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  1. Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice

    SciTech Connect

    Amirshahrokhi, K.; Dehpour, A.R.; Hadjati, J.; Sotoudeh, M.; Ghazi-Khansari, M.

    2008-10-01

    Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of {beta} cells by the immune system. Opioids have been shown to modulate a number of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this study was to determine the effect of methadone, a {mu}-opioid receptor agonist, on type 1 diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10mg/kg/day subcutaneously) for 24days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, an opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1{beta}, tumor necrosis factor-{alpha} and interferon-{gamma}] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of {beta} cells was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a protective effect against destruction of {beta} cells and insulitis in the MLDS model of type 1 diabetes.

  2. Curcumin pretreatment mediates antidiabetogenesis via functional regulation of adrenergic receptor subtypes in the pancreas of multiple low-dose streptozotocin-induced diabetic rats.

    PubMed

    Naijil, George; Anju, T R; Jayanarayanan, S; Paulose, C S

    2015-09-01

    Lifestyle modification pivoting on nutritional management holds tremendous potential to meet the challenge of management of diabetes. The current study hypothesizes that regular uptake of curcumin lowers the incidence of diabetes by functional regulation of pancreatic adrenergic receptor subtypes. The specific objective of the study was to identify the regulatory pathways implicated in the antidiabetogenesis effect of curcumin in multiple low-dose streptozotocin (MLD-STZ)-induced diabetic Wistar rats. Administration of MLD-STZ to curcumin-pretreated rats induced a prediabetic condition. Scatchard analysis, real-time polymerase chain reaction, and confocal microscopic studies confirmed a significant increase in α2-adrenergic receptor expression in the pancreas of diabetic rats. Pretreatment with curcumin significantly decreased α2-adrenergic receptor expression. The diabetic group showed a significant decrease in the expression of β-adrenergic receptors when compared with control. Pretreatment significantly increased β-adrenergic receptor expression to near control. When compared with the diabetic rats, a significant up-regulation of CREB, phospholipase C, insulin receptor, and glucose transporter 2 were observed in the pretreated group. Curcumin pretreatment was also able to maintain near control levels of cyclic adenosine monophosphate, cyclic guanosine monophosphate, and inositol triphosphate. These results indicate that a marked decline in α2-adrenergic receptor function relents sympathetic inhibition of insulin release. It also follows that escalated signaling through β-adrenergic receptors mediates neuronal stimulation of hyperglycemia-induced β-cell compensatory response. Curcumin-mediated functional regulation of adrenergic receptors and modulation of key cell signaling molecules improve pancreatic glucose sensing, insulin gene expression, and insulin secretion. PMID:26255758

  3. Multiple low-dose streptozotocin-induced diabetes in the mouse. Evidence for stimulation of a cytotoxic cellular immune response against an insulin-producing beta cell line.

    PubMed Central

    McEvoy, R C; Andersson, J; Sandler, S; Hellerström, C

    1984-01-01

    Mice were examined for the presence of splenocytes specifically cytotoxic for a rat insulinoma cell line (RIN) during the induction of diabetes by streptozotocin (SZ) in multiple low doses (Multi-Strep). Cytotoxicity was quantitated by the release of 51Cr from damaged cells. A low but statistically significant level of cytolysis (5%) by splenocytes was first detectable on day 8 after the first dose of SZ. The cytotoxicity reached a maximum of approximately 9% on day 10 and slowly decreased thereafter, becoming undetectable 42 d after SZ was first given. The time course of the in vitro cytotoxic response correlated with the degree of insulitis demonstrable in the pancreata of the Multi-Strep mice. The degree of cytotoxicity after Multi-Strep was related to the number of effector splenocytes to which the target RIN cells were exposed and was comparable to that detectable after immunization by intraperitoneal injection of RIN cells in normal mice. The cytotoxicity was specific for insulin-producing cells; syngeneic, allogeneic, and xenogeneic lymphocytes and lymphoblasts, 3T3 cells, and a human keratinocyte cell line were not specifically lysed by the splenocytes of the Multi-Strep mice. This phenomenon was limited to the Multi-Strep mice. Splenocytes from mice made diabetic by a single, high dose of SZ exhibited a very low level of cytotoxicity against the RIN cells. The cytotoxic response was also quantitated in splenocytes from control and Multi-Strep mice (10 d after the first dose of SZ) before and after culture with mitomycin-treated RIN cells in the presence of T cell growth factor (TCGF). The cytotoxicity of the Multi-Strep splenocytes was enhanced more than fivefold after such culture, suggesting the proliferation of an effector cell that could be stimulated and supported in vitro by TCGF. These results support the hypothesis that cell-mediated anti-beta cell autoimmunity may play a role in the destruction of the beta cells in this animal model. The

  4. Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Xianchu; Mo, Yanzhi; Gong, Jingbo; Li, Zhuang; Peng, Huan; Chen, Jiaxue; Wang, Qichao; Ke, Zhaowen; Xie, Jingtao

    2016-04-01

    Previous research has indicated that Diabetes is a high risk of learning and memory deficits. Puerarin, an isoflavonoid extracted from Kudzu roots, has been reported to possess antioxidant, anti-inflammatory, anti-apoptotic and anti-diabetic properties which are useful in the treatment of various diseases. Recently, Puerarin was found to have the effects on learning and memory performances in humans and animal models. However, up to now, there is no detailed evidence on the effect of Puerarin on diabetes-associated cognitive decline (DACD). In this study, we designed to assess the effects of Puerarin on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model and exploring its potential mechanism. Diabetic rats were treated with Puerarin (100 mg/kg per d) for 7 days. The learning and memory function was evaluated by morris water maze test. The acetylcholinesterase (AChE), choline acetylase (ChAT), oxidative indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] and inflammatory cytokine (TNF-a, IL-1β and IL-6) were measured in hippocampus by using corresponding commercial kits. mRNA and Protein levels of Bcl-2 were analyzed by RT-PCR and Westernblot. The results showed that supplementation of Puerarin improved the learning and memory performances compared with the STZ group by the morris water maze test. In addition, Puerarin supplement significantly prevented AChE and MDA activities, increased ChAT and SOD activities, and alleviated the protein level of TNF-α, IL-1β and IL-6 in the hippocampus compared with the STZ group. Moreover, the pretreatment with Puerarin also significantly increased the Bcl-2 expression. It is concluded that Puerarin possesses neuroprotection to ameliorate cognitive deficits in streptozotocin-induced diabetic rats by anti-inflammatory, antioxidant and antiapototic effects. PMID:26686502

  5. Curcumin ameliorates streptozotocin-induced heart injury in rats.

    PubMed

    Abo-Salem, Osama M; Harisa, Gamaleldin I; Ali, Tarek M; El-Sayed, El-Sayed M; Abou-Elnour, Fatma M

    2014-06-01

    Heart failure (HF) is one of diabetic complications. This work was designed to investigate the possible modulatory effect of curcumin against streptozotocin-induced diabetes and consequently HF in rats. Rats were divided into control, vehicle-treated, curcumin-treated, diabetic-untreated, diabetic curcumin-treated, and diabetic glibenclamide-treated groups. Animal treatment was started 5 days after induction of diabetes and extended for 6 weeks. Diabetic rats showed significant increase in serum glucose, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, nitric oxide, lactate dehydrogenase, cardiac malondialdehyde, plasma levels of interleukin-6, and tumor necrosis factor-alpha, and also showed marked decrease in serum high-density lipoprotein-cholesterol, cardiac reduced glutathione, and cardiac antioxidant enzymes (catalase, superoxide dismutase, and glutathione-S-transferase). However, curcumin or glibenclamide treatment significantly mitigated such changes. In conclusion, curcumin has a beneficial therapeutic effect in diabetes-induced HF, an effect that might be attributable to its antioxidant and suppressive activity on cytokines. PMID:24760747

  6. Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats

    PubMed Central

    Liu, Xianchu; Liu, Ming; Mo, Yanzhi; Peng, Huan; Gong, Jingbo; Li, Zhuang; Chen, Jiaxue; Xie, Jingtao

    2016-01-01

    Objective(s): Previous research demonstrated that diabetes is one of the leading causes of learning and memory deficits. Naringin, a bioflavonoid isolated from grapefruits and oranges, has potent protective effects on streptozotocin (STZ)-induced diabetic rats. Recently, the effects of naringin on learning and memory performances were monitored in many animal models of cognitive impairment. However, to date, no studies have investigated the ameliorative effects of naringin on diabetes-associated cognitive decline (DACD). In this study, we investigated the effects of naringin, using a STZ-injected rat model and explored its potential mechanism. Materials and Methods: Diabetic rats were treated with naringin (100 mg/kg/d) for 7 days. The learning and memory function were assessed by Morris water maze test. The oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)] and inflammatory cytokines (TNF-a, IL-1β, and IL-6) were measured in hippocampus using corresponding commercial kits. The mRNA and protein levels of PPARγ were evaluated by real time (RT)-PCR and Western blot analysis. Results: The results showed that supplementation of naringin improved learning and memory performances compared with the STZ group. Moreover, naringin supplement dramatically increased SOD levels, reduced MDA levels, and alleviated TNF-α, IL-1β, and IL-6 compared with the STZ group in the hippocampus. The pretreatment with naringin also significantly increased PPARγ expression. Conclusion: Our results showed that naringin may be a promising therapeutic agent for improving cognitive decline in DACD. PMID:27279986

  7. Carvedilol Ameliorates Early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Morsy, Mohamed A.; Ibrahim, Salwa A.; Amin, Entesar F.; Kamel, Maha Y.; Abdelwahab, Soha A.; Hassan, Magdy K.

    2014-01-01

    Diabetic nephropathy results in end-stage renal disease. On the other hand, carvedilol has been reported to have various pharmacological properties. The aim of this study therefore is to evaluate the possible protective effect of carvedilol on streptozotocin-induced early diabetic nephropathy and various mechanisms underlie this effect in rats. Single i.p. injection of streptozotocin (65 mg/kg) was administered to induce early diabetic nephropathy in Wistar rats. Oral administration of carvedilol at a dose level of 1 and 10 mg/kg daily for 4 weeks resulted in nephroprotective effect as evident by significant decrease in serum creatinine level, urinary albumin/creatinine ratio, and kidney index as well as renal levels of malondialdehyde, nitric oxide, tumor necrosis factor-α, and cyclooxygenase-2 with a concurrent increase in creatinine clearance and renal reduced glutathione level compared to diabetic untreated rats. The protective effect of carvedilol was confirmed by renal histopathological examination. The electron microscopic examination indicated that carvedilol could effectively ameliorate glomerular basement membrane thickening and podocyte injury. In conclusion, carvedilol protects rats against streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant as well as anti-inflammatory activities, and ameliorating podocyte injury. PMID:24991534

  8. Total saponin of Dioscoreae hypoglaucae rhizoma ameliorates streptozotocin-induced diabetic nephropathy

    PubMed Central

    Guo, Changrun; Ding, Gang; Huang, Wenzhe; Wang, Zhenzhong; Meng, Zhaoqing; Xiao, Wei

    2016-01-01

    Background Diabetic nephropathy has become the most common cause of morbidity and mortality in diabetic patients. Therefore, there is an urgent need for more effective and safer drugs for use in this condition. Purpose The aims of this study were to investigate the ameliorative effects of total saponin of Dioscoreae hypoglaucae rhizoma (TSD) on diabetic nephropathy and to explore the potential underlying mechanism(s). Methods Rats with streptozotocin-induced diabetes were orally treated with TSD at 40, 80, and 160 mg/kg/d for 12 weeks. At the end of the treatment, blood, urine, and kidneys were collected for biochemical and histological examination. Results The results demonstrated that TSD significantly decreased the fasting blood glucose, glycosylated hemoglobin, urinary protein, serum creatinine, and blood urea nitrogen levels in diabetic rats. The results of histological examinations showed that TSD ameliorated glomerular and tubular pathological changes in diabetic rats. Furthermore, TSD significantly prevented oxidative stress and reduced the renal levels of advanced glycation end products, transforming growth factor-β1, connective tissue growth factor, and tumor necrosis factor-α. Conclusion This study demonstrated the renoprotective effects of TSD in experimental diabetic nephropathy via a number of different mechanisms. PMID:26966352

  9. Extract of Moringa oleifera leaves ameliorates streptozotocin-induced Diabetes mellitus in adult rats.

    PubMed

    Yassa, Hanan Dawood; Tohamy, Adel Fathy

    2014-06-01

    Medicinal plants attract growing interest in the therapeutic management of Diabetes mellitus. Moringa oleifera is a remarkably nutritious vegetable with several antioxidant properties. The present study assessed the possible antioxidant and antidiabetic effects of an aqueous extract of M. oleifera leaves in treating streptozotocin-induced diabetic albino rats. The antidiabetic effects of aqueous extract of M. oleifera leaves were assessed histomorphometrically, ultrastructurally and biochemically. Fasting plasma glucose (FPG) was monitored and morphometric measurements of β-cells of islets of Langerhans (modified Gomori's stain) and collagen fibers (Mallory's trichrome stain) were performed. The antioxidant effects of M. oleifera leaves were determined by measuring the reduced glutathione and lipid peroxidation product, malondialdehyde, in pancreatic tissue. M. oleifera treatment significantly ameliorated the altered FPG (from 380% to 145%), reduced glutathione (from 22% to 73%) and malondialdehyde (from 385% to 186%) compared to control levels. The histopathological damage of islet cells was also markedly reversed. Morphometrically, M. oleifera significantly increased the areas of positive purple modified Gomori stained β-cells (from 60% to 91%) and decreased the area percentage of collagen fibers (from 199% to 120%) compared to control values. Experimental findings clearly indicate the potential benefits of using the aqueous extract of M. oleifera leaves as a potent antidiabetic treatment. PMID:24657072

  10. Depletion of T lymphocytes ameliorates cardiac fibrosis in streptozotocin-induced diabetic cardiomyopathy.

    PubMed

    Abdullah, Chowdhury S; Li, Zhao; Wang, Xiuqing; Jin, Zhu-Qiu

    2016-10-01

    T cell infiltration has been associated with increased coronary heart disease risk in patients with diabetes mellitus. Effect of modulation of T cell trafficking on diabetes-induced cardiac fibrosis has yet to be determined. Therefore, our aim was to investigate the circulatory T cell depletion-mediated cardioprotection in streptozotocin-induced diabetic cardiomyopathy. Fingolimod (FTY720), an immunomodulatory drug, was tested in wild-type (WT) C57BL/6 and recombination activating gene 1 (Rag1) knockout (KO) mice without mature lymphocytes in streptozotocin-induced type 1 diabetic model. FTY720 (0.3mg/kg/day) was administered intraperitoneally daily for the first 4weeks with interim 3weeks then resumed for another 4weeks in 11weeks study period. T lymphocyte counts, cardiac histology, function, and fibrosis were examined in diabetic both WT and KO mice. FTY720 reduced both CD4(+) and CD8(+) T cells in diabetic WT mice. FTY720-treated diabetic WT mouse myocardium showed reduction in CD3 T cell infiltration and decreased expression of S1P1 and TGF-β1 in cardiac tissue. Fibrosis was reduced after FTY720 treatment in diabetic WT mice. Rag1 KO mice exhibited no CD4(+) and CD8(+) T cells in the blood and CD3 T cells in the heart. Diabetic Rag1 KO mouse hearts appeared no fibrosis and exhibited preserved myocardial contractility. FTY720-induced antifibrosis was abolished in diabetic Rag1 KO mice. These findings demonstrate that chronic administration with FTY720 induces lymphopenia and protects diabetic hearts in WT mice whereas FTY720 increases cardiac fibrosis and myocardial dysfunction in diabetic Rag1 KO mice without mature lymphocytes. PMID:27494688

  11. Dipeptidyl peptidase-4 inhibition by Pterocarpus marsupium and Eugenia jambolana ameliorates streptozotocin induced Alzheimer's disease.

    PubMed

    Kosaraju, Jayasankar; Madhunapantula, Subbarao V; Chinni, Santhivardhan; Khatwal, Rizwan Basha; Dubala, Anil; Muthureddy Nataraj, Satish Kumar; Basavan, Duraiswamy

    2014-07-01

    Alzheimer's disease (AD), the most common form of dementia, is characterized by the loss of normal functions of brain cells and neuronal death, ultimately leading to memory loss. Recent accumulating evidences have demonstrated the therapeutic potential of anti-diabetic agents, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, for the treatment of Alzheimer's disease (AD), providing opportunities to explore and test the DPP-4 inhibitors for treating this fatal disease. Prior studies determining the efficacy of Pterocarpus marsupium (PM, Fabaceae) and Eugenia jambolana (EJ, Myrtaceae) extracts for ameliorating type 2 diabetes have demonstrated the DPP-4 inhibitory properties indicating the possibility of using of these extracts even for the treating AD. Therefore, in the present study, the neuroprotective roles of PM and EJ for ameliorating the streptozotocin (STZ) induced AD have been tested in rat model. Experimentally, PM and EJ extracts, at a dose range of 200 and 400mg/kg, were administered orally to STZ induced AD Wistar rats and cognitive evaluation tests were performed using radial arm maze and hole-board apparatus. Following 30 days of treatment with the extracts, a dose- and time-dependent attenuation of AD pathology, as evidenced by decreasing amyloid beta 42, total tau, phosphorylated tau and neuro-inflammation with an increase in glucagon-like peptide-1 (GLP-1) levels was observed. Therefore, PM and EJ extracts contain cognitive enhancers as well as neuroprotective agents against STZ induced AD. PMID:24667360

  12. Combination of telmisartan with sildenafil ameliorate progression of diabetic nephropathy in streptozotocin-induced diabetic model.

    PubMed

    El-Mahdy, Nageh Ahmed; El-Sayad, Magda El-Sayed; El-Kadem, Aya Hassan

    2016-07-01

    Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the world. Several signaling pathways are involved in the pathogenesis of DN including elevation in level of angiotensin II, formation of advanced glycation end products (AGE), activation of protein kinase c (PKC), and lipid accumulation. These pathways activate one another mutually leading to oxidative stress, increasing expression of transforming growth factor beta-1(TGF-β 1) and release of interleukins and adhesion molecules, so the aim of this study is to interrupt more than pathogenic pathway to ameliorate the progression of DN. In the present study, white male rats (N=48) were divided into six groups (8 rats each), the first two groups served as normal control and a control vehicle group while the remaining four groups were rendered diabetic by a single intraperitoneal injection of Streptozotocin (STZ) and being left for 4 weeks to develop DN. Thereafter, the rats were divided into DN group, DN group receiving Telmisartan or Sildenafil or Telmisartan Sildenafil combination. After the specified treatment period, urine samples were collected (using metabolic cages) to measure proteinuria, animals were then euthanized, blood and tissue samples were collected for measurement of Blood glucose,BUN, S.Cr, LDL, NO, TGF-β1, IL-1β, AGEPs, and SOD. The combination therapy showed significant decrease in BUN, S.Cr,LDL, TGF-β1, IL-1β, Proteinuria and AGEPs and significant increase in SOD and NO. The findings showed that combination therapy was able to ameliorate DN and that the effects were superior to the single drugs alone. PMID:27261587

  13. Ameliorative Potentials of Ginger (Z. officinale Roscoe) on Relative Organ Weights in Streptozotocin induced Diabetic Rats

    PubMed Central

    Eleazu, C. O.; Iroaganachi, M.; Okafor, P. N.; Ijeh, I. I.; Eleazu, K. C.

    2013-01-01

    The ameliorating potentials of ginger incorporated feed (10%) on the relative organ weights of Streptozotocin (STZ) induced diabetic rats was investigated. The experiment lasted for three weeks. Results show that administration of 10% ginger feed to the diabetic rats of group 3, resulted in a 29.81% decrease in their resulting hyperglycemia with a corresponding amelioration of elevated urinary protein, sugars, specific gravity as well as renal growth. In addition, administration of the ginger incorporated feeds to the diabetic rats of group 3, resulted in 9.88% increase in body weight with a corresponding 60.24% increase in growth compared with the non-diabetic rats administered standard rat pellets that had 6.21% increase in weight with a corresponding 60.14% increase in growth unlike the diabetic control rats that recorded 28.62% decrease in body weight with a corresponding 239.9% decrease in growth rates. Analysis of the chemical composition of the flour of the ginger incorporated feed indicated that it contained moderate amounts of moisture, crude fibre, alkaloids, saponins, tannins, Fe and Zn but considerable amounts of proteins, lipids, carbohydrates, ash, flavonoids, calcium, magnesium, potassium, phosphorous and energy value. There was no significant difference (P>0.05) in the liver and relative liver weights of the diabetic control rats and the diabetic -ginger treated rats. In addition, there were no significant differences in the kidney weights of the non-diabetic, diabetic control and diabetic treated rats (P>0.05) while there were significant differences in the relative kidney weights of the non-diabetic rats and the diabetic rats treated with ginger feeds (P<0.05). Results show that the use of ginger in the dietary management of diabetes mellitus could be a breakthrough in the search for novel plants that could prevent the development of diabetic glomerular hypertrophy. PMID:23847458

  14. Saxagliptin: a dipeptidyl peptidase-4 inhibitor ameliorates streptozotocin induced Alzheimer's disease.

    PubMed

    Kosaraju, Jayasankar; Gali, Chaitanya Chakravarthi; Khatwal, Rizwan Basha; Dubala, Anil; Chinni, Santhivardhan; Holsinger, R M Damian; Madhunapantula, V Subba Rao; Muthureddy Nataraj, Satish Kumar; Basavan, Duraiswamy

    2013-09-01

    Type 2 diabetes (T2D) is one of the major risk factors associated with Alzheimer's disease (AD). Recent studies have found similarities in molecular mechanisms that underlie the respective degenerative developments in the two diseases. Pharmacological agents, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, which increase the level of glucagon-like peptide-1 (GLP-1) and ameliorate T2D, have become valuable candidates as disease modifying agents in the treatment of AD. In addition, endogenous GLP-1 levels decrease amyloid beta (Aβ) peptide and tau phosphorylation in AD. The present study examines the efficacy of Saxagliptin, a DPP-4 inhibitor in a streptozotocin (STZ) induced rat model of AD. Three months following induction of AD by intracerebral administration of streptozotocin, animals were orally administered Saxagliptin (0.25, 0.5 and 1 mg/kg) for 60 days. The effect of the DPP-4 inhibitor on hippocampal GLP-1 levels, Aβ burden, tau phosphorylation, inflammatory markers and memory retention were evaluated. The results reveal an attenuation of Aβ, tau phosphorylation and inflammatory markers and an improvement in hippocampal GLP-1 and memory retention following treatment. This remarkable therapeutic effect of Saxagliptin mediated through DPP-4 inhibition demonstrates a unique mechanism for Aβ and tau clearance by increasing GLP-1 levels and reverses the behavioural deficits and pathology observed in AD. PMID:23603201

  15. Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats.

    PubMed

    Mao, Xiao-Yuan; Cao, Dan-Feng; Li, Xi; Yin, Ji-Ye; Wang, Zhi-Bin; Zhang, Ying; Mao, Chen-Xue; Zhou, Hong-Hao; Liu, Zhao-Qian

    2014-01-01

    The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis. PMID:24857910

  16. Russelioside B, a pregnane glycoside ameliorates hyperglycemia in streptozotocin induced diabetic rats by regulating key enzymes of glucose metabolism.

    PubMed

    Abdel-Sattar, Essam; El-Maraghy, Shohda A; El-Dine, Riham Salah; Rizk, Sherine M

    2016-05-25

    An alternative strategy to treat diabetes mellitus is the use of various natural agents possessing hypoglycemic effect. Caralluma quadrangula has been used in Saudi traditional medicine in cases of thirst and hunger and for the treatment of diabetes. The present study was designed to evaluate the improving effect of russelioside B, a pregnane glycoside isolated from Caralluma quadrangula on glucose metabolism in the liver of streptozotocin-induced diabetic rats. Diabetes mellitus was induced in rats by a single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Experimental rats were administered russelioside B at a dose of 50 mg/kg body weight once a day for 30 days. The results showed that RB improved the fasting serum glucose level, glycated hemoglobin percent, serum insulin level and lipid profile. A significant improvement was observed upon the administration of russelioside B on the activities of the key enzymes of carbohydrate metabolism (glucokinase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, and glycogen phosphorylase) in the liver of diabetic rats. Further, russelioside B administration to diabetic rats reverted gene expression of glucokinase, glucose-6-phosphatase, glycogen synthase and glycogen synthase kinase-3β to near normal levels. In conclusion, russelioside B possess antidiabetic and antihyperlipidemic effect in streptozotocin induced diabetic rats. Hence, administration of russelioside B may represent a potentially useful strategy for the management of diabetes. PMID:27038876

  17. Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats

    PubMed Central

    Niwa, Atsuko; Tajiri, Takashi; Higashino, Hideaki

    2011-01-01

    Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg−1 d−1), Agaricus blazei (1 g kg−1 d−1) or Smallanthus sonchifolius (4 g kg−1 d−1) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-α production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic β-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic β-cells mass. PMID:21562638

  18. Traditional Chinese Medicine Tang-Luo-Ning Ameliorates Sciatic Nerve Injuries in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Zou, Da-Wei; Gao, Yan-Bin; Zhu, Zhi-Yao; Zhou, Hui; Zhang, Tao-Jing; Li, Bu-Man; Wang, Jin-Yang; Li, Min-Zhou; Ma, Ming-Fei; Zhang, Na

    2013-01-01

    Diabetic peripheral neuropathy (DPN) is a common microvascular complication of diabetes associated with high disability rate and low quality of life. Tang-Luo-Ning (TLN) is an effective traditional Chinese medicine for the treatment of DPN. To illustrate the underlying neural protection mechanisms of TLN, the effect of TLN on electrophysiology and sciatic nerve morphology was investigated in a model of streptozotocin-induced DPN, as well as the underlying mechanism. Sciatic motor nerve conduction velocity and digital sensory nerve conduction velocity were reduced in DPN and were significantly improved by TLN or α-lipoic acid at 10 and 20 weeks after streptozotocin injection. It was demonstrated that TLN intervention for 20 weeks significantly alleviated pathological injury as well as increased the phosphorylation of ErbB2, Erk, Bad (Ser112), and the mRNA expression of neuregulin 1 (Nrg1), GRB2-associated binding protein 1 (Gab1), and mammalian target of rapamycin (Mtor) in injured sciatic nerve. These novel therapeutic properties of TLN to promote Schwann cell survival may offer a promising alternative medicine for the patients to delay the progression of DPN. The underlying mechanism may be that TLN exerts neural protection effect after sciatic nerve injury through Nrg1/ErbB2→Erk/Bad Schwann cell survival signaling pathway. PMID:24288572

  19. Pyrroloquinoline quinone ameliorates oxidative stress and lipid peroxidation in the brain of streptozotocin-induced diabetic mice.

    PubMed

    Kumar, Narendra; Kar, Anand

    2015-01-01

    Diabetes, characterized by hyperglycemia, leads to several complications through the generation of reactive oxygen species and initiates tissue damage. Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant, as it protects cells from oxidative damage. In this study, we elucidated the hitherto unknown potential of PQQ to ameliorate the brain damage caused by diabetes mellitus and the associated hyperglycemia-induced oxidative damage. Administration of a single dose of streptozotocin (STZ), i.e., 150 mg·(kg body mass)(-1) significantly enhanced the brain tissue levels of lipid peroxidation and hydroperoxidation and decreased the levels of antioxidants. It also increased the serum levels of glucose, cholesterol, and triglycerides. However, when STZ-treated animals received PQQ (20 mg·(kg body mass)(-1)·d(-1), for 15 days), this significantly decreased the serum levels of glucose and lipid peroxidation products, and increased the activities of antioxidants in the diabetic mouse brain. These findings suggest that PQQ has the potential to ameliorate STZ-induced oxidative damage in the brain, as well as the STZ-induced diabetes. PMID:25474723

  20. Insulin-Producing Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells In Vitro Ameliorate Streptozotocin-Induced Diabetic Hyperglycemia

    PubMed Central

    Xin, Ying; Jiang, Xin; Wang, Yishu; Su, Xuejin; Sun, Meiyu; Zhang, Lihong; Tan, Yi; Wintergerst, Kupper A.; Li, Yan; Li, Yulin

    2016-01-01

    Background The two major obstacles in the successful transplantation of islets for diabetes treatment are inadequate supply of insulin-producing tissue and immune rejection. Induction of the differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) into insulin-producing cells (IPCs) for autologous transplantation may alleviate those limitations. Methods hMSCs were isolated and induced to differentiate into IPCs through a three-stage differentiation protocol in a defined media with high glucose, nicotinamide, and exendin-4. The physiological characteristics and functions of IPCs were then evaluated. Next, about 3 × 106 differentiated cells were transplanted into the renal sub-capsular space of streptozotocin (STZ)-induced diabetic nude mice. Graft survival and function were assessed by immunohistochemistry, TUNEL staining and measurements of blood glucose levels in the mice. Results The differentiated IPCs were characterized by Dithizone (DTZ) positive staining, expression of pancreatic β-cell markers, and human insulin secretion in response to glucose stimulation. Moreover, 43% of the IPCs showed L-type Ca2+ channel activity and similar changes in intracellular Ca2+ in response to glucose stimulation as that seen in pancreatic β-cells in the process of glucose-stimulated insulin secretion. Transplantation of functional IPCs into the renal subcapsular space of STZ-induced diabetic nude mice ameliorated the hyperglycemia. Immunofluorescence staining revealed that transplanted IPCs sustainably expressed insulin, c-peptide, and PDX-1 without apparent apoptosis in vivo. Conclusions IPCs derived from hMSCs in vitro can ameliorate STZ-induced diabetic hyperglycemia, which indicates that these hMSCs may be a promising approach to overcome the limitations of islet transplantation. PMID:26756576

  1. Amelioration of pancreatic and renal derangements in streptozotocin-induced diabetic rats by polyphenol extracts of Ginger (Zingiber officinale) rhizome.

    PubMed

    Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin

    2015-12-01

    Free and bound polyphenol extracts of Zingiber officinale rhizome were investigated for their antidiabetic potential in the pancreatic and renal tissues of diabetic rats at a dose of 500mg/kg body weight. Forty Wistar rats were completely randomized into five groups: A-E consisting of eight animals each. Group A (control) comprises normal healthy animals and were orally administered 1.0mL distilled water on a daily basis for 42 days while group B-E were made up of 50mg/kg streptozotocin (STZ)-induced diabetic rats. Group C and D received 1.0mL 500mg/kg body weight free and bound polyphenol extracts respectively while group E received 1.0mL 0.6mg/kg of glibenclamide. Administration of the extracts to the diabetic rats significantly reduced (p<0.05) serum glucose and urea concentrations, increased (p<0.05) serum insulin and Homeostatic Model Assessment for β-cell dysfunction (HOMA-β) while the level of creatinine and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were not affected. Histological examination of the pancreas and kidney revealed restoration of the structural derangements caused by streptozotocin in the polyphenol extracts treated diabetic rats compared to the control groups. Therefore, polyphenols from Zingiber officinale could ameliorate diabetes-induced pancreatic and renal derangements in rats. PMID:26349770

  2. Ruscogenin ameliorates diabetic nephropathy by its anti-inflammatory and anti-fibrotic effects in streptozotocin-induced diabetic rat

    PubMed Central

    2014-01-01

    and fibronectin in the diabetic kidneys. Conclusions Our data demonstrated that ruscogenin suppressed the inflammation and ameliorated the structural and functional abnormalities of the diabetic kidney in rats might be associated with inhibition of NF-κB mediated inflammatory genes expression. PMID:24666993

  3. Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Perez Gutierrez, Rosa Martha; Madrigales Ahuatzi, Diana; Horcacitas, Maria del Carmen; Garcia Baez, Efren; Cruz Victoria, Teresa; Mota-Flores, Jose Maria

    2014-01-01

    Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis. PMID:24523819

  4. Ameliorative Potentials of Cocoyam (Colocasia esculenta L.) and Unripe Plantain (Musa paradisiaca L.) on the Relative Tissue Weights of Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Eleazu, C. O.; Iroaganachi, M.; Eleazu, K. C.

    2013-01-01

    Aim. To investigate the ameliorating potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiaca L.) incorporated feeds on the renal and liver growths of diabetic rats, induced with 55 and 65 mg/kg body weight of Streptozotocin. Method. The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity (SPGR) in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The chemical composition and antioxidant screening of the test feeds were carried out using standard techniques. Results. Administration of the test feeds for 21 days to the diabetic rats of groups 4 and 5, resulted in 58.75% and 38.13% decreases in hyperglycemia and amelioration of their elevated urinary protein, glucose, SPGR, and relative kidney weights. The diabetic rats administered cocoyam incorporated feeds, had 2.71% and 19.52% increases in weight and growth rates, the diabetic rats administered unripe plantain incorporated feeds had 5.12% and 29.52% decreases in weight and growth rates while the diabetic control rats had 28.69%, 29.46%, 248.9% and 250.14% decreases in weights and growth rates. The cocoyam incorporated feeds contained higher antioxidants, minerals and phytochemicals except alkaloids than unripe plantain feed. Conclusion. Cocoyam and unripe plantain could be useful in the management of diabetic nephropathy. PMID:23971053

  5. Pyrroloquinoline quinone (PQQ) has potential to ameliorate streptozotocin-induced diabetes mellitus and oxidative stress in mice: A histopathological and biochemical study.

    PubMed

    Kumar, Narendra; Kar, Anand

    2015-10-01

    Enhanced oxidative stress and hyperglycemia are associated with diabetes mellitus (DM). As pyrroloquinoline quinone (PQQ) is known to protect cells from oxidative stress, the present study was undertaken to reveal the hitherto unknown effects of PQQ in DM and associated problems in different tissues. Forty two mice were randomly divided into six groups. Group I receiving only citrate buffer served as the normal control, while group II animals were injected with citrate buffer and PQQ at 20 mg/kg for 15 days and served as test drug control. Animals of groups III-VI were rendered diabetic by single dose of streptozotocin (STZ, 150 mg/kg body weight), following which PQQ at a dose of 5, 10 and 20 mg/kg, was injected to the animals of group IV, V and VI respectively for 15 days. At the end, alterations in serum indices such as glucose, different lipids, insulin, amylase, urea, uric acid, serum glutamate pyruvate transaminase and serum glutamate oxaloacetate transaminase; tissue antioxidants and histopathological alterations in liver, kidney and pancreas were evaluated. STZ-treated animals developed oxidative stress as indicated by a significant increase in tissue lipid peroxidation (LPO) and lipid hydroperoxide, serum glucose, total cholesterol, triglyceride and urea, with a parallel decrease in the levels of serum insulin and tissue antioxidants. When diabetic animals received different doses of PQQ, these adverse effects were ameliorated. However, 20 mg/kg of PQQ appeared to be most effective. Findings revealed for the first time that PQQ has the potential to mitigate STZ-induced DM and oxidative damage in different organs of mice, suggesting that it may ameliorate diabetes mellitus and associated problems. PMID:26343954

  6. AB096. Taurine supplementation improves erectile function in rats with streptozotocin-induced type 1 diabetes via amelioration of penile fibrosis and endothelial dysfunction

    PubMed Central

    Ruan, Yajun; Li, Mingchao; Wang, Tao; Yang, Jun; Rao, Ke; Wang, Shaogang; Yang, Weimin; Liu, Jihong; Ye, Zhangqun

    2016-01-01

    Objective For patients with diabetes, erectile dysfunction (ED) is common and greatly affects quality of life. However, these patients often exhibit a poor response to first-line oral phosphodiesterase type 5 inhibitors. The aim of this study was to investigate whether taurine, a sulfur-containing amino acid, affects diabetic ED (DED). Methods Type 1 diabetes mellitus was induced in male rats using streptozotocin. After 12 weeks, an apomorphine test was conducted to confirm DED. Only rats with DED were administered taurine or vehicle for four weeks. Age-matched nondiabetic rats were administered saline intraperitoneally for four weeks. Erectile function was evaluated by electrical stimulation of the cavernous nerve. Histologic and molecular alterations of the corpus cavernosum also were analyzed. Results Erectile function was significantly reduced in the diabetic rats compared with in the nondiabetic rats, and was ameliorated in the diabetic rats treated with taurine. The corpus cavernosum of the rats with DED exhibited severe fibrosis and decreased smooth muscle content. Deposition of extracellular matrix proteins was increased in the diabetic rats, while expression of endothelial nitric oxide synthase/cyclic guanosine monophosphate/nitric oxide pathway–related proteins was reduced. Taurine supplementation restored erectile response as well as histologic and molecular alterations. Conclusions Taurine supplementation improves erectile function in rats with DED probably by potential antifibrotic activity. This finding provides evidence for a potential new therapy for DED.

  7. Antidiabetic efficacy of citronellol, a citrus monoterpene by ameliorating the hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Srinivasan, Subramani; Muruganathan, Udaiyar

    2016-04-25

    Diabetes mellitus is a clinically complex disease characterized by chronic hyperglycemia with metabolic disturbances. During diabetes, endogenous hepatic glucose production is increased as a result of impaired activities of the key enzymes of carbohydrate metabolism. The purpose of the present study was to evaluate the antidiabetic efficacy of citronellol, a citrus monoterpene in streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (40 mg/kg b.w). STZ induced diabetic rats received citronellol orally at the doses of 25, 50, and 100 mg/kg b.w for 30 days. In this study the levels of plasma glucose, insulin, hemoglobin (Hb), glycated hemoglobin (HbA1C), glycogen, and the activities of carbohydrate metabolic enzymes, liver and kidney markers were evaluated. Oral administration of citronellol (50 mg/kg) for 30 days dose dependently improved the levels of insulin, Hb and hepatic glycogen with significant decrease in glucose and HbA1C levels. The altered activities of carbohydrate metabolic enzymes, hepatic and kidney markers were restored to near normal. Citronellol supplement was found to be effective in preserving the normal histological appearance of hepatic cells and insulin-positive β-cells in STZ-rats. Our results suggest that administration of citronellol attenuates the hyperglycemia in the STZ-induced diabetic rats by ameliorating the key carbohydrate metabolic enzymes and could be developed as a functional and nutraceutical ingredient in combating diabetes mellitus. PMID:26944432

  8. Ginsenoside Rg1 ameliorates diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress-induced apoptosis in a streptozotocin-induced diabetes rat model.

    PubMed

    Yu, Haitao; Zhen, Juan; Yang, Yang; Gu, Jinning; Wu, Suisheng; Liu, Quan

    2016-04-01

    Ginsenoside Rg1 has been demonstrated to have cardiovascular protective effects. However, whether the cardioprotective effects of ginsenoside Rg1 are mediated by endoplasmic reticulum (ER) stress-induced apoptosis remain unclear. In this study, among 80 male Wistar rats, 15 rats were randomly selected as controls; the remaining 65 rats received a diet rich in fat and sugar content for 4 weeks, followed by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) to establish a diabetes model. Seven days after STZ injection, 10 rats were randomly selected as diabetic model (DM) controls, 45 eligible diabetic rats were randomized to three treatment groups and administered ginsenoside Rg1 in a dosage of 10, 15 or 20 mg/kg/day, respectively. After 12 weeks of treatment, rats were killed and serum samples obtained to determine cardiac troponin (cTn)-I. Myocardial tissues were harvested for morphological analysis to detect myocardial cell apoptosis, and to analyse protein expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and Caspase-12. Treatment with ginsenoside Rg1 (10-20 mg/kg) significantly reduced serum cTnI levels compared with DM control group (all P < 0.01). Ginsenoside Rg1 (15 and 20 mg/kg) significantly reduced the percentage of apoptotic myocardial cells and improved the parameters of cardiac function. Haematoxylin and eosin and Masson staining indicated that ginsenoside Rg1 could attenuate myocardial lesions and myocardial collagen volume fraction. Additionally, ginsenoside Rg1 significantly reduced GRP78, CHOP, and cleaved Caspase-12 protein expression in a dose-dependent manner. These findings suggest that ginsenoside Rg1 appeared to ameliorate diabetic cardiomyopathy by inhibiting ER stress-induced apoptosis in diabetic rats. PMID:26869403

  9. The Antidiabetic Effect of Garlic Oil is Associated with Ameliorated Oxidative Stress but Not Ameliorated Level of Pro-inflammatory Cytokines in Skeletal Muscle of Streptozotocin-induced Diabetic Rats

    PubMed Central

    Liu, Cheng-Tzu; Hsu, Tien-Wei; Chen, Ke-Ming; Tan, Ya-Ping; Lii, Chong-Kuei; Sheen, Lee-Yan

    2012-01-01

    Oxidative stress and inflammatory condition has been broadly accepted being associated with the progression of diabetes. On the other hand, garlic (大蒜 dà suàn, bulb of Allium sativum) has been shown to possess both antioxidant and anti-inflammatory action in several clinical conditions. Our previous study demonstrated that treatment with garlic oil improves oral glucose tolerance and insulin tolerance and improves the insulin-stimulated utilization of glucose to synthesize glycogen in skeletal muscle in streptozotocin (STZ)-induced diabetes, in vivo and ex vivo, respectively. The aim of the present study is to investigate the antioxidant and anti-inflammatory effects of garlic oil (GO) in the skeletal muscle of diabetic rats. Rats with STZ-induced diabetes received GO (10, 50, or 100 mg/kg body weight) or corn oil by gavage every other day for 3 weeks. Control rats received corn oil only. GO dose-dependently improved insulin sensitivity, as assessed by the insulin tolerance test, and oral glucose tolerance. GO significantly elevated total glutathione and glutathione peroxidase activity and lowered the nitrate/nitrite content in skeletal muscle at 50 and 100 mg/kg and significantly elevated glutathione reductase activity and lowered lipid peroxidation at 100 mg/kg. By contrast, GO did not reverse diabetes-induced elevation of IL-1β and TNF-α in skeletal muscle at any tested dose. On the other hand, GO elevated the expression of GLUT4 in skeletal muscle along with glycogen content as observed with PAS staining. In conclusion, the antidiabetic effect of garlic oil is associated with ameliorated oxidative stress in skeletal muscle. PMID:24716126

  10. Tripterygium Glycosides Tablet Ameliorates Renal Tubulointerstitial Fibrosis via the Toll-Like Receptor 4/Nuclear Factor Kappa B Signaling Pathway in High-Fat Diet Fed and Streptozotocin-Induced Diabetic Rats.

