakage, hepatic bile production, or tissue levels of ATP after reperfusion of the livers. Fibrinolytic preflush, however, resulted in a relevant and significant improvement of structural integrity as well as functional and metabolic recovery. Compromised vascular tissue perfusion upon organ harvest in NHBD triggers graft dysfunction after cold storage and can easily be circumvented by temporary fibrinolysis before graft retrieval.

Paeoniflorin improves cardiac function and decreases adverse postinfarction left ventricular remodeling in a rat model of acute myocardial infarction.

PubMed

Chen, Hengwen; Dong, Yan; He, Xuanhui; Li, Jun; Wang, Jie

2018-01-01

Paeoniflorin (PF) is the active component of Paeonia lactiflora Pall. or Paeonia veitchii Lynch. This study was, therefore, aimed to evaluate the improvement and mechanism of the PF on ventricular remodeling in rats with acute myocardial infarction (AMI). In this study, AMI model was established by ligating the anterior descending coronary artery in Wistar rats. After 4 weeks gavage of PF, the apparent signs and the left ventricle weight index of Wistar rats were observed. The left ventricular ejection fraction (LVEF) was evaluated by Doppler ultrasonography. Changes in cardiac morphology were observed by pathologic examination, and apoptosis was observed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, enzyme-linked immunosorbent assay was used to detect the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) interleukin-10 (IL-10) and brain natriuretic peptide (BNP). Immunohistochemistry and Western blot method were applied to detect Caspase-3 and Caspase-9. Compared with the model control, the survival conditions of rats in all treatment groups were generally improved after PF treatment. LVEF was significantly increased, and both left ventricular end-diastolic inner diameter and left ventricular end-systolic inner diameter were significantly reduced. Moreover, pathologic examination showed that the myocardium degeneration of the rats treated with PF was decreased, including neater arrangement, more complete myofilament, more uniform gap and less interstitial collagen fibers. Furthermore, the mitochondrial structure of cardiomyocytes was significantly improved. The ultrastructure was clear, and the arrangement of myofilament was more regular. Also, the expression of Caspase-3 and Caspase-9 was inhibited, and apoptosis was obviously reduced in the PF treatment groups. BNP, TNF-α and IL-6 were also decreased and IL-10 was increased in the treated rats. PF could significantly improve the LVEF of rats. It decreased adverse left ventricular remodeling after myocardial infarction in rat models. The potential mechanism could be that PF decreased and inhibited BNP, TNF-α and IL-6, increased IL-10 and further inhibited the expression of Caspase-3 and Caspase-9, thus promoting ventricular remodeling.

Acetyl-L-carnitine improves aged brain function.

PubMed

Kobayashi, Satoru; Iwamoto, Machiko; Kon, Kazuo; Waki, Hatsue; Ando, Susumu; Tanaka, Yasukazu

2010-07-01

The effects of acetyl-L-carnitine (ALCAR), an acetyl derivative of L-carnitine, on memory and learning capacity and on brain synaptic functions of aged rats were examined. Male Fischer 344 rats were given ALCAR (100 mg/kg bodyweight) per os for 3 months and were subjected to the Hebb-Williams tasks and AKON-1 task to assess their learning capacity. Cholinergic activities were determined with synaptosomes isolated from brain cortices of the rats. Choline parameters, the high-affinity choline uptake, acetylcholine (ACh) synthesis and depolarization-evoked ACh release were all enhanced in the ALCAR group. An increment of depolarization-induced calcium ion influx into synaptosomes was also evident in rats given ALCAR. Electrophysiological studies using hippocampus slices indicated that the excitatory postsynaptic potential slope and population spike size were both increased in ALCAR-treated rats. These results indicate that ALCAR increases synaptic neurotransmission in the brain and consequently improves learning capacity in aging rats.

The effect of red grape juice on Alzheimer's disease in rats

PubMed Central

Siahmard, Zahra; Alaei, Hojjatollah; Reisi, Parham; Pilehvarian, Ali Asghar

2012-01-01

Background: Alzheimer's disease is a neurodegenerative disease appearing as a result of free radicals and oxidative stress. Antioxidants agents boost memory and control Alzheimer's disease. Since red grape juice contains antioxidant agents, its effects on speed of learning and improvement of memory was studied in Alzheimer's rats. Materials and Methods: Alzheimer's model was induced by bilateral infusion of streptozocine into lateral ventricles of brain of male rats. Rats drank 10% red grape juice for 21 days. Passive avoidance learning test was used for measuring memory and learning in rats. Results: Our results showed that learning and memory in STZ-group decreased significantly compared to Sham group. However, intake of red grape juice increased speed of learning and improvement of memory in Alzheimer's rats. Conclusions: Our results suggest that there are active ingredients in red grape juice, which probably have therapeutic and preventive effects on cognitive impairments in Alzheimer's disease. PMID:23326794

The effect of red grape juice on Alzheimer's disease in rats.

PubMed

Siahmard, Zahra; Alaei, Hojjatollah; Reisi, Parham; Pilehvarian, Ali Asghar

2012-01-01

Alzheimer's disease is a neurodegenerative disease appearing as a result of free radicals and oxidative stress. Antioxidants agents boost memory and control Alzheimer's disease. Since red grape juice contains antioxidant agents, its effects on speed of learning and improvement of memory was studied in Alzheimer's rats. Alzheimer's model was induced by bilateral infusion of streptozocine into lateral ventricles of brain of male rats. Rats drank 10% red grape juice for 21 days. Passive avoidance learning test was used for measuring memory and learning in rats. Our results showed that learning and memory in STZ-group decreased significantly compared to Sham group. However, intake of red grape juice increased speed of learning and improvement of memory in Alzheimer's rats. Our results suggest that there are active ingredients in red grape juice, which probably have therapeutic and preventive effects on cognitive impairments in Alzheimer's disease.

[Decreasing reperfusion damage with N-acetylcysteine in experimental pancreas transplantion].

PubMed

Mayer, H; Thies, J; Schmidt, J; Gebhard, M M; Herfarth, C; Klar, E

1998-01-01

In this study we investigated the effect of donor and recipient conditioning with N-acetylcysteine on the ischemia/reperfusion injury after experimental pancreas-transplantation. We performed standardized pancreaticoduodenal transplantation in male lewis rats. The pancreas was perfused with UW-solution, harvested and conserved at 4 degrees C. Cold ischemia time was 1.5 hours and 16 hours respectively. The microcirculation in the transplanted organ was quantified by means of intravital microscopy 1.5 hours after implantation and reperfusion in the recipient. After 16 hours of cold ischemia we found a significant reduction in capillary erythrocyte velocity and a significantly enhanced leucocyte/endothelium interaction. The treatment with N-acetylcysteine resulted in a significant improvement of these microcirculatory disorders after prolonged cold ischemia.

A Surgical Model in Male Obese Rats Uncovers Protective Effects of Bile Acids Post-Bariatric Surgery

PubMed Central

Setchell, Kenneth DR; Kirby, Michelle; Myronovych, Andriy; Ryan, Karen K.; Ibrahim, Samar H.; Berger, Jose; Smith, Kathi; Toure, Mouhamadoul; Woods, Stephen C.; Seeley, Randy J.

2013-01-01

Bariatric surgery elevates serum bile acids. Conjugated bile acid administration, such as tauroursodeoxycholic acid (TUDCA), improves insulin sensitivity, whereas short-circuiting bile acid circulation through ileal interposition surgery in rats raises TUDCA levels. We hypothesized that bariatric surgery outcomes could be recapitulated by short circuiting the normal enterohepatic bile circulation. We established a model wherein male obese rats underwent either bile diversion (BD) or Sham (SH) surgery. The BD group had a catheter inserted into the common bile duct and its distal end anchored into the middistal jejunum for 4–5 weeks. Glucose tolerance, insulin and glucagon-like peptide-1 (GLP-1) response, hepatic steatosis, and endoplasmic reticulum (ER) stress were measured. Rats post-BD lost significantly more weight than the SH rats. BD rats gained less fat mass after surgery. BD rats had improved glucose tolerance, increased higher postprandial glucagon-like peptide-1 response and serum bile acids but less liver steatosis. Serum bile acid levels including TUDCA concentrations were higher in BD compared to SH pair-fed rats. Fecal bile acid levels were not different. Liver ER stress (C/EBP homologous protein mRNA and pJNK protein) was decreased in BD rats. Bile acid gavage (TUDCA/ursodeoxycholic acid [UDCA]) in diet-induced obese rats, elevated serum TUDCA and concomitantly reduced hepatic steatosis and ER stress (C/EBP homologous protein mRNA). These data demonstrate the ability of alterations in bile acids to recapitulate important metabolic improvements seen after bariatric surgery. Further, our work establishes a model for focused study of bile acids in the context of bariatric surgery that may lead to the identification of therapeutics for metabolic disease. PMID:23592746

Effect of chronic low-dose tadalafil on penile cavernous tissues in diabetic rats.