    PubMed

    Ma, Ze-Jun; Zhang, Xiao-Na; Li, Li; Yang, Wei; Wang, Shan-Shan; Guo, Xin; Sun, Pei; Chen, Li-Ming

    2015-01-01

    Tripterygium glycosides tablet (TGT) is a Chinese traditional medicine that has been shown to protect podocytes from injury and reduce the proteinuria. The aim of this study was to assess the effect of TGT on renal tubulointerstitial fibrosis and its potential mechanism in high-fat diet fed and STZ-induced diabetic rats. Rats were randomly divided into normal control rats (NC group), diabetic rats without drug treatment (DM group), and diabetic rats treated with TGT (1, 3, or 6 mg/kg/day, respectively) for 8 weeks. The results showed that 24 h proteinuria and urinary N-acetyl-glucosaminidase (NAG) in diabetic rats were decreased by TGT treatment without affecting blood glucose. Masson's trichrome stains showed that apparent renal tubulointerstitial fibrosis was found in DM group, which was ameliorated by TGT treatment. The expression of α-SMA was significantly decreased, accompanied by increased expression of E-cadherin in TGT-treated rats, but not in untreated DM rats. Further studies showed that TGT administration markedly reduced expression of TLR4, NF-κB, IL-1β, and MCP-1 in TGT-treated diabetic rats. These results showed that TGT could ameliorate renal tubulointerstitial fibrosis, the mechanism which may be at least partly associated with the amelioration of EMT through suppression of the TLR4/NF-κB pathway. PMID:26347890

  11. Compound A, a selective glucocorticoid receptor agonist, inhibits immunoinflammatory diabetes, induced by multiple low doses of streptozotocin in mice

    PubMed Central

    Saksida, T; Vujicic, M; Nikolic, I; Stojanovic, I; Haegeman, G; Stosic-Grujicic, S

    2014-01-01

    Background and Purpose Type 1 diabetes is a multifactorial inflammatory disease that develops as a result of deregulated immune responses, causing progressive autoimmune destruction of insulin-producing beta cells of pancreas. 2-((4-acetoxyphenyl)-2-chloro-N-methyl) ethylammonium chloride, compound A (CpdA), is a selective glucocorticoid receptor (GR) agonist that displays strong anti-inflammatory and immunomodulatory activities. We investigated the therapeutic effectiveness of CpdA in a pharmacological model of type 1 diabetes in mice. Experimental Approach The utility of CpdA in diabetes prevention was evaluated in vivo through its prophylactic administration to male C57BL/6 mice that received multiple low doses of streptozotocin for immunoinflammatory diabetes induction. The effect of CpdA on disease development was studied by measuring blood glucose and insulin level, histopathological examination, determination of the nature of infiltrating cells, pro- and anti-inflammatory cytokine production, and signalling pathways. Key Results Prophylactic in vivo therapy with CpdA conferred protection against development of immunoinflammatory diabetes in mice by dampening the M1/Th1/Th17 immune response and switching it towards an anti-inflammatory M2/Th2/Treg profile, thus preserving beta cell function. Conclusions and Implications Anti-diabetic properties of CpdA are mediated through modulation of immune cell-mediated pathways, but without triggering adverse events. These findings provide basic information for the therapeutic use of selective GR agonists in the amelioration of islet-directed autoimmunity. PMID:25158597

  12. The Hypoglycemic and Antioxidant Activity of Cress Seed and Cinnamon on Streptozotocin Induced Diabetes in Male Rats

    PubMed Central

    Qusti, Safaa; Balashram, Sarah A.

    2016-01-01

    The present study aimed to estimate the stimulation of pancreas of rats with streptozotocin induced diabetes using 20% (w/w) garden cress seed (Lepidium sativum) and cinnamon methanol extracts. The positive control diabetic group showed a significant increase in fasting blood sugar, lipid peroxide, interleukin-6, carboxymethyl lysine, serum uric acid, urea, creatinine, immunoglobulins, and urine albumin and a significant decrease in antioxidant enzymes, sodium ions, potassium ions, and urine creatinine. Severe histopathological changes in the kidney and pancreas tissues in hyperglycemic rats were also shown in the positive control diabetic group. Meanwhile, the groups that were treated with 20% garden cress seed and cinnamon methanol extracts showed a significant decrease in fasting blood sugar and all elevated abovementioned biochemical parameters and an increase in the lowered ones restoring them nearly to the normal levels of G1. Kidney and pancreas tissues were also ameliorated and restored nearly to the normal status. Both garden cress seed and cinnamon methanol extracts succeeded in controlling hyperglycemia in rats with streptozotocin induced diabetes and ameliorated the biochemical and histopathological changes because of their antioxidant activity acquired by their possession of phenolic phytochemicals. PMID:27525022

  13. Anti-hyperglycemic and Anti-hyperlipidemic Effects of Bryonia Laciniosa Seed Extract and its Saponin Fraction in Streptozotocin-induced Diabetes in Rats

    PubMed Central

    Patel, SB; Santani, D; Shah, MB; Patel, VS

    2012-01-01

    Bryonia laciniosa Linn. (Cucurbitaceae) seed is used in traditional medicine for a number of ailments including metabolic disorders. This investigation was carried out to investigate the anti-hyperglycemic and anti-hyperlipidemic potential of the ethanolic extract of seeds of B. laciniosa Linn. and its saponin fraction in streptozotocin-induced diabetic rats. The ethanolic extract (250 and 500 mg/kg; p.o.) and saponin fraction (100 and 200 mg/kg; p.o.) were administered to diabetic rats and standard drug insulin (5 IU/kg; i.p.) to the group serving as a positive control. Effects of the ethanolic extract and saponin fraction on various biochemical parameters were studied in diabetic rats. Data were statistically analysed by one-way ANOVA followed by Dunnett's t-test. Oral administration of the ethanolic extract and saponin fraction for 28 days to streptozotocin-induced diabetes rats significantly (P < 0.05) decreased the levels of blood glucose and improved the levels of plasma insulin. The levels of triglycerides, cholesterol, high density lipoprotein, low density lipoprotein, very low density lipoprotein, aspartate amino transferase and alanine amino transferase, urea, and creatinine were markedly altered in streptozotocin-induced diabetic rats. Oral administration of the ethanolic extract and saponin fraction restored all these biochemical parameters to near control levels. This study reveals the efficacy of B. laciniosa seed extract and its saponin fraction in the amelioration of diabetes and its associated complications. PMID:23112536

  14. Protease-activated receptor-1 deficiency protects against streptozotocin-induced diabetic nephropathy in mice.

    PubMed

    Waasdorp, Maaike; Duitman, JanWillem; Florquin, Sandrine; Spek, C Arnold

    2016-01-01

    Endogenously administered activated protein C ameliorates diabetic nephropathy (DN) in a protease-activated receptor-1 (PAR-1)-dependent manner, suggesting that PAR-1 activation limits the progression of DN. Activation of PAR-1 in fibroblast-like cells, however, induces proliferation and extracellular matrix production, thereby driving fibrotic disease. Considering the key role of mesangial proliferation and extracellular matrix production during DN, PAR-1 may in fact potentiate diabetes-induced kidney injury. To determine the net effect of PAR-1 in DN, streptozotocin-induced DN was studied in wild type and PAR-1 deficient mice. Subsequent mechanistic insight was obtained by assessing profibrotic responses of mesangial and tubular epithelial cells in vitro, following PAR-1 stimulation and inhibition. Despite having similar glucose levels, PAR-1 deficient mice developed less kidney damage after induction of diabetes, as evidenced by diminished proteinuria, plasma cystatin C levels, expansion of the mesangial area, and tubular atrophy. In vitro, PAR-1 signaling in mesangial cells led to increased proliferation and expression of matrix proteins fibronectin and collagen IV. Conversely, a reduction in both proliferation and fibronectin deposition was observed in diabetic PAR-1 deficient mice. Overall, we show that PAR-1 plays an important role in the development of DN and PAR-1 might therefore be an attractive therapeutic target to pursue in DN. PMID:27618774

  15. Rhizome of Anemarrhena asphodeloides counteracts diabetic ophthalmopathy progression in streptozotocin-induced diabetic rats.

    PubMed

    Li, Xuan; Cui, Xiaobing; Wang, Jinjin; Yang, Jie; Sun, Xiaoyu; Li, Xiaodong; Zhu, Quan; Li, Wei

    2013-08-01

    Diabetic ophthalmopathy (DO) impairs patients' eyesight and even causes blindness. Here, we investigated the effect of 60% ethanol extract of the rhizome of Anemarrhenae asphodeloides (ERA), which is commonly used in Chinese medicine formulae in treating diabetes, on DO progression. Blood glucose, insulin, advanced glycation end products (AGE), super oxygen dehydrogenises (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels in serum and sorbitol concentration in the lens were measured. Retinal endothelium/pericyte (E/P) ratio was evaluated, and structural changes of the retina and lens were observed. Effects of mangiferin and neomangiferin, the two major components of ERA, on subnormal growth of pericytes induced by high glucose were also detected. It was found that the activities of SOD and GSH-Px in serum were increased, whereas MDA and AGE levels in serum and sorbitol concentration in the lens were decreased in ERA-treated DO rats. E/P ratio was decreased, and the pathological changes of the lens and retina were alleviated by ERA treatment. Moreover, the subnormal growth of pericytes induced by high glucose was ameliorated by mangiferin and neomangiferin. These results indicated that ERA could effectively prevent DO progression in streptozotocin-induced diabetic rats, and mangiferin and neomangiferin may be the main effective components. PMID:23148017

  16. Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats.

    PubMed

    Chen, Xiaofei; Zhao, Tong; Huang, Xin; Wu, Liying; Wu, Kuiwu; Fan, Ming; Zhu, Lingling

    2016-05-01

    Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas β-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88 ± 5.69 mmol/L vs. 14.79 ± 5.84 mmol/L, p < 0.05), while it was not different in diabetic rats after hypoxic treatment (13.14 ± 5.77 mmol/L vs. 14.79 ± 5.84 mmol/L, p > 0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 ± 5.77 mmol/L vs. 19.88 ± 5.69 mmol/L, p<0.05). Plasma fructosamine in diabetic rats receiving intermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28 ± 0.11 vs. 1.39 ± 0.11, p < 0.05), while there were no significant changes in body weight, plasma insulin and β-cell mass. HOMA-IR in diabetic rats after hypoxic treatment was also lower compared with diabetic rats after normoxic treatment (3.48 ± 0.48 vs. 3.86 ± 0.42, p < 0.05). Moreover, intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular

  17. Restoration of renal hemodynamics and functions during black cumin (Nigella sativa) administration in streptozotocin-induced diabetic rats

    PubMed Central

    Yusuksawad, Mariem; Chaiyabutr, Narongsak

    2012-01-01

    Background Black cumin (Nigella sativa) is an ancient herbal medicine recommended by the World Health Organization. The antioxidant and antihyperglycemic effects of black cumin are well established. Amelioration of renal dysfunction in nephrotoxic rats with black cumin treatment has also been noted. However, the effect of black cumin treatment on renal dysfunction in diabetes mellitus has not been clarified. In this study, the effect of black cumin oil (BC) on changes in renal dysfunction and renal hemodynamics in streptozotocin-induced diabetic rats was evaluated. Methods The experiments were performed in male Sprague Dawley rats, divided into four groups (seven in each group): (1) normal rats given tap water (CON); (2) normal rats administered with BC (CON-BC); (3) diabetic rats given tap water only (STZ); and (4) diabetic rats administered with BC (STZ-BC). Diabetes mellitus was induced in the rats by an injection of streptozotocin. BC was given orally at the dose of 1000 mg/kg body weight to the rat in either CON-BC or STZ-BC every day for 8 weeks. Renal hemodynamics and functions in each rat were studied. Results Renal hemodynamic changes in STZ-BC rats appeared to increase in terms of glomerular filtration rate, effective renal plasma flow, and effective renal blood flow, while renal vascular resistance and filtration fraction were decreased in comparison with diabetic rats given tap water only (STZ). An improvement of renal tubular dysfunction in STZ-BC rats was indicated by the decreases in fractional excretion of water and Mg++. Conclusion An administration of BC can restore changes in renal hemodynamics and renal dysfunction in streptozotocin-induced diabetic rats.

  18. Effects of arctiin on streptozotocin-induced diabetic retinopathy in Sprague-Dawley rats.

    PubMed

    Lu, Lai-chun; Zhou, Wei; Li, Zhuo-heng; Yu, Cai-ping; Li, Chen-wen; Luo, Ming-he; Xie, Hong

    2012-08-01

    Diabetic retinopathy is one of the most common and severe complications of diabetes mellitus. Arctiin, a bioactive compound isolated from the dry seeds of Arctium lappa L., has been reported to have antidiabetic activity. In this study, we investigated the effect of arctiin on the serum glucose and HBA1c levels, the blood viscosity, and VEGF expression in the retinal tissues of rats with diabetic retinopathy. We first extracted arctiin from Fructus Arctii and then investigated its chemopreventive effect on streptozotocin-induced diabetic retinopathy in male Sprague-Dawley rats. After the induction of diabetes using streptozotocin (30 mg/kg, i. p.), the rats were randomly divided into five groups (n = 20 per group) and treated with intragastric doses of 30, 90, or 270 mg/kg/d wt of arctiin, 100 mg/kg/d wt of calcium dobesilate, or 0.5 % CMC-Na. Twenty nondiabetic sham-treated rats were treated with 0.5 % CMC-Na. The occurrence of diabetic retinopathy did not differ dramatically among the groups. However, at week 16, the glycosylated haemoglobin (HBA1c) level was significantly decreased in all of the arctiin-treated groups when compared with the control group, and the serum glucose level was also decreased in the rats treated with the highest dose of arctiin. In addition, treatment with arctiin ameliorated retinal oedema, detachment of the retina, and VEGF expression in the retina, as detected using histological and immunochemical examinations. Finally, arctiin increased the viability of retinal microvascular endothelial cells in vitro. Together, these findings demonstrate that arctiin decreases the severity of diabetic complications, demonstrating the importance of this compound as an inhibitor of diabetic retinopathy. PMID:22753037

  19. Nobiletin attenuates cardiac dysfunction, oxidative stress, and inflammatory in streptozotocin: induced diabetic cardiomyopathy.

    PubMed

    Zhang, Ning; Yang, Zheng; Xiang, Shi-Zhao; Jin, Ya-Ge; Wei, Wen-Ying; Bian, Zhou-Yan; Deng, Wei; Tang, Qi-Zhu

    2016-06-01

    Diabetic cardiomyopathy, characterized by the presence of diastolic and/or systolic myocardial dysfunction, is one of the major causes of heart failure. Nobiletin, which is extracted from the fruit peel of citrus, is reported to possess anti-inflammatory, anti-oxidative, and hypolipidemic properties. The purpose of this study was to investigate whether nobiletin exerts the therapeutic effect on streptozotocin-induced diabetic cardiomyopathy (DCM) in mice. 80 experimental male C57BL mice were randomly assigned into four groups: sham + vehicle (VEH/SH), sham + nobiletin (NOB/SH), DCM + vehicle (VEH/DM), and DCM + nobiletin (NOB/DM). Nobiletin treatment ameliorated cardiac dysfunction in the DCM group, as shown by the result of echocardiography and hemodynamic measurements. Nobiletin treatment also blunted the mRNA expression of NADPH oxidase isoforms p67(phox), p22(phox), and p91(phox), and abated oxidative stress. Although administration of diabetic mice with nobiletin did not significantly effect the level of blood glucose, it decreased the TGF-β1, CTGF, fibronectin, and collagen Iα expressions and blunted cardiac fibrosis. In addition, nobiletin inhibited the activation of c-Jun NH2-terminal kinase (JNK), P38, and NF-κB in the cardiac tissue of diabetic mice. Collectively, our study indicates that treatment with nobiletin mitigates cardiac dysfunction and interstitial fibrosis, and these beneficial of nobiletin may belong to the suppression of JNK, P38, and NF-κB signaling pathways. PMID:27160937

  20. Beneficial Effects of Scutellaria baicalensis on Penile Erection in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Li, Xiang; Lee, Yun Jung; Kim, Hye Yoom; Tan, Rui; Park, Min Cheol; Kang, Dae Gill; Lee, Ho Sub

    2016-04-01

    We have reported that ethanol extracts of the root from Scutellaria baicalensis Georgi (ESB) relax cavernous smooth muscles via the NO/cGMP system and Ca[Formula: see text]-sensitive K[Formula: see text] channels in the rabbit corpus cavernosum. In the present study, erectile function was assessed by intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrical stimulation of the cavernous nerve. The ICP/MAP ratio was dose-dependently increased by the treatment of ESB in normal SD rats ([Formula: see text]). To investigate the beneficial effect of ESB on erectile dysfunction in a diabetic animal model, male SD rats were injected with streptozotocin (60[Formula: see text]mg/kg) and then 300[Formula: see text]mg/kg/day ESB was administered daily for eight weeks. In our in vivo study, administration of ESB in STZ rats significantly increased the ICP, ICP/MAP ratio, area under the curve (AUC), as well as the cavernous cGMP levels. Morphometric analyses showed that ESB administration increased both smooth muscle volume and the regular arrangement of collagen fibers compared to the STZ group. The protein expression levels of endothelial nitric oxide synthase (eNOS) and SM [Formula: see text]-actin from penile tissues were also significantly increased in the ESB-treated rats. Taken together, these results suggest that ESB ameliorates penile erectile dysfunction via the activation of the NO/cGMP pathways of the penile corpus cavernosum in a streptozotocin-induced diabetic rat model. PMID:27080943

  1. Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe) on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin; Ashafa, Anofi Omotayo Tom

    2013-01-01

    This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125 mg/kg, 250 mg/kg, and 500 mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500 mg/kg body weight of free and bound polyphenols from Z. officinale to streptozotocin-induced (50 mg/kg) diabetic rats significantly reduced (P < 0.05) the fasting blood glucose compared to control groups. There was significant increase (P < 0.05) in the antioxidant enzymes activities in the animals treated with both polyphenols. Similarly, the polyphenols normalised the activities of some carbohydrate metabolic enzymes (hexokinase and phosphofructokinase) in the liver of the rats treated with it and significantly reduced (P < 0.05) the activities of liver function enzymes. The results from the present study have shown that both free and bound polyphenols from Z. officinale especially the free polyphenol could ameliorate liver disorders caused by diabetes mellitus in rats. This further validates the use of this species as medicinal herb and spice by the larger population of Nigerians. PMID:24367390

  2. Use of unripe plantain (Musa paradisiaca) in the management of diabetes and hepatic dysfunction in streptozotocin induced diabetes in rats

    PubMed Central

    Okafor, Polycarp

    2015-01-01

    Aim This study aims to investigate the effect of unripe plantain (Musa paradisiaca) on markers of hepatic dysfunction in streptozotocin induced diabetic rats. Methods Blood glucose; relative liver weight (RLW); relative kidney weight (RKW); relative heart weight (RHW); relative pancreatic weight (RPW); serum and hepatic serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP); serum amylase, lipase, total, and conjugated bilirubin; and chemical analysis of the test feed were determined using standard techniques. Results The diabetic rats had significant alteration (P < 0.05) of blood glucose; RLW; RKW; RPW; serum and hepatic AST, ALT, and ALP; serum total and conjugated bilirubin; and serum lipase activities compared with nondiabetic while these parameters were significantly improved (P < 0.05) in the rats fed unripe plantain. There were no significant differences (P > 0.05) in the RHW of the rats in the three groups, as well as significant decreases (P < 0.05) in the amylase levels of the diabetic rats compared with the nondiabetic, but there was nonsignificant increase (P > 0.05) in the amylase levels of the rats fed unripe plantain compared with the nondiabetic rats. The test and standard rat feeds contained considerable amount of proteins, carbohydrates, fats, phenols, and crude fiber. Conclusion Amelioration of acute pancreatitis by unripe plantain could play a key role in its management of diabetes and related complications. PMID:25838921

  3. Extract of Sesbania grandiflora Ameliorates Hyperglycemia in High Fat Diet-Streptozotocin Induced Experimental Diabetes Mellitus

    PubMed Central

    Panigrahi, Ghanshyam; Panda, Chhayakanta; Patra, Arjun

    2016-01-01

    Background. Sesbania grandiflora has been traditionally used as antidiabetic, antioxidant, antipyretic, and expectorant and in the management of various ailments. Materials and Methods. The study evaluates the antidiabetic activity of methanolic extract of Sesbania grandiflora (MESG) in type 2 diabetic rats induced by low dose streptozotocine and high fat diet. Diabetic rats were given vehicle, MESG (200 and 400 mg/kg, p.o.), and the standard drug, metformin (10 mg/kg), for 28 days. During the experimental period, body weight, abdominal girth, food intake, fasting serum glucose, urine analyses were measured. Insulin tolerance test was carried out on 25th day of drug treatment period. Serum analyses for lipid profile and SGOT and SGPT and serums creatinine, urea, protein, SOD, and MDA were also carried out. At the end of the experiment, animals were euthanized, the liver and pancreas were immediately dissected out, and the ratio of pancreas to body weight and hepatic glycogen were calculated. Results. MESG (200 and 400 mg/kg, p.o.) induced significant reduction (P < 0.05) of raised blood glucose levels in diabetic rats and also restored other parameters to normal level. Conclusion. Therefore, it is concluded that MESG has potential antihyperglycemic and antihyperlipemic activities and alleviate insulin resistance conditions. PMID:27313954

  4. Extract of Sesbania grandiflora Ameliorates Hyperglycemia in High Fat Diet-Streptozotocin Induced Experimental Diabetes Mellitus.

    PubMed

    Panigrahi, Ghanshyam; Panda, Chhayakanta; Patra, Arjun

    2016-01-01

    Background. Sesbania grandiflora has been traditionally used as antidiabetic, antioxidant, antipyretic, and expectorant and in the management of various ailments. Materials and Methods. The study evaluates the antidiabetic activity of methanolic extract of Sesbania grandiflora (MESG) in type 2 diabetic rats induced by low dose streptozotocine and high fat diet. Diabetic rats were given vehicle, MESG (200 and 400 mg/kg, p.o.), and the standard drug, metformin (10 mg/kg), for 28 days. During the experimental period, body weight, abdominal girth, food intake, fasting serum glucose, urine analyses were measured. Insulin tolerance test was carried out on 25th day of drug treatment period. Serum analyses for lipid profile and SGOT and SGPT and serums creatinine, urea, protein, SOD, and MDA were also carried out. At the end of the experiment, animals were euthanized, the liver and pancreas were immediately dissected out, and the ratio of pancreas to body weight and hepatic glycogen were calculated. Results. MESG (200 and 400 mg/kg, p.o.) induced significant reduction (P < 0.05) of raised blood glucose levels in diabetic rats and also restored other parameters to normal level. Conclusion. Therefore, it is concluded that MESG has potential antihyperglycemic and antihyperlipemic activities and alleviate insulin resistance conditions. PMID:27313954

  5. Melatonin intake since weaning ameliorates steroidogenic function and sperm motility of streptozotocin-induced diabetic rats.

    PubMed

    da Costa, C F P; Gobbo, M G; Taboga, S R; Pinto-Fochi, M E; Góes, R M

    2016-05-01

    Melatonin may be used as an antioxidant in therapy against systemic sequelae caused by oxidative stress in diabetes. However, as melatonin has a major role in regulating reproductive activity, its consequence on reproductive parameters under diabetes needs to be better clarified. We have studied whether prior and concomitant treatment of juvenile Wistar rats with low doses of melatonin interferes in reproductive damage induced by experimental diabetes after 1 and 8 weeks. The consequences of melatonin administration since weaning on reproductive parameters of healthy rats at adulthood were also evaluated. Melatonin was provided in drinking water (10 μg/kg b.w./day) after weaning (5-week-old). Diabetes was induced by streptozotocin injection (4.5 mg/100 g b.w.) at 13-week-old rats, and rats were euthanized 1 and 8 weeks after disease onset. Diabetes decreased circulating testosterone levels (~35% to 1 week; ~62% to 2 months; p < 0.01) but did not affect testes sperm counts. Two months of diabetes reduced the sperm reserve and led to atrophy of epididymal cauda. Both 1-week and 2-month diabetes impaired sperm motility, decreased the number of spermatozoa with progressive movement, and increased the number of immotile sperm. Melatonin intake reduced serum testosterone levels ~29% in healthy 14-week-old and ~23% in 21-week-old rats and reduced daily testicular sperm production ~26% in the latter disease stage, but did not interfere in sperm reserves and transit time for both experimental periods. Exogenous melatonin prevented the serum testosterone decrease and damage to sperm motility in diabetic rats and attenuated reduction in sperm counts and transit time induced by 1-week diabetes but did not avoid this decrease at 2-month diabetes. Low doses of melatonin administered prior to and during experimental diabetes attenuated damage to testicular steroidogenic activity and preserved sperm motility, but not sperm reserves in the rat. Our data indicated a differential action of melatonin in normoglycemic and hyperglycemic conditions, particularly in sperm motility and testosterone production by Leydig cells. PMID:27037637

  6. Amelioration of Streptozotocin-Induced Diabetes in Mice with Cells Derived from Human Marrow Stromal Cells

    PubMed Central

    Zhao, Min; Amiel, Stephanie A.; Ajami, Sanaz; Jiang, Jie; Rela, Mohamed; Heaton, Nigel; Huang, Guo Cai

    2008-01-01

    Background Pluri-potent bone marrow stromal cells (MSCs) provide an attractive opportunity to generate unlimited glucose-responsive insulin-producing cells for the treatment of diabetes. We explored the potential for human MSCs (hMSCs) to be differentiated into glucose-responsive cells through a non-viral genetic reprogramming approach. Methods and Findings Two hMSC lines were transfected with three genes: PDX-1, NeuroD1 and Ngn3 without subsequent selection, followed by differentiation induction in vitro and transplantation into diabetic mice. Human MSCs expressed mRNAs of the archetypal stem cell markers: Sox2, Oct4, Nanog and CD34, and the endocrine cell markers: PDX-1, NeuroD1, Ngn3, and Nkx6.1. Following gene transfection and differentiation induction, hMSCs expressed insulin in vitro, but were not glucose regulated. After transplantation, hMSCs differentiated further and ∼12.5% of the grafted cells expressed insulin. The graft bearing kidneys contained mRNA of insulin and other key genes required for the functions of beta cells. Mice transplanted with manipulated hMSCs showed reduced blood glucose levels (from 18.9+/−0.75 to 7.63+/−1.63 mM). 13 of the 16 mice became normoglycaemic (6.9+/−0.64 mM), despite the failure to detect the expression of SUR1, a K+-ATP channel component required for regulation of insulin secretion. Conclusions Our data confirm that hMSCs can be induced to express insulin sufficient to reduce blood glucose in a diabetic mouse model. Our triple gene approach has created cells that seem less glucose responsive in vitro but which become more efficient after transplantation. The maturation process requires further study, particularly the in vivo factors influencing the differentiation, in order to scale up for clinical purposes. PMID:18628974

  7. Ameliorative effect of Noni fruit extract on streptozotocin-induced memory impairment in mice.

    PubMed

    Pachauri, Shakti D; Verma, Priya Ranjan P; Dwivedi, Anil K; Tota, Santoshkumar; Khandelwal, Kiran; Saxena, Jitendra K; Nath, Chandishwar

    2013-08-01

    This study evaluated the effects of a standardized ethyl acetate extract of Morinda citrifolia L. (Noni) fruit on impairment of memory, brain energy metabolism, and cholinergic function in intracerebral streptozotocin (STZ)-treated mice. STZ (0.5 mg/kg) was administered twice at an interval of 48 h. Noni (50 and 100 mg/kg, postoperatively) was administered for 21 days following STZ administration. Memory function was evaluated using Morris Water Maze and passive avoidance tests, and brain levels of cholinergic function, oxidative stress, energy metabolism, and brain-derived neurotrophic factor (BDNF) were estimated. STZ caused memory impairment in Morris Water Maze and passive avoidance tests along with reduced brain levels of ATP, BDNF, and acetylcholine and increased acetylcholinesterase activity and oxidative stress. Treatment with Noni extract (100 mg/kg) prevented the STZ-induced memory impairment in both behavioral tests along with reduced oxidative stress and acetylcholinesterase activity, and increased brain levels of BDNF, acetylcholine, and ATP level. The study shows the beneficial effects of Noni fruit against STZ-induced memory impairment, which may be attributed to improved brain energy metabolism, cholinergic neurotransmission, BDNF, and antioxidative action. PMID:23838966

  8. Hypoglycemic effect of Aloe vera gel on streptozotocin-induced diabetes in experimental rats.

    PubMed

    Rajasekaran, S; Sivagnanam, K; Ravi, K; Subramanian, S

    2004-01-01

    In the present study an attempt has been made to evaluate the presence of hypoglycemic activity in the alcoholic extract of Aloe vera gel. Effects of oral administration of A. vera extract at a concentration of 200 and 300 mg/kg of body weight on (a) normal fasted rats, (b) oral glucose-loaded rats, and (c) streptozotocin-induced diabetic rats have been studied. A. vera extract maintain the glucose homeostasis by controlling the carbohydrate metabolizing enzymes. PMID:15117555

  9. Antidiabetic effect of Merremia emarginata Burm. F. in streptozotocin induced diabetic rats

    PubMed Central

    Gandhi, G Rajiv; Sasikumar, P

    2012-01-01

    Objective To investigate the antidiabetic property of Merremia emarginata (M. emarginata) Burm. F. plant in streptozotocin induced diabetic rats. Methods The dose dependent effects of 28 days oral treatment with methanol extract (100, 200 and 400 mg/kg) from the plant of M. emarginata on blood glucose level, body weight, insulin, total hemoglobin, glycosylated haemoglobin (HbA1C), total protein, serum urea, serum creatinine and carbohydrate metabolizing enzymes were evaluated in streptozotocin induced diabetic rats. Histology of pancreas was also studied. Results A significant decrease in blood glucose, serum urea and serum creatinine and significant increase in body weight, insulin and protein level were observed in diabetic rats treated with M. emarginata. Treatment with M. emarginata resulted in a significant reduction of HbA1C and an increase in total hemoglobin level. The activities of carbohydrate metabolizing enzymes such as hexokinase were significantly increased whereas glucose-6-phosphatase, fructose-1, 6-bisphosphatase were significantly decreased by the administration of M. emarginata in diabetic rats. Histology of diabetic rats treated with M. emarginata showed the pancreatic β-cells regeneration. Conclusions These findings suggest that M. emarginata has potent antidiabetic activity in streptozotocin induced diabetic rats. PMID:23569914

  10. Antihyperlipidemic Effect of Peucedanum Pastinacifolium Extract in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Movahedian, Ahmad; Zolfaghari, Behzad; Sajjadi, S. Ebrahim; Moknatjou, Reza

    2010-01-01

    INTRODUCTION: Dyslipidemia is one of the most common complications of diabetes mellitus, significantly contributing to cardiovascular morbidity and mortality in diabetic patients. Peucedanum pastinacifolium Boiss. & Hausskn. is commonly used as an antihyperlipidemic vegetable in Iranian folk medicine. MATERIAL AND METHODS: In this study, we examined a hydroalcoholic extract of the aerial parts of Peucedanum pastinacifolium to determine its lipid-lowering activity in normal and streptozotocin (STZ)-induced diabetic rats. Experimental diabetes mellitus was induced by a single intraperitoneal administration of streptozotocin. Normal and streptozotocin-induced diabetic rats were separated into four groups. The groups were fed with 0, 125, 250 or 500 mg/kg body weight of Peucedanum Pastinacifolium hydroalcoholic Extract (PPE) in aqueous solution for 30 days. RESULTS: The results show that there were significant (P < 0.05) increases in total serum cholesterol, triglyceride and low-density lipoprotein cholesterol (LDL-C) and a decrease in high-density lipoprotein cholesterol (HDL-C) in streptozotocin-induced diabetic rats. Treatment of diabetic rats with PPE over a period of a month returned these levels close to control levels. CONCLUSION: These results suggest that PPE has hypolipidemic effects in streptozotocin-induced diabetic rats. PMID:20613940

  11. Improvement of erectile dysfunction by the active pepide from Urechis unicinctus by high temperature/pressure and ultra - wave assisted lysis in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Kim, Kang Sup; Bae, Woong Jin; Kim, Su Jin; Kang, Kyong-Hwa; Kim, Se-Kwon; Cho, Hyuk Jin; Hong, Sung-Hoo; Lee, Ji Youl; Kim, Sae Woong

    2016-01-01

    ABSTRACT Introduction: We investigate the effect of active peptide from Urechis unicinctus (UU) by high temperature/pressure and ultra-wave assisted lysis on erectile dysfunction in streptozotocin-induced diabetic rats. Materials and Methods: Forty 12-week-old Sprague-Dawley rats were used in this study. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (50mg/kg). One week later, the diabetic rats were randomly divided into four groups: normal control, untreated diabetes control, and groups treated with 100 or 500mg/kg/d UU peptide. Rats were fed with UU peptide by intragastric administration for 8 weeks. After 8 weeks, penile hemodynamic function was evaluated in all groups by measuring the intracavernosal pressure after electrostimulating the cavernous nerve. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) activities were measured and endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) protein expression was determined by Western blot. Results: Maximum intracavernosal pressure in diabetic control rats decreased significantly compared to normal control rats, and was increased significantly compared to untreated diabetic rats after UU peptide supplementation. Treatment with the higher dose of UU peptide significantly increased the NO and cGMP levels compared with the diabetic control group. Decreased activity and expression eNOS and nNOS were found in the diabetic rats compared with the normal control group. Decreased eNOS and nNOS in diabetic rats were improved by UU peptide administration. Conclusions: Active peptide from UU ameliorates erectile function in a streptozotocin induced diabetic rat model of erectile dysfunction. PMID:27564297

  12. Hypoglycemic Effect of Calotropis gigantea Linn. Leaves and Flowers in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Rathod, Nanu R; Chitme, Havagiray R; Irchhaiya, Raghuveer; Chandra, Ramesh

    2011-01-01

    Objectives To evaluate the hypoglycemic and anti-diabetic activity of chloroform extract of Calotropis gigantea leaves and flowers in normal rats and streptozotocin induced diabetes. Methods The hypoglycemic activity in normal rats was carried out by treatment using chloroform extract of Calotropis gigantea leaf and flower 10, 20 and 50 mg/kg, orally. The oral glucose tolerance test was carried out by administering glucose (2 g/kg, p.o), to non-diabetic rats treated with leaf and flowers extracts at oral doses 10, 20 and 50 mg/kg, p.o and glibenclamide 10 mg/kg. The serum glucose was then measured at 0, 1.5, 3 and 5 hr after administration of extracts/drug. Streptozotocin-induced diabetic rats were administered the same doses of leaf and flower extracts, and standard drugs glibenclamide was given to the normal rats or 0.5 ml of 5% Tween-80, for 27 days. The blood sample from all groups collected by retro-orbital puncture on 7, 14, 21 and 27th days after administration of the extracts/drug and used for the estimation of serum glucose levels using the glucose kit. Results The Calotropis gigantea leaves and flowers extracts were effective in lowering serum glucose levels in normal rats. Improvement in oral glucose tolerance was also registered by treatment with Calotropis gigantean. The administration of leaf and flower extracts to streptozotocin-induced diabetic rats showed a significant reduction in serum glucose levels. Conclusion It is concluded that chloroform extracts of Calotropis gigantea leaves and flowers have significant anti-diabetic activity. PMID:22043394

  13. Anti-hyperglycemic activity of selenium nanoparticles in streptozotocin-induced diabetic rats

    PubMed Central

    Al-Quraishy, Saleh; Dkhil, Mohamed A; Abdel Moneim, Ahmed Esmat

    2015-01-01

    The study was designed to investigate the anti-hyperglycemic activity of selenium nanoparticles (SeNPs) in streptozotocin-induced diabetic rats. Fifty-five mg/kg of streptozotocin was injected in rats to induce diabetes. Animals either treated with SeNPs alone or with insulin (6 U/kg) showed significantly decreased fasting blood glucose levels after 28 days of treatment. The serum insulin concentration in untreated diabetic animals was also enhanced by SeNPs. The results demonstrated that SeNPs could significantly decrease hepatic and renal function markers, total lipid, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels, and glucose-6-phosphatase activity. At the same time, SeNPs increased malic enzyme, hexokinase and glucose-6-phosphate dehydrogenase activity, liver and kidney glycogen contents, and high-density lipoprotein cholesterol levels. In addition, SeNPs were able to prevent the histological injury in the hepatic and renal tissues of rats. However, insulin injection also exhibited a significant improvement in diabetic animals after 28 days of treatment. This study suggests that SeNPs can alleviate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats, possibly by eliciting insulin-mimetic activity. PMID:26604749

  14. Amla (Emblica officinalis Gaertn.) extracts reduce oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Rao, T P; Sakaguchi, N; Juneja, L R; Wada, E; Yokozawa, T

    2005-01-01

    The antioxidant properties of amla extracts and their effects on the oxidative stress in streptozotocin-induced diabetes were examined in rats. Amla in the form of either the commercial enzymatic extract SunAmla (Taiyo Kagaku Co. Ltd., Yokkaichi, Japan) (20 or 40 mg/kg of body weight/day) or a polyphenol-rich fraction of ethyl acetate extract (10 or 20 mg/kg of body weight/day) was given orally for 20 days to the streptozotocin-induced diabetic rats. Amla extracts showed strong free radical scavenging activity. Amla also showed strong inhibition of the production of advanced glycosylated end products. The oral administration of amla extracts to the diabetic rats slightly improved body weight gain and also significantly alleviated various oxidative stress indices of the serum of the diabetic rats. The elevated serum levels of 5-hydroxymethylfurfural, which is a glycosylated protein that is an indicator of oxidative stress, were significantly reduced dose-dependently in the diabetic rats fed amla. Similarly, the serum level of creatinine, yet another oxidative stress parameter, was also reduced. Furthermore, thiobarbituric acid-reactive substances levels were significantly reduced with amla, indicating a reduction in lipid peroxidation. In addition, the decreased albumin levels in the diabetic rats were significantly improved with amla. Amla also significantly improved the serum adiponectin levels. These results form the scientific basis supporting the efficacy of amla for relieving the oxidative stress and improving glucose metabolism in diabetes. PMID:16176148

  15. Antioxidant properties of Momordica Charantia (bitter gourd) seeds on Streptozotocin induced diabetic rats.

    PubMed

    Sathishsekar, Dhanasekar; Subramanian, Sorimuthu

    2005-01-01

    The aim of the present study is to investigate the antioxidant activities of the aqueous extract of seeds of two varieties, namely a country and hybrid variety of Momordica charantia (MCSEt1 and MCSEt2) respectively in streptozotocin induced diabetic rats. Oral administration of both the seed extracts at a concentration of 150 mg/kg b.w for 30 days showed a significant decrease in fasting blood glucose, hepatic and renal thiobarbituric acid reactive substances and hydroperoxides. The treatment also resulted in a significant increase in reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase in the liver and kidney of diabetic rats. The results clearly suggest that seeds of Momordica charantia treated group may effectively normalize the impaired antioxidant status in streptozotocin induced-diabetes than the glibenclamide treated groups. The extract exerted rapid protective effects against lipid peroxidation by scavenging of free radicals there by reducing the risk of diabetic complications. The effect was more pronounced in MCSEt1 compared to MCSEt2. PMID:15927932

  16. Hypolipidemic, Hepatoprotective and Renoprotective Effects of Cydonia Oblonga Mill. Fruit in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Mirmohammadlu, Mansur; Hosseini, Seyed Hojjat; Kamalinejad, Mohammad; Esmaeili Gavgani, Majid; Noubarani, Maryam; Eskandari, Mohammad Reza

    2015-01-01

    Diabetes mellitus is associated with complications in several different systems of the body, and the incidence of diabetes is rapidly increasing worldwide. The objective of the present study was to evaluate the effect of aqueous extract of Cydonia oblonga Mill. Fruit on lipid profile and some biochemical parameters in streptozotocin-induced diabetic rats. The extract showed anti hyper lipidemic activity as evidenced by significant decreases in serum triglyceride, total cholesterol, and low density lipoprotein cholesterol (LDL-C) levels along with the elevation of high density lipoprotein cholesterol (HDL-C) in the diabetic rats. The biochemical liver functional tests were also analyzed and it was shown that serum biomarkers of liver dysfunction, including alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were significantly reduced in aqueous extract of Cydonia oblonga Mill. treated diabetic rats. In addition, our results showed that the oral administration of the extract prevented diabetes-induced increase in serum urea and creatinine levels as the markers of renal dysfunction. In conclusion, the present study indicates that aqueous extract of Cydonia oblonga Mill. Is able to improve some of the symptoms associated with diabetes and possesses hypolipidemic, hepatoprotective, and renoprotective effects in streptozotocin-induced diabetic rats. PMID:26664388

  17. Antihyperglycemic Activity of Houttuynia cordata Thunb. in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Kumar, Manish; Prasad, Satyendra K.; Krishnamurthy, Sairam; Hemalatha, Siva

    2014-01-01

    Present study is an attempt to investigate plausible mechanism involved behind antidiabetic activity of standardized Houttuynia cordata Thunb. extract in streptozotocin-induced diabetic rats. The plant is used as a medicinal salad for lowering blood sugar level in North-Eastern parts of India. Oral administration of extract at 200 and 400 mg/kg dose level daily for 21 days showed a significant (P < 0.05) decrease in fasting plasma glucose and also elevated insulin level in streptozotocin-induced diabetic rats. It also significantly reversed all the alterations in biochemical parameters, that is, total lipid profile, blood urea, creatinine, protein, and antioxidant enzymes in liver, pancreas, and adipose tissue of diabetic rats. Furthermore, we have demonstrated that the extract significantly reversed the expression patterns of various glucose homeostatic enzyme genes like GLUT-2, GLUT-4, and caspase-3 levels but did not show any significant effect on PPAR-γ protein expressions. Additionally, the extract positively regulated mitochondrial membrane potential and succinate dehydrogenase (SDH) activity in diabetic rats. The findings justified the antidiabetic effect of H. cordata which is attributed to an upregulation of GLUT-4 and potential antioxidant activity, which may play beneficial role in resolving complication associated with diabetes. PMID:24707284

  18. Antihyperglycemic Activity of Houttuynia cordata Thunb. in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Kumar, Manish; Prasad, Satyendra K; Krishnamurthy, Sairam; Hemalatha, Siva

    2014-01-01

    Present study is an attempt to investigate plausible mechanism involved behind antidiabetic activity of standardized Houttuynia cordata Thunb. extract in streptozotocin-induced diabetic rats. The plant is used as a medicinal salad for lowering blood sugar level in North-Eastern parts of India. Oral administration of extract at 200 and 400 mg/kg dose level daily for 21 days showed a significant (P < 0.05) decrease in fasting plasma glucose and also elevated insulin level in streptozotocin-induced diabetic rats. It also significantly reversed all the alterations in biochemical parameters, that is, total lipid profile, blood urea, creatinine, protein, and antioxidant enzymes in liver, pancreas, and adipose tissue of diabetic rats. Furthermore, we have demonstrated that the extract significantly reversed the expression patterns of various glucose homeostatic enzyme genes like GLUT-2, GLUT-4, and caspase-3 levels but did not show any significant effect on PPAR- γ protein expressions. Additionally, the extract positively regulated mitochondrial membrane potential and succinate dehydrogenase (SDH) activity in diabetic rats. The findings justified the antidiabetic effect of H. cordata which is attributed to an upregulation of GLUT-4 and potential antioxidant activity, which may play beneficial role in resolving complication associated with diabetes. PMID:24707284

  19. Effect of tangeretin, a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Sundaram, Ramalingam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2014-05-15

    The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide - a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential. PMID:24629597

  20. The Potential Benefits and Adverse Effects of Phytic Acid Supplement in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Omoruyi, F. O.; Budiaman, A.; Eng, Y.; Olumese, F. E.; Hoesel, J. L.; Ejilemele, A.; Okorodudu, A. O.

    2013-01-01

    In this study, the effect of phytic acid supplement on streptozotocin-induced diabetic rats was investigated. Diabetic rats were fed rodent chow with or without phytic acid supplementation for thirty days. Blood and organ samples were collected for assays. The average food intake was the highest and the body weight gain was the lowest in the group fed phytic acid supplement compared to the diabetic and normal control groups. There was a downward trend in intestinal amylase activity in the group fed phytic acid supplement compared to the other groups. The spike in random blood glucose was the lowest in the same group. We noted reduced serum triglycerides and increased total cholesterol and HDL cholesterol levels in the group fed phytic acid supplement. Serum alkaline phosphatase and alanine amino transferase activities were significantly (P < 0.05) increased by phytic acid supplementation. Systemic IL-1β level was significantly (P < 0.05) elevated in the diabetic control and supplement treated groups. The liver lipogenic enzyme activities were not significantly altered among the groups. These results suggest that phytic acid supplementation may be beneficial in the management of diabetes mellitus. The observed adverse effect on the liver may be due to the combined effect of streptozotocin-induced diabetes and phytic acid supplementation. PMID:24454345

  1. Hypolipidemic, Hepatoprotective and Renoprotective Effects of Cydonia Oblonga Mill. Fruit in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Mirmohammadlu, Mansur; Hosseini, Seyed Hojjat; Kamalinejad, Mohammad; Esmaeili Gavgani, Majid; Noubarani, Maryam; Eskandari, Mohammad Reza

    2015-01-01

    Diabetes mellitus is associated with complications in several different systems of the body, and the incidence of diabetes is rapidly increasing worldwide. The objective of the present study was to evaluate the effect of aqueous extract of Cydonia oblonga Mill. Fruit on lipid profile and some biochemical parameters in streptozotocin-induced diabetic rats. The extract showed anti hyper lipidemic activity as evidenced by significant decreases in serum triglyceride, total cholesterol, and low density lipoprotein cholesterol (LDL-C) levels along with the elevation of high density lipoprotein cholesterol (HDL-C) in the diabetic rats. The biochemical liver functional tests were also analyzed and it was shown that serum biomarkers of liver dysfunction, including alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were significantly reduced in aqueous extract of Cydonia oblonga Mill. treated diabetic rats. In addition, our results showed that the oral administration of the extract prevented diabetes-induced increase in serum urea and creatinine levels as the markers of renal dysfunction. In conclusion, the present study indicates that aqueous extract of Cydonia oblonga Mill. Is able to improve some of the symptoms associated with diabetes and possesses hypolipidemic, hepatoprotective, and renoprotective effects in streptozotocin-induced diabetic rats. PMID:26664388

  2. The Effect of Grape Seed Extracts on Serum Paraoxonase Activities in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Kıyıcı, Aysel; Gökbel, Hakkı; Belviranlı, Muaz

    2010-01-01

    Abstract Procyanidins, a group of flavonoids, are oligomeric forms of catechins that are abundant in red wine, grapes, cocoa, and apples. Paraoxonase acts as an antioxidant enzyme and protects low-density lipoprotein-cholesterol against oxidation. In our study we aimed to evaluate the effects of grape seed extract (GSE) on paraoxonase activities in streptozotocin-induced diabetic rats. Our study included four groups of rats: Group I (n = 8), control; Group II (n = 10), GSE-supplemented; Group III (n = 6), streptozotocin-induced diabetic; and Group IV (n = 7), GSE-supplemented diabetic rats. Serum paraoxonase activities were determined with a spectrophotometric method. Paraoxonase activities in Group III were significantly lower than in the other three groups (P < .001, P < .001, and P = .005 for Groups I, II, and IV, respectively), and Group IV showed increased paraoxonase activities compared to Group III (P = .005). This is the first study to show an association between paraoxonase status and GSE supplementation and demonstrated that GSE increased paraoxonase activities. This beneficial effect of GSE was more obvious in the diabetic group, which was more prone to atherosclerotic events compared to the healthy population. PMID:20388041

  3. Aqueous extract of Berberis integerrima root improves renal dysfunction in streptozotocin induced diabetic rats

    PubMed Central

    Ashraf, Hossein; Heidari, Reza; Nejati, Vahid; Ilkhanipoor, Minoo

    2013-01-01

    Objective: Barberry root extract contains various alkaloids that are considered as antioxidants. Beneficial effect of aqueous extract of Berberis integerrima root (AEBIR) was evaluated for renal function in diabetic rats induced by STZ. Material and Methods: Diabetes was induced by i.p. injection of streptozotocin (65 mg/kg bw) to rats, after 15 h of fasting. Diabetic rats were randomly grouped and treated daily with AEBIR and glibenclamide by gavage for 42 days. After 6 weeks of study, all the rats were sacrificed and some biochemical parameters of serum and urine were measured and their kidneys tissues were processed for light microscopy. Results: Streptozotocin induced a significant rise in fasting blood glucose, serum creatinine, blood urea nitrogen, urine glucose, urine protein, urine albumin, and water intake and a significant decrease in body weight, serum protein, urine urea, and urine creatinine. There was a significant restoration of these parameters to near normal after administration of the AEBIR and also by glibenclamide (0.6 mg/kg bw). The activity of the extract at dose of 500 mg/kg in all parameters except blood glucose and urine glucose was more than that of the standard drug, glibenclamide (0.6 mg/kg, p.o.). Histopathological changes of kidney samples were comparable with respective control. Conclusion: These results suggested that aqueous extract of Berberis Integerrima root improves renal dysfunction in streptozotocin-induced diabetic rats through controlling blood glucose and renal protective effects. PMID:25050261

  4. Antidiabetic and Antioxidant Properties of Triticum aestivum in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Mohan, Yogesha; Jesuthankaraj, Grace Nirmala; Ramasamy Thangavelu, Narendhirakannan

    2013-01-01

    The antidiabetic and antioxidant potential of Triticum aestivum were evaluated by using in vivo methods in normal and streptozotocin-induced diabetic rats. Diabetes was induced in the Wistar strain albino rats by injecting streptozotocin at a dose of 55 mg/kg body weight. Ethanolic extracts of Triticum aestivum at doses of 100 mg/kg body weight were administered orally for 30 days. Various parameters were studied and the treatment group with the extract showed a significant increase in the liver glycogen and a significant decrease in fasting blood glucose, glycosylated hemoglobin levels, and serum marker enzyme levels. The total cholesterol and serum triglycerides levels, low density lipoprotein, and very low density lipoprotein were also significantly reduced and the high density lipoprotein level was significantly increased upon treatment with the Triticum aestivum ethanol extract. A significant decrease in the levels of lipid peroxides, superoxide dismutase, and glutathione peroxidise and increase in the levels of vitamin E, catalase, and reduced glutathione were observed in Triticum aestivum treated diabetic rats. Thus, from this study we conclude that ethanolic extract of Triticum aestivum exhibited significant antihyperglycemic, hypolipidemic, and antioxidant activities in streptozotocin-induced diabetic rats. PMID:24416041

  5. Tracing Fasting Glucose Fluxes with Unstressed Catheter Approach in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Wu, Hui; Xu, Xiao; Meng, Ying; Xia, Fangzhen; Zhai, Hualing; Lu, Yingli

    2014-01-01

    Objective. Blood glucose concentrations of type 1 diabetic rats are vulnerable, especially to stress and trauma. The present study aimed to investigate the fasting endogenous glucose production and skeletal muscle glucose uptake of Streptozotocin induced type 1 diabetic rats using an unstressed vein and artery implantation of catheters at the tails of the rats as a platform. Research Design and Methods. Streptozotocin (65 mg·kg−1) was administered to induce type 1 diabetic state. The unstressed approach of catheters of vein and artery at the tails of the rats was established before the isotope tracer injection. Dynamic measurement of fasting endogenous glucose production was assessed by continuously infusing stable isotope [6, 6-2H2] glucose, while skeletal muscle glucose uptake by bolus injecting radioactively labeled [1-14C]-2-deoxy-glucose. Results. Streptozotocin induced type 1 diabetic rats displayed polydipsia, polyphagia, and polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhanced fasting endogenous glucose production and reduced glucose uptake in skeletal muscle compared to nondiabetic rats. Conclusions. The dual catheters implantation at the tails of the rats together with isotope tracers injection is a save time, unstressed, and feasible approach to explore the glucose metabolism in animal models in vivo. PMID:24772449

  6. Prevention of multiple low-dose streptozotocin (MLD-STZ) diabetes in mice by an extract from gum resin of Boswellia serrata (BE).

    PubMed

    Shehata, Ahmed M; Quintanilla-Fend, L; Bettio, Sabrina; Singh, C B; Ammon, H P T

    2011-09-15

    Type 1-diabetes is an autoimmune disease, where a chronic inflammatory process finally causes β-cell death and insulin deficiency. Extracts from gum resin of Boswellia serrata (BE) have been shown to posses anti-inflammatory properties especially by targeting factors/mediators related to autoimmune diseases. Multiple low dose-streptozotocin (MLD-STZ) treatment is a method to induce diabetes in animals similar to Type 1 diabetes in humans. It was aimed to study whether or not a BE could prevent hyperglycemia, inflammation of pancreatic islets and increase of proinflammatory cytokines in the blood in MLD-STZ treated mice. In BK+/+ wild type mice, 5 days of daily treatment with 40 mg/kg STZ i.p. produced permanent increase of blood glucose, infiltration of lymphocytes into pancreatic islets (CD3-stain), apoptosis of periinsular cells (staining for activated caspase 3) after 10 days as well as shrinking of islet tissue after 35 days (H&E staining). This was associated with an increase of granulocyte colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF) and proinflammatory cytokines (IL-1A, IL-1B, IL-2, IL-6, IFN-γ, TNF-α) in the blood. Whereas BE alone did not affect blood glucose in non diabetic mice, in STZ treated mice simultaneous i.p. injection of 150 mg/kg of BE over 10 days prevented animals from increase of blood glucose levels. Histochemical studies showed, that i.p. injection of 150 mg/kg BE for 10 days starting with STZ treatment, avoided lymphocyte infiltration into islets, apoptosis of periinsular cells and shrinking of islet size 35 days after STZ. As far as the cytokines tested are concerned, there was a significant inhibition of the increase of G-CSF and GM-CSF. BE also significantly prevented the increase of IL-1A, IL-1B, IL-2, IL-6, IFN-γ and TNF-α. It is concluded that extracts from the gum resin of Boswellia serrata prevent islet destruction and consequent hyperglycemia in an animal model of type 1

  7. Effect of Vitamin C Supplementation on Platelet Aggregation and Serum Electrolytes Levels in Streptozotocin-Induced Diabetes Mellitus in Rats.

    PubMed

    Owu, Daniel U; Nwokocha, Chukwuemeka R; Ikpi, Daniel E; Ogar, Emmanuel I

    2016-01-01

    Diabetes mellitus (DM) is a disease condition characterised by hyperglycemia; free radical and abnormalhaematological indices. Vitamin C can reduce free radical generation and ameliorate adverse conditions of diabetes mellitus.The aim of the present study is to investigate the effect of vitamin C on platelet aggregation and electrolyte levels in Type 1DM. Male Wistar rats were divided into four groups namely control, DM, DM +Vitamin C and Vitamin C groups. Rats weremade diabetic with a single dose of streptozotocin (65 mg/kg) intraperitoneally. Vitamin C was administered orally todiabetic and normal rats at 200 mg/kg body weight for 28 days. Blood samples were analyzed for hematological parameters,platelet aggregation, and serum electrolyte levels. Blood glucose in DM+ Vitamin C group (9.9 ± 1.8 mmol/L) wassignificantly reduced (p<0.01) compared to DM group (32.2 ± 2.1 mmol/L) and significantly higher (p<0.05) than control(4.4 ± 0.8 mmol/L). Haemoglobin (Hb) concentration in DM group (12 ± 0.1 g/dL) was significantly reduced (p<0.01) whencompared with control groups (14 ± 0.24 g/dL) and significantly increased (p<0.05) in the DM+vitamin C group (13.5 ± 0.5g/dL) compared with the diabetic group. The mean corpuscular volume values in DM (68.66 ± 0.5 fL) and DM+vitamin Cgroups (68.11 ± 0.4 fL) were significantly higher (p<0.01) than the control (59.49 ± 0.5fL). Platelet count in DM group (523± 8.5 x109/L) was significantly raised (p<0.01) when compared to control (356 ± 6.2 x109/L) and significantly reduced(p<0.01) in DM+ vitamin C-treated group (385 ± 7.8 x109/L) compared with DM group. Platelet aggregation and serumsodium/potassium ratios was significantly reduced (p<0.01) in DM+vitamin C compared with DM group. These resultssuggest that oral vitamin C administration increases haemoglobin, reduced plasma glucose level, platelet count, serumsodium/potassium ion ratio and inhibits platelet aggregation in streptozotocin-induced DM in rats. PMID:27574765

  8. AB240. Therapeutic effects of adipose-derived stem cells-based micro-tissues on erectile dysfunction in streptozotocin-induced diabetic rats

    PubMed Central

    Hui, Yu; Yang, Bicheng; Lei, Hongen; Guan, Ruili; Xin, Zhongcheng

    2016-01-01

    Background This study aimed to explore the therapeutic effects of adipose-derived stem cells (ADSCs)-based micro-tissues (MTs) on erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. Methods Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg/kg) and eight weeks later, the determined diabetic rats randomly got intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs or MTs. Another eight normal rats equally received IC injection of PBS. MTs were generated with a hanging drop method and the injected cells were tracked in ADSCs and MTs 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. Results 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 better improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle and endothelial contents in diabetic rats, ameliorated local inflammation in CC. Conclusions IC injection of MTs improves the erectile function and histopathological changes in streptozotocin-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.

  9. Proteomic analysis of glycated proteins from streptozotocin-induced diabetic rat kidney.

    PubMed

    Chougale, Ashok D; Bhat, Shweta P; Bhujbal, Swapnil V; Zambare, Mandar R; Puntambekar, Shraddha; Somani, Rahul S; Boppana, Ramanamurthy; Giri, Ashok P; Kulkarni, Mahesh J

    2012-01-01

    Glycation of proteins leading to formation of advanced glycation end products (AGEs) has been considered as one of the important causes of diabetic nephropathy. Therefore, in this study, glycated proteins were detected by anti-AGE antibodies from kidney of streptozotocin-induced diabetic rat showing nephropathic symptoms, by using two dimensional electrophoresis and western blot analysis. These glycated proteins were identified and characterized by using combination of peptide mass finger printing and tandem mass spectrometric approaches. Glycated proteins identified included proteins from metabolic pathways, oxidative stress, cell signaling, and transport. Several of the proteins modified by glycation were involved in glucose metabolism. The extent of glycation was higher in diabetes compared to control, in the glycated proteins that were common to both control and diabetic kidney. Two dimensional electrophoresis proteins profiling of glycated proteins suggest that four of the glycated proteins were significantly up regulated in diabetes. PMID:21516357

  10. Hypoglycaemic, hypolipidemic and antioxidant properties of tulsi (Ocimum sanctum linn) on streptozotocin induced diabetes in rats.

    PubMed

    Hussain, E H; Jamil, K; Rao, M

    2001-07-01

    Effect of oral administration of 200 mg/Kg body weight of the aqueous extract ofOcimum sanctum (Tulsi) mixed with diet for eight weeks to diabetic (streptozotocin induced) rats was studied. There was significant reduction in fasting blood glucose, serum lipid profile, lipid peroxidation products, (LPO) and improvement in glucose tolerance. The aqueous extract also decreased LPO formation (thiobarbituric acid reactive substances TBARS) and increased antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione transferase (GT) and one antioxidant reduced glutathione (GSH) in plasma and rat liver, lung, kidney and brain. The decrease in TBARS and increase in GSH, SOD, CAT, GPX, and GT clearly shows the antioxidant property ofOcimum sanctum. PMID:23105316

  11. Effect of All-Trans Retinoic Acid on the Pancreas of Streptozotocin-Induced Diabetic Rat.

    PubMed

    Eltony, Sohair A; Elmottaleb, Nashwa A; Gomaa, Asmaa M; Anwar, Mamdouh M; El-Metwally, Tarek H

    2016-03-01

    All-trans Retinoic acid (atRA) is instructive for the development of endocrine pancreas and is an integral component of β-cell induction protocols. We showed that atRA induces glucose-responsive endocrine transdifferentiation of pleomorphic pancreatic ductal adenocarcinoma cells in vitro. This study aimed to detect the role of atRA in improving the histological changes of the pancreas in diabetic rats. Forty young male Wistar rats were used and divided into three groups. Group I: normal vehicle control (N = 5). Group II: streptozotocin-induced diabetic rats (N = 20) were followed up at 0.0, 1, 2, and 4 weeks. Group III: streptozotocin-induced diabetic rats (N = 15) treated with atRA (2.5 mg/kg/day), were followed up at 1, 2, and 4 weeks. Specimens from the pancreas were processed for light, electron microscopy and pancreatic insulin mRNA expression. Blood samples were assayed for the levels of glucose, insulin, and total peroxides. In the atRA-treated group, the number of the islets and the islet area significantly increased. Strong insulin-immunoreactive endocrine-like cells were observed nearby the pancreatic acini and the interlobular ducts. Interestingly, insulin-positive cells seemed to arise from pancreatic acinar and ductal epithelium. Ultrastructurally, ß-cells, acinar, and ductal cells restored their normal appearance. Pancreatic insulin mRNA and blood indices were almost normalized. AtRA improved the histological changes of the pancreas and the blood indices in diabetic rats. PMID:26704900

  12. Pain modality and spinal glia expression by streptozotocin induced diabetic peripheral neuropathy in rats

    PubMed Central

    Kim, Sok Ho; Kwon, Jung Kee

    2012-01-01

    Pain symptoms are a common complication of diabetic peripheral neuropathy or an inflammatory condition. In the most experiments, only one or two evident pain modalities are observed at diabetic peripheral neuropathy according to experimental conditions. Following diabetic peripheral neuropathy or inflammation, spinal glial activation may be considered as an important mediator in the development of pain. For this reason, the present study was aimed to address the induction of pain modalities and spinal glial expression after streptozotocin injection as compared with that of zymosan inflammation in the rat. Evaluation of pain behavior by either thermal or mechanical stimuli was performed at 3 weeks or 5 hours after either intravenous streptozotocin or zymosan. Degrees of pain were divided into 4 groups: severe, moderate, mild, and non-pain induction. On the mechanical allodynia test, zymosan evoked predominantly a severe type of pain, whereas streptozotocin induced a weak degree of pain (severe+moderate: 57.1%). Although zymosan did not evoke cold allodynia, streptozotocin evoked stronger pain behavior, compared with zymosan (severe+moderate: 50.0%). On the other hand, the high incidence of thermal hyperalgesia (severe+moderate: 90.0%) and mechanical hyperalgesia (severe+moderate: 85.7%) by streptozotocin was observed, as similar to that of zymosan. In the spinal cord, the increase of microglia and astrocyte was evident by streptozotocin, only microglia was activated by zymosan. Therefore, it is recommended that the selection of mechanical and thermal hyperalgesia is suitable for the evaluation of streptozotocin induced diabetic peripheral neuropathy. Moreover, spinal glial activation may be considered an important factor. PMID:22787487

  13. Antineuropathic effect of 7-hydroxy-3,4-dihydrocadalin in streptozotocin-induced diabetic rodents

    PubMed Central

    2014-01-01

    Background Painful neuropathy is the most common and debilitating complication of diabetes and results in hyperalgesia and allodynia. Hyperglycemia clearly plays a key role in the development and progression of diabetic neuropathy. Current therapeutic approaches are only partially successful and they are only thought to reduce the pain associated with peripheral neuropathy. Some natural products offer combined antioxidant, anti-inflammatory and antinociceptive properties that may help to treat in a more integrative manner this condition. In this regard, the purpose of this study was to investigate the antineuropathic effect of 7-hydroxy-3,4-dihydrocadalin in streptozotocin-induced diabetic rats and mice without glucose control as well as the possible mechanism of action involved in this effect. Methods Rats and mice were injected with 50 or 200 mg/kg streptozotocin, respectively, to produce hyperglycemia. The formalin test and von Frey filaments were used to assess the nociceptive activity. Rota-rod was utilized to measure motor activity and malondialdehyde assay to determine anti-oxidative properties. Results After 3 weeks of diabetes induction, chemical hyperalgesia was observed in streptozotocin-injected rats. Oral acute administration of 7-hydroxy-3,4-dihydrocadalin (0.3–30 mg/kg) decreased in a dose-dependent manner formalin-evoked hyperalgesia in diabetic rats. In addition, methiothepin (non-selective 5-HT receptor antagonist, 1 mg/kg, i.p.) and ODQ (guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (opioid receptor antagonist, 1 mg/kg, s.c.), prevented 7-hydroxy-3,4-dihydrocadalin-induced antihyperalgesic effect. The anti-hyperalgesic effect of 7-hydroxy-3,4-dihydrocadalin was similar to that produced by pregabalin (10 mg/kg, p.o.). Furthermore, oral acute administration of 7-hydroxy-3,4-dihydrocadalin (30 mg/kg) reduced streptozotocin-induced changes in malondialdehyde concentration from plasma samples. Unlike pregabalin, 7-hydroxy-3

  14. The effects of caffeic acid phenethyl ester on streptozotocin-induced diabetic liver injury.

    PubMed

    Taslidere, E; Gul, M; Elbe, H; Cetin, A; Vardi, N; Ozyalin, F; Turkoz, Y

    2016-01-01

    The aim of the present study was to clarify the role of oxidative stress in streptozotocin induced liver injury and the possible protective effect of caffeic acid phenethyl ester (CAPE) using histological and biochemical parameters. 32 male Wistar rats were divided into 4 groups as follows: Group 1: Control animals, Group 2: Control animals given CAPE Group 3: STZ-induced diabetic animals (DM group), Group 4: STZ-induced diabetic rats given CAPE (DM+CAPE group). All the injections started on the same day of single-dose STZ injection and continued for 20 days. At the end of this period, livers were removed and processed for routine histological procedures. Biochemical parameters and morphological changes were examined. In DM group, blood glucose levels were significantly increased compared with the control group. Significant increases in tissue malondialdehyde (MDA) level and decreases in superoxide dismutase (SOD) and total glutathione (GSH) activities were detected in DM group. Administration of CAPE significantly reduced these values. STZ-induced histopathological alterations including inflammatory cell infiltration around portal triad, congestion, loss of glycogen in the hepatocytes. Additionally, degenerative cellular alterations, such as numerous vacuolizations including myelinic figure formation, pyknotic nuclei with peripheral localization of heterochromatin condensation and mitochondrial elongation were observed in cytoplasm of hepatocytes. CAPE significantly reduced these histopathological changes. Our results indicate that CAPE should be considered in the prevention of oxidative stress in diabetic liver. PMID:27215964

  15. Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice.

    PubMed

    Tian, Cai-Ming; Jiang, Xin; Ouyang, Xiao-Xi; Zhang, Ya-Ou; Xie, Wei-Dong

    2016-07-01

    The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin (BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase (pAMPK) expression and decreased tumor necrosis factor alpha (TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of pAMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies. PMID:27507202

  16. Stimulation of insulin secretion by Viscum album (mistletoe) leaf extract in streptozotocin-induced diabetic rats.

    PubMed

    Eno, A E; Ofem, O E; Nku, C O; Ani, E J; Itam, E H

    2008-06-01

    Twenty male white rats (250-300 g) of Wistar strain were randomly divided into two batches, the normoglycaemic batch and the streptozotocin-induced diabetic batch often rats each. Animals in each batch were further divided into two groups of five rats per group. After an overnight fast (12 hrs), animals in each group received D-glucose load (2.0 g/kg.i.v) under pentobarbital anaesthesia, with or without the crude extract (100 mg/kg/iv). Blood samples were collected intravenously at 15 min intervals for 3 hrs. for analysis of glucose, insulin and glucagon levels. From the results, the extract (100 mg/kg) did not appear to have any significant effect on the blood glucose level of normal rats, but produced about 35.3% decrease in the diabetic rats. Despite the apparent lack of action on glucose level of normal rats, the extract stimulated insulin secretion by about 92.9% (% control) in this group, and about 81.5% in the diabetic group (% control). The glucagon level was not altered by the extract in the normal rats. In the diabetic group, there was mild but significant suppression ofglucagon level after the first 1 hr. which lasted for about 50 min. We suggest that this extract from V. album leaves may possess antihyperglycaemic, insulinotropic, and possibly, mild glucagonostatic agent(s) and may therefore be a candidate for the anti-diabetic drugs. PMID:18939397

  17. Antihyperglycemic and antioxidant activity of Clitorea ternatea Linn. on streptozotocin-induced diabetic rats.

    PubMed

    Talpate, Karuna A; Bhosale, Uma A; Zambare, Mandar R; Somani, Rahul

    2013-10-01

    Ethanol extract of Clitorea ternatea Linn. (EECT) was evaluated for its antihyperglycemic and antioxidative activity in normal and streptozotocin-induced diabetic rats. Antihyperglycemic activity of EECT was studied in normal fasted and glucose fed hyperglycemic and epinephrine induced hyperglycemic rats by estimating fasting serum glucose (FSG) by glucose oxidisae or peroxidase enzymatic method. Antioxidant activity of EECT was studied by assaying lipid peroxide/Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), total nitric oxide, catalase (CAT) and glutathione levels in diabetic rats. The EECT (200 and 400 mg/kg) showed significant antihyperglycemic activity by decreasing FSG in all hyperglycemic models except epinephrine induced hyperglycemic rats; in which improvement in FSG was observed only with EECT in 400 mg/kg dose, whereas significant decrease in TBARS (P < 0.001), nitric oxide (P < 0.001) and significant increase in SOD (P < 0.001), CAT (P < 0.01) and reduced glutathione levels (P < 0.001) was observed in animals treated with EECT (200 and 400 mg/kg) compared to diabetic control group. The results indicated that EECT has remedial effects on hyperglycemia and oxidative stress in diabetic rats. PMID:24696583

  18. Heat stress attenuates skeletal muscle atrophy of extensor digitorum longus in streptozotocin-induced diabetic rats.

    PubMed

    Nonaka, K; Une, S; Akiyama, J

    2015-09-01

    To investigate whether heat stress attenuates skeletal muscle atrophy of the extensor digitorum longus (EDL) muscle in streptozotocin-induced diabetic rats, 12-week-old male Wistar rats were randomly assigned to four groups (n = 6 per group): control (Con), heat stress (HS), diabetes mellitus (DM), and diabetes mellitus/heat stress (DM + HS). Diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg). Heat stress was induced in the HS and DM + HS groups by immersion of the lower half of the body in hot water at 42 °C for 30 min; it was initiated 7 days after injection of streptozotocin, and was performed once a day, five times a week for 3 weeks. The muscle fiber cross-sectional area of EDL muscles from diabetic and non-diabetic rats was determined; heat stress protein (HSP) 72 and HSP25 expression levels were also analyzed by western blotting. Diabetes-induced muscle fiber atrophy was attenuated upon heat stress treatment in diabetic rats. HSP72 and HSP25 expression was upregulated in the DM + HS group compared with the DM group. Our findings suggest that heat stress attenuates atrophy of the EDL muscle by upregulating HSP72 and HSP25 expression. PMID:26551745

  19. Pycnogenol improves left ventricular function in streptozotocin-induced diabetic cardiomyopathy in rats.

    PubMed

    Klimas, Jan; Kmecova, Jana; Jankyova, Stanislava; Yaghi, Diana; Priesolova, Elena; Kyselova, Zuzana; Musil, Peter; Ochodnicky, Peter; Krenek, Peter; Kyselovic, Jan; Matyas, Stefan

    2010-07-01

    We studied whether Pycnogenol (PYC) may attenuate the development of experimental streptozotocin-induced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)-producing molecules (gp91(phox)-containing NADPH oxidase and NO-signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91(phox) (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha-tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect these expression abnormalities. Our study shows that PYC corrects diabetic cardiac dysfunction, probably by its metabolic and direct radical scavenging activity without affecting the molecular maladaptations of ROS-producing enzymes and cytoskeletal components. PMID:19957251

  20. Hypoglycemic and hypolipidemic effects of Aronia melanocarpa fruit juice in streptozotocin-induced diabetic rats.

    PubMed

    Valcheva-Kuzmanova, S; Kuzmanov, K; Tancheva, S; Belcheva, A

    2007-03-01

    Aronia melanocarpa fruit juice (AMFJ) is rich in phenolic antioxidants, especially flavonoids from the anthocyanin subclass. The aim of the present study was to investigate the influence of AMFJ on plasma glucose and lipids in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (50 mg/kg). AMFJ was applied by gavage at doses of 10 and 20 ml/kg for 6 weeks to normal and diabetic rats. Streptozotocin caused a significant elevation of plasma glucose by 141% and of plasma triglycerides (TG) by 64% in comparison with normal control rats and induced statistically insignificant elevations of total cholesterol and LDL-cholesterol and a reduction of HDL-cholesterol. Applied to normal rats, AMFJ did not influence plasma glucose and lipid levels. Applied to diabetic rats, AMFJ (10 and 20 ml/kg) significantly reduced plasma glucose by 44% and 42% and TG by 35% and 39%, respectively, to levels that did not significantly differ from those of the normal control rats and counteracted the influence of streptozotocin on total cholesterol, LDL-cholesterol and HDL-cholesterol. In conclusion, AMFJ significantly decreased the streptozotocin-induced abnormalities in blood glucose and TG in diabetic rats and might be useful in prevention and control of diabetes mellitus and diabetes-associated complications. PMID:17440626

  1. Cooked common beans (Phaseolus vulgaris L.) modulate renal genes in streptozotocin-induced diabetic rats.

    PubMed

    Lomas-Soria, Consuelo; Pérez-Ramírez, Iza F; Caballero-Pérez, Juan; Guevara-Gonzalez, Ramón G; Guevara-Olvera, Lorenzo; Loarca-Piña, Guadalupe; Guzman-Maldonado, Horacio S; Reynoso-Camacho, Rosalía

    2015-07-01

    Food consumption with different bioactive compounds could reduce the risk of diabetic complications. This study was designed to evaluate the effect of cooked common beans on differentially expressed genes in whole kidney homogenates of streptozotocin-induced diabetic rats. After 4weeks of treatment with a cooked bean supplemented (10%) diet, animals fed with Flor de Mayo bean (FMB) exerted the greatest protective effect, since they presented the lowest blood glucose levels, consistent with an increase in blood insulin levels, a decrease in urine albumin and urea levels and an increase in creatinine clearance (P≤.05). Regarding the gene expression of kidneys evaluated using expressed sequence tag, consumption of cooked beans improved the expression of Glu1, Cps1, Ipmk, Cacna1c, Camk1, Pdhb, Ptbp3 and Pim1, which are related to the elimination of ammonium groups, the regulation of inflammatory and oxidative response, as well as cell signaling and apoptosis. In addition, the beneficial effects observed were not related to their polyphenolic and saponin profile, suggesting the activity of other bioactive compounds or the synergistic interaction of these compounds. These results suggest that the consumption of cooked common beans (FMB) might be used as an alternative for the regulation of genes related to renal alterations. PMID:25863648

  2. Increased Inner Ear Susceptibility to Noise Injury in Mice With Streptozotocin-Induced Diabetes

    PubMed Central

    Fujita, Takeshi; Yamashita, Daisuke; Katsunuma, Sayaka; Hasegawa, Shingo; Tanimoto, Hitoshi; Nibu, Ken-ichi

    2012-01-01

    We aimed to investigate the pathophysiology of diabetes-associated hearing impairment in type 1 diabetes using mice with streptozotocin-induced diabetes (C57BL/6J; male). Hearing function was evaluated 1, 3, and 5 months after induction of diabetes (five diabetic and five control animals per time point) using auditory-evoked brain stem responses (ABRs). Mice (four diabetic and four control) were exposed to loud noise (105 dB) 5 months after induction of diabetes. ABRs were measured before and after noise exposure. Cochlear blood flows were measured by laser-Doppler flowmeter. Spiral ganglion cells (SGCs) were counted. Vessel endothelial cells were observed by CD31 immunostaining. Chronologic changes in the ABR threshold shift were not significantly different between the diabetic and control groups. However, vessel walls in the modiolus of the cochleae were significantly thicker in the diabetic group than the control group. Additionally, recovery from noise-induced injury was significantly impaired in diabetic mice. Reduced cochlea blood flows and SGC loss were observed in diabetic mice cochleae after noise exposure. Our data suggest that diabetic cochleae are more susceptible than controls to loud noise exposure, and decreased cochlear blood flow due to sclerosis of the vessels and consequent loss of SGCs are possible mechanisms of hearing impairment in diabetic patients. PMID:22851574

  3. Evaluation of Antihyperglycemic Activity of Citrus limetta Fruit Peel in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    KunduSen, Sriparna; Haldar, Pallab K.; Gupta, Malaya; Mazumder, Upal K.; Saha, Prerona; Bala, Asis; Bhattacharya, Sanjib; Kar, Biswakanth

    2011-01-01

    The present paper aims to evaluate antihyperglycemic activity of methanol extract of Citrus limetta fruit peel (MECL) in streptozotocin-induced (STZ; 65 mg/kg b.w.) diabetic rats. Three days after STZ induction, diabetic rats received MECL orally at 200 and 400 mg kg−1 body weight daily for 15 days. Glibenclamide (0.5 mg kg−1 p. o.) was used as reference drug. Blood glucose levels were measured on 0th, 4th, 8th, and 15th days of study. Serum biochemical parameters namely, SGOT, SGPT and ALP were estimated. The TBARS and GSH levels of pancreas, kidney, and liver were determined. MECL significantly (P < 0.001) and dose dependently normalized blood glucose levels and serum biochemical parameters, decreased lipid peroxidation, and recovered GSH as compared to those of STZ control. The present paper infers that in STZ-induced diabetic Wistar rats, C. limetta fruit peel demonstrated a potential antihyperglycemic effect which may be attributed to its antioxidant property. PMID:22363893

  4. Enhanced susceptibility of mice with streptozotocin-induced diabetes to type II group B streptococcal infection.

    PubMed Central

    Edwards, M S; Fuselier, P A

    1983-01-01

    Since diabetes mellitus predisposes adults to group B streptococcal (GBS) bacteremia, a murine model of streptozotocin-induced diabetes and type II GBS bacteremia was developed to assess certain immune factors which might influence susceptibility to infection. In diabetic mice, the 50% lethal dose for two strains of type II GBS was significantly lower (greater than 1 log10 decrease in CFU per milliliter) than in control animals. This enhanced virulence of GBS for diabetic animals was associated with prolonged bacteremia, persistent sequestration of organisms in the splanchnic reticuloendothelial system, and a shift from splenic to hepatic clearance. Although immunization of control and diabetic animals resulted in high concentrations of type-specific serum antibody, it had no effect on late reticuloendothelial system sequestration in diabetics. In contrast, depletion of complement by treatment of mice with cobra venom factor blocked reticuloendothelial system clearance and resulted in fatal infection in both diabetic and control mice. These results indicate that neither type-specific antibody nor an intact complement system is adequate for effective clearance of type II GBS bacteremia in mice with experimentally induced diabetes. This clearance deficit could be the result of a defect in hepatocyte membrane receptors necessary for removal of this encapsulated microorganism. PMID:6339383

  5. Streptozotocin-induced diabetes blocks the positive feedback release of luteinizing hormone in the female rat.

    PubMed

    Kienast, S G; Fadden, C; Steger, R W

    1993-01-01

    The effects of streptozotocin-induced (STZ) diabetes on the release of gonadotropins was studied in female rats. In the first experiment, rats were ovariectomized and 2 days later were injected with STZ. Three weeks later rats were treated with estrogen and progesterone and blood samples were taken via intraatrial cannulae for luteinizing hormone (LH) assay. Afternoon surges of LH were seen in 4/5 control but 0/8 STZ rats. Pituitary responses to LH-releasing hormone in vitro did not differ. In the 2nd experiment, ovariectomized estrogen-primed rats were killed prior to and during a progesterone-induced LH surge. As in Experiment 1, STZ-treatment inhibited the LH surge but did not effect the afternoon rise in median eminence norepinephrine turnover which has previously been shown to be important in stimulating LH release. Turnover of norepinephrine in the anterior hypothalamus was depressed in the diabetic rats both prior to and during the expected time of the LH surge. Dopamine turnover was depressed in all three brain regions studied. It can be concluded that the positive feedback control of LH release is severely attenuated in diabetic rats but the mechanism explaining the loss is not clear. Diabetes-induced alterations in hypothalamic catecholamine metabolism may be involved but further work is needed to more carefully define these relationships. PMID:8221130

  6. Intranasal delivery of nanomicelle curcumin promotes corneal epithelial wound healing in streptozotocin-induced diabetic mice.