PubMed

Mostafa, Mohamed E; Senbel, Amira M; Mostafa, Taymour

2013-06-01

To assess the effect of chronic low-dose administration of tadalafil (Td) on penile cavernous tissue in induced diabetic rats. The study investigaged 48 adult male albino rats, comprising a control group, sham controls, streptozotocin-induced diabetic rats, and induced diabetic rats that received Td low-dose daily (0.09 mg/200 g weight) for 2 months. The rats were euthanized 1 day after the last dose. Cavernous tissues were subjected to histologic, immunohistochemical, morphometric studies, and measurement of intracavernosal pressure and mean arterial pressure in anesthetized rats. Diabetic rats demonstrated dilated cavernous spaces, smooth muscles with heterochromatic nuclei, degenerated mitochondria, vacuolated cytoplasm, and negative smooth muscle immunoreactivity. Nerve fibers demonstrated a thick myelin sheath and intra-axonal edema, where blood capillaries exhibited thick basement membrane. Diabetic rats on Td showed improved cavernous organization with significant morphometric increases in the area percentage of smooth muscles and elastic tissue and a significant decrease of fibrous tissue. The Td-treated group showed enhanced erectile function (intracavernosal pressure/mean arterial pressure) at 0.3, 0.5, 1, 3, and 5 Hz compared with diabetic group values at the respective frequencies (P <.05) that approached control values. Chronic low-dose administration of Td in diabetic rats is associated with substantial improvement of the structure of penile cavernous tissue, with increased smooth muscles and elastic tissue, decreased fibrous tissue, and functional enhancement of the erectile function. This raises the idea that the change in penile architecture with Td treatment improves erectile function beyond its half-life and its direct pharmacologic action on phosphodiesterase type 5. Copyright © 2013 Elsevier Inc. All rights reserved.

Beneficial effects of enriched environment following status epilepticus in immature rats.

PubMed

Faverjon, S; Silveira, D C; Fu, D D; Cha, B H; Akman, C; Hu, Y; Holmes, G L

2002-11-12

There is increasing evidence that enriching the environment can improve cognitive and motor deficits following a variety of brain injuries. Whether environmental enrichment can improve cognitive impairment following status epilepticus (SE) is not known. To determine whether the environment in which animals are raised influences cognitive function in normal rats and rats subjected to SE. Rats (n = 100) underwent lithium-pilocarpine-induced SE at postnatal (P) day 20 and were then placed in either an enriched environment consisting of a large play area with toys, climbing objects, and music, or in standard vivarium cages for 30 days. Control rats (n = 32) were handled similarly to the SE rats but received saline injections instead of lithium-pilocarpine. Rats were then tested in the water maze, a measure of visual-spatial memory. A subset of the rats were killed during exposure to the enriched or nonenriched environment and the brains examined for dentate granule cell neurogenesis using bromodeoxyuridine (BrdU) and phosphorylated cyclic AMP response element binding protein (pCREB) immunostaining, a brain transcription factor important in long-term memory. Both control and SE rats exposed to the enriched environment performed significantly better than the nonenriched group in the water maze. There was a significant increase in neurogenesis and pCREB immunostaining in the dentate gyrus in both control and SE animals exposed to the enriched environment compared to the nonenriched groups. Environmental enrichment resulted in no change in SE-induced histologic damage. Exposure to an enriched environment in weanling rats significantly improves visual-spatial learning. Even following SE, an enriched environment enhances cognitive function. An increase in neurogenesis and activation of transcription factors may contribute to this enhanced visual-spatial memory.

Effect of combination therapy consisting of enalapril, α-lipoic acid, and menhaden oil on diabetic neuropathy in a high fat/low dose streptozotocin treated rat.

PubMed

Davidson, Eric P; Holmes, Amey; Coppey, Lawrence J; Yorek, Mark A

2015-10-15

We have previously demonstrated that treating diabetic rats with enalapril, an angiotensin converting enzyme (ACE) inhibitor, α-lipoic acid, an antioxidant, or menhaden oil, a natural source of omega-3 fatty acids can partially improve diabetic peripheral neuropathy. In this study we sought to determine the efficacy of combining these three treatments on vascular and neural complications in a high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes. Rats were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of streptozotocin. Eight weeks after the onset of hyperglycemia diabetic rats were treated with a combination of enalapril, α-lipoic acid and menhaden oil. Diabetic rats not receiving treatment were continued on the high fat diet. Glucose clearance was impaired in diabetic rats and significantly improved with treatment. Diabetes caused steatosis, elevated serum lipid levels, slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber profiles, decrease in cornea sub-basal nerve fiber length and corneal sensitivity and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treating diabetic rats with the combination of enalapril, α-lipoic acid and menhaden oil reversed all these deficits to near control levels except for motor nerve conduction velocity which was also significantly improved compared to diabetic rats but remained significantly decreased compared to control rats. These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes. Published by Elsevier B.V.

Aqueous extract of lavender (Lavandula angustifolia) improves the spatial performance of a rat model of Alzheimer's disease.

PubMed

Kashani, Masoud Soheili; Tavirani, Mostafa Rezaei; Talaei, Sayyed Alireza; Salami, Mahmoud

2011-04-01

Alzheimer's disease (AD) is one of the most important neurodegenerative disorders. It is characterized by dementia including deficits in learning and memory. The present study aimed to evaluate the effects of aqueous extract of lavender (Lavandula angustifolia) on spatial performance of AD rats. Male Wistar rats were first divided into control and AD groups. Rat model of AD was established by intracerebroventricular injection of 10 μg Aβ1-42 20 d prior to administration of the lavender extract. Rats in both groups were then introduced to 2 stages of task learning (with an interval of 20 d) in Morris water maze, each followed by one probe test. After the first stage of spatial learning, control and AD animals received different doses (50, 100 and 200 mg/kg) of the lavender extract. In the first stage of experiment, the latency to locate the hidden platform in AD group was significantly higher than that in control group. However, in the second stage of experiment, control and AD rats that received distilled water (vehicle) showed similar performance, indicating that the maze navigation itself could improve the spatial learning of AD animals. Besides, in the second stage of experiment, control and AD rats that received lavender extract administration at different doses (50, 100, and 200 mg/ kg) spent less time locating the platform (except for the AD rats with 50 mg/kg extract treatment), as compared with their counterparts with vehicle treatment, respectively. In addition, lavender extract significantly improved the performance of control and AD rats in the probe test, only at the dose of 200 mg/kg, as compared with their counterparts with vehicle treatment. The lavender extract can effectively reverse spatial learning deficits in AD rats.

Can apricot kernels fatty acids delay the atrophied hepatocytes from progression to fibrosis in dimethylnitrosamine (DMN)-induced liver injury in rats?

PubMed

Abdel-Rahman, Manal K

2011-07-07

The present study was aimed to analyze the chemical composition of ground apricot kernel (GAK) and examine its effect on hepatic fibrosis in vivo induced by dimethylnitrosamine (DMN) in rats. Hepatic fibrosis was induced by intraperitoneal injections of 10 mg/kg DMN for 3 consecutive days each week over a period of 4 wk. The rats were randomly assigned to five groups of nine rats each: the negative control group (NC), the hepatic fibrosis group (PC), hepatic fibrosis supplemented with GAK (0.5 mg/kg/BW/rat), hepatic fibrosis supplemented with GAK (1 mg/kg/BW/rat) and hepatic fibrosis supplemented with GAK (1.5 mg/kg/BW/rat). Rats were killed, blood was collected and livers were excised for biochemical measurements and histological examination. Results indicate that the diet supplemented with GAK led to improving liver function, lipid peroxides, and liver CAT, SOD and GSH. These results were confirmed by liver histology. Hierarchically high levels f GAK (1.5 mg/kg/BW/rat) gave the best results compared to other tested levels. This study demonstrates that GAK administration specifically (1.5 mg/kg/BW/rat) can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis. Furthermore, a human trial would be applied specially GAK is a part of Egyptian diet. The act of why high amounts of GAK was improved biochemical values compared to low or moderate levels tested in this study may be due to increase levels of oleic acid and other polyphenols in apricot kernels.