    PubMed

    Guo, Chuanlong; Li, Mengshuang; Qi, Xia; Lin, Guiming; Cui, Fenghua; Li, Fengjie; Wu, Xianggen

    2016-01-01

    Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy. PMID:27405815

  7. Ultrastructural changes in the hypothalamic supraoptic nucleus of the streptozotocin-induced diabetic rat.

    PubMed Central

    Dheen, S T; Tay, S S; Wong, W C

    1994-01-01

    Ultrastructural and morphometric studies were undertaken on the hypothalamic supraoptic nucleus of streptozotocin-induced diabetic rats over a period of 1 y. At 3 d, a few dendrites showing electron-dense cytoplasm and dilated rER were dispersed in the neuropil among seemingly normal neuronal somata. At 1-6 months, the somata contained numerous vacuoles of various sizes which probably originated from fragmented and dilated rER. Numerous unidentifiable vacuolated and electron-dense neuronal profiles were also seen in the neuropil. At 9-12 months, the number of degenerating electron-dense axon terminals and dendrites was markedly increased in diabetic rats. Glial cells containing electron-dense debris in their cytoplasm were involved in phagocytosis. At all time intervals studied, the mean cross-sectional cell area and mean cross-sectional nuclear area of supraoptic nuclei neurons of diabetic rats were significantly increased in comparison with age-matched controls injected with normal saline. The causative factors for these changes are not clear. However, it is suggested that the osmotic stress caused by chronic dehydration in the diabetic animals may be partly or wholly responsible for these ultrastructural changes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:7928649

  8. Antihyperglycemic and antioxidant activity of Clitorea ternatea Linn. on streptozotocin-induced diabetic rats

    PubMed Central

    Talpate, Karuna A.; Bhosale, Uma A.; Zambare, Mandar R.; Somani, Rahul

    2013-01-01

    Ethanol extract of Clitorea ternatea Linn. (EECT) was evaluated for its antihyperglycemic and antioxidative activity in normal and streptozotocin-induced diabetic rats. Antihyperglycemic activity of EECT was studied in normal fasted and glucose fed hyperglycemic and epinephrine induced hyperglycemic rats by estimating fasting serum glucose (FSG) by glucose oxidisae or peroxidase enzymatic method. Antioxidant activity of EECT was studied by assaying lipid peroxide/Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), total nitric oxide, catalase (CAT) and glutathione levels in diabetic rats. The EECT (200 and 400 mg/kg) showed significant antihyperglycemic activity by decreasing FSG in all hyperglycemic models except epinephrine induced hyperglycemic rats; in which improvement in FSG was observed only with EECT in 400 mg/kg dose, whereas significant decrease in TBARS (P < 0.001), nitric oxide (P < 0.001) and significant increase in SOD (P < 0.001), CAT (P < 0.01) and reduced glutathione levels (P < 0.001) was observed in animals treated with EECT (200 and 400 mg/kg) compared to diabetic control group. The results indicated that EECT has remedial effects on hyperglycemia and oxidative stress in diabetic rats. PMID:24696583

  9. Nutraceutical potential of Aerva lanata (L.) Juss. ex Schult ameliorates secondary complications in streptozotocin-induced diabetic rats.

    PubMed

    Riya, M P; Antu, K A; Pal, S; Srivastava, A K; Sharma, S; Raghu, K G

    2014-09-01

    Nutraceuticals provide health benefits beyond their basic nutrition by modulating a number of biochemical pathways. They are derived from natural products and have gained recognition worldwide as an adjuvant or therapy in the treatment of metabolic disorders such as diabetes. Although the regulation of blood glucose with drugs and insulin greatly reduces the incidence of secondary complications, the need for long-term treatment raises issues of tolerance and affordability. Therefore, the aim of the present study is to explore the nutraceutical potential of Aerva lanata, a herb widely used for its culinary and therapeutic potential in streptozotocin (STZ)-induced diabetic rats. Treatment with 70% ethanolic extract (ALE) at 500 mg per kg b.w per day for 21 days significantly improved the fasting blood glucose (120.33 ± 1.99 mg dL(-1)), insulin level (9.81 ± 0.38 mU L(-1)), HbA1c (7.3 ± 0.36%) and glycogen content in the liver (35.33 ± 1.38 mg g(-1) protein) and muscle (7.67 ± 0.11 mg g(-1) protein) compared to diabetic controls. The extract also showed a significant decrease in blood glucose by 47.29% towards the end of 2 h in oral glucose tolerance test on Day 21. Its therapeutic potential could be partly attributable to the presence of flavonoids, tannins and terpenes (alpha amyrin, betulin and beta sitosterol) along with micronutrients such as potassium, magnesium, calcium and zinc. Hence, we suggest the suitability of Aerva lanata as a nutraceutical for diabetic patients. PMID:24993661

  10. Ameliorative effect of Withania coagulans on dyslipidemia and oxidative stress in nicotinamide-streptozotocin induced diabetes mellitus.

    PubMed

    Shukla, Kirtikar; Dikshit, Piyush; Tyagi, Mool Kumar; Shukla, Rimi; Gambhir, Jasvinder K

    2012-10-01

    Present study aims to evaluate the effect of Withania coagulans fruit (aqWC) on diabetic-dyslipidemia and antioxidant/oxidant status in DM. Diabetic animals were treated with aqWC at a dose of 250 mg/kg bw for 30 days. Lipid profile, MDA, GSH, SOD, FRAP, HMG CoA reductase and acetyl CoA carboxylase activities were estimated in blood and tissues. Total cholesterol, TAG and LDL were significantly elevated whereas HDL was decreased in diabetic animals (p<0.05), simultaneously the lipid content and HMG CoA reductase activities were also increased, whereas acetyl CoA carboxylase activity decreased significantly in tissues of diabetic animals. MDA was increased and antioxidants such as SOD, GSH and FRAP decreased significantly in DM (p<0.05). Oral administration of aqWC to diabetic animals produced significant improvement in serum lipid profile and tissue lipid content. Activity of HMG CoA reductase decreased, whereas acetyl CoA carboxylase activity increased significantly in tissues after aqWC treatment. Administration of aqWC to diabetic animals also showed significant increase in antioxidant levels i.e., GSH, SOD, FRAP and reduced level of MDA in blood and tissue homogenates as compared to diabetic controls (p<0.05). These results suggest that aqWC treatment improved lipid profile and decreased oxidative stress in diabetes mellitus. PMID:22842119

  11. Ameliorative Effect of Zinc Oxide Nanoparticles on Antioxidants and Sperm Characteristics in Streptozotocin-Induced Diabetic Rat Testes

    PubMed Central

    Afifi, Mohamed; Almaghrabi, Omar A.; Kadasa, Naif Mohammed

    2015-01-01

    The present study investigated the impact of zinc oxide nanoparticles (ZnONPs) on the oxidative status and sperm characteristics in diabetic rat testicular tissue. Forty male albino rats were used in this study; 10 of them served as a control and 30 rats were injected with a single dose (100 mg/kg) of streptozotocin intraperitoneally. They were subdivided into diabetic, diabetic + ZnONPs (10 mg/kg B.W.), and diabetic and cotreated with ZnONPs + insulin groups. The sperm count and motility were assessed. The activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GRD), and Glutathion-S-Transferase (GST) were determined in the testicular tissue. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated in the testicular tissue. Sperm count and motility increased in ZnONPs treated diabetic rats. A significant increase in the activity and mRNA expression of SOD, CAT, GPx, GRD, and GST was shown in ZnONPs treated diabetic rats. MDA significantly decreased, while GSH increased in testicular tissue of ZnONPs treated diabetic rats. It was concluded that ZnONPs either alone or in combination with insulin have the ability to increase the sperm count and motility and protect the testicular tissue against the oxidative stress induced by diabetes in rats. PMID:26581756

  12. Dietary supplementation with astaxanthin may ameliorate sperm parameters and DNA integrity in streptozotocin-induced diabetic rats

    PubMed Central

    Bahmanzadeh, Maryam; Vahidinia, Aliasghar; Mehdinejadiani, Shayesteh; Shokri, Saeed

    2016-01-01

    Objective Diabetes mellitus (DM) is known to cause many systemic complications as well as male infertility. Astaxanthin (ASTX) is a powerful antioxidant that is involved in a variety of biologically active processes, including those with anti-diabetes effects. The present study investigates the effect of ASTX on the spermatozoa function in streptozotocin (STZ)-induced diabetic rats. Methods We divided 30 adult rats into three groups (10 rats per group), with a control group that received corn oil mixed with chow. DM was induced by intra-peritoneal injection of STZ. Eight weeks after the STZ injection, half of the diabetic animals were used as diabetic controls, and the rest were treated with ASTX for 56 days. Then the parameters and chromatin integrity of the epididymal sperm were analyzed using chromomycin A3, toluidine blue (TB), and acridine orange (AO) staining. Results The count, viability, and motility of the epididymal sperm were decreased significantly in the STZ group in comparison with the control group (count and viability, p<0.001; motility, p<0.001;0.01). ASTX increased normal morphology and viable spermatozoa compared to the STZ group (morphology, p=0.001; viability, p<0.001;0.05). The percentage of abnormal chromatins in TB and AO staining was higher in the STZ group compared to the control group (p<0.001;0.001). The mean percentage of TB and AO positive spermatozoa in STZ rats was significantly lower in the STZ+ASTX group (TB, p=0.001; AO, p<0.001;0.05). Conclusion This study observed that in vivo ASTX treatment partially attenuates some detrimental effect of diabetes. Conversely, ASTX improved sperm viability, normal morphology, and DNA integrity. PMID:27358826

  13. Ameliorative Effect of Zinc Oxide Nanoparticles on Antioxidants and Sperm Characteristics in Streptozotocin-Induced Diabetic Rat Testes.

    PubMed

    Afifi, Mohamed; Almaghrabi, Omar A; Kadasa, Naif Mohammed

    2015-01-01

    The present study investigated the impact of zinc oxide nanoparticles (ZnONPs) on the oxidative status and sperm characteristics in diabetic rat testicular tissue. Forty male albino rats were used in this study; 10 of them served as a control and 30 rats were injected with a single dose (100 mg/kg) of streptozotocin intraperitoneally. They were subdivided into diabetic, diabetic + ZnONPs (10 mg/kg B.W.), and diabetic and cotreated with ZnONPs + insulin groups. The sperm count and motility were assessed. The activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GRD), and Glutathion-S-Transferase (GST) were determined in the testicular tissue. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated in the testicular tissue. Sperm count and motility increased in ZnONPs treated diabetic rats. A significant increase in the activity and mRNA expression of SOD, CAT, GPx, GRD, and GST was shown in ZnONPs treated diabetic rats. MDA significantly decreased, while GSH increased in testicular tissue of ZnONPs treated diabetic rats. It was concluded that ZnONPs either alone or in combination with insulin have the ability to increase the sperm count and motility and protect the testicular tissue against the oxidative stress induced by diabetes in rats. PMID:26581756

  14. Resveratrol Ameliorates the Components of Hepatic Inflammation and Apoptosis in a Rat Model of Streptozotocin-Induced Diabetes.

    PubMed

    Pektaş, Mehmet Bilgehan; Sadi, Gökhan; Koca, Halit Bugra; Yuksel, Yasemin; Vurmaz, Ayhan; Koca, Tulay; Tosun, Murat

    2016-02-01

    Preclinical Research Trans-resveratrol has a wide range of biological effects that reflect its antioxidant, anti-inflammatory, anticarcinogenic and cardioprotective properties. This study was conducted to elucidate the potential role of resveratrol on hepatic inflammation and the apoptotic pathway components Bcl-2, Bax and p53 in a streptozotocin (STZ)-induced rat model of diabetes mellitus. Inflammatory and apoptotic biomarkers indicated a reduction in hepatic erythropoietin (1.26-fold) and increased asymmetric dimethylarginine (3.9-fold), visfatin (1.6-fold), inflammatory interleukins and TNF-α contents (approximately twofold each) in the diabetic animals. Induction of inducible nitric oxide synthase gene (2.04-fold) and protein expression (1.24-fold) was also observed. Immunohistochemical studies showed enhancement of the apoptotic biomarkers Bax and p53 in diabetic animals. STZ-induced diabetic male Wistar rats were treated with resveratrol (20 mg/kg/day i.p.). Resveratrol succeeded to recover most of these inflammatory and apoptotic elements. Therefore, inflammatory and apoptotic pathways were proved to be affected by STZ-induced diabetes in several aspects and resveratrol might contribute hepatoprotective effects as evidenced from this study. PMID:26748675

  15. β-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia

    PubMed Central

    Egerod, Kristoffer L.; Jin, Chunyu; Petersen, Pia Steen; Wierup, Nils; Sundler, Frank; Holst, Birgitte; Schwartz, Thue W.

    2011-01-01

    Mice deficient in the zinc-sensor GPR39, which has been demonstrated to protect cells against endoplasmatic stress and cell death in vitro, display moderate glucose intolerance and impaired glucose-induced insulin secretion. Here, we use the Tet-On system under the control of the proinsulin promoter to selectively overexpress GPR39 in the β cells in a double transgenic mouse strain and challenge them with multiple low doses of streptozotocin, which in the wild-type littermates leads to a gradual increase in nonfasting glucose levels and glucose intolerance observed during both food intake and OGTT. Although the overexpression of the constitutively active GPR39 receptor in animals not treated with streptozotocin appeared by itself to impair the glucose tolerance slightly and to decrease the β-cell mass, it nevertheless totally protected against the gradual hyperglycemia in the steptozotocin-treated animals. It is concluded that GPR39 functions in a β-cell protective manner and it is suggested that it is involved in some of the beneficial, β-cell protective effects observed for Zn++ and that GPR39 may be a target for antidiabetic drug intervention. PMID:22164158

  16. Protective effects of bestatin in the retina of streptozotocin-induced diabetic mice.

    PubMed

    Hossain, Ahamed; Heron, David; Davenport, Ian; Huckaba, Thomas; Graves, Richard; Mandal, Tarun; Muniruzzaman, Syed; Wang, Shusheng; Bhattacharjee, Partha S

    2016-08-01

    CD13/APN (aminopeptidase N) was first identified as a selective angiogenic marker expressed in tumor vasculature and is considered a target for anti-cancer therapy. CD13 was also reported to express in non-diabetic, hypoxia-induced retinal neovascularization. Whether diabetes induces upregulation of CD13 expression in the retina is unknown. We hypothesize that at an early stage of non-proliferative diabetic retinopathy (NPDR) characterized by disruption of blood-retinal barrier (BRB) permeability is related to upregulated expression of CD13 because of its known role in extracellular matrix (ECM) degradation. The purpose of this study is to evaluate the role of CD13/APN and the therapeutic efficacy of a CD13/APN inhibitor in a mouse model of streptozotocin-induced NPDR. Hyperglycemic C57Bl/6 mice 26 weeks after streptozotocin (STZ) injection were intravitreally injected with a sustained release formulation of CD13/APN inhibitor bestatin. At 15th day of post-bestatin treatment, mouse retinas were evaluated for vascular permeability by Evans blue dye extravasation assay, fluorescent angiography of retinal vascular permeability and leukostasis. Retinal protein extracts were analyzed by Western blot to determine the effects of bestatin treatment on the expression of CD13/APN related inflammatory mediators of ECM degradation and angiogenesis. Intravitreal bestatin treatment significantly inhibited retinal vascular permeability and leukostasis. This treatment also significantly inhibited retinal expression of CD13, ECM degrading proteases (heparanase and MMP9 and angiogenic molecules (HIF-1α and VEGF). Intravitreal CD13 inhibition may relate to furthering our knowledge on the protective effect of bestatin against diabetic retinal vasculature abnormalities through inhibition of retinal permeability, leukostasis, inflammatory molecules of ECM degradation and angiogenesis. PMID:27344955

  17. Streptozotocin-induced insulin deficiency leads to development of behavioral deficits in rats.

    PubMed

    Haider, Saida; Ahmed, Saara; Tabassum, Saiqa; Memon, Zahida; Ikram, Mehwish; Haleem, Darakhshan J

    2013-03-01

    Diabetes mellitus is one of the most common serious metabolic disorders in humans that develops due to diminished production of insulin (type I) or resistance to its effect (type II and gestational). The present study was designed to determine the neuropsychological deficits produced following streptozotocin-induced diabetes in rats. Rats were made diabetic by the intra-peritoneal administration of 60 mg/kg streptozotocin (STZ) which induces type-1 diabetes by the destruction "β-cells" of pancreas. Body weight, food and water intake was monitored daily. Open field test (OFT) model, forced swim test (FST) and Morris water maze (MWM) model were performed for the evaluation of ambulation, depression-like symptoms and memory effects, respectively. After 10 days of diabetes induction the exploratory activity of rats was monitored by OFT while depression-like symptoms and memory effects in rats were analyzed by FST and MWM. Results showed that there was no significant effect of STZ-induced diabetes on body weight but food and water intake of STZ-induced diabetic rats was significantly increased. Exploratory activity was significantly decreased and short-term and long-term memory was significantly impaired while the depression-like symptoms was significantly increased in STZ diabetic rats. Thus, it may be suggested that STZ-induced diabetes alters the brain functions and may play an important role in the pathophysiology of certain behavioral deficits like depression, impaired learning and memory functions related to diabetes. This finding may be of relevance in the pathophysiology and in the clinical picture, which could be related to an altered brain serotonin metabolism and neurotransmission and may possibly be related to neuropsychiatric disorders in diabetic patients. PMID:22878975

  18. Streptozotocin-induced diabetes prolongs twitch duration without affecting the energetics of isolated ventricular trabeculae

    PubMed Central

    2014-01-01

    Background Diabetes induces numerous electrical, ionic and biochemical defects in the heart. A general feature of diabetic myocardium is its low rate of activity, commonly characterised by prolonged twitch duration. This diabetes-induced mechanical change, however, seems to have no effect on contractile performance (i.e., force production) at the tissue level. Hence, we hypothesise that diabetes has no effect on either myocardial work output or heat production and, consequently, the dependence of myocardial efficiency on afterload of diabetic tissue is the same as that of healthy tissue. Methods We used isolated left ventricular trabeculae (streptozotocin-induced diabetes versus control) as our experimental tissue preparations. We measured a number of indices of mechanical (stress production, twitch duration, extent of shortening, shortening velocity, shortening power, stiffness, and work output) and energetic (heat production, change of enthalpy, and efficiency) performance. We calculated efficiency as the ratio of work output to change of enthalpy (the sum of work and heat). Results Consistent with literature results, we showed that peak twitch stress of diabetic tissue was normal despite suffering prolonged duration. We report, for the first time, the effect of diabetes on mechanoenergetic performance. We found that the indices of performance listed above were unaffected by diabetes. Hence, since neither work output nor change of enthalpy was affected, the efficiency-afterload relation of diabetic tissue was unaffected, as hypothesised. Conclusions Diabetes prolongs twitch duration without having an effect on work output or heat production, and hence efficiency, of isolated ventricular trabeculae. Collectively, our results, arising from isolated trabeculae, reconcile the discrepancy between the mechanical performance of the whole heart and its tissues. PMID:24731754

  19. Streptozotocin induces endoplasmic reticulum stress and apoptosis via disruption of calcium homeostasis in mouse pancreas.

    PubMed

    Ahn, Changhwan; An, Beum-Soo; Jeung, Eui-Bae

    2015-09-01

    Calcium homeostasis refers to the regulation of calcium ion concentration in the body. This concentration is tightly controlled by a stabilizing system consisting of calcium channels and calcium buffering proteins. Calcium homeostasis is crucial for cell survival. Various forms of cell death (e.g., necrosis and apoptosis) also share calcium signaling pathways and molecular effectors. Calcium acts not only as a ubiquitous second messenger involved in apoptosis along with various cell death inducers but also a regulator for the synthesis of enzymes/hormones such as insulin. We hypothesized that streptozotocin disrupts calcium homeostasis and the altered intracellular calcium levels may induce cell death. After streptozotocin administration, blood glucose level was increased while insulin levels decreased. The expression of insulin response markers also decreased relative to the vehicle group. L-type voltage-gated calcium channel expression and sarcoplasmic reticulum Ca(2+) ATPase were increased by streptozotocin. Calcium buffering protein calbindin-D9k and calmodulin family members were also increased. The expression of genes involved in transporting calcium ions to the endoplasmic reticulum (ER) was decrease while the expression of those affecting the removal of calcium from the ER was increased. Depletion of calcium from the ER leads to ER-stress and can induce apoptosis. In the streptozotocin-treatment group, apoptosis markers were increased. Taken together, these results imply that the disruption of calcium homeostasis by streptozotocin induces ER-stress and leads to the apoptosis of pancreatic cells. Additionally, findings from this study suggest that imbalances in calcium homeostasis could promote pancreatic beta cell death and result in type I diabetes. PMID:26003140

  20. Pentoxifylline improves cutaneous wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Babaei, Saeed; Bayat, Mohammad; Nouruzian, Mohsen; Bayat, Mehrnoush

    2013-01-30

    Worldwide, 15% of the 200 million diabetics suffer from diabetic wounds. In 1997, the cost for amputation of toes and limbs that resulted from infected diabetic foot ulcers ranged from $25,000-$40,000 per incident. Increasing numbers of research have shown the positive influence of pentoxifylline (PTX) on healing skin wounds. In this study, we evaluate the effect of systemic PTX (25mg/kg bid) on wound healing in 80 diabetic rats (DB) by secondary intention. Wounds (20 mm × 5 mm) were identically inflicted on the skin area of the backs of all rats. On day 15 following surgery, a band of skin (4 mm × 60 mm) that contained wound was extracted for biomechanical testing. For histologic analysis, both experimental (DB+PTX) and control, receiving distilled water (DB+DW) groups were further subdivided into day 3 and 7 groups. Rats were sacrificed three and seven days after surgery, and a sample from each wound was taken. All specimens were sectioned stereologically and stained with H&E. Cell counts were performed by stereological methods. Semi-quantitative evaluation of matrix metalloproteinases (MMPs) and inhibitor-1 was performed by Reversed Transcription-PCR and UVI TEC software. For statistical analysis we used student's t-test. Collectively, the results of this study demonstrate that there was significant improvement with PTX in all biomechanical parameters. Histologically, PTX reduced inflammation by day seven. Quantitatively, by day five, PTX reduced expression of MMPs and increased TIMP-1 expression. These findings revealed that PTX significantly improved wound healing indices in streptozotocin-induced DB. PMID:23220163

  1. Reduced proximal tubule angiotensin II receptor expression in streptozotocin-induced diabetes mellitus.

    PubMed

    Cheng, H F; Burns, K D; Harris, R C

    1994-12-01

    Diabetes mellitus is characterized by alterations in the intrarenal renin-angiotensin system, including decreases in glomerular angiotensin II (Ang II) receptor density. Since Ang II regulates proximal tubule transport function, the present studies examined whether diabetes altered expression of proximal tubule receptors. In basolateral membranes from 14 day streptozotocin-induced diabetic rats, specific binding of 125I Ang II was decreased to 53 +/- 8% of control (3.2 +/- 0.5 vs. 1.5 +/- 0.2 fmol/mg protein; N = 7; P < 0.02). Similarly, in proximal tubule brush border membranes from diabetic animals, specific binding was decreased to 63 +/- 11% of control (1.1 +/- 0.2 vs 0.6 +/- 0.1 fmol/mg protein; N = 9; P < 0.05). Concomitant insulin treatment reversed the decrease in specific binding of 125I Ang II to basolateral membranes (109 +/- 26% of control; N = 3) and to brush border membranes (85 +/- 17% of control; N = 6). In order to determine if changes in expression of type-1 Ang II receptors (AT1R) accompanied the changes in binding, quantitative polymerase chain reaction of AT1R mRNA was performed and expressed as the ratio of the amplified AT1R to that of an Msc1/Msc1 internal deletion mutant and normalized to that of beta-actin. In total RNA from proximal tubule suspensions of diabetic animals, AT1R mRNA expression decreased by 38% (21 +/- 3 vs. 13 +/- 2 cpm AT1R/cpm deletion mutant/cpm beta actin/10(6); N = 4; P < 0.0025). Insulin treatment reverted AT1R mRNA expression to control levels (22 +/- 3 cpm AT1R/cpm deletion mutant/cpm beta actin/10(6); P < 0.001 compared to the untreated group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7700017

  2. Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats.

    PubMed

    Amaral, Liliany S de Brito; Silva, Fernanda A; Correia, Vicente B; Andrade, Clara Ef; Dutra, Bárbara A; Oliveira, Márcio V; Magalhães, Amélia Cm de; Volpini, Rildo A; Seguro, Antonio C; Coimbra, Terezila M; Soares, Telma de J

    2016-02-01

    This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups: sedentary control (C + Se); trained control (C + Ex); sedentary diabetic (D + Se); trained diabetic (D + Ex) and previously trained diabetic (D + PEx). The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D + PEx, D + Ex and C + Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17β-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-β1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17β-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D + PEx group compared to D + Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-β1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney. PMID:26490345

  3. Sesame effects on testicular damage in streptozotocin-induced diabetes rats

    PubMed Central

    Khaneshi, Fereshteh; Nasrolahi, Ozra; Azizi, Shahriar; Nejati, Vahid

    2013-01-01

    Objective(s): Reproductive dysfunction is a consequence of diabetes. Diabetes is associated with changes in testicular tissue. Sesame oil contains large amounts of polyunsaturated fatty acids and lignin with antioxidant activity, vitamin E, and monounsaturated fatty acid (MUFA). The present study investigated the effects of sesame on testis histology and male reproductive parameters in streptozotocin-induced diabetic rats. Materials and Methods: Thirty mature male Wistar rats were randomly divided into three groups, i.e., control (C), diabetic-control (DC), and sesame-treated diabetic rats (SD). Diabetes was induced by a single dose of streptozotocin (65 mg/kg; i.p). The animals were treated by a single intraperitoneal sesame extract injection (100 mg/kg b.w.) once daily for 6 weeks. Results: The biochemical analysis revealed that the diabetes resulted in significant (p<0.05) reduction in spermiogenesis, testosterone, LH, and FSH levels. Light microscopic analysis showed remarkable (p<0.05) reduction in STD (seminiferous tubules diameter), SPI (spermatogenesis index) thickness of the epithelium, and significant increase in thickness of the interstitial tissue in the diabetic group compared with the control group. Simultaneous administration of the sesame could fairly up-regulate testosterone, LH, and FSH of the animals in this group. However, some differences were manifested with improved histological features as thickness of the epithelium, seminiferous tubules diameter, and spermatogenesis index. Conclusion: These data demonstrated that sesame significantly improved diabetes complication in rat testis. This study suggested that sesame might have a protective effect against oxidative stress-induced impaired testicular functions in diabetic rats. PMID:25050292

  4. Propranolol improves cutaneous wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Romana-Souza, Bruna; Nascimento, Adriana P; Monte-Alto-Costa, Andréa

    2009-06-01

    Sympathetic nerve failure has been proposed as a contributing factor in impaired cutaneous wound healing in diabetes mellitus. Nevertheless, no studies have shown whether beta-adrenoceptor blockade through beta-blocker (e.g., propranolol) administration may alter healing of diabetic cutaneous lesions. This study evaluated macro- and microscopically the effects of propranolol administration on cutaneous wound healing in streptozotocin-induced diabetic rats. Acute diabetes was induced by a single intraperitoneal injection of streptozotocin 14 days before wounding. Animals were treated with propranolol (50 mg/kg) dissolved in drinking water; controls received water only. Administration of beta-receptor antagonist began 1 day before wounding and was continued daily until euthanasia. A full-thickness excisional lesion (1 cm(2)) was created. The wound area was measured weekly and the animals were killed 14 days after wounding. Lesions and adjacent skin were formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin-eosin, Sirius red, and toluidine blue, and immunostained for CD-68, alpha-smooth muscle actin and proliferating cell nuclear antigen. The wound area was significantly smaller in the propranolol-treated group than in the control group 7 and 14 days after wounding. Inflammatory cell numbers and metalloproteinase-9 levels were reduced in the propranolol-treated group compared to the control group 14 days after wounding. Cell proliferation, mast cell number, collagen deposition, blood vessel density, and nitric oxide levels were increased in the propranolol-treated group compared to the control group 14 days after wounding. Propranolol administration improves cutaneous wound healing of hyperglycemic diabetic rats by reducing the local inflammatory response and improving subsequent phases of the repair process. PMID:19344703

  5. Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats

    NASA Technical Reports Server (NTRS)

    Pamnani, M. B.; Chen, S.; Haddy, F. J.; Yuan, C.; Mo, Z.

    1998-01-01

    We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

  6. Effect of Livingstone Potato (Plectranthus esculenthus N.E.Br) on Diabetes and Its Complications in Streptozotocin Induced Diabetes in Rats

    PubMed Central

    Eleazu, Kate Chinedum; Ironkwe, Adanma; Iroaganachi, Mercy Amarachi

    2014-01-01

    Background The effect of livingstone potato (Plectranthus esculenthus N.E.Br) on diabetes and its complications in Streptozotocin induced diabetic rats was investigated. The duration of the experiment was 4 weeks. Methods The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The liver and kidney function parameters in the serum of the rats were determined using Biosystem Kits. Results The diabetic rats given livingstonepotato incorporated feeds, had 129.7% decrease in their hyperglycemia with corresponding amelioration of their elevated urinary protein, sugars, specific gravity, renal growth, liver growth as well as 15.64% decrease in body weights compared with the nondiabetic rats that had 5.54% decrease in blood glucose and 20.39% increase in body weight unlike the diabetic control rats that had 18.34% decrease in blood glucose and 52.68% decrease in body weight. There were significant differences (P<0.05) in the relative liver, pancreas, and kidney weights of the diabetic rats given livingstone potato feeds compared with the diabetic control while there were no significant differences (P>0.05) in the relative heart weights of all the rats in the three different groups. In terms of liver and kidney function parameters, values obtained for the diabetic rats given livingstone potato incorporated feeds were not significantly different from that of the nondiabetic rats except for total bilurubin, aspartate transaminase, and creatinine (P>0.05) while they were significantly different from the values obtained for the diabetic control rats (P<0.05). In addition, the serum amylase of the diabetic control rats were significantly higher (P<0.05) than that of the nondiabetic and diabetic rats treated with livingstone potato incorporated feeds. Conclusion Results show the antidiabetic actions of livingstone potato and

  7. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    PubMed Central

    Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gülay; Erdem, Özlem; Alkan, Metin; Arslan, Mustafa; Özer, Abdullah; Şivgin, Volkan; Çomu, Faruk Metin

    2015-01-01

    Objective Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion Taken together, our data indicate that

  8. Oral hypoglycaemic activity of Ipomoea aquatica in streptozotocin-induced, diabetic wistar rats and Type II diabetics.

    PubMed

    Malalavidhane, T S; Wickramasinghe, S M D N; Perera, M S A; Jansz, E R

    2003-11-01

    Ipomoea aquatica Forsk is a common green leafy vegetable consumed in many parts of the world. The present study was designed to investigate the oral hypoglycaemic activity of Ipomea aquatica in streptozotocin induced diabetic Wistar rats, and Type II diabetic patients. Experimental diabetes was induced with streptozotocin in Wistar rats. The rats were then divided into test and control groups. In addition to the standard feed given to both groups the test was fed with the shredded leaves of Ipomoea aquatica (3.4 g/kg) for one week. Type II diabetic patients were subjected to a glucose challenge before and after a single dose of blended I. aquatica. Patients acted as their own controls. The results revealed that consumption of the shredded, fresh, edible portion of I. aquatica for one week, effectively reduced the fasting blood sugar level of streptozotocin-induced diabetic rats (p = 0.01). When subjected to a glucose challenge, the Type II diabetic subjects showed a significant reduction (p = 0.001) in the serum glucose concentration 2 h after the glucose load. However, it was not significantly reduced at 1 h (p < 0.09) post glucose load. There was a 29.4% decrease in the serum glucose concentration of the diabetic patients when treated with the plant extract. PMID:14595595

  9. Effect of Aqueous Extract of Tephrosia purpurea on Cardiovascular Complications and Cataract Associated with Streptozotocin-induced Diabetes in Rats

    PubMed Central

    Bhadada, Shraddha V.; Goyal, R. K.

    2015-01-01

    Tephrosia purpurea has been reported to possess antidiabetic activity, however, its effects on cardiovascular complications and cataract associated with diabetes have not been studied. The objective of the present study was to investigate the effects of aqueous extract of Tephrosia purpurea on cardiovascular complications and cataract associated with streptozotocin-induced diabetes in rats. Sprague Dawley rats of either sex were made diabetic with streptozotocin (45 mg/kg, i.v.). Treatment of aqueous extract of Tephrosia purpurea was given in the dose of 300 and 500 mg/kg/day, p.o for 8 weeks. Various hemodynamic (blood pressure, heart rate, +dp/dt, -dp/dt) and biochemical (serum glucose, cholesterol, triglycerides, creatinine, urea, lactate dehydrogenase and creatinine kinase) parameters were recorded after 8 weeks of the treatment. To evaluate cataract, various biochemical estimations were done in eye lens. Streptozotocin produced hyperglycemia; hypoinsulinemia; hyperlipidemia; increased blood pressure; increased creatinine, cardiac enzymes, reduction in heart rate and cardiac hypertrophy in rats and all these changes were prevented by the treatment with aqueous extract of Tephrosia purpurea in both the doses. Streptozotocin also produced decrease in soluble protein and reduced glutathione in lens of rats that was prevented by aqueous extract of Tephrosia purpurea. Our data suggest that aqueous extract of Tephrosia purpurea prevents not only the streptozotocin-induced metabolic abnormalities but also cardiovascular complications as well as reduce the risk of development of cataract. PMID:26798165

  10. Effect of Aqueous Extract of Tephrosia purpurea on Cardiovascular Complications and Cataract Associated with Streptozotocin-induced Diabetes in Rats.

    PubMed

    Bhadada, Shraddha V; Goyal, R K

    2015-01-01

    Tephrosia purpurea has been reported to possess antidiabetic activity, however, its effects on cardiovascular complications and cataract associated with diabetes have not been studied. The objective of the present study was to investigate the effects of aqueous extract of Tephrosia purpurea on cardiovascular complications and cataract associated with streptozotocin-induced diabetes in rats. Sprague Dawley rats of either sex were made diabetic with streptozotocin (45 mg/kg, i.v.). Treatment of aqueous extract of Tephrosia purpurea was given in the dose of 300 and 500 mg/kg/day, p.o for 8 weeks. Various hemodynamic (blood pressure, heart rate, +dp/dt, -dp/dt) and biochemical (serum glucose, cholesterol, triglycerides, creatinine, urea, lactate dehydrogenase and creatinine kinase) parameters were recorded after 8 weeks of the treatment. To evaluate cataract, various biochemical estimations were done in eye lens. Streptozotocin produced hyperglycemia; hypoinsulinemia; hyperlipidemia; increased blood pressure; increased creatinine, cardiac enzymes, reduction in heart rate and cardiac hypertrophy in rats and all these changes were prevented by the treatment with aqueous extract of Tephrosia purpurea in both the doses. Streptozotocin also produced decrease in soluble protein and reduced glutathione in lens of rats that was prevented by aqueous extract of Tephrosia purpurea. Our data suggest that aqueous extract of Tephrosia purpurea prevents not only the streptozotocin-induced metabolic abnormalities but also cardiovascular complications as well as reduce the risk of development of cataract. PMID:26798165

  11. Antihyperglycemic, antihyperlipidemic and antiglycation effects of Byrsonima crassifolia fruit and seed in normal and streptozotocin-induced diabetic rats.

    PubMed

    Perez-Gutierrez, Rosa Martha; Muñiz-Ramirez, Alethia; Gomez, Yolanda Gomez; Ramírez, Esther Bautista

    2010-12-01

    The hypoglycemic effects of hexane, chloroform and methanol extracts from fruits and seeds of Byrsonima crassifolia were evaluated by oral administration to normoglycemic and streptozotocin-induced severe diabetic rats (SD). The anti-diabetic effect was examined by blood glucose, triglycerides, lipid peroxidation, total cholesterol levels in the serum, glycogen content of liver and skeletal muscles, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and oxidized glutathione (GSSG) levels. The most active extracts were obtained with hexane. Hexane and chloroform extracts from fruits and seeds of Byrsonima crassifolia increased the levels of SOD, GSH, GSSG and CAT, hepatic glycogen content, glucose-6-phosphatase (G6Pase) and the plasma insulin levels. They also decreased glucokinase (GK) and TBAR (thiobarbituric acid assay). In conclusion, Byrsonima crassifolia possesses significant antihyperglycemic properties after 4 h of a single oral dose. It can also improve hyperlipidemia and hyperinsulinemia in streptozotocin-induced diabetic rats. Both extracts exhibited significant inhibitory activity against AGEs (advanced glycation end products) formation with IC(50) values ranging from 94.3 to 138.7 μg/ml. Therefore, B. crassifolia can be considered as a potential safe anti-diabetic agent. PMID:20734144

  12. Preventive effects of garlic (Allium sativum) on oxidative stress and histopathology of cardiac tissue in streptozotocin-induced diabetic rats.

    PubMed

    Naderi, R; Mohaddes, G; Mohammadi, M; Alihemmati, A; Badalzadeh, R; Ghaznavi, R; Ghyasi, R; Mohammadi, Sh

    2015-12-01

    Since some complications of diabetes mellitus may be caused or exacerbated by an oxidative stress, the protective effects of garlic (Allium sativum) were investigated in the blood and heart of streptozotocin-induced diabetic rats. Twenty-eight male Wistar rats were randomly divided into four groups: control, garlic, diabetic, and diabetic+garlic. Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (50 mg/kg) in male rats. Rats were fed with raw fresh garlic homogenate (250 mg/kg) six days a week by gavage for a period of 6 weeks. At the end of the 6th week blood samples and heart tissues were collected and used for determination of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and histological evaluation. Induction of diabetes increased MDA levels in blood and homogenates of heart. In diabetic rats treated with garlic, MDA levels decreased in blood and heart homogenates. Treatment of diabetic rats with garlic increased SOD, GPX and CAT in blood and heart homogenates. Histopathological finding of the myocardial tissue confirmed a protective role for garlic in diabetic rats. Thus, the present study reveals that garlic may effectively modulate antioxidants status in the blood and heart of streptozotocin induced-diabetic rats. PMID:26690030

  13. Effects of intravitreal injection of netrin-1 in retinal neovascularization of streptozotocin-induced diabetic rats

    PubMed Central

    Yu, Yao; Zou, Jing; Han, Yun; Quyang, Luowa; He, Hui; Hu, Peihong; Shao, Yi; Tu, Ping

    2015-01-01

    Background In a previous study, we confirmed that netrin-1 acts as an antiangiogenic factor by inhibiting alkali burn-induced corneal neovascularization in rats. Here, we continue working on the role of netrin-1 in retinal neovascularization. Methods Using an in vitro angiogenesis assay, we detected the effects of netrin-1 on human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion at concentrations of 0.1 μg/mL or 5 μg/mL. We intravitreally injected 0.1 μg/mL or 5 μg/mL netrin-1 into streptozotocin-induced rats to assess retinal neovascularization using retinal electrophysiology and electroretinography, enzyme-linked immunosorbent assay, fundus fluoresce in angiography, measurement of inner blood retinal barrier, retinal hematoxylin-eosin staining, and retinal flat-mount fluorescence assays. Results Human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion were upregulated by netrin-1 at a concentration of 0.1 μg/mL (P<0.05), while 5 μg/mL netrin-1 had an opposite effect (P<0.05) in our in vitro angiogenesis assay. Retinal electrophysiology testing revealed that intravitreal injection of netrin-1 affected the amplitude of a- and b-waves (a-wave: 0.1 μg/mL netrin-1 =17.67±3.39 μm, 5 μg/mL netrin-1 =28.50±1.31 μm, phosphate-buffered saline [PBS]-treated =17.67±3.39 μm; b-wave: 0.1 μg/mL netrin-1 =44.67±4.80 μm, 5 μg/mL netrin-1 =97.17±9.63 μm, PBS-treated =44.67±4.80 μm) and the expression of VEGF-A (no-treatment rats, 9.29±0.80 pg/mL; PBS-treated rats, 19.64±3.77 pg/mL; 0.1 μg/mL netrin-1 treated rats, 21.37±3.64 pg/mL; 5 μg/mL netrin-1 treated rats, 9.85±0.54 pg/mL, at 6 weeks after induction). By comparing fluoresce in angiography, level of inner blood retinal barrier breakdown (% of control), retinal hematoxylin-eosin staining, and collagen-IV fluorescence assays in the retinas of PBS-treated rats, netrin-1 was found to suppress and

  14. The Ethanol Extract of Zingiber zerumbet Attenuates Streptozotocin-Induced Diabetic Nephropathy in Rats

    PubMed Central

    Tzeng, Thing-Fong; Liou, Shorong-Shii; Chang, Chia Ju; Liu, I-Min

    2013-01-01

    The ethanol extract from the rhizome of Zingiber zerumbet (L.) Smith (EEZZR) has been indicated to possess an insulin-like property by ameliorating hyperglycemia in diabetes. We aimed to investigate whether EEZZR exerts an ameliorative effect on renal damage in diabetes induced by streptozotocin (STZ). Diabetic rats were treated orally with EEZZR (200 and 300 mg kg−1 per day) or metformin (100 mg kg−1 per day) for 8 weeks. The plasma glucose, creatinine, and blood urea nitrogen as well as urine protein levels and the ratio of kidney weight to body weight were significantly elevated in diabetic rats. EEZZR displayed similar characteristics to those of metformin in reducing hyperglycemia and renal dysfunction in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following the treatment with EEZZR. In addition, the protein expressions of renal nephrin and podocin in diabetic rats were significantly increased following the treatment with EEZZR. The AMP-activated protein kinase (AMPK) protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. EEZZR treatment significantly rescued the AMPK phosphorylation compared to nontreated diabetic group. This study suggested that the renoprotective effects of EEZZR may be similar, with the action of metformin, to the prevention of AMPK dephosphorylation and upregulate the expressions of renal nephrin and podocin. PMID:23476687

  15. Anti-diabetic effects of Monascus purpureus NTU 568 fermented products on streptozotocin-induced diabetic rats.

    PubMed

    Shi, Yeu-Ching; Pan, Tzu-Ming

    2010-07-14

    Red-mold-fermented products have the unique ability to economically produce many secondary metabolites and are known to improve blood circulation. Diabetes mellitus is a chronic disease that is characterized by hyperglycemia caused by insufficient insulin action. In the current study, we examine the effect of Monascus purpureus NTU 568 fermented products on fasting blood glucose and oral glucose tolerance testing (OGTT) in streptozotocin-induced diabetic rats. After 8 weeks of being fed with red-mold-fermented products at a dose of 200 mg/kg, the experimental results indicate that oral administration of red-mold-fermented products can delay the development of the plasma glucose level in rats. A significant reduction was found in urine sugar and urine protein levels. The study scientifically validates the widely claimed use of red-mold-fermented products as an ethnomedicine to treat diabetes mellitus. PMID:20557124

  16. Enhanced synthesis and secretion of apolipoprotein E from sciatic nerves of streptozotocin-induced diabetic rats after injury

    SciTech Connect

    Ishibashi, S.; Yamada, N.; Oka, Y.; Shimano, H.; Mori, N.; Yoon, T.H.; Shimada, M.; Kanazawa, Y.; Akanuma, Y.; Murase, T.

    1988-08-30

    To elucidate the pathogenesis of diabetic neuropathy, synthesis and secretion of apolipoprotein E (apo E) from sciatic nerves after injury was studied in normal and streptozotocin-induced diabetic rats. Seven, 14, 28, 45 and 59 days after making crush injury on sciatic nerves with concomitant administration of streptozotocin (50 mg/kg body weight), the nerves were taken out and incubated with (/sup 35/S)methionine. The (/sup 35/S)labeled apo E was precipitated with specific antiserum. The amounts of apo E secreted into medium by nerves of diabetic rats were 7 times greater than those of non-diabetic rats 7 days after injury. This enhanced secretion of apo E was relatively selective for this protein, since the ratio of the immunoprecipitable apo E to the TCA preciptitable protein in the medium increased in diabetic rats. Intriguing possibility deduced from these results is that the secretion of apo E is involved in the development of diabetic neuropathy.

  17. In Vivo Evaluation of Anti Diabetic, Hypolipidemic, Antioxidative Activities of Saudi Date Seed Extract on Streptozotocin Induced Diabetic Rats

    PubMed Central

    Mohieldein, Abdelmarouf

    2016-01-01

    Introduction Phoenix dactylifera (date palm) is major fruit of gulf region. In folk medicine; dates have been traditionally use. The date seed is used as hypoglycaemic, expectorant, tonic, aphrodisiac, antidiarrheic and mouth hygiene. Aim This study intended to evaluate the anti-diabetic, hypolipidaemic and antioxidative activities of date seed extract in diabetes-induced rats. Materials and Methods Total of seven groups of rats, consisting of control rats and streptozotocin induced diabetic rats treated with aqueous seed extract in concentration of 100g/L in dosage of 10ml/day/rat. To evaluate the anti-diabetic property, glucose and weight was analysed weekly and at the end of eight week all rats were sacrificed. To evaluate the hypolipidaemic and antioxidative activities, serum cholesterol, triglyceride, malondialdehyde, superoxide dismutase, 8-hydroxy-2’-deoxyguanosine were estimated. Liver enzymes and kidney function tests were performed. Moreover to verify the glycaemic effect; glycated haemoglobin and serum insulin was performed. Results Aqueous seed extract in concentration of 100 gm/L in dosage of 10ml/day/rat brings a significant reduction of blood glucose levels in diabetic rats in comparison of control rats. There were significant differences in the investigated clinical chemistry and oxidative stress parameters between control and diabetic rats with both seed extract of Ajwa and Sukkari dates. Conclusion Present study verifies the antidiabetic property, of aqueous seed extracts of two different varieties of dates namely Ajwa and Sukkari of Kingdom of Saudi on streptozotocin induced Diabetic rats. Prolong treatments with the extract restores the function of liver and kidney and balance the oxidative stress condition in diabetic treated rats. PMID:27134893

  18. Effects of Icariside II on corpus cavernosum and major pelvic ganglion neuropathy in streptozotocin-induced diabetic rats.

    PubMed

    Bai, Guang-Yi; Zhou, Feng; Hui, Yu; Xu, Yong-De; Lei, Hong-En; Pu, Jin-Xian; Xin, Zhong-Cheng

    2014-01-01

    Diabetic erectile dysfunction is associated with penile dorsal nerve bundle neuropathy in the corpus cavernosum and the mechanism is not well understood. We investigated the neuropathy changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and the effects of Icariside II (ICA II) on improving neuropathy. Thirty-six 8-week-old Sprague-Dawley rats were randomly distributed into normal control group, diabetic group and ICA-II treated group. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 2 groups including a saline treated placebo group and an ICA II-treated group (5 mg/kg/day, by intragastric administration daily). Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (immunofluorescence and immunohistochemical staining) and transmission electron microscopy detecting. Diabetic animals exhibited a decreased density of dorsal nerve bundle in penis. The neurofilament of the dorsal nerve bundle was fragmented in the diabetic rats. There was a decreased expression of nNOS and NGF in the diabetic group. The ICA II group had higher density of dorsal nerve bundle, higher expression of NGF and nNOS in the penis. The pathological change of major pelvic nerve ganglion (including the microstructure by transmission electron microscope and the neurite outgrowth length of major pelvic nerve ganglion tissue cultured in vitro) was greatly attenuated in the ICA II-treated group (p < 0.01). ICA II treatment attenuates the diabetes-related impairment of corpus cavernosum and major pelvic ganglion neuropathy in rats with Streptozotocin-Induced Diabetes. PMID:25517034

  19. Antihyperglycemic and antihyperlipidemic effects of hydroalcoholic extract of Securigera securidaca seeds in streptozotocin-induced diabetic rats

    PubMed Central

    Rajaei, Ziba; Hadjzadeh, Mousa-Al-Reza; Moradi, Reyhaneh; Ghorbani, Ahmad; Saghebi, Ahmad

    2015-01-01

    Background: Hyperlipidemia is an associated complication of diabetes mellitus. Lowering of serum lipid levels seems to be associated with a decrease in the risk of vascular disease and related complications. The purpose of the current study was to evaluate the antihyperglycemic and antihyperlipidemic effects of the hydroalcoholic extract of Securigera securidaca seeds in streptozotocin-induced diabetic rats. Materials and Methods: Female Wistar rats were randomly divided into four groups as follows: Control, diabetic, and diabetic rats treated with the Securigera extract at doses of 100 and 200 mg/kg. The animals were rendered diabetic by a single intraperitoneal injection of 55 mg/kg streptozotocin. Diabetic rats received the Securigera extract daily in drinking water from the day on which diabetes was confirmed for 4 weeks. The levels of serum glucose and lipids were spectrophotometrically measured in all groups at weeks 0 (before diabetes induction), 2, and 4. Results: The results showed that there was a significant increase in serum glucose, triglycerides, total cholesterol, and low density lipoprotein (LDL)-cholesterol in streptozotocin-induced diabetic rats, accompanied by a decrease in high density lipoprotein (HDL)-cholesterol. Treatment of diabetic rats with S. securidaca seed extract at a dose of 200 mg/kg over a 4-week period significantly reduced the levels of serum glucose, total cholesterol, and LDL-cholesterol and increased the level of HDL-cholesterol, compared to diabetic untreated rats. Conclusions: Securigera extract at a dose of 200 mg/kg exhibited hypoglycemic and hypolipidemic activities in streptozotocin-diabetic rats during the 4-week treatment period. This provides a valid scientific basis for using it in the treatment of diabetes in Iranian folk medicine. PMID:25709998

  20. Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats

    PubMed Central

    FATANI, AMAL JAMIL; AL-REJAIE, SALIM SALIH; ABUOHASHISH, HATEM MUSTAFA; AL-ASSAF, ABDULLAH; PARMAR, MIHIR YOGESHKUMAR; OLA, MOHAMMAD SHAMSUL; AHMED, MOHAMMED MAHBOOBUDDIN

    2015-01-01

    The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF

  1. Effects of low-level light therapy on streptozotocin-induced diabetic kidney.

    PubMed

    Lim, Jinhwan; Sanders, Ruth A; Snyder, Ann C; Eells, Janis T; Henshel, Diane S; Watkins, John B

    2010-05-01

    Hyperglycemia causes oxidative damage in tissues prone to complications in diabetes. Low-level light therapy (LLLT) in the red to near infrared range (630-1000nm) has been shown to accelerate diabetic wound healing. To test the hypothesis that LLLT would attenuate oxidative renal damage in Type I diabetic rats, male Wistar rats were made diabetic with streptozotocin (50mg/kg, ip), and then exposed to 670nm light at a dose of 9J/cm(2) once per day for 14weeks. The activity and expression of catalase and the activity of Na K-ATPase increased in kidneys of light-treated diabetic rats, whereas the activity and expression of glutathione peroxidase and the expression of Na K-ATPase were unchanged. LLLT lowered the values of serum BUN, serum creatinine, and BUN/creatinine ratio. In addition, LLLT augmented the activity and expression of cytochrome c oxidase, a primary photoacceptor molecule in the mitochondrial respiratory chain, and reduced the formation of the DNA adduct 8-hydroxy-2'-deoxyguanosine in kidney. LLLT improved renal function and antioxidant defense capabilities in the kidney of Type I diabetic rats. Thus, 670nm LLLT may be broadly applicable to the amelioration of renal complications induced by diabetes that disrupt antioxidant defense mechanisms. PMID:20356759

  2. Aldosterone Antagonists in Monotherapy Are Protective against Streptozotocin-Induced Diabetic Nephropathy in Rats

    PubMed Central

    Banki, Nora F.; Ver, Agota; Wagner, Laszlo J.; Vannay, Adam; Degrell, Peter; Prokai, Agnes; Gellai, Renata; Lenart, Lilla; Szakal, Dorottya-Nagy; Kenesei, Eva; Rosta, Klara; Reusz, Gyorgy; Szabo, Attila J.; Tulassay, Tivadar; Baylis, Chris; Fekete, Andrea

    2012-01-01

    Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers. PMID:22761931

  3. Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats.

    PubMed

    Banki, Nora F; Ver, Agota; Wagner, Laszlo J; Vannay, Adam; Degrell, Peter; Prokai, Agnes; Gellai, Renata; Lenart, Lilla; Szakal, Dorottya-Nagy; Kenesei, Eva; Rosta, Klara; Reusz, Gyorgy; Szabo, Attila J; Tulassay, Tivadar; Baylis, Chris; Fekete, Andrea

    2012-01-01

    Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers. PMID:22761931

  4. Effect of spent turmeric on kidney glycoconjugates in streptozotocin-induced diabetic rats

    PubMed Central

    2014-01-01

    Background Curcumin known to have number of medicinal use and masked the fiber containing ukonan like active polysaccharide in turmeric and its pharmacological effect will be addressed on diabetic nephropathy particularly the glycoconjugates of extracellular components viz., glycoproteins and glycosaminoglycans - heparan sulfate (HS). Methods Male Wistar rats were maintained on AIN-76 diet containing 10% spent turmeric and were grouped into control and STZ induced diabetes SFC/TFC and SFD/TFD, respectively. Diabetic status was monitored using blood and urine, and at the end, harvested kidneys were used to study the amelioration of glycoprotiens (collagen) and HS by enzymatic digestion, spectrophotometric, hydroxyproline and agarose electrophoretic methods. Results In the present study spent turmeric (10%) fed diabetic rats showed improved glomerular filtration rate (50%), kidney enlargement (60%) and other glycoconjugate metabolism in kidney. Increased collagen content in diabetic group was observed by hydroxyproline estimation (24%) and periodic acid-Schiff’s (PAS) staining. Furthermore, elevated activities of enzymes involved in the synthesis and degradation of glycosaminoglycans (GAGs) were significantly lowered in spent turmeric fed diabetic group. Improvement in total GAGs (43%) and sulfate content (18%) followed by fractionation of GAGs using specific enzymes led to HS (28%) in the spent turmeric fed diabetic group, when compared to starch fed diabetic group and was further confirmed by electrophoresis of GAG. Conclusion These results clearly indicate beneficial role of spent turmeric in controlling glycoconjugates such as glycoproteins and heparan sulfate related kidney complications during diabetes. PMID:26413492

  5. Chloroquine improves left ventricle diastolic function in streptozotocin-induced diabetic mice.

    PubMed

    Yuan, Xun; Xiao, Yi-Chuan; Zhang, Gui-Ping; Hou, Ning; Wu, Xiao-Qian; Chen, Wen-Liang; Luo, Jian-Dong; Zhang, Gen-Shui

    2016-01-01

    Diabetes is a potent risk factor for heart failure with preserved ejection fraction (HFpEF). Autophagy can be activated under pathological conditions, including diabetic cardiomyopathy. The therapeutic effects of chloroquine (CQ), an autophagy inhibitor, on left ventricle function in streptozotocin (STZ)-induced diabetic mice were investigated. The cardiac function, light chain 3 (LC3)-II/LC3-I ratio, p62, beclin 1, reactive oxygen species, apoptosis, and fibrosis were measured 14 days after CQ (ip 60 mg/kg/d) administration. In STZ-induced mice, cardiac diastolic function was decreased significantly with normal ejection fraction. CQ significantly ameliorated cardiac diastolic function in diabetic mice with HFpEF. In addition, CQ decreased the autophagolysosomes, cardiomyocyte apoptosis, and cardiac fibrosis but increased LC3-II and p62 expressions. These results suggested that CQ improved the cardiac diastolic function by inhibiting autophagy in STZ-induced HFpEF mice. Autophagic inhibitor CQ might be a potential therapeutic agent for HFpEF. PMID:27621594

  6. Neuromodulatory Effects of Hesperidin in Mitigating Oxidative Stress in Streptozotocin Induced Diabetes

    PubMed Central

    Varshney, Laxmi; Khan, Mohammad Haaris Ajmal; Salman, Mohd.; Naseem, Mehar; Wajid, Saima

    2014-01-01

    Oxidative stress has been implicated in pathogenesis of streptozotocin- (STZ-) induced diabetes mellitus and its complication in central nervous system (CNS). Recent studies have provided insights on antioxidants and their emergence as potential therapeutic and nutraceutical. The present study examined the hypothesis that hesperidin (HP) ameliorates oxidative stress and may be a limiting factor in the extent of CNS complication following diabetes. To test this hypothesis rats were divided into four groups: control, diabetic, diabetic-HP treated, and vehicle for HP treatment group. Diabetes mellitus was induced by a single injection of STZ (65 mg/kg body weight). Three days after STZ injection, HP was given (50 mg/kg b.wt. orally) once daily for four weeks. The results of the present investigation suggest that the significant elevated levels of oxidative stress markers were observed in STZ-treated animals, whereas significant depletion in the activity of nonenzymatic antioxidants and enzymatic antioxidants was witnessed in diabetic rat brain. Neurotoxicity biomarker activity was also altered significantly. HP treatment significantly attenuated the altered levels of oxidative stress and neurotoxicity biomarkers. Our results demonstrate that HP exhibits potent antioxidant and neuroprotective effects on the brain tissue against the diabetic oxidative damage in STZ-induced rodent model. PMID:25050332

  7. Chloroquine improves left ventricle diastolic function in streptozotocin-induced diabetic mice

    PubMed Central

    Yuan, Xun; Xiao, Yi-Chuan; Zhang, Gui-Ping; Hou, Ning; Wu, Xiao-Qian; Chen, Wen-Liang; Luo, Jian-Dong; Zhang, Gen-Shui

    2016-01-01

    Diabetes is a potent risk factor for heart failure with preserved ejection fraction (HFpEF). Autophagy can be activated under pathological conditions, including diabetic cardiomyopathy. The therapeutic effects of chloroquine (CQ), an autophagy inhibitor, on left ventricle function in streptozotocin (STZ)-induced diabetic mice were investigated. The cardiac function, light chain 3 (LC3)-II/LC3-I ratio, p62, beclin 1, reactive oxygen species, apoptosis, and fibrosis were measured 14 days after CQ (ip 60 mg/kg/d) administration. In STZ-induced mice, cardiac diastolic function was decreased significantly with normal ejection fraction. CQ significantly ameliorated cardiac diastolic function in diabetic mice with HFpEF. In addition, CQ decreased the autophagolysosomes, cardiomyocyte apoptosis, and cardiac fibrosis but increased LC3-II and p62 expressions. These results suggested that CQ improved the cardiac diastolic function by inhibiting autophagy in STZ-induced HFpEF mice. Autophagic inhibitor CQ might be a potential therapeutic agent for HFpEF. PMID:27621594

  8. Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy.

    PubMed

    Akhtar, Md Sayeed; Pillai, Krishna Kolappa; Hassan, Quamrul; Ansari, Shahid Husain; Ali, Javed; Akhtar, Mohammed; Najmi, Abul Kalam

    2016-01-01

    Diabetic cardiomyopathy plays a major role in morbidity and mortality among cardiovascular disorder-related complications. This study was designed to explore long-term benefits of Levosimendan (LEVO) along with Ramipril and Insulin. Diabetic cardiomyopathy was induced using streptozotocin (STZ) at the dose of 25 mg/kg/body weight/day for three consecutive days in Wistar rats. Rats were randomly divided into 10 groups and treatments were started after 2 weeks of STZ administration. A gradual but severe hyperglycemia ((§§§)p < 0.001) was observed in all STZ-treated groups except those received insulin (2  U/day). LEVO alone and in combination with Ramipril and Insulin normalized (**p < 0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p < 0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment. Myofibril degeneration, mitochondrial fibrosis and vacuolization occurred after STZ treatment, were also reversed by LEVO in combination with Ramipril and Insulin. The combination of LEVO with Ramipril and Insulin improved hemodynamic functions, maintained cardiac enzymes and ameliorated myofibril damage in diabetic cardiomyopathy. PMID:26207881

  9. Intestinal lipids and minerals in streptozotocin-induced diabetic rats fed bitter yam (Dioscorea polygonoides) sapogenin extract.

    PubMed

    Omoruyi, Felix O; McAnuff-Harding, Marie A; Asemota, Helen N

    2006-10-01

    Yam is the leading form of staple for millions of people in the tropical and subtropical countries. They are good sources of carbohydrate. However, the protein content of yam is low. The effect of bitter yam sapogenin extract or commercial diosgenin on faecal minerals and intestinal lipids in streptozotocin-induced diabetic rats was studied. Sapogenin extract or commercial diosgenin (1%) supplemented diets were fed to diabetic male Wistar rats for three weeks. Bitter yam sapogenin extract or commercial diosgenin did not significantly alter faecal magnesium, calcium, and zinc excretion but significantly decreased faecal sodium and potassium excretion. The absorption of iron was impaired by bitter yam sapogenin extract or commercial diosgenin during the first week of feeding. Bitter yam sapogenin extract or commercial diosgenin supplements significantly decreased intestinal lipids towards normal. Faecal lipids excreted was significantly higher in diabetic rats fed bitter yam sapogenin extract or commercial diosgenin for the three weeks period compared to the diabetic control group. These results show that bitter yam sapogenin extract or commercial diosgenin does not have the same effects on mineral excretion in diabetes. There was no direct correlation between the decrease in excretion of mono-valent cations and the activity of intestinal Na+/K+ATPase. PMID:17105702

  10. Studies on the Antidiabetic Activities of Cordyceps militaris Extract in Diet-Streptozotocin-Induced Diabetic Sprague-Dawley Rats

    PubMed Central

    Dong, Yuan; Jing, Tianjiao; Meng, Qingfan; Liu, Chungang; Hu, Shuang; Ma, Yihang; Liu, Yan; Lu, Jiahui; Cheng, Yingkun; Teng, Lirong

    2014-01-01

    Due to substantial morbidity and high complications, diabetes mellitus is considered as the third “killer” in the world. A search for alternative antidiabetic drugs from herbs or fungi is highly demanded. Our present study aims to investigate the antidiabetic activities of Cordyceps militaris on diet-streptozotocin-induced type 2 diabetes mellitus in rats. Diabetic rats were orally administered with water extract or alcohol extract at 0.05 g/kg and 2 g/kg for 3 weeks, and then, the factors levels related to blood glucose, lipid, free radicals, and even nephropathy were determined. Pathological alterations on liver and kidney were examined. Data showed that, similar to metformin, Cordyceps militaris extracts displayed a significant reduction in blood glucose levels by promoting glucose metabolism and strongly suppressed total cholesterol and triglycerides concentration in serum. Cordyceps militaris extracts exhibit antioxidative effects indicated by normalized superoxide dismutase and glutathione peroxidase levels. The inhibitory effects on blood urea nitrogen, creatinine, uric acid, and protein revealed the protection of Cordyceps militaris extracts against diabetic nephropathy, which was confirmed by pathological morphology reversion. Collectively, Cordyceps militaris extract, a safe pharmaceutical agent, presents excellent antidiabetic and antinephropathic activities and thus has great potential as a new source for diabetes treatment. PMID:24738047

  11. Attenuation of nonenzymatic glycation, hyperglycemia, and hyperlipidemia in streptozotocin-induced diabetic rats by chloroform leaf extract of Azadirachta indica

    PubMed Central

    Gutierrez, Rosa Martha Pérez; Gómez, Yolanda Gómez Y.; Guzman, Mónica Damián

    2011-01-01

    Background: The hypoglycemic effects of hexane, chloroform and methanol extracts of leaves of Azadirachta indica (AI) were evaluated by oral administration in streptozotocin-induced severe diabetic rats (SD). Materials and Methods: The effect of chronic oral administration of the extract for 28 days was evaluated in streptozotozin diabetic rats. Lipid peroxidation, glycogen content of liver and skeletal muscles, insulin, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), oxidized glutathione (GSSG) levels were determined. In addition, advanced glycation end product formation (AGEs) was evaluated. Results: The most active extracts were obtained with chloroform. Chloroform extract from AI shows increased levels of SOD, GSH, GSSG and CAT, hepatic glycogen content, glucose-6-phosphatase and insulin plasma levels, which also decreased the glucokinase (GK), lipid peroxidation and insulin resistance. The chloroform extract exhibited significant inhibitory activity against advanced glycation end product formation with an IC50 average range of 79.1 mg/ml. Conclusion: Azadirachta indica can improve hyperlipidemia and hyperinsulinema in streptozocin-induced diabetic rats and, therefore, AI can be potentially considered to be an antidiabetic-safe agent. PMID:21969798

  12. Vitamin B6 Supplementation Improves Oxidative Stress and Enhances Serum Paraoxonase/Arylesterase Activities in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Taş, Sibel; Sarandöl, Emre

    2014-01-01

    The purpose of this study was to investigate the effects of vitamin B6 (Vit B6) on oxidant and antioxidant status in streptozotocin-induced diabetic rats. Thirty-two Wistar rats were divided into four groups: control (C), control + Vit B6 group (C + Vit B6), diabetes (D), and diabetes + Vit B6 group (D + Vit B6). Vit B6 (4 mg/kg body weight) was administered in drinking water for 4 weeks after the induction of diabetes. Vitamin B6 reduced serum total cholesterol level in the C + Vit B6 (P < 0.01) and D + Vit B6 (P < 0.05) groups. Plasma and tissue malondialdehyde levels were reduced in the C + Vit B6 and D + Vit B6 groups. Whole blood glutathione peroxidase (GSH-Px) and erythrocyte superoxide dismutase (SOD) activities were higher in the D group (P < 0.05). GSH-Px and SOD activities were increased in C + Vit B6 group while these parameters decreased in the D + Vit B6 group. Paraoxonase and arylesterase activities were decreased in the D group while they were increased in C + Vit B6 and D + Vit B6 groups. The results of present study suggest that vitamin B6 supplementation might be a promising adjunctive agent for improving oxidative stress and metabolic disturbances and for preventing diabetic complications including atherogenesis. PMID:25431786

  13. Restoration of cardiomyocyte function in streptozotocin-induced diabetic rats after treatment with vanadate in a tea decoction.

    PubMed

    Clark, Tod A; Maddaford, Thane G; Tappia, Paramjit S; Heyliger, Clayton E; Ganguly, Pallab K; Pierce, Grant N

    2010-12-01

    Diabetes mellitus is associated with abnormal cardiomyocyte Ca(2+) transients and contractile performance. We investigated the possibility that an alteration in inositol trisphosphate/phospholipase C (IP₃/PLC) signalling may be involved in this dysfunction. Phosphatidic acid stimulates cardiomyocyte contraction through an IP₃/PLC signaling cascade. We also tested a novel therapeutic intervention to assess its efficacy in reversing any potential defects. Diabetes was induced in Sprague-Dawley rats by streptozotocin treatment and maintained for an 8 week experimental period. Active cell shortening was significantly depressed in cardiomyocytes obtained from diabetic and insulin-treated diabetic rats in comparison to normal control animals. Perfusion of the cells with phosphatidic acid induced an increase in contraction of control rat cardiomyocytes whereas its effect was inhibitory in cells from streptozotocin-induced diabetic rats. Diabetic rats were also treated orally with vanadate administered in a black tea extract (T/V) for the 8 week period. T/V treatment resulted in a contractile response that was not different from cells of control animals. Furthermore, cardiomyocytes from T/V-treated animals exhibited significantly improved Ca(2+) transients in comparison to diabetic animals and exhibited a normalized response to phosphatidic acid perfusion. It is concluded that a T/V glycemic therapy is capable of preventing the defect in IP₃/PLC signaling that occurs in diabetes and can restore normal cardiac contractile function. PMID:20874687

  14. Antihyperglycaemic effects of ethanol extracts of Carica papaya and Pandanus amaryfollius leaf in streptozotocin-induced diabetic mice.

    PubMed

    Sasidharan, Sreenivasan; Sumathi, Vello; Jegathambigai, Naidu Rameshwar; Latha, Lachimanan Yoga

    2011-12-01

    Diabetes mellitus is a global disease that is increasing in an alarming rate. The present study was undertaken to study the antidiabetic effect of the ethanol extracts of Carica papaya and Pandanus amaryfollius on streptozotocin-induced diabetic mice. The results of the present study indicated that there was no significant difference in the body weight of the treated groups when compared to diabetic control. Whereas, there was significant (P < 0.05) decrease in the blood glucose level of the plant-treated groups compared to the diabetic control. Histologically the pancreas of the treated groups indicated significant regeneration of the β-cells when compared to the diabetic control. The liver tissues of the treated group indicated a reduction in fatty changes and pyknotic nucleus. The kidney tissues of the treated groups indicated significant recovery in the cuboidal tissue. The results from the phytochemical screening indicated the presence of flavonoids, alkaloids, saponin and tannin in C. papaya and P. amaryfollius. The antidiabetic effect of C. papaya and P. amaryfollius observed in the present study may be due to the presence of these phytochemicals. PMID:21707251

  15. Bixin and Norbixin Have Opposite Effects on Glycemia, Lipidemia, and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Zanchi, Mariane Magalhães; Bochi, Guilherme Vargas; Somacal, Sabrina

    2014-01-01

    The present study investigated the effects of oral administration of annatto carotenoids (bixin (BIX) and norbixin (NBIX)) on glucose levels, lipid profiles, and oxidative stress parameters in streptozotocin (STZ)-induced diabetic rats. Animals were treated for 30 days in the following groups: nondiabetic control, diabetic vehicle, diabetic 10 mg/kg BIX, diabetic 100 mg/kg BIX, diabetic 10 mg/kg NBIX, diabetic 100 mg/kg NBIX, diabetic metformin, and diabetic insulin. Blood glucose, LDL cholesterol, and triglyceride levels were reduced in the diabetic rats treated with BIX. BIX treatment prevented protein oxidation and nitric oxide production and restored superoxide dismutase activity. NBIX treatment did not change most parameters assessed, and at the highest dose, it increased LDL cholesterol and triglycerides levels and showed prooxidant action (increased protein oxidation and nitric oxide levels). These findings suggested that BIX could have an antihyperglycemic effect, improve lipid profiles, and protect against damage induced by oxidative stress in the diabetic state. Because NBIX is a water-soluble analog of BIX, we propose that lipophilicity is crucial for the protective effect of annatto carotenoids against streptozotocin-induced diabetes. PMID:24624139

  16. A comparison of wound healing rate following treatment with aftamed and chlorine dioxide gels in streptozotocin-induced diabetic rats.

    PubMed

    Al-Bayaty, Fouad; Abdulla, Mahmood Ameen

    2012-01-01

    Background and Purpose. This study aimed to evaluate the wound healing activities of Aftamed and chlorine dioxide gels in streptozotocin-induced diabetic rats. Experimental Approach. Forty-eight Sprague Dawley rats were chosen for this study, divided into 4 groups. Diabetes was induced. Two-centimeter-diameter full-thickness skin excision wounds were created. Animals were topically treated twice daily. Groups 1, the diabetic control group, were treated with 0.2 mL of sterile distilled water. Group 2 served as a reference standard were treated with 0.2 mL of Intrasite gel. Groups 3 and 4 were treated with 0.2 mL of Aftamed and 0.2 mL of chlorine dioxide gels respectively. Granulation tissue was excised on the 10th day and processed for histological and biochemical analysis. The glutathione peroxidase ,superoxide dismutase activities and the malondialdehyde (MDA) levels were determined. Results. Aftamed-treated wounds exhibited significant increases in hydroxyproline, cellular proliferation, the number of blood vessels, and the level of collagen synthesis. Aftamed induced an increase in the free radical-scavenging enzyme activity and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in the MDA level. Conclusions. This study showed that Aftamed gel is able to significantly accelerate the process of wound healing in diabetic rats. PMID:22666291

  17. Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes.

    PubMed

    Song, Fang; Xue, Yunxia; Dong, Dong; Liu, Jun; Fu, Ting; Xiao, Chengju; Wang, Hanqing; Lin, Cuipei; Liu, Peng; Zhong, Jiajun; Yang, Yabing; Wang, Zhaorui; Pan, Hongwei; Chen, Jiansu; Li, Yangqiu; Cai, Dongqing; Li, Zhijie

    2016-01-01

    The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea. PMID:27611469

  18. Biological Activities of Chinese Propolis and Brazilian Propolis on Streptozotocin-Induced Type 1 Diabetes Mellitus in Rats

    PubMed Central

    Zhu, Wei; Chen, Minli; Shou, Qiyang; Li, Yinghua; Hu, Fuliang

    2011-01-01

    Propolis is a bee-collected natural product and has been proven to have various bioactivities. This study tested the effects of Chinese propolis and Brazilian propolis on streptozotocin-induced type 1 diabetes mellitus in Sprague-Dawley rats. The results showed that Chinese propolis and Brazilian propolis significantly inhibited body weight loss and blood glucose increase in diabetic rats. In addition, Chinese propolis-treated rats showed an 8.4% reduction of glycated hemoglobin levels compared with untreated diabetic rats. Measurement of blood lipid metabolism showed dyslipidemia in diabetic rats and Chinese propolis helped to reduce total cholesterol level by 16.6%. Moreover, oxidative stress in blood, liver and kidney was improved to various degrees by both Chinese propolis and Brazilian propolis. An apparent reduction in levels of alanine transaminase, aspartate transaminase, blood urea nitrogen and urine microalbuminuria-excretion rate demonstrated the beneficial effects of propolis in hepatorenal function. All these results suggested that Chinese propolis and Brazilian propolis can alleviate symptoms of diabetes mellitus in rats and these effects may partially be due to their antioxidant ability. PMID:21785625

  19. Activation of κ-opioid receptor exerts the glucose-homeostatic effect in streptozotocin-induced diabetic mice.

    PubMed

    Shang, Yulong; Guo, Fan; Li, Juan; Fan, Rong; Ma, Xinliang; Wang, Yuemin; Feng, Na; Yin, Yue; Jia, Min; Zhang, Shumiao; Zhou, Jingjun; Wang, Hongbing; Pei, Jianming

    2015-02-01

    Opioid and its receptors play important roles in glucose homeostasis. However, few reports were available for the study of κ-opioid receptor in glucose regulation. In our study, we found that the blood glucose of diabetic mice dropped significantly following the treatment with U50,488H (a selective κ-opioid receptor agonist). This phenomenon was time-dependent and associated with the coincident alteration of Glut4 translocation in the skeleton muscles. U50,488H increased the serum adiponectin, but not serum insulin in diabetic mice. U50,488H increased the AdipoR1 expression at both mRNA and protein levels. It also promoted AMPK phosphorylation and Glut4 translocation. All these effects were abolished by nor-BNI (a selective κ-opioid receptor antagonist). These findings suggest that activation of κ-opioid receptor reduces hyperglycemia in streptozotocin-induced diabetic mice. This effect is associated with the translocation of Glut4 and might be relevant to increased adiponectin, AdipoR1, and AMPK phosphorylation. PMID:25186835

  20. Investigation of the in vivo antioxidative activity of Cynara scolymus (artichoke) leaf extract in the streptozotocin-induced diabetic rat.

    PubMed

    Magielse, Joanna; Verlaet, Annelies; Breynaert, Annelies; Keenoy, Begoña Manuel Y; Apers, Sandra; Pieters, Luc; Hermans, Nina

    2014-01-01

    The in vivo antioxidant activity of a quantified leaf extract of Cynara scolymus (artichoke) was studied. The aqueous artichoke leaf extract (ALE), containing 1.5% caffeoylquinic acid with chlorogenic acid being most abundant (0.30%), and luteolin-7-O-glucoside as major flavonoid (0.15%), was investigated by evaluating the effect on different oxidative stress biomarkers, after 3 wk oral supplementation in the streptozotocin-induced diabetic rat model. Apart from two test groups (0.2 g ALE/kg BW/day and 1 g ALE/kg BW/day, where BW is body weight), a healthy control group, untreated oxidative stress group, and vitamin E treated group (positive control) were included. A 0.2 g/kg BW/day of ALE decreased oxidative stress: malondialdehyde and 8-hydroxydeoxyguanosine levels significantly diminished, whereas erythrocyte glutathione levels significantly increased. A 1.0 g/kg BW/day ALE did not show higher antioxidant activity. PMID:24254201

  1. Withania coagulans fruit extract reduces oxidative stress and inflammation in kidneys of streptozotocin-induced diabetic rats.

    PubMed

    Ojha, Shreesh; Alkaabi, Juma; Amir, Naheed; Sheikh, Azimullah; Agil, Ahmad; Fahim, Mohamed Abdelmonem; Adem, Abdu

    2014-01-01

    The present study was carried out to investigate the changes in oxidative and inflammatory status in streptozotocin-induced diabetic rat's kidneys and serum following treatment with Withania coagulans, a popular herb of ethnomedicinal significance. The key markers of oxidative stress and inflammation such as inflammatory cytokines (IL-1β, IL-6, and TNF-α) and immunoregulatory cytokines (IL-4 and IFN-γ) were increased in kidneys along with significant hyperglycemia. However, treatment of four-month diabetic rats with Withania coagulans (10 mg/kg) for 3 weeks significantly attenuated hyperglycemia and reduced the levels of proinflammatory cytokines in kidneys. In addition, Withania coagulans treatment restored the glutathione levels and inhibited lipid peroxidation along with marked reduction in kidney hypertrophy. The present study demonstrates that Withania coagulans corrects hyperglycemia and maintained antioxidant status and reduced the proinflammatory markers in kidneys, which may subsequently reduce the development and progression of renal injury in diabetes. The results of the present study are encouraging for its potential use to delay the onset and progression of diabetic renal complications. However, the translation of therapeutic efficacy in humans requires further studies. PMID:25295146

  2. Short- and long-term effects of various Citrullus colocynthis seed extracts in normal and streptozotocin-induced diabetic rats.

    PubMed

    Benariba, Nabila; Djaziri, Rabeh; Zerriouh, Bouchra Hanane; Bellakhdar, Wafaa; Hupkens, Emeline; Boucherit, Zahia; Malaisse, Willy J

    2012-12-01

    In the light of previous findings, the major aim of the present study was to investigate the potential beneficial effects of various Citrullus colocynthis L. seed extracts on such variables as glucose tolerance, body weight gain, pancreas, liver, kidney, testis, epididymal fat and diaphragm muscle weight, as well as serum cholesterol, triglyceride, urea, creatinine, transaminases and alkaline phosphatase concentrations in an animal model of type-1 diabetes mellitus, i.e. streptozotocin-induced diabetic rats. For purpose of comparison, a comparable study was conducted in normal rats. Both the immediate and long-term effects of the plant extracts were assessed in rats injected daily, up to 3 weeks after the start of the experiments. The results of this study reinforce the view that both a crude aqueous extract and a n-butanol extract from the Citrullus colocynthis L. seeds may represent the best candidates in order to eventually identify a component suitable for the treatment of both type-1 and type-2 diabetic subjects. PMID:22992982

  3. Effect ofOcimum sanctum (Tulsi) and vitamin E on biochemical parameters and retinopathy in streptozotocin induced diabetic rats.

    PubMed

    Halim, Eshrat M; Mukhopadhyay, A K

    2006-09-01

    This study was carried out to see the effect of the aqueous extract ofOcitum sanctum Linn (Tulsi) with Vitamin E on biochemical parameters and retinopathy in the streptozotocin-induced diabetic albino male rats. Adult albino male rats weighing 150-200 gm were made diabetic by intraperitoneal injection of streptozotocin in the dose 60 mg/kg in citrate buffer (pH 6.3). The diabetic animals were left for one month to develop retinopathy. Biochemical parameters like plasma glucose, oral glucose tolerance and glycosylated hemoglobin HbA(1c), were measured along with lipid profile, and enzymes like glutathione peroxidase (GPX), lipid peroxidase (LPO), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in normal, untreated diabetic rats and diabetic rats treated withOcimum sanctum L extracts and vitamin E. Fluorescein angiography test was done for assessing retinopathy. Results on biochemical parameters were analyzed statistically by using ANOVA followed by Dunnet's 't'-test. A p-value of <0.05 was considered as significant. Evaluation of biochemical profile in treated groups showed statistically significant reduction in plasma levels of glucose, HbA(1c), lipid profile and LPO, and elevation of GPX, SOD, CAT and GST. Treatment of the diabetic animals withOcimum sanctum and Vitamin E, alone and in combination for 16 weeks showed reversal of most of the parameters studied including plasma glucose levels. Angiography showed improvement in retinal changes following combined antidiabetic treatment. PMID:23105641

  4. Beneficial effects of mangiferin isolated from Salacia chinensis on biochemical and hematological parameters in rats with streptozotocin-induced diabetes.

    PubMed

    Sellamuthu, Periyar Selvam; Arulselvan, Palanisamy; Fakurazi, Sharida; Kandasamy, Murugesan

    2014-01-01

    Salacia chinensis L. is a traditional Southeast Asian herbal medicine and used in the treatment of diabetes. To investigate the antidiabetic properties of mangiferin from Salacia chinensis and its beneficial effect on toxicological and hematological parameters in streptozotocin induced diabetic rats. Mangiferin was orally treated with the dose of 40 mg/kg body weight/day for 30 days to diabetic rats. Biochemical (blood glucose, uric acid, urea and creatinine), toxicological (AST, ALT and ALP) and hematological parameters (red and white blood cells) and their functional indices were evaluated in diabetic treated groups with mangiferin and glibenclamide. Mangiferin treated diabetic rats significantly (p<0.05) lowered the level of blood glucose, in addition, altered the levels of biochemical parameters including urea, uric acid, and creatinine. Toxicological parameters including AST, ALT and ALP were also significantly reduced after treatment with mangiferin in diabetic rats. Similarly, the levels of red blood, white blood cells and their functional indices were significantly improved through the administration of mangiferin. Thus, our results indicate that mangiferin present in S. chinensis possesses antidiabetic properties and nontoxic nature against chemically induced diabetic rats. Further experimental investigations are warrant to make use of its relevant therapeutic effect to substantiate its ethno-medicinal usage. PMID:24374436

  5. The protective effects of insulin and natural honey against hippocampal cell death in streptozotocin-induced diabetic rats.