Can apricot kernels fatty acids delay the atrophied hepatocytes from progression to fibrosis in dimethylnitrosamine (DMN)-induced liver injury in rats?

PubMed Central

2011-01-01

Background and aims The present study was aimed to analyze the chemical composition of ground apricot kernel (GAK) and examine its effect on hepatic fibrosis in vivo induced by dimethylnitrosamine (DMN) in rats. Methods and results Hepatic fibrosis was induced by intraperitoneal injections of 10 mg/kg DMN for 3 consecutive days each week over a period of 4 wk. The rats were randomly assigned to five groups of nine rats each: the negative control group (NC), the hepatic fibrosis group (PC), hepatic fibrosis supplemented with GAK (0.5 mg/kg/BW/rat), hepatic fibrosis supplemented with GAK (1 mg/kg/BW/rat) and hepatic fibrosis supplemented with GAK (1.5 mg/kg/BW/rat). Rats were killed, blood was collected and livers were excised for biochemical measurements and histological examination. Results indicate that the diet supplemented with GAK led to improving liver function, lipid peroxides, and liver CAT, SOD and GSH. These results were confirmed by liver histology. Hierarchically high levels f GAK (1.5 mg/kg/BW/rat) gave the best results compared to other tested levels. Conclusion This study demonstrates that GAK administration specifically (1.5 mg/kg/BW/rat) can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis. Furthermore, a human trial would be applied specially GAK is a part of Egyptian diet. The act of why high amounts of GAK was improved biochemical values compared to low or moderate levels tested in this study may be due to increase levels of oleic acid and other polyphenols in apricot kernels PMID:21736706

Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-κB in a rat model.

PubMed

Yu, Xiaofeng; Zhao, Lijun; Yu, Zhiping; Yu, Changzheng; Bi, Jianfei; Sun, Binglong; Cong, Haibo

2017-08-01

As a specific inhibitor of neutrophil elastase, sivelestat sodium hydrate has primarily been used in the treatment of acute lung injury caused by various factors since its approval in 2002. Sivelestat sodium hydrate also improves post-traumatic knee osteoarthritis (KOA), although its underlying mechanisms of action have yet to be elucidated. The aim of the current study was to determine if sivelestat sodium hydrate improves post-traumatic KOA through nuclear factor (NF)-κB in a rat model. Treatment with sivelestat sodium hydrate significantly inhibited the induction of structural changes and significantly increased the vertical episode count and ipsilateral static weight bearing of the joint in KOA rats (all P<0.01). Sivelestat sodium hydrate significantly inhibited tumor necrosis factor-α and interleukin-6 production, serum nitrite levels, inducible nitric oxide synthase protein expression and high mobility group box 1 (HMGB1) secretion in KOA rats compared with the model group (all P<0.01). Sivelestat sodium hydrate also significantly suppressed p50/p65 DNA binding activity and NF-κB and phosphorylated inhibitor of κB protein expression in the joints of KOA rats compared with the model group (all P<0.01). These results suggest that sivelestat sodium hydrate improves post-traumatic KOA through HMGB1 and NF-κB in rats.

Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-κB in a rat model

PubMed Central

Yu, Xiaofeng; Zhao, Lijun; Yu, Zhiping; Yu, Changzheng; Bi, Jianfei; Sun, Binglong; Cong, Haibo

2017-01-01

As a specific inhibitor of neutrophil elastase, sivelestat sodium hydrate has primarily been used in the treatment of acute lung injury caused by various factors since its approval in 2002. Sivelestat sodium hydrate also improves post-traumatic knee osteoarthritis (KOA), although its underlying mechanisms of action have yet to be elucidated. The aim of the current study was to determine if sivelestat sodium hydrate improves post-traumatic KOA through nuclear factor (NF)-κB in a rat model. Treatment with sivelestat sodium hydrate significantly inhibited the induction of structural changes and significantly increased the vertical episode count and ipsilateral static weight bearing of the joint in KOA rats (all P<0.01). Sivelestat sodium hydrate significantly inhibited tumor necrosis factor-α and interleukin-6 production, serum nitrite levels, inducible nitric oxide synthase protein expression and high mobility group box 1 (HMGB1) secretion in KOA rats compared with the model group (all P<0.01). Sivelestat sodium hydrate also significantly suppressed p50/p65 DNA binding activity and NF-κB and phosphorylated inhibitor of κB protein expression in the joints of KOA rats compared with the model group (all P<0.01). These results suggest that sivelestat sodium hydrate improves post-traumatic KOA through HMGB1 and NF-κB in rats. PMID:28810618

Targeting Germinal Matrix Hemorrhage-Induced Overexpression of Sodium-Coupled Bicarbonate Exchanger Reduces Posthemorrhagic Hydrocephalus Formation in Neonatal Rats.

PubMed

Li, Qian; Ding, Yan; Krafft, Paul; Wan, Weifeng; Yan, Feng; Wu, Guangyong; Zhang, Yixin; Zhan, Qunling; Zhang, John H

2018-01-31

Germinal matrix hemorrhage (GMH) is a leading cause of mortality and lifelong morbidity in preterm infants. Posthemorrhagic hydrocephalus (PHH) is a common complication of GMH. A sodium-coupled bicarbonate exchanger (NCBE) encoded by solute carrier family 4 member 10 gene is expressed on the choroid plexus basolateral membrane and may play a role in cerebrospinal fluid production and the development of PHH. Following GMH, iron degraded from hemoglobin has been linked to PHH. Choroid plexus epithelial cells also contain iron-responsive element-binding proteins (IRPs), IRP1, and IRP2 that bind to mRNA iron-responsive elements. The present study aims to resolve the following issues: (1) whether the expression of NCBE is regulated by IRPs; (2) whether NCBE regulates the formation of GMH-induced hydrocephalus; and (3) whether inhibition of NCBE reduces PHH development. GMH model was established in P7 rat pups by injecting bacterial collagenase into the right ganglionic eminence. Another group received iron trichloride injections instead of collagenase. Deferoxamine was administered intraperitoneally for 3 consecutive days after GMH/iron trichloride. Solute carrier family 4 member 10 small interfering RNA or scrambled small interfering RNA was administered by intracerebroventricular injection 24 hours before GMH and followed with an injection every 7 days over 21 days. NCBE expression increased while IRP2 expression decreased after GMH/iron trichloride. Deferoxamine ameliorated both the GMH-induced and iron trichloride-induced decrease of IRP2 and decreased NCBE expressions. Deferoxamine and solute carrier family 4 member 10 small interfering RNA improved cognitive and motor functions at 21 to 28 days post GMH and reduced cerebrospinal fluid production as well as the degree of hydrocephalus at 28 days after GMH. Targeting iron-induced overexpression of NCBE may be a translatable therapeutic strategy for the treatment of PHH following GMH. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Ameliorative effect of parsley oil on cisplatin-induced hepato-cardiotoxicity: A biochemical, histopathological, and immunohistochemical study.