    PubMed

    Jafari Anarkooli, Iraj; Barzegar Ganji, Hossein; Pourheidar, Maryam

    2014-01-01

    We investigated the effects of insulin and honey as antioxidants to prevent the hippocampal cell death in streptozotocin-induced diabetic rats. We selected sixty Wister rats (5 groups of 12 animals each), including the control group (C), and four diabetic groups (control (D) and 3 groups treated with insulin (I), honey (H), and insulin plus honey (I + H)). Diabetes was induced by streptozotocin injection (IP, 60 mg/kg). Six weeks after the induction of diabetes, the group I received insulin (3-4 U/kg/day, SC), group H received honey (5 mg/kg/day, IP), and group I + H received a combination of the above at the same dose. Groups C and D received normal saline. Two weeks after treatment, rats were sacrificed and the hippocampus was extracted. Neuronal cell death in the hippocampal region was examined using trypan blue assay, "H & E" staining, and TUNEL assay. Cell viability assessment showed significantly lower number of living cells in group D than in group C. Besides, the mean number of living cells was significantly higher in group I, H, and I + H compared to group D. Therefore, it can be concluded that the treatment of the diabetic rats with insulin, honey, and a combination of insulin and honey can prevent neuronal cell death in different hippocampal areas of the studied samples. PMID:24745031

  6. The Protective Effects of Insulin and Natural Honey against Hippocampal Cell Death in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Jafari Anarkooli, Iraj; Barzegar Ganji, Hossein; Pourheidar, Maryam

    2014-01-01

    We investigated the effects of insulin and honey as antioxidants to prevent the hippocampal cell death in streptozotocin-induced diabetic rats. We selected sixty Wister rats (5 groups of 12 animals each), including the control group (C), and four diabetic groups (control (D) and 3 groups treated with insulin (I), honey (H), and insulin plus honey (I + H)). Diabetes was induced by streptozotocin injection (IP, 60 mg/kg). Six weeks after the induction of diabetes, the group I received insulin (3-4 U/kg/day, SC), group H received honey (5 mg/kg/day, IP), and group I + H received a combination of the above at the same dose. Groups C and D received normal saline. Two weeks after treatment, rats were sacrificed and the hippocampus was extracted. Neuronal cell death in the hippocampal region was examined using trypan blue assay, “H & E” staining, and TUNEL assay. Cell viability assessment showed significantly lower number of living cells in group D than in group C. Besides, the mean number of living cells was significantly higher in group I, H, and I + H compared to group D. Therefore, it can be concluded that the treatment of the diabetic rats with insulin, honey, and a combination of insulin and honey can prevent neuronal cell death in different hippocampal areas of the studied samples. PMID:24745031

  7. Absence of inducible nitric oxide synthase reduces myocardial damage during ischemia reperfusion in streptozotocin-induced hyperglycemic mice.

    PubMed

    Marfella, Raffaele; Di Filippo, Clara; Esposito, Katherine; Nappo, Francesco; Piegari, Elena; Cuzzocrea, Salvatore; Berrino, Liberato; Rossi, Francesco; Giugliano, Dario; D'Amico, Michele

    2004-02-01

    We investigated the role of inducible nitric oxide synthase (iNOS) on ischemic myocardial damage and angiogenic process in genetically deficient iNOS (iNOS(-/-)) mice and wild-type littermates (iNOS(+/+)), with and without streptozotocin-induced (70 mg/kg intravenously) diabetes. After ischemia (25 min) and reperfusion (120 min), both iNOS(+/+) and iNOS(-/-) diabetic mice (blood glucose 22 mmol/l) had myocardial infarct size greater than their respective nondiabetic littermates (P < 0.01). Myocardial infarct size (P < 0.05), apoptotic index (P < 0.005), and tissue levels of tumor necrosis factor (P < 0.01), interleukin-6 (P < 0.01), and interleukin-18 (P < 0.01) were higher in nondiabetic iNOS(-/-) mice compared with nondiabetic iNOS(+/+) mice. As compared with diabetic iNOS(-/-) mice, diabetic iNOS(+/+) mice showed a greater infarct size (P < 0.01) associated with the highest tissue levels of nitrotyrosine and proinflammatory cytokines, as well as apoptosis. The beneficial role of iNOS in modulating defensive responses against ischemia/reperfusion injury seems to be abolished in diabetic mice. PMID:14747298

  8. Chronic food restriction and streptozotocin-induced diabetes differentially alter prodynorphin mRNA levels in rat brain regions.

    PubMed

    Berman, Y; Devi, L; Spangler, R; Kreek, M J; Carr, K D

    1997-06-01

    It was previously reported that chronic food restriction and streptozotocin-induced diabetes lead to brain region-specific changes in levels of Prodyn-derived peptides. These changes parallel behavioral adaptations that are reversed by opioid antagonists. In the present study, effects of food restriction and diabetes on Prodyn gene expression were measured in rat brain regions using a quantitative solution hybridization mRNA assay. Picogram amounts of Prodyn mRNA were determined in extracts of five brain regions. The highest density of Prodyn mRNA was observed in extracts of nucleus accumbens (4.68 pg/microg total RNA), bed nucleus of the stria terminalis (4.18 pg/microg), and in caudate nucleus (3.51 pg/microg). Lower levels were observed in the lateral hypothalamus (1.87 pg/microg) and central nucleus of the amygdala (1.22 pg/microg). Food restriction and diabetes both markedly increased the levels of Prodyn mRNA in the central amygdala (163% and 93%, respectively). Levels in the lateral hypothalamus were also increased (35% and 29%, respectively), though only the food-restriction effect was statistically significant. Neither treatment altered prodynorphin mRNA levels in the caudate nucleus, nucleus accumbens or bed nucleus of the stria terminalis. These results suggest that dynorphin neurons in central amygdala and lateral hypothalamus may be involved in behavioral or physiological adaptations to sustained metabolic need. PMID:9191075

  9. Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes

    PubMed Central

    Song, Fang; Xue, Yunxia; Dong, Dong; Liu, Jun; Fu, Ting; Xiao, Chengju; Wang, Hanqing; Lin, Cuipei; Liu, Peng; Zhong, Jiajun; Yang, Yabing; Wang, Zhaorui; Pan, Hongwei; Chen, Jiansu; Li, Yangqiu; Cai, Dongqing; Li, Zhijie

    2016-01-01

    The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea. PMID:27611469

  10. Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rats.

    PubMed

    Prasath, Gopalan Sriram; Sundaram, Chinnakrishnan Shanmuga; Subramanian, Sorimuthu Pillai

    2013-10-01

    Persistent hyperglycemia is associated with chronic oxidative stress which contributes to the development and progression of diabetes-associated complications. The sensitivity of pancreatic β-cells to oxidative stress has been attributed to their low content of antioxidants compared with other tissues. Bioactive compounds with potent antidiabetic properties have been shown to ameliorate hyperglycemia mediated oxidative stress. Recently, we have reported that oral administration of fisetin (10 mg/Kg b.w.), a bioflavonoid found to be present in strawberries, persimmon, to STZ-induced experimental diabetic rats significantly improved normoglycemia. The present study was aimed to evaluate the antioxidant potential of fisetin in both in vitro and in vivo. Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Fisetin was administered orally for 30 days. At the end of the study, all animals were killed. Blood samples were collected for the biochemical estimations. The antioxidant status was evaluated. Histological examinations were performed on pancreatic tissues. Fisetin treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin. The treatment also improved the antioxidant status in pancreas as well as plasma of diabetic rats indicating the antioxidant potential of fisetin. In addition, the results of DPPH and ABTS assays substantiate the free radical scavenging activity of fisetin. Histological studies of the pancreas also evidenced the tissue protective nature of fisetin. It is concluded that, fisetin possesses antioxidant and anti-inflammatory property and may be considered as an adjunct for the treatment of diabetes. PMID:23277230

  11. Antioxidant protection of Malaysian tualang honey in pancreas of normal and streptozotocin-induced diabetic rats.

    PubMed

    Erejuwa, O O; Sulaiman, S A; Wahab, M S; Sirajudeen, K N S; Salleh, M S Md; Gurtu, S

    2010-09-01

    Glucotoxicity contributes to beta-cell dysfunction through oxidative stress. Our previous study demonstrated that tualang honey ameliorated renal oxidative stress and produced hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. This present study investigated the hypothesis that hypoglycemic effect of tualang honey might partly be due to protection of pancreas against oxidative stress. Diabetes was induced by a single dose of STZ (60 mg/kg; ip). Diabetic rats were randomly divided into two groups and administered distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). Similarly, two groups of non-diabetic rats received distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). The animals were treated orally for 28 days. At the end of the treatment period, the honey-treated diabetic rats had significantly (p<0.05) reduced blood glucose levels [8.8 (5.8)mmol/L; median (interquartile range)] compared with the diabetic control rats [17.9 (2.6)mmol/L]. The pancreas of diabetic control rats showed significantly increased levels of malondialdehyde (MDA) and up-regulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Catalase (CAT) activity was significantly reduced while glutathione-S-transferase (GST) and glutathione reductase (GR) activities remained unchanged in the pancreas of diabetic rats. Tualang honey significantly (p<0.05) reduced elevated MDA levels. Honey treatment also restored SOD and CAT activities. These results suggest that hypoglycemic effect of tualang honey might be attributed to its antioxidative effect on the pancreas. PMID:20398890

  12. Beneficial effects of an Andrographis paniculata extract and andrographolide on cognitive functions in streptozotocin-induced diabetic rats.

    PubMed

    Thakur, Ajit Kumar; Rai, Geeta; Chatterjee, Shyam Sunder; Kumar, Vikas

    2016-09-01

    Context Andrographolide containing Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts is often used for treatments of diabetes and other inflammatory disorders commonly accompanying cognitive and other psychiatric disorders. Objective To compare the efficacies of a standardised A. paniculata extract (AP) and pure andrographolide on cognitive functions, oxidative stress and cholinergic function in diabetic rats. Materials and methods Streptozotocin-induced diabetic Charles Foster albino rats treated orally with a hydro-methanolic A. paniculata leaf extract (50, 100 and 200 mg/kg/day), or with pure andrographolide (15, 30 and 60 mg/kg/day) for 10 consecutive days, were subjected to Morris water maze test. After the test, acetylcholinesterase, superoxide dismutase (SOD), and catalase (CAT) activities and lipid peroxidation (LPO) in brain tissues were assessed. Results Acetylcholinesterase activity in pre-frontal cortex and hippocampus of diabetic rats was 2.1 and 2.6 times higher compared to nondiabetic rats. LPO was 1.6 times higher and decreased SOD (56.3%) and CAT (44.9%) activities in pre-frontal cortex of diabetic rats compared to nondiabetic rats. AP or andrographolide treatments dose dependently attenuated cognitive deficits, reduced acetylcholinesterase activity, oxidative stress, improved diabetic hyperglycemia and insulin deficiency. All observed effects of AP were quantitatively almost equal to those expected from its analytically quantified andrographolide content. Discussion and conclusion Reported observations are the very first ones suggesting beneficial effects of andrographolide against diabetes associated cognitive deficits, increased acetylcholinesterase activity and deteriorated antioxidative status. Efforts to exploit A. paniculata extracts enriched in andrographolide as preventive measures against such disorders can be warranted. PMID:26810454

  13. Mediation of beta-endorphin by isoferulic acid to lower plasma glucose in streptozotocin-induced diabetic rats.

    PubMed

    Liu, I-Min; Chen, Wang-Chuan; Cheng, Juei-Tang

    2003-12-01

    We investigated the mechanism(s) by which isoferulic acid lowers plasma glucose levels in streptozotocin-induced diabetic rats (STZ-diabetic rats). In STZ-diabetic rats, isoferulic acid dose dependently lowered plasma glucose concentrations and increased plasma beta-endorphin-like immunoreactivity (BER). Both of these effects of isoferulic acid were abolished by pretreatment of rats with tamsulosin or 2-[2,6-dimethoxyphenoxyethyl]aminomethyl-1,4-benzodioxane hydrochloride (WB 4101) at doses sufficient to block alpha1-adrenoceptors. Also, isoferulic acid enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that could be abolished by treatment with alpha1-adrenoceptor antagonists. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of isoferulic acid, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Naloxone and naloxonazine inhibited the plasma glucose-lowering activity of isoferulic acid at doses sufficient to block opioid mu-receptors. In contrast with the effect in wild-type diabetic mice, isoferulic acid failed to lower plasma glucose levels in opioid mu-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with isoferulic acid three times in 1 day resulted in an increase in the expression of the glucose transporter subtype 4 form in soleus muscle. This effect was blocked by alpha1-adrenoceptor or opioid mu-receptor antagonists. The reduction of elevated mRNA or protein level of hepatic phosphoenolpyruvate carboxykinase was also impeded in the same groups of STZ-diabetic rats. In conclusion, our results suggest that isoferulic acid may activate alpha1-adrenoceptors to enhance the secretion of beta-endorphin, which can stimulate the opioid mu-receptors to increase glucose use or/and reduce hepatic gluconeogenesis, resulting in a decrease of plasma glucose in STZ-diabetic rats. PMID:12975496

  14. Deletion of thioredoxin-interacting protein improves cardiac inotropic reserve in the streptozotocin-induced diabetic heart.

    PubMed

    Myers, Ronald B; Fomovsky, Gregory M; Lee, Samuel; Tan, Max; Wang, Bing F; Patwari, Parth; Yoshioka, Jun

    2016-06-01

    Although the precise pathogenesis of diabetic cardiac damage remains unclear, potential mechanisms include increased oxidative stress, autonomic nervous dysfunction, and altered cardiac metabolism. Thioredoxin-interacting protein (Txnip) was initially identified as an inhibitor of the antioxidant thioredoxin but is now recognized as a member of the arrestin superfamily of adaptor proteins that classically regulate G protein-coupled receptor signaling. Here we show that Txnip plays a key role in diabetic cardiomyopathy. High glucose levels induced Txnip expression in rat cardiomyocytes in vitro and in the myocardium of streptozotocin-induced diabetic mice in vivo. While hyperglycemia did not induce cardiac dysfunction at baseline, β-adrenergic challenge revealed a blunted myocardial inotropic response in diabetic animals (24-wk-old male and female C57BL/6;129Sv mice). Interestingly, diabetic mice with cardiomyocyte-specific deletion of Txnip retained a greater cardiac response to β-adrenergic stimulation than wild-type mice. This benefit in Txnip-knockout hearts was not related to the level of thioredoxin activity or oxidative stress. Unlike the β-arrestins, Txnip did not interact with β-adrenergic receptors to desensitize downstream signaling. However, our proteomic and functional analyses demonstrated that Txnip inhibits glucose transport through direct binding to glucose transporter 1 (GLUT1). An ex vivo analysis of perfused hearts further demonstrated that the enhanced functional reserve afforded by deletion of Txnip was associated with myocardial glucose utilization during β-adrenergic stimulation. These data provide novel evidence that hyperglycemia-induced Txnip is responsible for impaired cardiac inotropic reserve by direct regulation of insulin-independent glucose uptake through GLUT1 and plays a role in the development of diabetic cardiomyopathy. PMID:27037370

  15. Oleanolic acid prevents progression of streptozotocin induced diabetic nephropathy and protects renal microstructures in Sprague Dawley rats

    PubMed Central

    Dubey, Vishal K.; Patil, Chandragouda R.; Kamble, Sarika M.; Tidke, Priti S.; Patil, Kalpesh R.; Maniya, Pragnesh J.; Jadhav, Ramchandra B.; Patil, Sudha P.

    2013-01-01

    Objective: To study the effect of oleanolic acid (OA) on streptozotocin induced diabetic nephropathy in Sprague Dawley rats. Materials and Methods: Four weeks after intra-peritoneal injection of streptozotocin (STZ; 55 mg/kg), the rats with proteinuria were grouped as: Control (non-diabetic, treated orally with vehicle), diabetic control (treated orally with vehicle) and three diabetic groups receiving 20, 40 and 60 mg/kg/day oral doses of OA. At the end of 8 weeks, urine and serum samples from the rats were processed for determination of creatinine, BUN and GFR. The kidney samples were processed for determination of weight changes, oxidative stress related parameters like catalase, superoxide dismutase and reduced glutathione levels. A part of one kidney from each rat was used for transmission electron microscopy (TEM). Result: As evident in TEM, OA inhibited the nephropathy induced alterations in podocyte integrity, basement membrane thickness and spacing between the podocytes at 60 mg/kg dose. It increased GFR and reduced oxidative stress in the kidneys in a dose dependent manner. These findings conclusively demonstrate the efficacy of OA in diabetic nephropathy. Significant decrease in the oxidative stress in kidneys indicates the role of anti-oxidant mechanisms in the effects of OA. However, OA is known to act through multiple mechanisms like inhibition of the generation of advanced glycation end products and improving the insulin secretion. These mechanisms might have contributed to its efficacy. Conclusion: These results conclusively demonstrate the efficacy of OA in diabetic nephropathy through its possible antioxidant activity. PMID:23662024

  16. Antidiabetic properties and mechanism of action of Gynura procumbens water extract in streptozotocin-induced diabetic rats.

    PubMed

    Hassan, Zurina; Yam, Mun Fei; Ahmad, Mariam; Yusof, Ahmad Pauzi M

    2010-01-01

    Gynura procumbens (Lour.) Merr (family Compositae) is cultivated in Southeast Asia, especially Indonesia, Malaysia and Thailand, for medicinal purposes. This study evaluated the in vivo hypoglycemic properties of the water extract of G. procumbens following 14 days of treatment and in vitro in RIN-5F cells. Glucose absorption from the intestines and its glucose uptake in abdominal skeletal muscle were assessed. The antidiabetic effect of water extract of G. procumbens leaves was investigated in streptozotocin-induced diabetic rats. The intraperitoneal glucose tolerance test (IPGTT) was performed in diabetic rats treated with G. procumbens water extract for 14 days. In the IPGTT, blood was collected for insulin and blood glucose measurement. After the IPGTT, the pancreases were collected for immunohistochemical study of β-cells of the islets of Langerhans. The possible antidiabetic mechanisms of G. procumbens were assessed through in vitro RIN-5F cell study, intestinal glucose absorption and glucose uptake by muscle. The results showed that G. procumbens significantly decreased blood glucose levels after 14 days of treatment and improved outcome of the IPGTT. However, G. procumbens did not show a significant effect on insulin level either in the in vivo test or the in vitro RIN-5F cell culture study. G. procumbens also showed minimal effects on β-cells of the islets of Langerhans in the pancreas. However, G. procumbens only significantly increased glucose uptake by muscle tissues. From the findings we can conclude that G. procumbens water extract exerted its hypoglycemic effect by promoting glucose uptake by muscles. PMID:21150821

  17. Effect of streptozotocin-induced diabetes on myocardial blood flow reserve assessed by myocardial contrast echocardiography in rats

    PubMed Central

    Cosyns, Bernard; Droogmans, Steven; Hernot, Sophie; Degaillier, Céline; Garbar, Christian; Weytjens, Caroline; Roosens, Bram; Schoors, Danny; Lahoutte, Tony; Franken, Philippe R; Van Camp, Guy

    2008-01-01

    The role of structural and functional abnormalities of small vessels in diabetes cardiomyopathy remains unclear. Myocardial contrast echocardiography allows the quantification of myocardial blood flow at rest and during dipyridamole infusion. The aim of the study was to determine the myocardial blood flow reserve in normal rats compared with Streptozotocin-induced diabetic rats using contrast echocardiography. We prospectively studied 40 Wistar rats. Diabetes was induced by intravenous streptozotocin in 20 rats. All rats underwent baseline and stress (dipyridamole: 20 mg/kg) high power intermittent imaging in short axis view under anaesthesia baseline and after six months. Myocardial blood flow was determined and compared at rest and after dipyridamole in both populations. The myocardial blood flow reserve was calculated and compared in the 2 groups. Parameters of left ventricular function were determined from the M-mode tracings and histological examination was performed in all rats at the end of the study. At six months, myocardial blood flow reserve was significantly lower in diabetic rats compared to controls (3.09 ± 0.98 vs. 1.28 ± 0.67 ml min-1 g-1; p < 0.05). There were also a significant decrease in left ventricular function and a decreased capillary surface area and diameter at histology in the diabetic group. In this animal study, diabetes induced a functional alteration of the coronary microcirculation, as demonstrated by contrast echocardiography, a decrease in capillary density and of the cardiac systolic function. These findings may offer new insights into the underlying mechanisms of diabetes cardiomyopathy. PMID:18764943

  18. Effect of low-level laser therapy on healing of tenotomized Achilles tendon in streptozotocin-induced diabetic rats.

    PubMed

    Nouruzian, Mohsen; Alidoust, Morteza; Bayat, Mohammad; Bayat, Mehernoush; Akbari, Mohammad

    2013-02-01

    Diabetes mellitus (DM) is associated with musculoskeletal damage. Investigations have indicated that healing of the surgically tenotomized Achilles tendon was considerably augmented following low-level laser therapy (LLLT) in non-diabetic, healthy animals. The aim of the present study was to evaluate the effect of LLLT on the Achilles tendon healing in streptozotocin-induced diabetic (STZ-D) rats via a biomechanical evaluating method. Thirty-three rats were divided into non-diabetic (n = 18) and diabetic (n = 15) groups. DM was induced in the rats by injections of STZ. The right Achilles tendons of all rats were tenotomized 1 month after STZ injections. The two experimental groups (n = 6 for each group) of non-diabetic rats were irradiated with a helium-neon (He-Ne) laser at 2.9 and 11.5 J/cm(2) for ten consecutive days. The two experimental groups of diabetic rats (n = 5 for each group) were irradiated with a He-Ne laser at 2.9 and 4.3 J/cm(2) for ten consecutive days. The tendons were submitted to a tensiometric test. Significant improvements in the maximum stress (MS) values (Newton per square millimeter) were found following LLLT at 2.9 J/cm(2) in both the non-diabetic (p = 0.031) and diabetic (p = 0.019) experimental groups when compared with their control groups. LLLT at 2.9 J/cm(2) to the tenotomized Achilles tendons in the non-diabetic and diabetic rats significantly increased the strength and MS of repairing Achilles tendons in our study. PMID:22370620

  19. Effects of Aqueous Extract of Berberis integerrima Root on Some Physiological Parameters in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ashraf, Hossein; Heidari, Reza; Nejati, Vahid; Ilkhanipoor, Minoo

    2013-01-01

    Diabetes mellitus is a common endocrine disorder. Anti-diabetic agents from natural and synthetic sources are available for the treatment of this disease. Berberis integerrima is a medicinal shrub used in conventional therapy for a number of diseases. The aim of the present study was to investigate the effects of aqueous extract of Berberis integerrima root (AEBI) on some physiological parameters in normal and streptozotocin-induced (STZ-induced) diabetic male Wistar rats. STZ-induced diabetic rats showed significant increases in the levels of blood glucose, triglycerides (TG), total cholesterol (TC), low density lipoprotein LDL-cholesterol (LDL-C), creatinine (Cr), urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin while body weight, high density lipoprotein HDL-cholesterol (HDL-C) and total protein levels were significantly decreased compared to normal rats. Treatment of diabetic rats with different doses of aqueous extract of Berberis integerrima root (250 and 500 mg/Kg bw) resulted in a significant decrease in blood glucose, triglycerides, cholesterol, LDL-cholesterol, ALT, AST, ALP, total bilirubin, creatinine and urea while HDL-cholesterol and total protein levels were markedly increased after six weeks compared to untreated diabetic rats. The effects of the AEBI at dose of 500 mg/Kg in all parameters except blood glucose (similar) is more than to the standard drug, glibenclamide (0.6 mg/Kg, p.o.). The results of this study indicate that the tested aqueous extract of Berberis integerrima root possesses hypoglycemic, hypolipidemic and antioxidant effects in STZ-induced diabetic rats. PMID:24250618

  20. Effect of natural honey from Ilam and metformin for improving glycemic control in streptozotocin-induced diabetic rats

    PubMed Central

    Nasrolahi, Ozra; Heidari, Reza; Rahmani, Fatima; Farokhi, Farah

    2012-01-01

    Objective(s): Diabetes mellitus is a public health problem and one of the five leading causes of death globally. In the present study, the effect of Metformin with natural honey was investigated on glycemia in the Streptozotocin-induced diabetic rats. Materials and Methods: Thirty Wistar male rats were randomly divided into six groups including C: non diabetic rats received distilled water, CH: non diabetic rats received honey, CD: diabetic rats administered with distilled water, DM: Metformin treated diabetic rats, DH: honey treated diabetic rats, and DMH: diabetic rats treated with a combination of Metformin and natural honey. Diabetes was induced by a single dose of Streptozotocin (65 mg/kg; i.p.). The animals were treated by oral gavage once daily for four weeks. At the end of the treatment period, the animals were sacrificed and their blood samples collected. Amount of glucose, triglyceride (TG), total cholesterol (TC), HDL cholesterol, LDL cholesterol, VLDL cholesterol, total bilirubin, and albumin were determined in serum. Results: Group CD: showed hyperglycemia (252.2±4.1 mg/dl), while level of blood glucose was significantly (p<0.01) reduced in groups DH (124.2±2.7 mg/dl), DM (108.0±3.4 mg/dl), and DMH (115.4±2.1 mg/dl). Honey in combination with Metformin significantly (p<0.01) reduced level of bilirubin but Metformin alone did not reduce bilirubin. Honey alone and in combination with Metformin also significantly reduced triglycerides, total cholesterol, LDL, VLDL and increased HDL, but Metformin did not reduced triglycerides and increased HDL. Conclusion: The results of the present study demonstrated that consuming natural honey with Metformin improves glycemic control and is more useful than consuming Metformin alone. The higher therapeutic effect of Ilam honey on lipid abnormalities than Tualang honey was also evident. PMID:25050251

  1. Boron promotes streptozotocin-induced diabetic wound healing: roles in cell proliferation and migration, growth factor expression, and inflammation.

    PubMed

    Demirci, Selami; Doğan, Ayşegül; Aydın, Safa; Dülger, Esra Çikler; Şahin, Fikrettin

    2016-06-01

    Acute wounds do not generally require professional treatment modalities and heal in a predictable fashion, but chronic wounds are mainly accompanied with infection and prolonged inflammation, leading to healing impairments and continuous tissue degradation. Although a vast amount of products have been introduced in the market, claiming to provide a better optimization of local and systemic conditions of patients, they do not meet the expectations due to being expensive and not easily accessible, requiring wound care facilities, having patient-specific response, low efficiency, and severe side-effects. In this sense, developing new, safe, self-applicable, effective, and cheap wound care products with broad-range antimicrobial activity is still an attractive area of international research. In the present work, boron derivatives [boric acid and sodium pentaborate pentahydrate (NaB)] were evaluated for their antimicrobial activity, proliferation, migratory, angiogenesis, gene, and growth factor expression promoting effects on dermal cells in vitro. In addition, boron-containing hydrogel formulation was examined for its wound healing promoting potential using full-thickness wound model in streptozotocin-induced diabetic rats. The results revealed that while both boron compounds significantly increased proliferation, migration, vital growth factor, and gene expression levels of dermal cells along with displaying remarkable antimicrobial effects against bacteria, yeast, and fungi, NaB displayed greater antimicrobial properties as well as gene and growth factor expression inductive effects. Animal studies proved that NaB-containing gel formulation enhanced wound healing rate of diabetic animals and histopathological scores. Overall data suggest a potential promising therapeutic option for the management of chronic wounds but further studies are highly warranted to determine signaling pathways and target metabolisms in which boron is involved to elucidate the limitations

  2. Vitamin D₃ improves decline in cognitive function and cholinergic transmission in prefrontal cortex of streptozotocin-induced diabetic rats.

    PubMed

    Alrefaie, Zienab; Alhayani, Abdulmone'em

    2015-01-01

    Complications of diabetes mellitus include cognitive impairments and functional changes in the brain. The present study aimed to investigate the possible beneficial effect of vitamin D3 on episodic memory and cholinergic transmission in the prefrontal cortex of streptozotocin-induced diabetic rats. Thirty male Wistar rats (150-200 g) were included into control, diabetic and diabetic supplemented with vitamin D3 groups. Diabetes was induced by single intraperitoneal injection of streptozotocin 45 mg/kg in citrate buffer. Vitamin D3 was administered orally in a dose of 500 IU/kg/day in corn oil for 10 weeks. Then rats were subjected to novel object recognition test to examine for episodic memory. Animals were sacrificed under diethyl ether anesthesia and prefrontal cortices were dissected to measure the activity of choline acetyl transferase (CAT) and acetyle choline esterase (ACE) enzymes to assess for cholinergic transmission. Diabetic rats spent significantly less time exploring the novel object compared to control animals. Vitamin D3 significantly attenuated the diabetes-induced impairment so that animals again spent significantly more time exploring the novel object. The CAT activity was significantly decreased in diabetic animals while the ACE activity was significantly increased compared to control non-diabetic animals. Diabetes-induced alterations in enzyme activity in the prefrontal cortex were mitigated by vitamin D3 supplementation. The present findings demonstrate the potential effect of vitamin D3 supplementation on cognitive function in diabetic animals. It is possible that this effect is mediated through enhancing the prefrontal cortex cholinergic transmission. PMID:25835318

  3. Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice.

    PubMed

    Vujicic, Milica; Nikolic, Ivana; Kontogianni, Vassiliki G; Saksida, Tamara; Charisiadis, Pantelis; Vasic, Bobana; Stosic-Grujicic, Stanislava; Gerothanassis, Ioannis P; Tzakos, Andreas G; Stojanovic, Ivana

    2016-07-01

    Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp. hirtum (Greek oregano) contains antiinflammatory molecules, we hypothesized that it might be beneficial for the treatment of T1D. An ethyl acetate extract of oregano (EAO) was prepared from the leaves by a polar extraction method. Phytochemical composition was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface (LC/DAD/ESI-MS(n) ). In vitro immunomodulatory effect of EAO was estimated by measuring proliferation (MTT) or cytokine secretion (ELISA) from immune cells. Diabetes was induced by multiple low doses of streptozotocin (MLDS) in male C57BL/6 mice and EAO was administered intraperitoneally for 10 d. Determination of cellular composition (flow cytometry) and cytokine production (ELISA) was performed on 12th d after diabetes induction. EAO suppressed the function of both macrophages and lymphocytes in vitro. In vivo, EAO treatment significantly preserved pancreatic islets and reduced diabetes incidence in MLDS-challenged mice. Besides down-modulatory effect on macrophages, EAO reduced the number of total CD4(+) and activated CD4(+) CD25(+) T cells. Furthermore, EAO affected the number of T helper 1 (Th1) and T helper 17 (Th17) cells through downregulation of their key transcription factors T-bet and RORγT. Because EAO treatment protects mice from development of hyperglycemia by reducing proinflammatory macrophage/Th1/Th17 response, this plant extract could represent a basis for future diabetes therapy. PMID:27219840

  4. Antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Linn.) in streptozotocin-induced diabetic rats

    PubMed Central

    Petchi, Ramesh R.; Parasuraman, S.; Vijaya, C.

    2013-01-01

    Objective: To study the antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Asteraceae) in streptozotocin-induced diabetic rats. Materials and Methods: The whole plant of T. procumbens was collected in different regions of Madurai districts, Tamil Nadu. The air dried whole plant of T. procumbens was extracted with ethanol (95%) in a Soxhlet apparatus for 72 h. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/jk, i.p.) and nicotinamide (120 mg/kg, i.p) injection. The dry mass of the extract was used for preliminary phytochemical and pharmacological analysis. Diabetic rats were treated with glibenclamide (0.25 mg/kg, p.o.) or T. procumbens extract (250 and 500 mg/k, p.o.) for 21 consecutive days. The blood samples were collected at regular intervals to access hypoglycemic effect of an ethanolic extract of the whole plant of T. procumbens. At the end of the experiment, serum lipid profile and liver enzymes levels were analyzed for all the experimental animals and compared with diabetic control. Results: The preliminary phytochemical analysis of an ethanolic extract of the whole plant of T. procumbens indicated the presence of alkaloids, tannins, flavonoids, saponins, and phenolic compounds. The ethanolic extract of the whole plant of T. procumbens at 250 and 500 mg/kg has significant antidiabetic and antihyperlipidemic activities. The diabetic control animals exhibited a significant decrease in body weight compared with control animals. T. procumbens inhibited streptozotocin-induced weight loss and significantly alter the lipid levels. Conclusion: The ethanolic extract of the whole plant of T. procumbens showed significant antidiabetic and antihyperlipidemic activities against streptozotocin-induced diabetes in rats. PMID:24808679

  5. Evaluation of plasma H2S levels and H2S synthesis in streptozotocin induced Type-2 diabetes-an experimental study based on Swietenia macrophylla seeds

    PubMed Central

    Dutta, Moumita; Biswas, Utpal Kumar; Chakraborty, Runu; Banerjee, Piyasa; Raychaudhuri, Utpal; Kumar, Arun

    2014-01-01

    Objective To evaluate the plasma H2S levels and H2S synthesis activity in streptozotocin induced type 2 diabetes rats compared to the healthy controls and also to observe the effect of the aqueous extract of Swietenia macrophylla (S. macrophylla) seeds on the experimental groups. Methods Seeds of S. macrophylla were separated, washed, shed-dried and finally extract was prepared. Thirty two wistar rats were selected for the experimental study. Streptozotocin was used for the induction of diabetes. H2S concentration in plasma was measured. H2S synthesizing activity in plasma was measured. Statistical analysis have done using Microsoft excel, Office 2003. Values were expressed by mean±SD. P<0.05 were considered statistically significant. Results Fasting blood glucose level (7.74±0.02) mmol/L was significantly increased in diabetic rats. The glucose levels are significantly lowered in the rats treated with metformin (5.48±0.03) mmol/L as well as with aqueous extract of S. macrophylla seeds (3.72±0.04) mmol/L. The HbA1c percentages in different groups of study subjects also indicate similar trends. Our study shows both the plasma H2S levels (22.07±0.73) mmol/L and plasma H2S synthesis activity (0.411±0.005 mmol/100 g) are significantly reduced in the streptozotocin induced diabetic rats. Conclusions Although considering a small sample size, it can conclude that the fasting blood glucose levels are inversely related to plasma H2S levels as well as H2S synthesis activity in plasma and the extract of S. macrophylla is associated with increased plasma H2S levels with effective lowering of blood glucose in streptozotocin induced diabetic rats. PMID:25183134

  6. Preventive effect of L-carnosine on changes in the thermal nociceptive threshold in streptozotocin-induced diabetic mice.

    PubMed

    Kamei, Junzo; Ohsawa, Masahiro; Miyata, Shigeo; Tanaka, Shun-ichi

    2008-12-14

    Sensory abnormality is one of the serious complications in diabetes. Since the effective therapeutic regimen to ameliorate the diabetic sensory abnormality is very few, the present study was then designed to investigate the effect of zinc L-carnosine on the changes of nociceptive threshold in diabetic mice. Zinc L-carnosine (75-300 mg/kg, p.o.) was administered once daily from 1 day after streptozotocin treatment. Diabetic mice showed shorter tail-flick latency at 1-4 weeks after streptozotocin treatment and longer tail-flick latency at 6-9 weeks after its treatment. The shortened tail-flick latency in early stage of diabetic mice was ameliorated by treatment with zinc L-carnosine. Moreover, zinc L-carnosine also slowed the onset of hypoalgesia in diabetic mice. Tail-flick latency in non-diabetic mice was not affected by the zinc L-carnosine treatment, indicating that zinc L-carnosine did not affect normal nociceptive transmission. Moreover, L-carnosine, but not zinc sulfate, ameliorated the abnormal sensory perception in diabetic mice. Interestingly, the ameliorative effect of zinc l-carnosine on the abnormal sensory perception in diabetic mice is much stronger than that of L-carnosine. These results provide the evidence of the ameliorative potential of zinc L-carnosine on the progressive diabetic neuropathy. Moreover, L-carnosine combined with zinc shows more potent amelioration of abnormal sensory perception in diabetic mice than by itself. PMID:18930724

  7. Anti-diabetic effects of a series of vanadium dipicolinate complexes in rats with streptozotocin-induced diabetes.

    PubMed

    Willsky, Gail R; Chi, Lai-Har; Godzala, Michael; Kostyniak, Paul J; Smee, Jason J; Trujillo, Alejandro M; Alfano, Josephine A; Ding, Wenjin; Hu, Zihua; Crans, Debbie C

    2011-10-01

    The effects of oral treatment of rats with streptozotocin-induced diabetes with a range of vanadium dipicolinate complexes (Vdipic) and derivatives are reviewed. Structure-reactivity relationships are explored aiming to correlate properties such as stability, to their insulin-enhancing effects. Three types of modifications are investigated; first, substitutions on the aromatic ring, second, coordination of a hydroxylamido group to the vanadium, and third, changes in the oxidation state of the vanadium ion. These studies allowed us to address the importance of coordination chemistry, and redox chemistry, as modes of action. Dipicolinate was originally chosen as a ligand because the dipicolinatooxovanadium(V) complex (V5dipic), is a potent inhibitor of phosphatases. The effect of vanadium oxidation state (3, 4 or 5), on the insulin-enhancing properties was studied in both the Vdipic and VdipicCl series. Effects on blood glucose, body weight, serum lipids, alkaline phosphatase and aspartate transaminase were selectively monitored. Statistically distinct differences in activity were found, however, the trends observed were not the same in the Vdipic and VdipicCl series. Interperitoneal administration of the Vdipic series was used to compare the effect of administration mode. Correlations were observed for blood vanadium and plasma glucose levels after V5dipic treatment, but not after treatment with corresponding V4dipic and V3dipic complexes. Modifications of the aromatic ring structure with chloride, amine or hydroxyl groups had limited effects. Global gene expression was measured using Affymetrix oligonucleotide chips. All diabetic animals treated with hydroxyl substituted V5dipic (V5dipicOH) and some diabetic rats treated with vanadyl sulfate had normalized hyperlipidemia yet uncontrolled hyperglycemia and showed abnormal gene expression patterns. In contrast to the normal gene expression profiles previously reported for some diabetic rats treated with vanadyl

  8. Blunted endogenous GABA-mediated inhibition in the hypothalamic paraventricular nucleus of rats with streptozotocin-induced diabetes.

    PubMed

    Hassan, Zurina; Sattar, Munavvar Zubaid Abdul; Suhaimi, Farah Wahida; Yusoff, Nurul Hasnida Mohammed; Abdulla, Mohammed H; Yusof, Ahmad Pauzi M; Johns, Edward J

    2013-09-01

    The hypothalamic paraventricular nucleus (PVN) is involved in the regulation of sympathetic outflow and particularly affects the heart. This study sets out to determine the role of GABA of the paraventricular nucleus (PVN) in cardiovascular regulation in streptozotocin-induced diabetic rats. Pharmacological stimulation of glutamatergic receptors with DL-Homocysteic acid (200 mM in 100 nL) in the PVN region showed a significant depression in both mean arterial pressure (MAP) and heart rate (HR) of diabetic rats (Diabetic vs. non-diabetic: MAP 15.0 ± 1.5 vs. 35.8 ± 2.8 mmHg; HR 3.0 ± 2.0 vs. 30.0 ± 6.0 bpm, P < 0.05). Microinjection of bicuculline methiodide (1 mM in 100 nL), a GABAA receptor antagonist, produced an increase in baseline MAP and HR in both non-diabetic and diabetic rats. In the diabetic rats, bicuculline injection into the PVN reduced the pressor and HR responses (Diabetic vs. non-diabetic: MAP 6.2 ± 0.8 vs. 25.1 ± 2.2 mmHg; HR 1.8 ± 1.1 vs. 25.4 ± 6.2 bpm, P < 0.05). A microinjection of muscimol (2 mM in 100 nL), which is a GABAA receptor agonist, in the PVN elicited decreases in MAP and HR in both groups. The diabetic group showed a significantly blunted reduction in HR, but not MAP (Diabetic vs. non-diabetic: MAP -15.7 ± 4.0 vs. -25.0 ± 3.8 mmHg; HR -5.2 ± 2.1 vs. -39.1 ± 7.9 bpm). The blunted vasopressor and tachycardic responses to bicuculline microinjection in the diabetic rats are likely to result from decreased GABAergic inputs, attenuated release of endogenous GABA or alterations in GABAA receptors within the PVN. PMID:23242937

  9. Mediation of Endogenous β-endorphin by Tetrandrine to Lower Plasma Glucose in Streptozotocin-induced Diabetic Rats

    PubMed Central

    2004-01-01

    The role of β-endorphin in the plasma glucose-lowering action of tetrandrine in streptozotocin-induced diabetic rats (STZ-diabetic rats) was investigated. The plasma glucose concentration was assessed by the glucose oxidase method. The enzyme-linked immunosorbent assay was used to determine the plasma level of β-endorphin-like immunoreactivity (BER). The mRNA levels of glucose transporter subtype 4 (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats were detected by Northern blotting analysis. The expressed protein of GLUT4 or PEPCK was characterized by Western blotting analysis. Tetrandrine dose-dependently increased plasma BER in a manner parallel to the decrease of plasma glucose in STZ-diabetic rats. Moreover, the plasma glucose-lowering effect of tetrandrine was inhibited by naloxone and naloxonazine at doses sufficient to block opioid μ-receptors. Further, tetrandrine failed to produce plasma glucose-lowering action in opioid μ-receptor knockout diabetic mice. Bilateral adrenalectomy eliminated the plasma glucose-lowering effect and plasma BER-elevating effect of tetrandrine in STZ-diabetic rats. Both effects were abolished by treatment with hexamethonium or pentolinium at doses sufficient to block nicotinic receptors. Tetrandrine enhanced BER release directly from the isolated adrenal medulla of STZ-diabetic rats and this action was abolished by the blockade of nicotinic receptors. Repeated intravenous administration of tetrandrine (1.0 mg/kg) to STZ-diabetic rats for 3 days resulted in an increase in the mRNA and protein levels of the GLUT4 in soleus muscle, in addition to the lowering of plasma glucose. Similar treatment with tetrandrine reversed the elevated mRNA and protein levels of PEPCK in the liver of STZ-diabetic rats. The obtained results suggest that tetrandrine may induce the activation of nicotinic receptors in adrenal medulla to enhance the secretion of β-endorphin, which could

  10. Pancreatic Islet-Like Three-Dimensional Aggregates Derived From Human Embryonic Stem Cells Ameliorate Hyperglycemia in Streptozotocin-Induced Diabetic Mice.

    PubMed

    Shim, Joong-Hyun; Kim, JongHyun; Han, Jiyou; An, Su Yeon; Jang, Yu Jin; Son, Jeongsang; Woo, Dong-Hun; Kim, Suel-Kee; Kim, Jong-Hoon

    2015-01-01

    We previously reported the in vitro differentiation of human embryonic stem cells (hESCs) into pancreatic endoderm. Here we demonstrate that islet-like three-dimensional (3D) aggregates can be derived from the pancreatic endoderm by optimizing our previous protocol. Sequential treatment with Wnt3a, activin A, and noggin induced a transient upregulation of T and MixL1, followed by increased expression of endodermal genes, including FOXA2, SOX17, and CXCR4. Subsequent treatment with retinoic acid highly upregulated PDX1 expression. We also show that inhibition of sonic hedgehog signaling by bFGF/activin βB and cotreatment with VEGF and FGF7 produced many 3D cellular clusters that express both SOX17 and PDX1. We found for the first time that proteoglycans and vimentin(+) mesenchymal cells were mainly localized in hESC-derived PDX1(+) clusters. Importantly, treatment with chlorate, an inhibitor of proteoglycan sulfation, together with inhibition of Notch signaling significantly increased the expression of Neurog3 and NeuroD1, promoting a transition from PDX1(+) progenitor cells toward mature pancreatic endocrine cells. Purified dithizone(+) 3D aggregates generated by our refined protocol produced pancreatic hormones and released insulin in response to both glucose and pharmacological drugs in vitro. Furthermore, the islet-like 3D aggregates decreased blood glucose levels and continued to exhibit pancreatic features after transplantation into diabetic mice. Generation of islet-like 3D cell aggregates from human pluripotent stem cells may overcome the shortage of cadaveric donor islets for future cases of clinical islet transplantation. PMID:25397866

  11. Ameliorative Effect of Saffron Aqueous Extract on Hyperglycemia, Hyperlipidemia, and Oxidative Stress on Diabetic Encephalopathy in Streptozotocin Induced Experimental Diabetes Mellitus

    PubMed Central

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz

    2014-01-01

    Diabetic encephalopathy is one of the severe complications in patients with diabetes mellitus. Findings indicate that saffron extract has antioxidant properties but its underlying beneficial effects on diabetic encephalopathy were unclear. In the present study, the protective activities of saffron were evaluated in diabetic encephalopathy. Saffron at 40 and 80 mg/kg significantly increased body weight and serum TNF-α and decreased blood glucose levels, glycosylated serum proteins, and serum advanced glycation endproducts (AGEs) levels. Furthermore, significant increase in HDL and decrease (P < 0.05) in cholesterol, triglyceride, and LDL were observed after 28 days of treatment. At the end of experiments, the hippocampus tissue was used for determination of glutathione content (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Furthermore, saffron significantly increased GSH, SOD, and CAT but remarkably decreased cognitive deficit, serum TNF-α, and induced nitric oxide synthase (iNOS) activity in hippocampus tissue. Our findings indicated that saffron extract may reduce hyperglycemia and hyperlipidemia risk and also reduce the oxidative stress in diabetic encephalopathy rats. This study suggested that saffron extract might be a promising candidate for the improvement of chemically induced diabetes and its complications. PMID:25114929

  12. Geniposide ameliorates learning memory deficits, reduces tau phosphorylation and decreases apoptosis via GSK3β pathway in streptozotocin-induced alzheimer rat model.

    PubMed

    Gao, Chong; Liu, Yueze; Jiang, Yuanhong; Ding, Jianming; Li, Lin

    2014-04-01

    Intracerebral-ventricular (ICV) injection of streptozotocin (STZ) induces an insulin-resistant brain state that may underlie the neural pathogenesis of sporadic Alzheimer disease (AD). Our previous work showed that prior ICV treatment of glucagon-like peptide-1 (GLP-1) could prevent STZ-induced learning memory impairment and tau hyperphosphorylation in the rat brain. The Chinese herbal medicine geniposide is known to relieve symptoms of type 2 diabetes. Because geniposide is thought to act as a GLP-1 receptor agonist, we investigated the potential therapeutic effect of geniposide on STZ-induced AD model in rats. Our result showed that a single injection of geniposide (50 μM, 10 μL) to the lateral ventricle prevented STZ-induced spatial learning deficit by about 40% and reduced tau phosphorylation by about 30% with Morris water maze test and quantitative immunohistochemical analysis, respectively. It has been known that tau protein can be phosphorylated by glycogen synthase kinase-3 (GSK3) and STZ can increase the activity of GSK3β. Our result with Western blot analysis showed that central administration of geniposide resulted in an elevated expression of GSK3β(pS-9) but suppressed GSK3β(pY-216) indicating that geniposide reduced STZ-induced GSK3β hyperactivity. In addition, ultrastructure analysis showed that geniposide averted STZ-induced neural pathology, including paired helical filament (PHF)-like structures, accumulation of vesicles in synaptic terminal, abnormalities of endoplasmic reticulum (ER) and early stage of apoptosis. In summary, our study suggests that the water soluble and orally active monomer of Chinese herbal medicine geniposide may serve as a novel therapeutic agent for the treatment of sporadic AD. PMID:24329968

  13. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Cheng, Poh-Guat; Sabaratnam, Vikineswary; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats. PMID:24348715

  14. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Cheng, Poh-Guat; Phan, Chia-Wei; Sabaratnam, Vikineswary; Abdullah, Noorlidah; Abdulla, Mahmood Ameen; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats. PMID:24348715

  15. High β-cell mass prevents streptozotocin-induced diabetes in thioredoxin-interacting protein-deficient mice

    PubMed Central

    Masson, Elodie; Koren, Shlomit; Razik, Fathima; Goldberg, Howard; Kwan, Edwin P.; Sheu, Laura; Gaisano, Herbert Y.; Fantus, I. George

    2010-01-01

    Thioredoxin-interacting protein (TxNIP) is an endogenous inhibitor of thioredoxin, a ubiquitous thiol oxidoreductase, that regulates cellular redox status. Diabetic mice exhibit increased expression of TxNIP in pancreatic islets, and recent studies suggest that TxNIP is a proapoptotic factor in β-cells that may contribute to the development of diabetes. Here, we examined the role of TxNIP deficiency in vivo in the development of insulin-deficient diabetes and whether it impacted on pancreatic β-cell mass and/or insulin secretion. TxNIP-deficient (Hcb-19/TxNIP−/−) mice had lower baseline glycemia, higher circulating insulin concentrations, and higher total pancreatic insulin content and β-cell mass than control mice (C3H). Hcb-19/TxNIP−/− did not develop hyperglycemia when injected with standard multiple low doses of streptozotocin (STZ), in contrast to C3H controls. Surprisingly, although β-cell mass remained higher in Hcb-19/TxNIP−/− mice compared with C3H after STZ exposure, the relative decrease induced by STZ was as great or even greater in the TxNIP-deficient animals. Consistently, cultured pancreatic INS-1 cells transfected with small-interfering RNA against TxNIP were more sensitive to cell death induced by direct exposure to STZ or to the combination of inflammatory cytokines interleukin-1β, interferon-γ, and tumor necrosis factor-α. Furthermore, when corrected for insulin content, isolated pancreatic islets from TxNIP−/− mice exhibited reduced glucose-induced insulin secretion. These data indicate that TxNIP functions as a regulator of β-cell mass and influences insulin secretion. In conclusion, the relative resistance of TxNIP-deficient mice to STZ-induced diabetes appears to be because of an increase in β-cell mass. However, TxNIP deficiency is associated with sensitization to STZ- and cytokine-induced β-cell death, indicating complex regulatory roles of TxNIP under different physiological and pathological conditions. PMID

  16. Protective Nature of Mangiferin on Oxidative Stress and Antioxidant Status in Tissues of Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Sellamuthu, Periyar Selvam; Arulselvan, Palanisamy; Kamalraj, Subban; Fakurazi, Sharida; Kandasamy, Murugesan

    2013-01-01

    Oxidative stress plays an important role in the progression of diabetes complications. The aim of the present study was to investigate the beneficial effect of oral administration of mangiferin in streptozotocin (STZ)-induced diabetic rats by measuring the oxidative indicators in liver and kidney as well as the ameliorative properties. Administration of mangiferin to diabetic rats significantly decreased blood glucose and increased plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and level of reduced glutathione (GSH) were significantly (P < 0.05) decreased while increases in the levels of lipidperoxidation (LPO) markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with mangiferin (40 mg/kg b.wt/day) for a period of 30 days showed significant ameliorative effects on all the biochemical and oxidative parameters studied. Diabetic rats treated with mangiferin restored almost normal architecture of liver and kidney tissues, which was confirmed by histopathological examination. These results indicated that mangiferin has potential ameliorative effects in addition to its antidiabetic effect in experimentally induced diabetic rats. PMID:24167738

  17. Effect of Hibiscus rosa sinensis Linn. ethanol flower extract on blood glucose and lipid profile in streptozotocin induced diabetes in rats.

    PubMed

    Sachdewa, Archana; Khemani, L D

    2003-11-01

    Blood glucose and total lipid levels were determined in streptozotocin induced diabetic rats after oral administration of an ethanol flower extract of Hibiscus rosa sinensis. A comparable hypoglycemic effect was evidenced from the data obtained after 7 and 21 days of oral administration of the extract and glibenclamide. Maximal diminution in blood glucose (41-46%) and insulin level (14%) was noticed after 21 days. The extract lowered the total cholesterol and serum triglycerides by 22 and 30%, respectively. The increase in HDL-cholesterol was much higher (12%) under the influence of the extract as compared to that of glibenclamide (1%). The hypoglycemic activity of this extract is comparable to that of glibenclamide but is not mediated through insulin release. Other possible mechanisms are discussed. PMID:14522433

  18. Antihyperglycemic and antihyperlipidemic activity of ethyl acetate fraction of Rhododendron arboreum Smith flowers in streptozotocin induced diabetic rats and its role in regulating carbohydrate metabolism

    PubMed Central

    Verma, Neeraj; Amresh, G; Sahu, PK; Rao, Ch V; Singh, Anil Pratap

    2012-01-01

    Objective To explore and identify the most potent antihyperglycemic fraction from the ethanol extract of Rhododendron arboreum (R. arboreum) flowers. Methods Normal and streptozotocin induced diabetic rats were treated with all four fractions of R. arboreum flowers for short term and with fraction 3 for long term study. On completion of the treatment, a range of indicators were tested including fasting blood glucose, plasma protein, haemoglobin A1C, insulin secretion, body weight, blood lipid profile and carbohydrate metabolism regulating enzymes of liver. Results In short term study, the fraction 3 (Active fraction) produced a significant (P<0.000 1) reduction (73.6%) in blood glucose level at a dose of 200 mg/kg after the treatment in the diabetic rats. Administration of active fraction (200 and 400 mg/kg) once daily for 30 d in streptozotocin diabetic rats resulted in a significant (P<0.001 to P<0.000 1) fall in blood glucose level, hemoglobin A1C, serum urea and creatinine with significant but a increase in insulin level similar to standard drug glybenclamide. Further, the active fraction showed antihyperlipidemic activity as evidenced by significant (P<0.001 to P<0.000 1) decreases in serum serum total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density cholesterol levels coupled together with elevation of high density lipoprotein cholesterol in the diabetic rats. Conclusions The active fraction of R. arboreum flowers decreases streptozotocin induced hyperglycemia by promoting insulin secretion and glycolysis and by decreasing gluconeogenesis. PMID:23569997

  19. Rhinacanthus nasutus Improves the Levels of Liver Carbohydrate, Protein, Glycogen, and Liver Markers in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Visweswara Rao, Pasupuleti; Madhavi, K.; Dhananjaya Naidu, M.; Gan, Siew Hua

    2013-01-01

    The present study was designed to investigate the total carbohydrate, total protein, and glycogen levels in the liver and to measure functional liver markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in streptozotocin-(STZ-) induced diabetic rats after treatment with methanolic extract of Rhinacanthus nasutus (R. nasutus). The methanolic extract of R. nasutus was orally administered at 200 mg/kg/day while glibenclamide was administered at 50 mg/kg/day. All animals were treated for 30 days before being sacrificed. The amounts of carbohydrate, glycogen, proteins, and liver markers (AST and ALT) were measured in the liver tissue of the experimental animals. The levels of carbohydrate, glycogen, and proteins were significantly reduced in the diabetic rats but were augmented considerably after 30 days of R. nasutus treatment. The elevated AST and ALT levels in diabetic rats showed a significant decline after treatment with R. nasutus for 30 days. These results show that the administration of R. nasutus ameliorates the altered levels of carbohydrate, glycogen, proteins, and AST and ALT observed in diabetic rats and indicate that R. nasutus restores overall metabolism and liver function in experimental diabetic rats. In conclusion, the outcomes of the present study support the traditional belief that R. nasutus could ameliorate the diabetic state. PMID:24204387

  20. Ensete superbum ameliorates renal dysfunction in experimental diabetes mellitus

    PubMed Central

    Sreekutty, MS; Mini, S

    2016-01-01

    Objective(s): Hyperglycemia mediated oxidative stress plays a key role in the pathogenesis of diabetic complications like nephropathy. In the present study, we evaluated the effect of ethanolic extract of Ensete superbum seeds (ESSE) on renal dysfunction and oxidative stress in streptozotocin-induced diabetic rats. Materials and Methods: Glucose, HbA1c, total protein, albumin, renal function markers (urea, uric acid and creatinine), and lipid peroxidation levels were evaluated. Renal enzymatic and non-enzymatic antioxidants were examined along with renal histopathological study. Results: ESSE (400 mg/kg BW t) administration reduced glucose and HbA1c, and improved serum total protein and albumin in diabetic rats. ESSE in diabetic rats recorded decrement in renal function markers and renal lipid peroxidation products along with significant increment in enzymatic and non-enzymatic antioxidants. Renal morphological abnormalities of diabetic rats were markedly ameliorated by E. superbum. Conclusion: These results suggest that the antioxidant effect of E. superbum could ameliorate oxidative stress and delay/prevent the progress of diabetic nephropathy in diabetes mellitus. PMID:27096072

  1. The antihyperglycemic effect of aerial parts of Salvia splendens (scarlet sage) in streptozotocin-induced diabetic-rats

    PubMed Central

    Kumar, P. Mahesh; Sasmal, D.; Mazumder, Papiya Mitra

    2010-01-01

    Salvia splendens (Labiatae) is widely used in Indian traditional medicine for the control of diabetes mellitus. In this study, the hypoglycemic effects produced by the acute and subacute administration of various extracts of S. splendens were investigated. Both the aqueous extract (SSAE) and the methanolic extract (SSME) from the aerial parts resulted in significant reductions of glycemia in streptozotocin (STZ)-induced diabetic rats after oral administration at a dose of 100 and 200 mg/kg, respectively. On oral administration, aqueous and methanolic extracts showed statistically significant (P < 0.001) effect by reducing the effect of glycemia in STZ-induced diabetic rats. These findings suggest the significant antihyperglycemic potential of the S. splendens extracts in ameliorating the diabetic conditions in diabetic rats. No significant effects were found in the normal rats. PMID:21808565

  2. The antihyperglycemic effect of aerial parts of Salvia splendens (scarlet sage) in streptozotocin-induced diabetic-rats.

    PubMed

    Kumar, P Mahesh; Sasmal, D; Mazumder, Papiya Mitra

    2010-05-01

    Salvia splendens (Labiatae) is widely used in Indian traditional medicine for the control of diabetes mellitus. In this study, the hypoglycemic effects produced by the acute and subacute administration of various extracts of S. splendens were investigated. Both the aqueous extract (SSAE) and the methanolic extract (SSME) from the aerial parts resulted in significant reductions of glycemia in streptozotocin (STZ)-induced diabetic rats after oral administration at a dose of 100 and 200 mg/kg, respectively. On oral administration, aqueous and methanolic extracts showed statistically significant (P < 0.001) effect by reducing the effect of glycemia in STZ-induced diabetic rats. These findings suggest the significant antihyperglycemic potential of the S. splendens extracts in ameliorating the diabetic conditions in diabetic rats. No significant effects were found in the normal rats. PMID:21808565

  3. Antidiabetic, renal/hepatic/pancreas/cardiac protective and antioxidant potential of methanol/dichloromethane extract of Albizzia Lebbeck Benth. stem bark (ALEx) on streptozotocin induced diabetic rats

    PubMed Central

    2014-01-01

    Background Hypoglycemic and/or anti-hyperglycemic activities have been recorded with numerous plants, many of which are used as traditional herbal treatments of diabetes. Albizzia Lebbeck Benth. stem bark have been used in traditional medicine along with some preliminary reports on its hypoglycemic action. The aim of present investigation was to evaluate the antidiabetic and antioxidant activities of methanolic extract of stem bark of Albizzia Lebbeck Benth. in streptozotocin induced diabetic rats. Methods The powdered stem bark of Albizzia Lebbeck Benth.. was extracted with methanol (MeOH) using soxhlation method and subjected to phytochemical analysis. The methanol/dichloromethane extract of Albizzia Lebbeck Benth. (ALEx) was concentrated to dryness using Rotary Evaporator. Diabetes was experimentally induced in the rats by single intraperitoneal administration of Streptozotocin (60 mg/kg). They glycemic control was measured by the blood glucose, glycated heamoglobin and plasma insulin. The oxidative stress was evaluated in the liver and kidney by level of antioxidant markers and various biochemical parameters were assessed in diabetic control and extract treated rats. Results Streptozotocin induced diabetic rats depicted the increased blood glucose levels, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), diminished level of high density lipoprotein cholesterol (HDL-c) level and perturb level of antioxidant markers. Oral administration of MeAL at a concentration of 100, 200, 300 and 400 mg/kg b.w daily for 30 days results a momentous decrease in fasting blood glucose, glycated heamoglobin and enhancement of plasma insulin level as compared with STZ induced diabetic rats. Furthermore, it significantly (p < 0.05) decreased the level of TC, TG, and LDL-c, VLDL-c. While it increases the level of HDL-c to a significant (p < 0.05) level. The treatment also resulted in a marked increase in reduced glutathione

  4. Effect of the hexane extract of Piper auritum on insulin release from β-cell and oxidative stress in streptozotocin-induced diabetic rat

    PubMed Central

    Gutierrez, Rosa Martha Perez

    2012-01-01

    Background: The large-leafed perennial plant Piper auritum known as Hoja Santa, is used for its leaves that because of their spicy aromatic scent and flavor have an important presence in Mexican cuisine, and in many regions, this plant is known for its therapeutic properties. Materials and Methods: In the present study, we investigated the effect of hexane, chloroform and methanol extracts from Piper auritum on cell culture system and the effect in streptozotocin-induced type 1 diabetic rats treated by 28 days on the physiological, metabolic parameters and oxidative stress. Results: The hexane extract of P. auritum (HS) treatment significantly reduced the intake of both food, water and body weight loss as well as levels of blood glucose, serum cholesterol, triglycerides and increase HDL-cholesterol. After 4-week administration of HS antioxidant enzyme as SOD, CAT, GSH, GPx in pancreas were determined. These enzyme increased significantly compared with those of the diabetic rats control and normal animals. For all estimated, the results of HS treated groups leading to a restoration of the defense mechanism. The treatment also improves pancreatic TBARS–reactive substance level and serum NO and iNOS. To determine the insulin releasing activity, after extract treatment the serum and pancreatic sections were processed for examination of insulin-releasing activity using an immunocytochemistry kit. The results showed that administration of the hexane extract (200 and 400 mg/kg) exhibited a significant increase in serum and pancreas tissue insulin. Administration of streptozotocin decreased the insulin secretory activity in comparison with intact rats, but treatment with the HS extract increased significantly the activity of the beta cells in comparison with the diabetic control rats. The extract decreased serum glucose in streptozotocin-induced diabetic rats and increased insulin release from the beta cells of the pancreas. In cultured RIN-5F cells, we examined whether

  5. Anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of Melastoma malabathricum Linn. leaves in streptozotocin induced diabetic rats

    PubMed Central

    2013-01-01

    Background Melastoma malabathricum (MM) Linn leaves traditionally use in the treatment of diabetic conditions. The aim of the present investigation was to evaluate the antioxidant, antihyperlipidemic and antidiabetic activity of methanolic extract taken from Melastoma malabathricum Linn (Melastomaceae). Methods The methanolic leaves extract of MM Linn leaves used for the study. Chemical test of different extract, acute toxicity study and oral glucose test was performed. Diabetes was induced in rat by single intra-peritoneal injection of streptozotocin (55 mg/kg). The rats were divided into following groups: Group I – normal control, Group II (Vehicle) – diabetic control, Group III (STZ-toxic) – MM I (100 mg/kg, p.o.), Group IV – MM II (250 mg/kg, p.o.), Group V – MM III (500 mg/kg, p.o.), Group VI – glibenclamide (10 mg/kg, p.o.). Bodyweight of each rat in the different groups was recorded daily. Biochemical and antioxidant enzyme parameters were determined on day 28. Histology of different organ (heart, liver, kidney, and pancreas) was performed after sacrificing the rats with euthanasia. Results The methanolic extract of MM did not show any acute toxicity up-to the dose of 2000 mg/kg and shown better glucose utilization in oral glucose tolerance test. Orally treatment of different doses of MM leaves extract decreased the level of serum glucose, glycated hemoglobin, glucose-6-phosphatase, fructose-1-6-biphosphate and increased the level of plasma insulin, hexokinase. MM treatment decreased liver malondialdehyde but increased the level of superoxide dismutase, catalase and glutathione peroxidase. In oral glucose tolerance test observed increased utilization of glucose. Streptozotocin induced diabetes groups rat treated with different doses of MM leaves extract and glibenclamide significantly increased the body weight. Histopathology analysis on different organ of STZ (streptozotocin) induced diabetic rat show there regenerative effect on the liver

  6. Salvianolic acid A protects against vascular endothelial dysfunction in high-fat diet fed and streptozotocin-induced diabetic rats.

    PubMed

    Yang, Xiu-Ying; Qiang, Gui-Fen; Zhang, Li; Zhu, Xiao-Ming; Wang, Shou-Bao; Sun, Lan; Yang, Hai-Guang; Du, Guan-Hua

    2011-10-01

    Salvianolic acid A (SalA) is one of the main active ingredients of Salvia miltiorrhizae. The objective of this study was to evaluate the effect of SalA on the diabetic vascular endothelial dysfunction (VED). The rats were given a high-fat and high-sucrose diet for 1 month followed by intraperitoneal injection of streptozotocin (30 mg/kg). The diabetic rats were treated with SalA (1 mg/kg, 90% purity) orally for 10 weeks after modeling, and were given a high-fat diet. Contractile and relaxant responses of aorta rings as well as the serum indications were measured. Our results indicated that SalA treatment decreased the level of serum Von Willebrand factor and ameliorated acetylcholine-induced relaxation and KCl-induced contraction in aorta rings of the diabetic rats. SalA treatment also reduced the serum malondialdehyde, the content of aortic advanced glycation end products (AGEs), and the nitric oxide synthase (NOS) activity as well as the expression of endothelial NOS protein in the rat aorta. Exposure of EA.hy926 cells to AGEs decreased the cell viability and changed the cell morphology, whereas SalA had protective effect on AGEs-induced cellular vitality. Our data suggested that SalA could protect against vascular VED in diabetes, which might attribute to its suppressive effect on oxidative stress and AGEs-induced endothelial dysfunction. PMID:21972802

  7. Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats.

    PubMed

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz; Farkhondeh, Tahereh

    2016-04-01

    Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress. PMID:26863330

  8. Peripheral nerve metabolism and zinc levels in streptozotocin induced diabetic rats. Effect of diets high in fish and corn oil

    SciTech Connect

    Burke, J.P.; Fenton, M.R. )

    1991-03-15

    This study was designed to assess the effects of diets high in fish and corn oil on peripheral nerve metabolism in streptozotocin (STZ) induced diabetic rats. A type I diabetic state was induced in female Sprague-Dawley rats by injection of STZ. Animals were divided into three dietary groups; normal rat chow, high corn oil diet and high fish oil diet. After 4 weeks animals were analyzed for nerve conduction velocity, bled and then sacrificed. Sciatic nerves were removed, processed and several biochemical parameters determined. Plasma zinc levels were elevated in the STZ normal chow group compared to non-diabetic controls. Both corn oil and fish oil diets tended to eliminate the rise in plasma zinc. Differences in subcellular distribution of zinc in sciatic nerves were also observed. Normal chow STZ animals displayed a 20% decrease in nerve conduction velocity compared to control. Dietary supplementation with either fish or corn oil seemed to ameliorate these effects. Biochemical analysis of Na{sup +}-K{sup +}-ATPase and protein kinase C revealed a decrease in activity in normal chow animals compared to control groups. Again, dietary intervention with either fish or corn oil seemed to return these activities back to normal. The results suggest a link between zinc metabolism and peripheral nerve metabolism which can be modified by dietary intervention.

  9. Antihypertriglyceridemia and Anti-Inflammatory Activities of Monascus-Fermented Dioscorea in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Shi, Yeu-Ching; Liao, Jiunn-Wang; Pan, Tzu-Ming

    2011-01-01

    The rice fermented by Monascus, called red mold rice (RMR), and has a long tradition in East Asia as a dietary staple. Monascus-fermented dioscorea called red mold dioscorea (RMD) contains various metabolites to perform the ability of reducing oxidative stress and anti-inflammatory response. We used Wistar rats and induced diabetes by injecting streptozotocin (STZ, 65 mg/kg i.p.). RMD was administered daily starting six weeks after disease onset. Throughout the experimental period, significantly (P < .05) lowered plasma glucose, triglyceride, cholesterol, free fatty acid and low density lipoprotein levels were observed in the RMD-treated groups. The RMD-treated diabetic rats showed higher activities of glutathione disulfide reductase, glutathione reductase, catalase and superoxide dismutase (P < .05) in the pancreas compared with the diabetic control rats. RMD also inhibited diabetes-induced elevation in the levels of interleukin (IL)-1β, IL-6, interferon-γ and tumor necrosis factor-α. Pancreatic β-cells damaged by STZ in the RMD supplemented groups were ameliorated. The results of this study clearly demonstrated that RMD possesses several treatment-oriented properties, including the control of hyperglycemia, antioxidant effects, pancreatic β-cell protection and anti-inflammatory effects. Considering these observations, it appears that RMD may be a useful supplement to delay the development of diabetes and its complications. PMID:21716679

  10. Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity

    PubMed Central

    Wu, Jinzi; Yan, Liang-Jun

    2015-01-01

    Chronic hyperglycemia and the corresponding glucotoxicity are the main pathogenic mechanisms of diabetes and its complications. Streptozotocin (STZ)-induced diabetic animal models are useful platforms for the understanding of β cell glucotoxicity in diabetes. As diabetes induced by a single STZ injection is often referred to as type 1 diabetes that is caused by STZ’s partial destruction of pancreas, one question often being asked is whether the STZ type 1 diabetes animal model is a good model for studying the mitochondrial mechanisms of β cell glucotoxicity. In this mini review, we provide evidence garnered from the literature that the STZ type 1 diabetes is indeed a suitable model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity. Evidence presented includes: 1) continued β cell derangement is due to chronic hyperglycemia after STZ is completely eliminated out of the body; 2) STZ diabetes can be reversed by insulin treatment, which indicates that β cell responds to treatment and shows ability to regenerate; and 3) STZ diabetes can be ameliorated or alleviated by administration of phytochemicals. In addition, mechanisms of STZ action and fundamental gaps in understanding mitochondrial mechanisms of β cell dysfunction are also discussed. PMID:25897251

  11. Comparison of effect of resveratrol and vanadium on diabetes related dyslipidemia and hyperglycemia in streptozotocin induced diabetic rats

    PubMed Central

    Mohamad Shahi, Majid; Haidari, Fatemeh; Shiri, Mohamad Reza

    2011-01-01

    Purpose: Resveratrol a natural polyphenolicstilbene derivative has wide variety of biological activities. There is also a large body of evidence demonstrating positive effect of resveratrol in treatment of various metabolic complications including metabolic syndrome, obesity, diabetes and dyslipidemia in adults. The purpose of this study was to investigate anti-hyperglycemic and anti-dyslipidemic effects of resveratrol. Methods: We used 40 diabetic streptozotocin Wistar rats. Rats were randomly divided into 5 treatment groups (n=8 in each) including normal control, normal treated with resveratrol, diabetic control, diabetic treated with vanadium , diabetic treated with resveratrol . Resveratrol (25 mg/kgbw) and vanadate (0.2 mg/kgbw) was orally gavaged for 40 days and blood samples were directly collected from heart. Results: Diabetic rats treated with resveratrol in comparison to control diabetic rats demonstrated a significant (p = 0.001) decline in serum glucose concentration, and high plasma concentrations of total cholesterol and LDL-c were reduced (p = 0.031, p = 0.004 respectively). Furthermore, body weight loss trend that observed in diabetic rats alleviated by resveratrol and vanadate. However triglyceride, VLDL-c and HDL-c levels did not changed significantly. Conclusion: In conclusion Resveratrol ameliorated dyslipidemia and hyperglycemia in diabetic rats. However further investigations in peculiar human studies are required. PMID:24312761

  12. Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment.

    PubMed

    Ahmed, Md Ejaz; Javed, Hayate; Khan, Mohd Moshahid; Vaibhav, Kumar; Ahmad, Ajmal; Khan, Andleeb; Tabassum, Rizwana; Islam, Farah; Safhi, Mohammed M; Islam, Fakhrul

    2013-10-01

    Oxidative stress is a critical contributing factor to age-related neurodegenerative disorders. Therefore, the inhibition of oxidative damage, responsible for chronic detrimental neurodegeneration, is an important strategy for neuroprotective therapy. Withania somnifera (WS) extract has been reported to have potent antioxidant and free radical quenching properties in various disease conditions. The present study evaluated the hypothesis that WS extract would reduce oxidative stress-associated neurodegeneration after intracerebroventricular injection of streptozotocin (ICV-STZ) in rats. To test this hypothesis, male Wistar rats were pretreated with WS extract at doses of 100, 200, and 300 mg/kg body weight once daily for 3 weeks. On day 22nd, the rats were infused bilaterally with ICV-STZ injection (3 mg/kg body weight) in normal saline while sham group received only saline. Two weeks after the lesioning, STZ-infused rats showed cognitive impairment in the Morris water maze test. The rats were sacrificed after 3 weeks of the lesioning for the estimation of the contents of lipid peroxidation, reduced glutathione, and activities of glutathione reductase, glutathione peroxidase, and catalase. Pretreatment with WS extract attenuated behavioral, biochemical, and histological alterations significantly in dose-dependent manner in the hippocampus and cerebral cortex of ICV-STZ-infused rats. These results suggest that WS affords a beneficial effect on cognitive deficit by ameliorating oxidative damage induced by streptozotocin in a model of cognitive impairment. PMID:23340606

  13. Extract of green tea leaves partially attenuates streptozotocin-induced changes in antioxidant status and gastrointestinal functioning in rats.

    PubMed

    Juśkiewicz, Jerzy; Zduńczyk, Zenon; Jurgoński, Adam; Brzuzan, Łucja; Godycka-Kłos, Irena; Zary-Sikorska, Ewa

    2008-05-01

    Rats with severe streptozotocin (STZ)-induced diabetes were subjected to dietary green tea extract supplementation at 2 doses (0.01% and 0.2%; GTL and GTH groups, respectively) to evaluate their effects on antioxidant, gastrointestinal, and renal parameters of experimental animals. The lower dietary supplementation reflects daily consumption of 3 cups of green tea for an average adult weighing 70 kg. Supplementation of a diet with green tea extract had no influence on elevated food intake, body weight loss, increased glucose concentration, or declined antioxidant capacity of water-soluble substances in plasma in the diabetic rats. In cases of intestinal maltase activity, attenuation of liver and kidney hypertrophy, triacylglycerol concentration, and aspartate aminotransferase activity in the serum, both dietary treatments normalized metabolic disorders caused by STZ injection to a similar extent. Unlike the GTL group, the GTH treatment significantly ameliorated development of diabetes-induced abnormal values for small intestinal saccharase and lactase activities, renal microalbuminuria, thiobarbituric acid-reactive substance content in kidney tissue, as well as total antioxidant status in the serum of rats. The GTH group was also characterized by higher antioxidant capacity of lipid-soluble substances in plasma and superoxide dismutase activity in the serum. Although the higher dose of green tea extract did not completely protect against STZ-induced hyperglycemia and oxidative stress in experimental rats, this study suggests that green tea extract ingested at high amounts may prove to be a useful therapeutic option in the reversal of diabetic dysfunction. PMID:19083430

  14. Antihyperglycemic effects of fruits of privet (Ligustrum obtusifolium) in streptozotocin-induced diabetic rats fed a high fat diet.

    PubMed

    Lee, Sang-Il; Oh, Sung-Hee; Park, Kun-Young; Park, Bum-Ho; Kim, Jeong-Sook; Kim, Soon-Dong

    2009-02-01

    The protective effects of freeze-dried privet (Ligustrum obtusifolium) fruits (PFs) were observed in streptozotocin (STZ)-induced diabetic rats on a high fat diet by measuring levels of blood glucose, serum insulin, fructosamine, and hepatic reactive oxygen species generating and scavenging enzyme activities. A PF-supplemented diet was prepared by mixing an AIN-76 diet with powdered PF (final concentration, 1% or 2%). It was fed to STZ-induced diabetic rats on a high fat diet for 6 weeks. Diabetic animals receiving the PF-supplemented diet showed a significant increase in body weight, feed efficiency ratio, liver, kidney, and heart weight, and serum glucose, insulin, and fructosamine levels compared with high fat diet-fed diabetic animals. The treatment with PF showed improved hepatic glutathione S-transferase, superoxide dismutase, and xanthine oxidase activities as well as glutathione and lipid peroxide levels in the diabetic animals. Intracellular swelling and vacuole formation in diabetic pancreatic beta- and delta-cells were ameliorated by the PF-supplemented diet. Furthermore, necrosis of tubular epithelial cells and dilatation of luminal space in diabetic kidneys exhibited near-noninjured condition. This is the first time an antihyperglycemic effect of L. obtusifolium fruit in STZ-induced diabetic rats has been identified. PMID:19298203

  15. Effect of Nigella sativa fixed and essential oils on antioxidant status, hepatic enzymes, and immunity in streptozotocin induced diabetes mellitus

    PubMed Central

    2014-01-01

    Background Nigella sativa fixed (NSFO) and essential (NSEO) oils have been used to treat diabetes mellitus and its complications. Present study was undertaken to explore and validate these folkloric uses. Methods Sprague dawley rats having streptozotocin (STZ) induced diabetes mellitus were used to assess the role of NSFO and NSEO in the management of diabetes complications. Parameters investigated were antioxidant potential, oxidative stress, and the immunity by in vivo experiments. Results The results indicated that STZ decreased the glutathione contents (25.72%), while NSFO and NSEO increased the trait significantly (P < 0.05). Experimental diets increased the tocopherol contents (P < 0.01) and enhanced the expression of hepatic enzymes (P < 0.01). Correlation matrix further indicated that antioxidant potential is positively associated (P < 0.05) responsible for the modulation of hepatic enzymes and the decrease of the nitric oxide production thus controlling the diabetes complications. Conclusions Overall, results of present study supported the traditional use of N. sativa and its derived products as a treatment for hyperglycemia and allied abnormalities. Moreover, N. sativa fixed and essential oils significantly ameliorate free radicals and improve antioxidant capacity thus reducing the risk of diabetic complications. PMID:24939518

  16. The Effect of Regular Moderate Exercise on miRNA-192 Expression Changes in Kidney of Streptozotocin-Induced Diabetic Male Rats

    PubMed Central

    Oghbaei, Hajar; Ahmadi Asl, Naser; Sheikhzadeh, Farzam; Alipour, Mohammad Reza; khamaneh, Amir Mahdi

    2015-01-01

    Purpose: The purpose of this study was to investigate the regular moderate exercise effect on the miR-192 expression changes in kidney of Streptozotocin- induced diabetic rats. Methods: Forty adult male Wistar rats were divided into four groups of 10, including Sedentary Control group, Healthy 60 days Exercise group, diabetic group and Diabetic 60 days Exercise. Diabetes was induced by injection of 60 mg/kg Streptozotocin and after 48 hour blood glucose levels higher than 250 mg/dl were included to diabetic rats. After 48 hour of induction diabetes, exercise protocol was begun. Animals performed 5 days of consecutive treadmill exercise (60 min/day) with 22 m/min speeds for 60 days. Kidney of the rats has removed and MicroRNA was extracted from kidney using miRCURYTM RNA isolation kit. Results: Exercise upregulated miR-192 expression level significantly in the kidney of diabetic rats in comparison to healthy group. There is not any significant change in miR-192 expression in diabetic 60 days exercise compared to control group. Conclusion: These results may indicate that exercise can help to prevent the progression of diabetic nephropathy. PMID:25789230

  17. Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands

    PubMed Central

    Knaś, M.; Daniszewska, I.; Klimiuk, A.; Kołodziej, U.; Waszkiel, D.; Ładny, J. R.; Żendzian-Piotrowska, M.