PubMed

Abdellatief, Suhair A; Galal, Azza A A; Farouk, Sameh M; Abdel-Daim, Mohamed M

2017-02-01

Cisplatin (cis-diamminedichloroplatinum, CDDP) is an effective DNA alkylating agent used in the treatment of different types of tumors; however, its clinical use is associated with hepato-cardiotoxicity. The current study was designed to assess the potential protective effect of parsley oil (PO) against CDDP-induced hepato-cardiotoxicity. For this purpose, 25 adult male rats were assigned into five groups, each containing five animals. Group I (control) was administered saline solution. Group II was administered PO at a dosage of 0.42ml/kg BW. Group III were administered CDDP at a dosage of 5mg/kg BW. Group IV was administered PO in addition to CDDP. Group V was administered saline solution in addition to CDDP, after which they were administered PO for five days. Oral administration of either saline solution or PO was performed each day for 10days, while administration of CDDP was via a single intraperitoneal injection five days following the commencement of the experiment. The recorded results revealed that CDDP induced obvious hepatic and cardiac injuries that were indicated by biochemical, histopathological, and immunohistochemical alterations, including elevation of serum hepatic and cardiac injury markers as well as proinflammatory cytokines. Moreover, CDDP induced an increase in the level of hepatic and cardiac injury biomarkers, decreases in the activities of antioxidant enzymes, a decrease in GSH concentration, and an increase in MDA concentration. CDDP also induced histopathological hepatocellular and myocardial changes, and overexpression of p53 and COX-2 in hepatic and cardiac tissues. Administration of PO either as a preventative medicine or as treatment significantly improved all the observed deleterious effects induced by CDDP in rat liver and heart. Thus, it may be concluded that PO, with its antioxidant, anti-inflammatory, and antiapoptotic activities, can potentially be used in the treatment of CDDP-induced hepatic and cardiac injuries. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

New synthetic thrombin inhibitors: molecular design and experimental verification.

PubMed

Sinauridze, Elena I; Romanov, Alexey N; Gribkova, Irina V; Kondakova, Olga A; Surov, Stepan S; Gorbatenko, Aleksander S; Butylin, Andrey A; Monakov, Mikhail Yu; Bogolyubov, Alexey A; Kuznetsov, Yuryi V; Sulimov, Vladimir B; Ataullakhanov, Fazoyl I

2011-01-01

The development of new anticoagulants is an important goal for the improvement of thromboses treatments. The design, synthesis and experimental testing of new safe and effective small molecule direct thrombin inhibitors for intravenous administration. Computer-aided molecular design of new thrombin inhibitors was performed using our original docking program SOL, which is based on the genetic algorithm of global energy minimization in the framework of a Merck Molecular Force Field. This program takes into account the effects of solvent. The designed molecules with the best scoring functions (calculated binding energies) were synthesized and their thrombin inhibitory activity evaluated experimentally in vitro using a chromogenic substrate in a buffer system and using a thrombin generation test in isolated plasma and in vivo using the newly developed model of hemodilution-induced hypercoagulation in rats. The acute toxicities of the most promising new thrombin inhibitors were evaluated in mice, and their stabilities in aqueous solutions were measured. New compounds that are both effective direct thrombin inhibitors (the best K(I) was <1 nM) and strong anticoagulants in plasma (an IC(50) in the thrombin generation assay of approximately 100 nM) were discovered. These compounds contain one of the following new residues as the basic fragment: isothiuronium, 4-aminopyridinium, or 2-aminothiazolinium. LD(50) values for the best new inhibitors ranged from 166.7 to >1111.1 mg/kg. A plasma-substituting solution supplemented with one of the new inhibitors prevented hypercoagulation in the rat model of hemodilution-induced hypercoagulation. Activities of the best new inhibitors in physiological saline (1 µM solutions) were stable after sterilization by autoclaving, and the inhibitors remained stable at long-term storage over more than 1.5 years at room temperature and at 4°C. The high efficacy, stability and low acute toxicity reveal that the inhibitors that were developed may be promising for potential medical applications.

EPO improved neurologic outcome in rat pups late after traumatic brain injury.

PubMed

Schober, Michelle E; Requena, Daniela F; Rodesch, Christopher K

2018-05-01

In adult rats, erythropoietin improved outcomes early and late after traumatic brain injury, associated with increased levels of Brain Derived Neurotrophic Factor. Using our model of pediatric traumatic brain injury, controlled cortical impact in 17-day old rats, we previously showed that erythropoietin increased hippocampal neuronal fraction in the first two days after injury. Erythropoietin also decreased activation of caspase3, an apoptotic enzyme modulated by Brain Derived Neurotrophic Factor, and improved Novel Object Recognition testing 14 days after injury. Data on long-term effects of erythropoietin on Brain Derived Neurotrophic Factor expression, histology and cognitive function after developmental traumatic brain injury are lacking. We hypothesized that erythropoietin would increase Brain Derived Neurotrophic Factor and improve long-term object recognition in rat pups after controlled cortical impact, associated with increased neuronal fraction in the hippocampus. Rats pups received erythropoietin or vehicle at 1, 24, and 48 h and 7 days after injury or sham surgery followed by histology at 35 days, Novel Object Recognition testing at adulthood, and Brain Derived Neurotrophic Factor measurements early and late after injury. Erythropoietin improved Novel Object Recognition performance and preserved hippocampal volume, but not neuronal fraction, late after injury. Improved object recognition in erythropoietin treated rats was associated with preserved hippocampal volume late after traumatic brain injury. Erythropoietin is approved to treat various pediatric conditions. Coupled with exciting experimental and clinical studies suggesting it is beneficial after neonatal hypoxic ischemic brain injury, our preliminary findings support further study of erythropoietin use after developmental traumatic brain injury. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction.

PubMed

Wang, Wei-Wei; Zhang, Yu; Huang, Xiao-Bing; You, Nan; Zheng, Lu; Li, Jing

2017-10-14

To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl 4 )-induced acute hepatic dysfunction. A rat model of HE was established with CCl 4 . Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was examined. FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating pro-inflammatory factors such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment. FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.

Effects of aniracetam on bladder overactivity in rats with cerebral infarction.

PubMed

Nakada, Y; Yokoyama, O; Komatsu, K; Kodama, K; Yotsuyanagi, S; Niikura, S; Nagasaka, Y; Namiki, M

2000-06-01

Aniracetam has been used to improve the mental condition of patients with cerebrovascular disease. Previous studies have demonstrated that aniracetam activates the residual functions of cholinergic neurons in damaged brain areas. In this study, the effects of aniracetam on bladder overactivity after left middle cerebral artery occlusion were assessed through oral or i.c.v. administration in sham-operated and cerebral infarcted rats. Oral administration of aniracetam (100 and 300 mg/kg) resulted in a significant and dose-dependent increase in bladder capacity in cerebral infarcted rats but had no effect on bladder capacity in sham-operated rats. Intracerebroventricular administration of aniracetam (0.25 and 2.5 microg/rat) resulted in a significant and dose-dependent increase in bladder capacity in cerebral infarcted rats but not in sham-operated rats. Aniracetam had no significant effect on bladder contraction pressure or micturition threshold pressure in either sham-operated or cerebral infarcted rats. Furthermore, i.c.v. administration of atropine (1 microg/rat), a muscarinic acetylcholine receptor antagonist, completely inhibited the enhancing effects of aniracetam on bladder capacity in cerebral infarcted rats. The effects of aniracetam on bladder overactivity are thought to be mediated in part by activation of cholinergic inhibitory mechanisms in the brain. These results indicate that aniracetam may improve the neurogenic voiding dysfunction observed in patients with cerebrovascular disease.

Department of Transportation Inhalation Test of Neutralized GB Hydrolysate in Sprague-Dawley Rats

DTIC Science & Technology

2009-05-01

a product solution resulting from chemically neutralizing GB with aqueous sodium hydroxide ( pH 12.8) as an acceptably treated waste that can be...transported offsite for secondary treatment. An acute inhalation toxicity test was conducted on a ph adjusted hydrolysate solution ( pH 7.8) to assess...day post-exposure period, an endpoint of the DOT study. The product solution from the neutralized ( pH 7.8) hydrolysate does not appear to pose an

Soy protein preserves basement membrane integrity through a synergistic effect on nephrin, matrix metalloproteinase and vascular endothelial growth factor.

PubMed

Palanisamy, Nallasamy; Anuradha, Carani Venkataraman

2011-01-01

Soy protein improves renal function and prevents albuminuria in diabetic rats. This study investigates whether the renoprotective effect of soy protein is related to sustenance of basement membrane integrity. Adult male albino rats were randomized into four groups and fed one of the following semi-synthetic diets consisting of corn starch (60%) and casein (20%; CCD), fructose (60%) and casein (20%; FCD), fructose (60%) and soy protein (20%; FSD), or corn starch (60%) and soy protein (20%; CSD). Plasma chemistry and renal changes were analyzed after 60 days. FCD rats displayed metabolic derangements and renal ultrastructural changes. FSD rats showed reduction in type IV collagen, tissue inhibitor for matrix metallo-proteinase-2, vascular endothelial growth factor and tumor necrosis factor-α expression and improved matrix metallo-proteinase expression. Renal architecture was preserved in these rats. Soy protein supplementation not only improved insulin sensitivity but also markedly attenuated renal basement membrane changes in fructose diet-fed rats. These findings provide evidence in support of the use of dietary soy protein in patients with diabetic kidney disease. Copyright © 2011 S. Karger AG, Basel.

G-CSF prevents caspase 3 activation in Schwann cells after sciatic nerve transection, but does not improve nerve regeneration.

PubMed

Frost, Hanna K; Kodama, Akira; Ekström, Per; Dahlin, Lars B

2016-10-15

Exogenous granulocyte-colony stimulating factor (G-CSF) has emerged as a drug candidate for improving the outcome after peripheral nerve injuries. We raised the question if exogenous G-CSF can improve nerve regeneration following a clinically relevant model - nerve transection and repair - in healthy and diabetic rats. In short-term experiments, distance of axonal regeneration and extent of injury-induced Schwann cell death was quantified by staining for neurofilaments and cleaved caspase 3, respectively, seven days after repair. There was no difference in axonal outgrowth between G-CSF-treated and non-treated rats, regardless if healthy Wistar or diabetic Goto-Kakizaki (GK) rats were examined. However, G-CSF treatment caused a significant 13% decrease of cleaved caspase 3-positive Schwann cells at the lesion site in healthy rats, but only a trend in diabetic rats. In the distal nerve segments of healthy rats a similar trend was observed. In long-term experiments of healthy rats, regeneration outcome was evaluated at 90days after repair by presence of neurofilaments, wet weight of gastrocnemius muscle, and perception of touch (von Frey monofilament testing weekly). The presence of neurofilaments distal to the suture line was similar in G-CSF-treated and non-treated rats. The weight ratio of ipsi-over contralateral gastrocnemius muscles, and perception of touch at any time point, were likewise not affected by G-CSF treatment. In addition, the inflammatory response in short- and long-term experiments was studied by analyzing ED1 stainable macrophages in healthy rats, but in neither case was any attenuation seen at the injury site or distal to it. G-CSF can prevent caspase 3 activation in Schwann cells in the short-term, but does not detectably affect the inflammatory response, nor improve early or late axonal outgrowth or functional recovery. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Intrapleural polymeric films containing cisplatin for malignant pleural mesothelioma in a rat tumour model: a preliminary study.

PubMed

Ampollini, Luca; Sonvico, Fabio; Barocelli, Elisabetta; Cavazzoni, Andrea; Bilancia, Rocco; Mucchino, Claudio; Cantoni, Anna Maria; Carbognani, Paolo

2010-03-01

This study aims to investigate the effect of intrapleural polymeric films containing cisplatin on the local recurrence of malignant pleural mesothelioma in a rat tumour model. An orthotopic rat recurrence model of malignant pleural mesothelioma was used. Five animals per group were evaluated. Polymeric films (4.5 cm diameter) for the local delivery of anticancer drug were constructed: hyaluronate, chitosan and the combined dual-layer polymers were loaded with cisplatin at a concentration of 100 mgm(-2). Animals without any adjuvant therapy were used as control. Mesothelioma cells were injected subpleurally in the anaesthetised rats. Six days later, a pleural tumour of 5.5mm was resected and a left pneumonectomy and pleural abrasion were performed. Thereafter, the cisplatin-loaded and unloaded films or cisplatin solution were intrapleurally applied, according to randomisation. After 6 days, animals were euthanised and organs harvested for morphological and histological evaluations. The primary endpoint was the volume of tumour recurrence. The secondary endpoints were treatment-related toxicity; cisplatin serum concentration evaluated at different time points; and cisplatin concentration in the pleura measured at autopsy. Analysis of variance (ANOVA) was used for statistical analysis. Bonferroni correction was applied for comparison between all groups. Tumour volume was significantly reduced in the hyaluronate cisplatin and hyaluronate-chitosan cisplatin groups in comparison to control groups (p=0.001 and p<0.0001, respectively). Animals treated with hyaluronate-chitosan cisplatin had a tumour recurrence significantly lesser than animals treated with cisplatin solution (p=0.003) and hyaluronate cisplatin (p=0.032). No toxicity related to the different treatments was observed. On postoperative days 1 and 2, cisplatin was detected in the serum at a concentration six- and sevenfold significantly higher in the hyaluronate cisplatin and hyaluronate-chitosan cisplatin groups, in comparison to cisplatin solution, and was maintained over time. Cisplatin levels in the pleura were higher in the hyaluronate-chitosan cisplatin group than in all others. Hyaluronate-chitosan cisplatin was significantly effective in reducing tumour recurrence compared with cisplatin solution. Hyaluronate and hyaluronate-chitosan loaded with cisplatin assured significantly higher and more prolonged plasmatic drug concentrations than cisplatin solution without increasing toxicity. Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Effects of Electro-Acupuncture on Ovarian P450arom, P450c17α and mRNA Expression Induced by Letrozole in PCOS Rats

PubMed Central

Wu, Huangan; Zhao, Jimeng; Cui, Yunhua; Liu, Huirong; Wu, Lingxiang; Shi, Yin; Zhu, Bing

2013-01-01

Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS). Abnormalities in enzymatic activity and the expression of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA) in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD) rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA) consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg−1 of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA) showed significantly decreased androgens (i.e., androstenedione and testosterone) with significantly increased estrogens (i.e., estrone, estradiol) and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive and endocrine metabolic disorders in PCOS. PMID:24260211

Effects of electro-acupuncture on ovarian P450arom, P450c17α and mRNA expression induced by letrozole in PCOS rats.

PubMed

Sun, Jie; Jin, Chunlan; Wu, Huangan; Zhao, Jimeng; Cui, Yunhua; Liu, Huirong; Wu, Lingxiang; Shi, Yin; Zhu, Bing

2013-01-01

Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS). Abnormalities in enzymatic activity and the expression of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA) in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD) rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA) consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg(-1) of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA) showed significantly decreased androgens (i.e., androstenedione and testosterone) with significantly increased estrogens (i.e., estrone, estradiol) and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive and endocrine metabolic disorders in PCOS.

A bicarbonate- and weak acid-permeable chloride conductance controlled by cytosolic Ca2+ and ATP in rat submandibular acinar cells.

PubMed

Ishikawa, T

1996-09-01

A Ca(2+)-activated Cl- conductance in rat submandibular acinar cells was identified and characterized using whole-cell patch-clamp technique. When the cells were dialyzed with Cs-glutamate-rich pipette solutions containing 2 mM ATP and 1 microM free Ca2+ and bathed in N-methyl-D-glucamine chloride (NMDG-Cl) or Choline-Cl-rich solutions, they mainly exhibited slowly activating currents. Dialysis of the cells with pipette solutions containing 300 nM or less than 1 nM free Ca2+ strongly reduced the Cl- currents, indicating the currents were Ca(2+)-dependent. Relaxation analysis of the "on" currents of slowly activating currents suggested that the channels were voltage-dependent. The anion permeability sequence of the Cl- channels was: NO3- (2.00) > I- (1.85) > or = Br- (1.69) > Cl- (1.00) > bicarbonate (0.77) > or = acetate (0.70) > propionate (0.41) > > glutamate (0.09). When the ATP concentration in the pipette solutions was increased from 0 to 10 mM, the Ca(2+)-dependency of the Cl- current amplitude shifted to lower free Ca2+ concentrations by about two orders of magnitude. Cells dialyzed with a pipette solution (pCa = 6) containing ATP-gamma S (2 mM) exhibited currents of similar magnitude to those observed with the solution containing ATP (2 mM). The addition of the calmodulin inhibitors trifluoperazine (100 microM) or calmidazolium (25 microM) to the bath solution and the inclusion of KN-62 (1 microM), a specific inhibitor of calmodulin kinase, or staurosporin (10 nM), an inhibitor of protein kinase C to the pipette solution had little, if any, effect on the Ca(2+)-activated Cl- currents. This suggests that Ca2+/Calmodulin or calmodulin kinase II and protein kinase C are not involved in Ca(2+)-activated Cl- currents. The outward Cl- currents at +69 mV were inhibited by NPPB (100 microM), IAA-94 (100 microM), DIDS (0.03-1 mM), 9-AC (300 microM and 1 mM) and DPC (1 mM), whereas the inward currents at -101 mV were not. These results demonstrate the presence of a bicarbonate- and weak acid-permeable Cl- conductance controlled by cytosolic Ca2+ and ATP levels in rat submandibular acinar cells.

Effect of Calendula officinalis hydroalcoholic extract on passive avoidance learning and memory in streptozotocin-induced diabetic rats

PubMed Central

Moradkhani, Shirin; Salehi, Iraj; Abdolmaleki, Somayeh; Komaki, Alireza

2015-01-01

Background: Medicinal plants, owing to their different mechanisms such as antioxidants effects, may improve learning and memory impairments in diabetic rats. Calendula officinalis (CO), has a significant antioxidant activity. Aims: To examine the effect of hydroalcoholic extract of CO on passive avoidance learning (PAL) and memory in streptozotocin (STZ)-induced diabetic male rats. Settings and Design: A total of 32 adult male Wistar rats were randomly allocated to four groups: Control, diabetic, control + extract of CO and diabetic control + extract of CO groups with free access to regular rat diet. Subjects and Methods: Diabetes in diabetic rats was induced by single intraperitoneal injection of 60 mg/kg STZ. After confirmation of diabetes, oral administration of 300 mg/kg CO extract to extract-treated groups have been done. PAL was tested 8 weeks after onset of treatment, and blood glucose and body weight were measured in all groups at the beginning and end of the experiment. Statistical Analysis Used: The statistical analysis of data was performed by ANOVA followed by least significant difference post-hoc analysis. Results: Diabetes decreased learning and memory. Effect of CO extract in retention test (after 24 and 48 h) has been shown a significant decrease in step-through latency and increase in time spent in the dark compartment part. Also the extract partially improved hyperglycemia and reduced body weight. Conclusion: Taken together, CO extract can improve PAL and memory impairments in STZ-diabetic rats. This improvement may be due to its antioxidant, anticholinergic activities or its power to reduce hyperglycemia. PMID:26120230

Vertical sleeve gastrectomy improves indices of metabolic disease in rodent model of surgical menopause.

PubMed

Lawson, William J; Shirey, Kristin; Spann, Redin A; Zamarripa, Carlos A; Hosler, Jonathan P; Grayson, Bernadette E

2017-04-01

Although women are the most common recipients of weight loss surgeries for the amelioration of the comorbidities of obesity, few studies have addressed the efficacy of these procedures with specific attention to reproductive stage. Here we ask in a rodent model of vertical sleeve gastrectomy (VSG) whether improvements to metabolic health are realized in women having received surgical menopause. Specifically we were interested in knowing whether rats made menopausal through surgical means would exhibit persistent hepatic steatosis as reported in previously pregnant, freely cycling female VSG rats or if it is resolved as reported in male VSG rats. All the rats first received ovariectomy (OVX) and then were placed on high-fat diet before either sham or VSG surgery (N = 12, 9) and then were monitored for resolution of obesity-related comorbidities. VSG was sufficient to reduce weight and adiposity in OVX females in comparison to obese rats (P < 0.001). Glucose tolerance (P < 0.05) was improved in OVX-VSG females with no change in insulin sensitivity. Both circulating (P < 0.01) and hepatic triglyceride (P < 0.01) levels were also reduced after VSG. Liver integrity was improved in OVX-VSG in comparison to OVX-obese as reflected by reduced aspartate aminotransferase levels (P < 0.05). The ability of mitochondria to generate adenosine triphosphate was maintained, and an increase in complex IV may decrease the production of mitochondrial reactive oxygen species. Taken together, VSG in OVX rats experience many positive benefits including the resolution of hepatic steatosis that persists in reproductively intact female rats after VSG.

CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy.

PubMed

Zhou, Zhike; Liu, Tingting; Sun, Xiaoyu; Mu, Xiaopeng; Zhu, Gang; Xiao, Ting; Zhao, Mei; Zhao, Chuansheng

2017-03-30

It has been showed that enriched environment (EE) enhances the hippocampal neurogenesis and improves the cognitive impairments, accompanied by the increased expressions of stromal cell-derived factor-1 (SDF-1) in adult rats of temporal lobe epilepsy (TLE). We examined whether the enhanced neurogenesis and improved cognitive functions induced by EE following seizures were mediated by SDF-1/CXCR4 pathway. Therefore, we investigated the effects of the EE combined with CXCR4 antagonist AMD3100 on neurogenesis, cognitive functions and the long-term seizure activity in the TLE model. Adult rats were randomly assigned as control rats, rats treated with EE, rats subjected to status epilepticus (SE), post-SE rats treated with EE, AMD3100 or EE combined with AMD3100 respectively. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the frequency and mean duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze test. EE treatment significantly, as well as improved cognitive impairments and decreased long-term seizure activity, and that these effects might be mediated through SDF-1/CXCR4 pathway during the chronic stage of TLE. Although AMD3100 reversed the effect of EE on neurogenesis, it did not abolish the cognitive improvement induced by EE following seizures. More importantly, EE combined with AMD3100 treatment significantly suppressed long-term seizure activity, which provided promising evidences to treat TLE. Copyright © 2017 Elsevier B.V. All rights reserved.

Detraining Differentially Preserved Beneficial Effects of Exercise on Hypertension: Effects on Blood Pressure, Cardiac Function, Brain Inflammatory Cytokines and Oxidative Stress

PubMed Central

Agarwal, Deepmala; Dange, Rahul B.; Vila, Jorge; Otamendi, Arturo J.; Francis, Joseph

2012-01-01

Aims This study sought to investigate the effects of physical detraining on blood pressure (BP) and cardiac morphology and function in hypertension, and on pro- and anti-inflammatory cytokines (PICs and AIC) and oxidative stress within the brain of hypertensive rats. Methods and Results Hypertension was induced in male Sprague-Dawley rats by delivering AngiotensinII for 42 days using implanted osmotic minipumps. Rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise (ExT) for 42 days, whereas, detrained groups underwent 28 days of exercise followed by 14 days of detraining. BP and cardiac function were evaluated by radio-telemetry and echocardiography, respectively. At the end, the paraventricular nucleus (PVN) was analyzed by Real-time RT-PCR and Western blot. ExT in AngII-infused rats caused delayed progression of hypertension, reduced cardiac hypertrophy, and improved diastolic function. These results were associated with significantly reduced PICs, increased AIC (interleukin (IL)-10), and attenuated oxidative stress in the PVN. Detraining did not abolish the exercise-induced attenuation in MAP in hypertensive rats; however, detraining failed to completely preserve exercise-mediated improvement in cardiac hypertrophy and function. Additionally, detraining did not reverse exercise-induced improvement in PICs in the PVN of hypertensive rats; however, the improvements in IL-10 were abolished. Conclusion These results indicate that although 2 weeks of detraining is not long enough to completely abolish the beneficial effects of regular exercise, continuing cessation of exercise may lead to detrimental effects. PMID:23285093

The nitric oxide donor, S-nitroso human serum albumin, as an adjunct to HTK-N cardioplegia improves protection during cardioplegic arrest after myocardial infarction in rats.

PubMed

Trescher, Karola; Dzilic, Elda; Kreibich, Maximilian; Gasser, Harald; Aumayr, Klaus; Kerjaschki, Dontscho; Pelzmann, Brigitte; Hallström, Seth; Podesser, Bruno K

2015-03-01

Currently available cardioplegic solutions provide excellent protection in patients with normal surgical risk; in high-risk patients, however, such as in emergency coronary artery bypass surgery, there is still room for improvement. As most of the cardioplegic solutions primarily protect myocytes, the addition of substances for protection of the endothelium might improve their protective potential. The nitric oxide donor, S-nitroso human serum albumin (S-NO-HSA), which has been shown to prevent endothelial nitric oxide synthase uncoupling, was added to the newly developed histidine-tryptophan-ketoglutarat (HTK-N) cardioplegia in an isolated heart perfusion system after subjecting rats to acute myocardial infarction (MI) and reperfusion. In male Sprague-Dawley rats, acute MI was induced by ligation for 1 h of the anterior descending coronary artery. After 2 h of in vivo reperfusion hearts were evaluated on an isolated erythrocyte-perfused working heart model. Cold ischaemia (4°C) for 60 min was followed by 45 min of reperfusion. Cardiac arrest was induced either with HTK (n = 10), HTK-N (n = 10) or HTK-N + S-NO-HSA (n = 10). In one group (HTK-N + S-NO-HSA plus in vivo S-NO-HSA; n = 9) an additional in vivo infusion of S-NO-HSA was performed. Post-ischaemic recovery of cardiac output (HTK: 77 ± 4%, HTK-N: 86 ± 7%, HTK-N + S-NO-HSA: 101 ± 5%, in vivo S-NO-HSA: 93 ± 8%), external heart work (HTK: 79 ± 5%, HTK-N: 83 ± 3%, HTK-N + S-NO-HSA: 101 ± 8%, in vivo S-NO-HSA: 109 ± 13%), coronary flow (HTK: 77 ± 4%, HTK-N: 94 ± 6%, HTK-N + S-NO-HSA: 118 ± 15%, in vivo S-NO-HSA: 113 ± 3.17%) [HTK-N + S-NO-HSA vs HTK P < 0.001; HTK-N + S-NO-HSA vs HTK-N P < 0.05] and left atrial diastolic pressure (HTK: 122 ± 31%, HTK-N: 159 ± 43%, HTK-N + S-NO-HSA: 88 ± 30, in vivo S-NO-HSA: 62 ± 10%) [HTK-N + S-NO-HSA vs HTK P < 0.05; in vivo S-NO-HSA vs HTK-N P < 0.05] were significantly improved in both S-NO-HSA-treated groups compared with HTK and HTK-N, respectively. This was accompanied by better preservation of high-energy phosphates (adenosine triphosphate; energy charge) and ultrastructural integrity on transmission electron microscopy. However, no additional benefit of in vivo S-NO-HSA infusion was observed. Addition of the NO donor, S-NO-HSA refines the concept of HTK-N cardioplegia in improving post-ischaemic myocardial perfusion. HTK-N with S-NO-HSA is a possible therapeutic option for patients who have to be operated on for acute MI. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Submerged-Culture Mycelia and Broth of the Maitake Medicinal Mushroom Grifola frondosa (Higher Basidiomycetes) Alleviate Type 2 Diabetes-Induced Alterations in Immunocytic Function.

PubMed

Chen, Ya-Hui; Lee, Chien-Hsing; Hsu, Tai-Hao; Lo, Hui-Chen

2015-01-01

Type 2 Diabetes mellitus (T2DM), a disease with impaired glucose, protein and lipid metabolism, low-grade chronic inflammation, and immune dysfunction, is a global public health crisis. We previously demonstrated that Grifola frondosa has bioactivities in improving glycemic responses in diabetic rats. Herein, we investigated the immunomodulatory effects of the submerged-culture mycelia and broth of G. frondosa on the peripheral blood cells (PBL) and splenocytes. Male Wistar rats were administered with saline (normal rats) or streptozotocin plus nicotinamide (T2DM rats) and were intragastrically administered with placebo, fermented mycelia, broth, or mycelia plus broth (1 g kg-1 day-1) for two weeks. In normal rats, ingestion of mycelia significantly decreased monocytes and ingestion of mycelia and broth significantly decreased the productions of interferon (IFN)-γ and interleukin (IL)-4 from the PBL and splenocytes. In T2DM rats, ingestion of mycelia, broth, and mycelia plus broth significantly alleviated the increases in 2 h postprandial blood glucose and the productions of IFN-γ from the T-leukocytes, IL-4, and IL-6 from the monocytes and IL-4 from the T-splenocytes, as well as significantly improved the productions of tumor-necrosis factor-α from the macrophages. In conclusion, submerged-culture mycelia and broth of G. frondosa may decrease cell-medicated immunity in normal rats and improve hyperglycemia and diabetes-induced alterations in cell-medicated and innate immunities in T2DM rats.

A casein diet added isoflavone-enriched soy protein favorably affects biomarkers of steatohepatitis in obese Zucker rats.

PubMed

Gudbrandsen, Oddrun Anita; Wergedahl, Hege; Berge, Rolf Kristian

2009-05-01

Dietary supplementation of a soy protein enriched with isoflavones (HDI) has been shown to improve fatty liver in obese rats. The main objective of this study was to investigate whether HDI would influence the inflammatory status in livers of obese rats with fatty liver. Male obese Zucker fa/fa rats were fed casein (controls) or casein supplemented with HDI (containing 4.00 g of genistein and 4.50 g of daidzein per kilogram of diet) for 6 wk. The HDI-fed rats had a markedly lower hepatic concentration of triacylglycerol when compared with controls. The decreased aspartate transaminase/alanine transaminase ratio in plasma, together with lower circulating levels of alkaline phosphatase and bile acids after HDI feeding, implied an improved hepatitis. This was supported by decreased plasma and hepatic mRNA levels of tumor necrosis factor-alpha, lower plasma levels of interleukin-1beta and monocyte chemoattractant protein-1, and an increased anti-inflammatory fatty acid index in plasma. HDI also seemed to protect the rats from oxidative damage, because the level of lipid peroxides in triacylglycerol-rich lipoproteins after in vitro copper oxidation was lower for HDI-fed rats when compared with controls. These results show that isoflavone-enriched soy protein favorably affects biomarkers of hepatic inflammation in obese Zucker fa/fa rats with fatty liver. Thus, dietary soy proteins enriched in isoflavones may be a promising agent to improve steatohepatitis in patients.

Improvement of Liver Cell Therapy in Rats by Dietary Stearic Acid

PubMed Central

Goradel, Nasser Hashemi; Eghbal, Mohammad Ali; Darabi, Masoud; Roshangar, Leila; Asadi, Maryam; Zarghami, Nosratollah; Nouri, Mohammad

2016-01-01

Background: Stearic acid is known as a potent anti-inflammatory lipid. This fatty acid has profound and diverse effects on liver metabolism. The aim of this study was to investigate the effect of stearic acid on markers of hepatocyte transplantation in rats with acetaminophen (APAP)-induced liver damage. Methods: Wistar rats were randomly assigned to 10-day treatment. Stearic acid was administered to the rats with APAP-induced liver damage. The isolated liver cells were infused intraperitoneally into rats. Blood samples were obtained to evaluate the changes in the serum liver enzymes, including activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and the level of serum albumin. To assess the engraftment of infused hepatocytes, rats were euthanized, and the liver DNA was used for PCR using sex-determining region Y (SRY) primers. Results: The levels of AST, ALT and ALP in the serum of rats with APAP-induced liver injury were significantly increased and returned to the levels in control group by day six. The APAP-induced decrease in albumin was significantly improved in rats through cell therapy, when compared with that in the APAP-alone treated rats. SRY PCR analysis showed the presence of the transplanted cells in the liver of transplanted rats. Conclusion: Stearic acid-rich diet in combination with cell therapy accelerates the recovering of hepatic dysfunction in a rat model of liver injury. PMID:27090202

DOE Office of Scientific and Technical Information (OSTI.GOV)

Comar, C.L.; Lengemann, F.W.; Wasserman, R.H. et al

Research activities during the past 6 years are reviewed. Results are reported for recent studies on adaptation to increased dietary Ca by dairy cows as a factor in the reduction of Sr/sup 90/ content of milk; the testing of a theoretical model of alkaline earth absorption in rats by a comparison of biological discrimination among Ca/sup 47/, Sr/sup 85/, and Ba/sup 133/ in the presence of glucose, lactose, and lysine; the effects of lactose on the intestinal absorption of Ca in rats; a comparison of the ileal absorption of Ca/ sup 47/ and Sr/sup 85/ by rats from solutions withmore » high and low concentrations of stable Ca; determinatione of the Ca, Mg, and total alkaline earth content in mucosal tissue and plasma of normally fed rats, fasted rats, and rats fed a lactose solution; an investigation of non-exchangeable Ca compartments in the plasma of sheep; the effect of lactose and vitamin D on calcification in the rachitic chick; the metabolism and milk content of I/sup 131/ of dairy cows after long-term daily administration of I/sup 131/; the absorption of Fe/sup 59/ in sheep; the development of a method for the estimation of parasitic blood loss in sheep by whole-body counting of Fe/sup 59/ retention; the development of a method for the simultaneous measurement of erythrocyte and plasma volume in sheep using Fe/sup 59/ as a tracer; the concentration of Na/sup 22/, Cl/sup 36/, and C/sup 14/ inulin in rat kidney and counter-current mechanisms for the production of concentrated urine in mammals; the effects of diuretics on the distribution of Na/ sup 22/, Fe/sup 59/-labeled erythrocytes, and I/sup 131/labeled albumin in rat kidneys; the effects of thiamine on nervous response to ultraviolet radiation in frogs and lobsters; the effects of gamma radiation on reproductive capabilities of young male rabbits; and an evaluation of the contamination of the food chain by fallout fission products, with emphasis on Sr/sup 90/, Cs/sup 137/, and I/sup 131/ intake from total diet and individual food items. A list is included of publications resulting from research conducted under this contract. (C.H.)« less

Green tea polyphenols supplementation improves bone microstructure in orchidectomized middle-Aged rats

USDA-ARS?s Scientific Manuscript database

Our recent study shows that green tea polyphenols (GTP) attenuate trabecular bone loss in ovariectomized middle-aged female rats. To investigate whether GTP prevents bone loss in male rats, 40 rats with and without oriectomy (ORX) were assigned to 4 groups in a 2 (sham vs. ORX)× 2 (no GTP and 0.5% G...

Enrichment and Training Improve Cognition in Rats with Cortical Malformations

PubMed Central

Jenks, Kyle R.; Lucas, Marcella M.; Duffy, Ben A.; Robbins, Ashlee A.; Gimi, Barjor; Barry, Jeremy M.; Scott, Rod C.

2013-01-01

Children with malformations of cortical development (MCD) frequently have associated cognitive impairments which reduce quality of life. We hypothesized that cognitive deficits associated with MCD can be improved with environmental manipulation or additional training. The E17 methylazoxymethanol acetate (MAM) exposure model bears many anatomical hallmarks seen in human MCDs as well as similar behavioral and cognitive deficits. We divided control and MAM exposed Sprague-Dawley rats into enriched and non-enriched groups and tested performance in the Morris water maze. Another group similarly divided underwent sociability testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post enrichment. A third group of control and MAM rats without enrichment were trained until they reached criterion on the place avoidance task. MAM rats had impaired performance on spatial tasks and enrichment improved performance of both control and MAM animals. Although MAM rats did not have a deficit in sociability they showed similar improvement with enrichment as controls. MRI revealed a whole brain volume decrease with MAM exposure, and an increase in both MAM and control enriched volumes in comparison to non-enriched animals. In the place avoidance task, MAM rats required approximately 3 times as long to reach criterion as control animals, but with additional training were able to reach control performance. Environmental manipulation and additional training can improve cognition in a rodent MCD model. We therefore suggest that patients with MCD may benefit from appropriate alterations in educational strategies, social interaction and environment. These factors should be considered in therapeutic strategies. PMID:24358362

Protective effects of AT1-receptor blocker and CA antagonist combination on renal function in salt loaded spontaneously hypertensive rats.

PubMed

Gjorgjievska, K; Zafirov, D; Jurhar-Pavlova, M; Cekovska, S; Atanasovska, E; Pavlovska, K; Zendelovska, D

2015-01-01

Salt sensitive hypertension is known to be a contributing factor for the progression of kidney disease. This study was undertaken to investigate the role of excessive dietary salt on renal function and to evaluate the effect of valsartan and amlodipin given as a combination therapy on blood pressure and parameters specific to the renal function in salt loaded SHR rats. 48 male SHR rats at age of 20 weeks and body weight ranging between 270-350 g were used. SHR rats were divided into 3 groups: control group of rats -SHRC (n = 16) given tab water ad libitum and two salt treated groups in which tab water was replaced with a solution of NaCl (1%) from age of 8 weeks given ad libitum: SHRVAL+AMLO group (n = 16) where investigated drugs were administered at a dose of 10 mg/kg/ b.w. (valsartan) and 5 mg/kg/ b.w. (amlodipin) by gavage and SHR NaCl group (n = 16) that received saline in the same volume and the same time intervals as the SHRVAL+AMLO group. For a period of 12 weeks we have investigated the effect of the VAL+AMLO drug combination on systolic blood pressure (SBP), body weight and renal function tests. Salt loading with 1% solution in the SHR NaCl group has lead to significant increase of blood pressure, proteinuria and decrease in creatinine clearance. Combined treatment with AT1 receptor blocker and calcium antagonist has managed to control blood pressure and ameliorated renal damage.

The effects of biological sex and gonadal hormones on learning strategy in adult rats.

PubMed

Hawley, Wayne R; Grissom, Elin M; Barratt, Harriet E; Conrad, Taylor S; Dohanich, Gary P

2012-02-28

When learning to navigate toward a goal in a spatial environment, rodents employ distinct learning strategies that are governed by specific regions of the brain. In the early stages of learning, adult male rats prefer a hippocampus-dependent place strategy over a striatum-dependent response strategy. Alternatively, female rats exhibit a preference for a place strategy only when circulating levels of estradiol are elevated. Notably, male rodents typically perform better than females on a variety of spatial learning tasks, which are mediated by the hippocampus. However, limited research has been done to determine if the previously reported male spatial advantage corresponds with a greater reliance on a place strategy, and, if the male preference for a place strategy is impacted by removal of testicular hormones. A dual-solution water T-maze task, which can be solved by adopting either a place or a response strategy, was employed to determine the effects of biological sex and hormonal status on learning strategy. In the first experiment, male rats made more correct arm choices than female rats during training and exhibited a bias for a place strategy on a probe trial. The results of the second experiment indicated that testicular hormones modulated arm choice accuracy during training, but not the preference for a place strategy. Together, these findings suggest that the previously reported male spatial advantage is associated with a greater reliance on a place strategy, and that only performance during the training phase of a dual-solution learning task is impacted by removal of testicular hormones. Copyright © 2011 Elsevier Inc. All rights reserved.

Alleviation of metabolic abnormalities induced by excessive fructose administration in Wistar rats by Spirulina maxima.

PubMed

Jarouliya, Urmila; Zacharia, J Anish; Kumar, Pravin; Bisen, P S; Prasad, G B K S

2012-03-01

Diabetes mellitus is a metabolic disorder characterized by hyperglycaemia. Several natural products have been isolated and identified to restore the complications of diabetes. Spirulina maxima is naturally occurring fresh water cyanobacterium, enriched with proteins and essential nutrients. The aim of the study was to determine whether S. maxima could serve as a therapeutic agent to correct metabolic abnormalities induced by excessive fructose administration in Wistar rats. Oral administration of 10 per cent fructose solution to Wistar rats (n = 5 in each group) for 30 days resulted in hyperglycaemia and hyperlipidaemia. Aqueous suspension of S. maxima (5 or 10%) was also administered orally once daily for 30 days. The therapeutic potential of the preparation with reference to metformin (500 mg/kg) was assessed by monitoring various biochemical parameters at 10 day intervals during the course of therapy and at the end of 30 days S. maxima administration. Significant (P<0.001) reductions in blood glucose, lipid profile (triglycerides, cholesterol and LDL, VLDL) and liver function markers (SGPT and SGOT) were recorded along with elevated level of HDL-C at the end of 30 days therapy of 5 or 10 per cent S. maxima aquous extract. Co-administration of S. maxima extract (5 or 10% aqueous) with 10 per cent fructose solution offered a significant protection against fructose induced metabolic abnormalities in Wistar rats. The present findings showed that S. maxima exhibited anti-hyperglycaemic, anti-hyperlipidaemic and hepatoprotective activity in rats fed with fructose. Further studies are needed to understand the mechanisms.