    2016-01-01

    Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM). Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2′-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14 (groups 2 and 4) days of experiment. Results. The unstimulated salivary flow in DM rats was reduced in the 2nd week, while the stimulated flow was decreased throughout the duration of the experiment versus control. OSI was elevated in both diabetic glands in the 1st and 2nd week, whereas 8-isoP and 8-OHdG were higher only in the parotid gland in the second week. PC and 4-HNE were increased in the 1st and 2nd week, whereas oxy-LDL/MDA was increased in the 2nd week in the diabetic parotid glands. Conclusions. Diabetes induces oxidative damage of the salivary glands, which seems to be caused by processes taking place in the salivary glands, independently of general oxidative stress. The parotid glands are more vulnerable to oxidative damage in these conditions. PMID:27478848

  18. Role of GABAB Receptor and L-Arg in GABA-Induced Vasorelaxation in Non-diabetic and Streptozotocin-Induced Diabetic Rat Vessels

    PubMed Central

    Kharazmi, Fatemah; Soltani, Nepton; Rezaei, Sana; Keshavarz, Mansoor; Farsi, Leila

    2015-01-01

    Background: Hypertension is considered an independent risk factor for cardiovascular mortality in diabetic patients. The present study was designed to determine the role of gamma amino butyric acid B (GABAB) receptor and L-arginine (L-Arg) in GABA-induced vasorelaxation in normal and streptozotocin-induced diabetic rat vessels. Methods: Diabetes was induced by a single i.p. injection of streptozotocin (STZ, 60 mg/kg). Eight weeks later, superior mesenteric arteries of all groups were isolated and perfused according to the McGregor method. Results: Baseline perfusion pressure of STZ diabetic rats was significantly higher than non-diabetic rats in both intact and denuded endothelium. In the presence of faclofen, a selective GABAB receptor blocker, GABA-induced relaxation in intact and denuded endothelium mesenteric beds of STZ diabetic rats was suppressed, but this response in non-diabetic rats was not suppressed. Our results showed that in the presence of L-Arg, a nitric oxide precursor, GABA induced vasorelaxation in both diabetic and non-diabetic vessels. Conclusion: From the results of this study, it may be concluded that the vasorelaxatory effect of GABA in diabetic vessel is mediated by the GABAB receptor and nitric oxide, but it seems that in non-diabetic vessel GABAB receptor does not play any role in GABA-induced vasorelaxation, but nitric oxide induced GABA relaxation in non-diabetic vessel. PMID:25864813

  19. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet

    PubMed Central

    El-Zeftawy, Marwa; Taha, Nabil; Mandour, Abdel Wahab

    2016-01-01

    The black cumin (Nigella sativa) “NS” or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling. PMID:27579151

  20. High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes in Rats Impacts Osteogenesis and Wnt Signaling in Bone Marrow Stromal Cells

    PubMed Central

    Yu, Weiqiang; Jiang, Xinquan; Zhang, Fuqiang

    2015-01-01

    Bone regeneration disorders are a significant problem in patients with type 2 diabetes mellitus. Bone marrow stromal cells (BMSCs) are recognized as ideal seed cells for tissue engineering because they can stimulate osteogenesis during bone regeneration. Therefore, the aim of this study was to investigate the osteogenic potential of BMSCs derived from type 2 diabetic rats and the pathogenic characteristics of dysfunctional BMSCs that affect osteogenesis. BMSCs were isolated from normal and high-fat diet+streptozotocin-induced type 2 diabetic rats. Cell metabolic activity, alkaline phosphatase (ALP) activity, mineralization and osteogenic gene expression were reduced in the type 2 diabetic rat BMSCs. The expression levels of Wnt signaling genes, such as β-catenin, cyclin D1 and c-myc, were also significantly decreased in the type 2 diabetic rat BMSCs, but the expression of GSK3β remained unchanged. The derived BMSCs were cultured on calcium phosphate cement (CPC) scaffolds and placed subcutaneously into nude mice for eight weeks; they were detected at a low level in newly formed bone. The osteogenic potential of the type 2 diabetic rat BMSCs was not impaired by the culture environment, but it was impaired by inhibition of the Wnt signaling pathway, likely due to an insufficient accumulation of β-catenin rather than because of GSK3β stimulation. Using BMSCs derived from diabetic subjects could offer an alternative method of regenerating bone together with the use of supplementary growth factors to stimulate the Wnt signaling pathway. PMID:26296196

  1. Preventive Effects of the Chinese Herbal Medicine Prescription Tangkuei Decoction for Frigid Extremities on Sciatic Neuropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Liu, Pengsong; Bian, Yuanyuan; Zhang, Hong; Jia, Aiming

    2016-01-01

    Ischemia and hypoxia are important physiological changes in diabetic peripheral neuropathy (DPN). Chinese herbal medicine prescription Tangkuei Decoction for Frigid Extremities (TDFE) is useful for increasing blood flow. To help determine whether TDFE could protect the peripheral nerves of diabetic patients from the degeneration caused by high blood glucose, TDFE was administered to streptozotocin-induced diabetic rats for 6 or 12 weeks. Plantar thermal stimulation reaction time thresholds, sciatic nerve conduction velocities, and the levels of HIF-1α mRNA, HIF-1α protein, VEGF protein, and the endothelial marker vWF in sciatic nerves were measured at the end of the sixth and twelfth weeks. The thermal thresholds and sciatic nerve conduction velocities of the rats differed after 12 weeks, and the sciatic nerves of the diabetic rats that were given TDFE displayed higher levels of HIF-1α protein, VEGF protein, and HIF-1α mRNA than those of the diabetic model rats. The results at 6 weeks differed from those at 12 weeks. These results suggest that the early preventive application of TDFE effectively delayed the development of DPN and that TDFE increased HIF-1α mRNA levels in the sciatic nerves of diabetic rats through 12 weeks of treatment. PMID:27057201

  2. Differential Responses to Blood Pressure and Oxidative Stress in Streptozotocin-Induced Diabetic Wistar-Kyoto Rats and Spontaneously Hypertensive Rats: Effects of Antioxidant (Honey) Treatment

    PubMed Central

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd Suhaimi Ab; Sirajudeen, Kuttulebbai N. S.; Salleh, Md Salzihan Md; Gurtu, Sunil

    2011-01-01

    Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress. PMID:21673929

  3. Neurons in the hippocampal CA1 region, but not the dentate gyrus, are susceptible to oxidative stress in rats with streptozotocin-induced type 1 diabetes

    PubMed Central

    Lee, Sang Gun; Yoo, Dae Young; Jung, Hyo Young; Nam, Sung Min; Kim, Jong Whi; Choi, Jung Hoon; Yi, Sun Shin; Won, Moo-Ho; Yoon, Yeo Sung; Hwang, In Koo; Moon, Seung Myung

    2015-01-01

    In this study, we investigated the effects of streptozotocin-induced type 1 diabetes on antioxidant-like protein-1 immunoreactivity, protein carbonyl levels, and malondialdehyde formation, a marker for lipid peroxidation, in the hippocampus. For this study, streptozotocin (75 mg/kg) was intraperitoneally injected into adult rats to induce type 1 diabetes. The three experimental parameters were determined at 2, 3, 4 weeks after streptozotocin treatment. Fasting blood glucose levels significantly increased by 20.7–21.9 mM after streptozotocin treatment. The number of antioxidant-like protein-1 immunoreactive neurons significantly decreased in the hippocampal CA1 region, but not the dentate gyrus, 3 weeks after streptozotocin treatment compared to the control group. Malondialdehyde and protein carbonyl levels, which are modified by oxidative stress, significantly increased with a peak at 3 weeks after malondialdehyde treatment, and then decreased 4 weeks after malondialdehyde treatment. These results suggest that neurons in the hippocampal CA1 region, but not the dentate gyrus, are susceptible to oxidative stress 3 weeks after malondialdehyde treatment. PMID:25878595

  4. Antidiabetic and haematological effect of aqueous extract of stem bark of Afzelia africana (Smith) on streptozotocin-induced diabetic Wistar rats

    PubMed Central

    Oyedemi, SO; Adewusi, EA; Aiyegoro, OA; Akinpelu, DA

    2011-01-01

    Objective To investigate the antidiabetic properties of aqueous extract of stem bark of Afzelia africana (A. africana) and its beneficial effect on haematological parameters in streptozotocin induced diabetic rats. Methods A total of 30 rats including 24 diabetic and 6 normal rats were used for this study. Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin. After being confirmed diabetic, animals were orally treated with distilled water or extracts at 100 or 200 mg/kg body weight daily for 10 days. The haematological parameters including red blood and white blood cells and their functional indices were evaluated in diabetic treated groups compared with the controls. Results The extract significantly reduced the blood glucose levels while the best result was obtained at 200 mg/kg body weight. The feed and water intake in diabetic rats were significantly reduced while weight loss was minimized at both dosages. Similarly, the levels of red blood, white blood cells and their functional indices were significantly improved after extract administration at both doses. Conclusions It can be concluded that the aqueous extract of bark of A. africana possesses antihyperglycemic properties. In addition, the extract can prevent various complications of diabetes and improve some haematological parameters. Further experimental investigation is needed to exploit its relevant therapeutic effect to substantiate its ethnomedicinal usage. PMID:23569792

  5. Studies on the insulinomimetic effects of benzylamine, exogenous substrate of semicarbazide-sensitive amine oxidase enzyme in streptozotocin induced diabetic rats.

    PubMed

    Soltész, Zs; Tábi, T; Halász, A S; Pálfi, M; Kocsis, E; Magyar, K; Tóth, M; Szökö, E

    2007-01-01

    Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO) is believed to be a bifunctional membrane protein. It is localized extracellularly and preferentially oxidizes short chain primary amines to aldehydes, hydrogen peroxide and ammonia, but also functions as an adhesion molecule, which is involved in leukocyte migration. Serum SSAO activity is increased in diabetic patients and animals and the aldehydes formed in the enzyme reaction may contribute to vascular damage. However, administration of exogenous substrates has been shown to improve glucose tolerance and reduce hyperglycaemia in diabetic animals. Hydrogen peroxide and/or its vanadate complexes have been suggested responsible for these effects. Streptozotocin induced diabetic rats were treated with benzylamine (BZA) +/- vanadate (V) or insulin. In contrast to insulin, BZA + V treatment did not reduce HbA(1C) levels. However, it reduced the elevated serum SSAO activity, decreased the accumulation of advanced-glycation end products and increased the bioavailability of nitric oxide in diabetic animals, similarly to insulin. BZA alone did not affect any of these parameters. PMID:17431735

  6. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet.

    PubMed

    Balbaa, Mahmoud; El-Zeftawy, Marwa; Ghareeb, Doaa; Taha, Nabil; Mandour, Abdel Wahab

    2016-01-01

    The black cumin (Nigella sativa) "NS" or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling. PMID:27579151

  7. Protective effects of Quercetin and chronic moderate exercise (training) against oxidative stress in the liver tissue of streptozotocin-induced diabetic rats.

    PubMed

    Chiş, I C; Mureşan, A; Oros, A; Nagy, A L; Clichici, S

    2016-03-01

    Background To investigate the protective effects of Quercetin administration associated with chronic moderate exercise (training) on oxidative stress in the liver in streptozotocin-induced diabetic rats. Methods Diabetic rats that performed exercise training were subjected to a swimming training program (1 hour/day, 5 days/week, 4 weeks). The diabetic rats received natural antioxidant, Quercetin (20 mg/kg body weight/day) for 4 weeks. At the end of the study, all animals were sacrificed and liver samples were collected for estimation: some oxidative stress markers (malondialdehyde, MDA and protein carbonyls groups, PC), the activity of antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT), reduced glutathione (GSH) level and reduced (GSH) and oxidized (GSSG) glutathione ratio. Results Diabetic rats submitted to exercise training showed significantly increased the oxidative stress markers (MDA and PC) and a reduction of antioxidant enzyme (SOD and CAT) activity, GSH level and GSH/ GSSG ratio in hepatic tissues. A decrease in the levels of oxidative stress markers associated with elevated activity of antioxidant enzymes, the GSH level and GSH/GSSG ratio in the hepatic tissue were observed in Quercetin-treated diabetic trained rats. Conclusions These findings suggest that Quercetin administration in association with chronic moderate exercise exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress in hepatic tissue. PMID:27030627

  8. Alleviation of hyperglycemia and hyperlipidemia by Phyllanthus virgatus forst extract and its partially purified fraction in streptozotocin induced diabetic rats

    PubMed Central

    Hashim, Arshya; Khan, M. Salman; Ahmad, Saheem

    2014-01-01

    Since, we previously demonstrated that sequentially extracted methanolic fraction showed marked antioxidant and antidiabetic property in vitro, the present study was design to evaluate the beneficial effects of Phyllanthus virgatus methanolic extract and its partially purified fraction on hyperglycemia and hyperlipidemia in streptozotocin (STZ) induced diabetic rats. The plant extract was subjected to repeated thin layer chromatographic fractionation followed by GC-MS analysis of active fraction. TLC data illustrated the presence of six prominent bands and the prelimnary screening of these bands against α-amylase inhibitory activity showed that the band with Rf value 0.514 has marked inhibitory property (IC50, 48 µg/ml). The diabetic rats were treated for four weeks with methanolic extract of P. virgatus (50 and 10 mg/rat/day), partially isolated active fraction (0.5 and 0.1 mg/rat/day) and glibenclamide (0.1 mg/rat/day). The level of fasting blood glucose (FBG), hemoglobin, glycated hemoglobin (HbA1c) and insulin were significantly alleviated in plant extract and partially purified fraction treated group after 28 days of administration. Moreover, total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and high density lipoprotein cholesterol (HDL-C) were also markedly ameliorated in the entire treatment group, with a maximum restoration observed in group treated with partially purified fraction (0.5 mg/rat/day). The results demonstrate a strong antidiabetic and hypolipidemic impact of plant extract and its partially purified fraction coupled with their potent antioxidative property, which can provide additional benefits in the inhibition of oxidative stress and hence in the prevention and treatment of diabetes as well as diabetes linked hyperlipidemia. PMID:26417304

  9. Comparison of the effects of levocetirizine and losartan on diabetic nephropathy and vascular dysfunction in streptozotocin-induced diabetic rats.

    PubMed

    Anbar, Hanan S; Shehatou, George S G; Suddek, Ghada M; Gameil, Nariman M

    2016-06-01

    This work was designed to investigate the effects of levocetirizine, a histamine H1 receptor antagonist, on diabetes-induced nephropathy and vascular disorder, in comparison to an angiotensin II receptor antagonist, losartan. Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of streptozotocin (50mg/kg). Diabetic rats were divided into three groups; diabetic, diabetic-levocetirizine (0.5mg/kg/day) and diabetic-losartan (25mg/kg/day). Treatments were started two weeks following diabetes induction and continued for additional eight weeks. At the end of the experiment, urine was collected and serum was separated for biochemical measurements. Tissue homogenates of kidney and aorta were prepared for measuring oxidative stress, nitric oxide (NO), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Moreover, histological analyses were conducted and aortic vascular reactivity was investigated. Levocetirizine improved renal function in diabetic rats (evidenced by mitigation of diabetes-induced changes in kidney to body weight ratio, serum albumin, urinary proteins and creatinine clearance). Moreover, levocetirizine attenuated the elevated renal levels of TNF-α and TGF-β1, ameliorated renal oxidative stress and restored NO bioavailability in diabetic kidney. These effects were comparable to or surpassed those produced by losartan. Moreover, levocetirizine, similar to losartan, reduced the enhanced responsiveness of diabetic aorta to phenylephrine. Histological evaluation of renal and aortic tissues further confirmed the beneficial effects of levocetirizine on diabetic nephropathy and revealed a greater attenuation of diabetes-induced vascular hypertrophy by levocetirizine than by losartan. In conclusion, levocetirizine may offer comparable renoprotective effect to, and possibly superior vasculoprotective effects than, losartan in streptozotocin-diabetic rats. PMID:27012991

  10. Targeting Apoptosis Signalling Kinase-1 (ASK-1) Does Not Prevent the Development of Neuropathy in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Newton, Victoria L.; Ali, Sumia; Duddy, Graham; Whitmarsh, Alan J.; Gardiner, Natalie J.

    2014-01-01

    Apoptosis signal-regulating kinase-1 (ASK1) is a mitogen-activated protein 3 kinase (MAPKKK/MAP3K) which lies upstream of the stress-activated MAPKs, JNK and p38. ASK1 may be activated by a variety of extracellular and intracellular stimuli. MAP kinase activation in the sensory nervous system as a result of diabetes has been shown in numerous preclinical and clinical studies. As a common upstream activator of both p38 and JNK, we hypothesised that activation of ASK1 contributes to nerve dysfunction in diabetic neuropathy. We therefore wanted to characterize the expression of ASK1 in sensory neurons, and determine whether the absence of functional ASK1 would protect against the development of neuropathy in a mouse model of experimental diabetes. ASK1 mRNA and protein is constitutively expressed by multiple populations of sensory neurons of the adult mouse lumbar DRG. Diabetes was induced in male C57BL/6 and transgenic ASK1 kinase-inactive (ASK1n) mice using streptozotocin. Levels of ASK1 do not change in the DRG, spinal cord, or sciatic nerve following induction of diabetes. However, levels of ASK2 mRNA increase in the spinal cord at 4 weeks of diabetes, which could represent a future target for this field. Neither motor nerve conduction velocity deficits, nor thermal or mechanical hypoalgesia were prevented or ameliorated in diabetic ASK1n mice. These results suggest that activation of ASK1 is not responsible for the nerve deficits observed in this mouse model of diabetic neuropathy. PMID:25329046

  11. Salacia chinensis L. extract ameliorates abnormal glucose metabolism and improves the bone strength and accumulation of AGEs in type 1 diabetic rats.

    PubMed

    Shirakawa, Jun-Ichi; Arakawa, Shoutaro; Tagawa, Tomoya; Gotoh, Kentaroh; Oikawa, Norihisa; Ohno, Rei-Ichi; Shinagawa, Masatoshi; Hatano, Kota; Sugawa, Hikari; Ichimaru, Kenta; Kinoshita, Sho; Furusawa, Chisato; Yamanaka, Mikihiro; Kobayashi, Masakazu; Masuda, Shuichi; Nagai, Mime; Nagai, Ryoji

    2016-06-15

    Although extracts of the roots and stems of Salacia chinensis have been used in folk medicines for chronic diseases such as rheumatism, irregular menstruation, asthma and diabetes mellitus, little is known about the mechanism by which Salacia chinensis extract (SCE) ameliorates these diseases. To clarify whether SCE ameliorates the progression of lifestyle-related diseases, the inhibitory effect of SCE on the formation of advanced glycation end products (AGEs) was analyzed in a rat model of streptozotocin-induced diabetes. Although the oral administration of SCE did not ameliorate the diabetes-induced decrease in body weight, it ameliorated the increase in glycoalbumin levels in diabetic rats. An analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) demonstrated that the levels of N(ε)-(carboxymethyl)lysine (CML) were highest in the femurs and that they increased by the induction of diabetes. The administration of SCE also ameliorated the decreased femur strength and the accumulation of CML. Furthermore, when all of the carbohydrates in the chow of diabetic rats were replaced with free glucose, the administration of SCE significantly ameliorated a diabetes-induced increase in glycoalbumin and decrease in serum creatinine level and body weight. This study provides evidence to support that SCE ameliorates diabetes-induced abnormalities by improving the uptake of glucose by various organs. PMID:27121272

  12. Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

    PubMed Central

    Rahavi, Hossein; Hashemi, Seyed Mahmoud; Soleimani, Masoud; Mohammadi, Jamal; Tajik, Nader

    2015-01-01

    Regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) might be applied for type 1 diabetes mellitus (T1DM) treatment. Thus, we proposed in vitro assessment of adipose tissue-derived MSCs (AT-MSCs) immunomodulation on autoimmune response along with beta cell protection in streptozotocin- (STZ-) induced diabetic C57BL/6 mice model. MSCs were extracted from abdominal adipose tissue of normal mice and cultured to proliferate. Diabetic mice were prepared by administration of multiple low-doses of streptozotocin. Pancreatic islets were isolated from normal mice and splenocytes prepared from normal and diabetic mice. Proliferation, cytokine production, and insulin secretion assays were performed in coculture experiments. AT-MSCs inhibited splenocytes proliferative response to specific (islet lysate) and nonspecific (PHA) triggers in a dose-dependent manner (P < 0.05). Decreased production of proinflammatory cytokines, such as IFN-γ, IL-2, and IL-17, and increased secretion of regulatory cytokines such as TGF-β, IL-4, IL-10, and IL-13 by stimulated splenocytes were also shown in response to islet lysate or PHA stimulants (P < 0.05). Finally, we demonstrated that AT-MSCs could effectively sustain viability as well as insulin secretion potential of pancreatic islets in the presence of reactive splenocytes (P < 0.05). In conclusion, it seems that MSCs may provide a new horizon for T1DM cell therapy and islet transplantation in the future. PMID:25893202

  13. Antidiabetic Effects of Yam (Dioscorea batatas) and Its Active Constituent, Allantoin, in a Rat Model of Streptozotocin-Induced Diabetes.

    PubMed

    Go, Hyeon-Kyu; Rahman, Md Mahbubur; Kim, Gi-Beum; Na, Chong-Sam; Song, Choon-Ho; Kim, Jin-Shang; Kim, Shang-Jin; Kang, Hyung-Sub

    2015-10-01

    The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas) powder (PY), water extract of yam (EY), and allantoin (the active constituent of yam) in streptozotocin (STZ)-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1), C-peptide, glycated hemoglobin (HbAlc), lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC), diabetic control (STZ), and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin). After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p < 0.001) compared to STZ (100%): 60% in STZ + PY, 55% in STZ + EY, and 63% in STZ + allantoin. With groups in the same order, there were significant decreases (p < 0.001) in HbAlc (100% as 24.4 ± 0.6 ng/mL, 78%, 75%, and 77%), total cholesterol (100% as 122 ± 3 mg/dL, 70%, 67%, and 69%), and low-density lipoprotein (100% as 29 ± 1 mg/dL, 45%, 48%, and 38%). There were also significant increases (p < 0.001) in insulin (100% as 0.22 ± 0.00 ng/mL, 173%, 209%, and 177%), GLP-1 (100% as 18.4 ± 0.7 pmol/mL, 160%, 166%, and 162%), and C-peptide (100% as 2.56 ± 0.10 ng/mL, 129%, 132%, and 130%). The treatment effectively ameliorated antioxidant stress as shown by a significant decrease (p < 0.001) in malondialdehyde (100% as 7.25 ± 0.11 nmol/mL, 87%, 86%, and 85%) together with increases (p < 0.01) in superoxide dismutase (100% as 167 ± 6 IU/mL, 147%, 159%, and 145%) and reduced glutathione (100% as 167 ± 6 nmol/mL, 123%, 141%, and 140%). The results indicate that yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of β-cells maintaining normal insulin and glucose

  14. Antidiabetic Effects of Yam (Dioscorea batatas) and Its Active Constituent, Allantoin, in a Rat Model of Streptozotocin-Induced Diabetes

    PubMed Central

    Go, Hyeon-Kyu; Rahman, Md. Mahbubur; Kim, Gi-Beum; Na, Chong-Sam; Song, Choon-Ho; Kim, Jin-Shang; Kim, Shang-Jin; Kang, Hyung-Sub

    2015-01-01

    The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas) powder (PY), water extract of yam (EY), and allantoin (the active constituent of yam) in streptozotocin (STZ)-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1), C-peptide, glycated hemoglobin (HbAlc), lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC), diabetic control (STZ), and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin). After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p < 0.001) compared to STZ (100%): 60% in STZ + PY, 55% in STZ + EY, and 63% in STZ + allantoin. With groups in the same order, there were significant decreases (p < 0.001) in HbAlc (100% as 24.4 ± 0.6 ng/mL, 78%, 75%, and 77%), total cholesterol (100% as 122 ± 3 mg/dL, 70%, 67%, and 69%), and low-density lipoprotein (100% as 29 ± 1 mg/dL, 45%, 48%, and 38%). There were also significant increases (p < 0.001) in insulin (100% as 0.22 ± 0.00 ng/mL, 173%, 209%, and 177%), GLP-1 (100% as 18.4 ± 0.7 pmol/mL, 160%, 166%, and 162%), and C-peptide (100% as 2.56 ± 0.10 ng/mL, 129%, 132%, and 130%). The treatment effectively ameliorated antioxidant stress as shown by a significant decrease (p < 0.001) in malondialdehyde (100% as 7.25 ± 0.11 nmol/mL, 87%, 86%, and 85%) together with increases (p < 0.01) in superoxide dismutase (100% as 167 ± 6 IU/mL, 147%, 159%, and 145%) and reduced glutathione (100% as 167 ± 6 nmol/mL, 123%, 141%, and 140%). The results indicate that yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of β-cells maintaining normal insulin and glucose

  15. Effects of Syzygium aromaticum-Derived Triterpenes on Postprandial Blood Glucose in Streptozotocin-Induced Diabetic Rats Following Carbohydrate Challenge

    PubMed Central

    Khathi, Andile; Serumula, Metse R.; Myburg, Rene B.; Van Heerden, Fanie R.; Musabayane, Cephas T.

    2013-01-01

    Purpose Recent reports suggest that the hypoglycaemic effects of the triterpenes involve inhibition of glucose transport in the small intestine. Therefore, the effects of Syzygium spp-derived triterpenes oleanolic acid (OA) and maslinic acid (MA) were evaluated on carbohydrate hydrolyzing enzymes in STZ-induced diabetic rats and consequences on postprandial hyperglycaemia after carbohydrate loading. Methods We determined using Western blot analysis the expressions of α-amylase and α-glucosidase and glucose transporters SGLT1 and GLUT2 in the small intestine intestines isolated from diabetic rats treated with OA/MA for 5 weeks. In vitro assays were used to assess the inhibitory activities of OA and MA against α-amylase, α-glucosidase and sucrase. Results OA and MA ameliorated postprandial hyperglycemia in carbohydrate loaded diabetic rats as indicated by the significantly small glucose area under the curve (AUC) in treated diabetic animals compared with that in untreated diabetic rats. Western blotting showed that OA and MA treatment not only down-regulated the increase of SGLT1 and GLUT2 expressions in the small intestine of STZ-induced diabetic rats, but also inhibited small intestine α-amylase, sucrase and α-glucosidase activity. IC50 values of OA against α-amylase (3.60 ± 0.18 mmol/L), α-glucosidase (12.40 ± 0.11 mmol/L) and sucrase (11.50 ± 0.13 mmol/L) did not significantly differ from those of OA and acarbose. Conclusions The results of suggest that OA and MA may be used as potential supplements for treating postprandial hyperglycemia. Novelty of the Work The present observations indicate that besides improving glucose homeostasis in diabetes, OA and MA suppress postprandial hyperglycaemia mediated in part via inhibition of carbohydrate hydrolysis and reduction of glucose transporters in the gastrointestinal tract. Inhibition of α-glucosidase and α-amylase can significantly decrease the postprandial hyperglycaemia after a mixed carbohydrate diet

  16. Ellagic acid inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and prevents atheroma formation in streptozotocin-induced diabetic rats.

    PubMed

    Rani, Uma P; Kesavan, Rushendhiran; Ganugula, Raghu; Avaneesh, T; Kumar, Uday P; Reddy, G Bhanuprakash; Dixit, Madhulika

    2013-11-01

    Plant-derived polyphenolic compounds have beneficial health effects. In the present study, we determined the ability of ellagic acid (EA) to prevent platelet-derived growth factor-BB (PDGF-BB)-induced proliferation of primary cultures of rat aortic smooth muscle cells (RASMCs). We also determined the ability of EA to prevent atherosclerosis in streptozotocin-induced diabetic rats. Proliferation of cells was measured via Alamar Blue assay and through propidium iodide-based cell cycle analysis in flow cytometer. Reactive oxygen species (ROS) were measured via 2',7'-dichlorofluorescin diacetate and Amplex red methods. Expression of proliferation markers and activation of kinases were assessed by immunoblot analysis. Cotreatment of primary cultures of RASMCs with 25 μmol/L of EA significantly reduced PDGF-BB (20 ng/ml)-induced proliferation by blocking S-phase entry. EA effectively blocked PDGF receptor-β (PDGFR-β) tyrosine phosphorylation, generation of intracellular ROS and downstream activation of extracellular signal-regulated kinase 1/2. It also blocked PDGF-BB-induced expression of cyclin D1. Computational molecular docking of EA with the PDGFR-β-PDGF-BB complex revealed two putative inhibitor binding sites which showed similar binding energies with the known PDGFR-β inhibitor AG1295. In diabetic rats, supplementation of diet with 2% EA significantly blocked diabetes-induced medial thickness, and lipid and collagen deposition in the arch of aorta. These were assessed through haematoxylin and eosin, Oil Red O and Masson's trichome staining, respectively. EA treatment also blocked cyclin D1 expression in medial smooth muscle cells in experimental animals. Thus, EA is effective in reducing atherosclerotic process by blocking proliferation of vascular smooth muscle cells. PMID:23866995

  17. Effect of Trigonella foenum-graecum (fenugreek) extract on blood glucose, blood lipid and hemorheological properties in streptozotocin-induced diabetic rats.

    PubMed

    Xue, Wan-Li; Li, Xuan-She; Zhang, Jian; Liu, Yong-Hui; Wang, Zhi-Lun; Zhang, Rui-Juan

    2007-01-01

    Trigonella foenum-graecum (fenugreek) seeds have previously been shown to have hypoglycemic and hypocholesterolemic effects on type 1 and type 2 diabetes mellitus patients and experimental diabetic animals. The Trigonella foenum-graecum extract has now been investigated for its effects on general properties, blood glucose and blood lipid, and hemorheological parameters in experimental diabetic rats. Streptozotocin-induced diabetic rats were administrated by oral intragastric intubation separately with low dose (0.44 g/kg.d), middle dose (0.87 g/kg.d), high dose (1.74 g/kg.d) of Trigonella foenum-graecum extract, and Metformin HCl (0.175 g/kg.d) for 6 weeks. Compared with diabetic group, rats treated with Trigonella foenum-graecum extract had an increase in body weight and a decrease in kidney /body weight ratio (p<0.05). Compared with diabetic group, rats treated Trigonella foenum-graecum extract had lower blood glucose, glycated hemoglobin, triglycerides, total cholestrol and higher higher-density-lipoprotein-cholesterol in a dose-dependent manner (p<0.05). The plasma viscosity, whole blood viscosity of high shear rate (200 s-1) and low shear rate (40 s-1), erythrocyte sedimentation rate, whole blood reduction viscosity and platelet conglutination were significantly reduced in diabetic rats treated with high and middle doses of Trigonella foenum-graecum extract, but not in those treated with low dose of Trigonella foenum-graecum extract. It may be concluded that Trigonella foenum-graecum extract can lower kidney /body weight ratio, blood glucose, blood lipid levels and improve hemorheological properties in experimental diabetic rats following repeated treatment for 6 weeks. PMID:17392143

  18. Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration

    PubMed Central

    Ali, Sumia; Driscoll, Heather E.; Newton, Victoria L.; Gardiner, Natalie J.

    2014-01-01

    Minocycline is an inhibitor of matrix metalloproteinases (MMPs) and has been shown to have analgesic effects. Whilst increased expression of MMPs is associated with neuropathic pain, MMPs also play crucial roles in Wallerian degeneration and nerve regeneration. In this study we examined the expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1/-2 in the sciatic nerve of control and streptozotocin-induced diabetic rats treated with either vehicle or minocycline by quantitative PCR and gelatin zymography. We assessed the effects of minocycline on nerve conduction velocity and intraepidermal nerve fibre (IENF) deficits in diabetic neuropathy and investigated the effects of minocycline or MMP-2 on neurite outgrowth from primary cultures of dissociated adult rat sensory neurons. We show that MMP-2 is expressed constitutively in the sciatic nerve in vivo and treatment with minocycline or diabetes leads to downregulation of MMP-2 expression and activity. The functional consequence of this is IENF deficits in minocycline-treated nondiabetic rats and an unsupportive microenvironment for regeneration in diabetes. Minocycline reduces levels of MMP-2 mRNA and nerve growth factor-induced neurite outgrowth. Furthermore, in vivo minocycline treatment reduces preconditioning-induced in vitro neurite outgrowth following a sciatic nerve crush. In contrast, the addition of active MMP-2 facilitates neurite outgrowth in the absence of neurotrophic support and pre-treatment of diabetic sciatic nerve substrata with active MMP-2 promotes a permissive environment for neurite outgrowth. In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using

  19. Effect of exogenous leptin on serum levels of lipids, glucose, renal and hepatic variables in both genders of obese and streptozotocin-induced diabetic rats

    PubMed Central

    Hayatdavoudi, Parichehr; Ghasemi, Mohsen; Zendehbad, Bamdad; Soukhtanloo, Mohammad; Golshan, Alireza; Hadjzadeh, Mousa Al-Reza

    2015-01-01

    Objective(s): Leptin exerts various effects on appetite and body weight. Disruption of the obesity gene is precedent to fatness. Insulin or glucose elevates leptin, but streptozotocin reduces it. However, controversial data exist for the effects of leptin on diabetes and leptin level in each gender. Leptin can damage the kidney function but little evidence exists for its hepatic effects. The aim of this study was to investigate the probable sex-dependent differences in blood sugar levels, lipid profile, and renal and hepatic biochemical factors in the obesity and streptozotocin-induced diabetic rats after leptin administration. Materials and Methods: Wistar rats of both sexes were randomly divided into two groups, namely obese and diabetic rats. Each group was further divided into male and female subgroups. Extra fat and carbohydrate was added to the diet to induce obesity. Furthermore, streptozotocin (55 mg/kg, IP) was injected to induce diabetes. The treatment groups received leptin (0.1 mg/kg SC) for 10 days, and then, blood samples were taken from the orbital sinus for laboratory evaluations. Results: Leptin resulted in a significant weight loss in both sexes (P<0.001), food intake reduction in male rats (P<0.05), LDL reduction in female rats (obese (P<0.05) and diabetic (P<0.001)), and glucose level decline in the female diabetic rats (P<0.001). However, total protein concentration, LFT (liver function tests), urea and creatinin concentrations among different groups did not show any significant changes. Conclusion: Leptin caused some discrepant results, especially regarding the LDL and glucose levels in diabetic female rats. PMID:26949493

  20. Cross-talks between microRNAs and mRNAs in pancreatic tissues of streptozotocin-induced type 1 diabetic mice

    PubMed Central

    TIAN, CAIMING; OUYANG, XIAOXI; LV, QING; ZHANG, YAOU; XIE, WEIDONG

    2015-01-01

    Network cross-talks between microRNAs (miRNAs) and mRNAs may be useful to elucidate the pathological mechanisms of pancreatic islet cells in diabetic individuals. The aim of the present study was to investigate the cross-talks between miRNAs and mRNAs in pancreatic tissues of streptozotocin-induced diabetic mice through microarray and bioinformatic methods. Based on the miRNA microarray, 64 upregulated and 72 downregulated miRNAs were observed in pancreatic tissues in diabetic mice compared to the normal controls. Based on the mRNA microarrray, 507 upregulated mRNAs and 570 downregulated mRNAs were identified in pancreatic tissues in diabetic mice compared to the normal controls. Notably, there were 246 binding points between upregulated miRNA and downregulated mRNAs; simultaneously, there were 583 binding points between downregulated miRNA and upregulated mRNAs. These changed mRNA may potentially involve the following signaling pathways: Insulin secretion, pancreatic secretion, mammalian target of rapamycin signaling pathway, forkhead box O signaling pathway and phosphatidylinositol 3-kinase-protein kinase B signaling. The fluctuating effects of miRNAs and matched mRNAs indicated that miRNAs may have wide cross-talks with mRNAs in pancreatic tissues of type 1 diabetic mice. The cross-talks may play important roles in contributing to impaired islet functions and the development of diabetes. However, further functional validation should be conducted in the future. PMID:26137232

  1. Pancreatic islet regeneration and some liver biochemical parameters of leaf extracts of Vitex doniana in normal and streptozotocin-induced diabetic albino rats

    PubMed Central

    Oche, Okpe; Sani, Ibrahim; Chilaka, Njoku Godwin; Samuel, Ndidi Uche; Samuel, Atabo

    2014-01-01

    Objective To test two water soluble extracts (aqueous and ethanolic) obtained from the leaves of Vitex doniana in normal and streptozotocin-induced diabetic rats for their effects on pancreatic endocrine tissues and serum marker enzymes for a period of 21 d. Methods A total of 55 rats divided into 11 groups of 5 rats each were assigned into diabetic and non-diabetic groups and followed by a daily administration of ethanolic and aqueous extracts for 21 d. Group 1 was the normal control while group 7 was treated with standard drug. Results The histopathological studies of the diabetic rats indicated increase in the volume density of islets, percent of β-cells and size of islet in the groups that received the plant extracts, which suggested regeneration of β-cells along with β-cells repairs, as compared with the non-treated diabetic control which showed complete degeneration of the islet cells. There was significant reduction (P<0.05) in the serum activities of marker enzymes, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in diabetes treated rats, whereas an insignificant increase (P>0.01) in the serum activities of marker enzymes was observed for non-diabetic treated rats. Results of total bilirubin, direct bilirubin and unconjugated bilirubin showed that diabetic control group was significantly higher (P<0.05) in total bilirubin and unconjugated bilirubin compared with treated groups while non-diabetic treated groups showed no significant increase (P>0.01) in total bilirubin and direct bilirubin compared with the normal control. Conclusion This herbal therapy appears to bring about repair/regeneration of the endocrine pancreas and hepatic cells protection in the diabetic rat. PMID:25182283

  2. Evaluating the effect of low-level laser therapy on healing of tentomized Achilles tendon in streptozotocin-induced diabetic rats by light microscopical and gene expression examinations.

    PubMed

    Aliodoust, Morteza; Bayat, Mohammad; Jalili, Mohammad Reza; Sharifian, Zainalabedin; Dadpay, Masoomeh; Akbari, Mohammad; Bayat, Mehrnoush; Khoshvaghti, Amir; Bayat, Homa

    2014-07-01

    Tendon healing is impaired in individuals diagnosed with diabetes mellitus (DM). According to research, there is considerable improvement in the healing of surgically tenotomized Achilles tendons following low-level laser therapy (LLLT) in non-diabetic, healthy animals. This study uses light microscopic (LM) and semi-quantitative reverse transcription PCR (RT-PCR) analyses to evaluate the ability of LLLT in healing Achilles tendons from streptozotocin-induced diabetic (STZ-D) rats. A total of 88 rats were randomly divided into two groups, non-diabetic and diabetic. DM was induced in the rats by injections of STZ. The right Achilles tendons of all rats were tenotomized 1 month after administration of STZ. Laser-treated rats were treated with a helium-neon (He-Ne) laser that had a 632.8-nm wavelength and 7.2-mW average power. Experimental group rats received a daily dose of 0.014 J (energy density, 2.9 J/cm(2)). Control rats did not receive LLLT. Animals were sacrificed on days 5, 10, and 15 post-operatively for semi-quantitative LM and semi-quantitative RT-PCR examinations of transforming growth factor-beta1 (TGF-β1) gene expression. The chi-square test showed that LLLT significantly reduced inflammation in non-diabetic rats compared with their non-diabetic controls (p = 0.02). LLLT significantly decreased inflammation in diabetic rats on days 5 (p = 0.03) and 10 (p = 0.02) compared to the corresponding control diabetic rats. According to the student's t test, LLLT significantly increased TGF-β1 gene expression in healthy (p = 0.000) and diabetic (p = 0.000) rats compared to their relevant controls. The He-Ne laser was effective in altering the inflammatory reaction and increasing TGF-β1 gene production. PMID:24622817

  3. Hyperglycemia-Induced Hypovolemia Is Involved in Early Cardiac Magnetic Resonance Alterations in Streptozotocin-Induced Diabetic Mice: A Comparison with Furosemide-Induced Hypovolemia

    PubMed Central

    Joubert, Michael; Bellevre, Dimitri; Legallois, Damien; Elie, Nicolas; Coulbault, Laurent; Allouche, Stéphane; Manrique, Alain

    2016-01-01

    Aims The aim of the study was to assess the early features of diabetic cardiomyopathy using cardiac magnetic resonance within the first week after streptozotocin injection in mice. We focused on the relationship between left ventricular function and hypovolemia markers in diabetic animals compared to a hypovolemic rodent model. Methods and Results Swiss mice were randomized into control (group C), streptozotocin-induced diabetes (group D) and furosemide-induced hypovolemia (group F) groups. Cardiac magnetic resonance, non-invasive blood pressure, urine volume, plasma markers of dehydration and cardiac histology were assessed in all groups. Mean blood glucose was higher in diabetic animals than in groups C and F (30.5±5.8 compared to 10.4±2.1 and 11.1±2.8 mmol/L, respectively; p<0.01). Diuresis was increased in animals from group D and F compared to C (14650±11499 and 1533±540 compared to 192±111 μL/24 h; p<0.05). End diastolic and end systolic volumes were lower in group D than in group C at week 1 (1.52±0.36 vs. 1.93±0.35 and 0.54±0.22 vs. 0.75±0.18 mL/kg, p<0.05). These left ventricular volume values in group D were comparable to those observed in the acute hypovolemia model (group F). Increased dehydration plasma markers and an absence of obvious intrinsic myocardial damage (evaluated by cardiac magnetic resonance and histology) suggest that a hemodynamic mechanism underlies the very early drop in left ventricular volumes in group D and provides a potential link to hyperglycemic osmotic diuresis. Conclusions Researchers using cardiac magnetic resonance in hyperglycemic rodent models should be aware of this hemodynamic mechanism, which may partially explain modifications in cardiac parameters in addition to diabetic myocardial damage. PMID:26901278

  4. Cholecystokinin expression in the β-cell leads to increased β-cell area in aged mice and protects from streptozotocin-induced diabetes and apoptosis.

    PubMed

    Lavine, Jeremy A; Kibbe, Carly R; Baan, Mieke; Sirinvaravong, Sirinart; Umhoefer, Heidi M; Engler, Kimberly A; Meske, Louise M; Sacotte, Kaitlyn A; Erhardt, Daniel P; Davis, Dawn Belt

    2015-11-15

    Cholecystokinin (CCK) is a peptide hormone produced in the gut and brain with beneficial effects on digestion, satiety, and insulin secretion. CCK is also expressed in pancreatic β-cells, but only in models of obesity and insulin resistance. Whole body deletion of CCK in obese mice leads to reduced β-cell mass expansion and increased apoptosis. We hypothesized that islet-derived CCK is important in protection from β-cell apoptosis. To determine the specific role of β-cell-derived CCK in β-cell mass dynamics, we generated a transgenic mouse that expresses CCK in the β-cell in the lean state (MIP-CCK). Although this transgene contains the human growth hormone minigene, we saw no expression of human growth hormone protein in transgenic islets. We examined the ability of MIP-CCK mice to maintain β-cell mass when subjected to apoptotic stress, with advanced age, and after streptozotocin treatment. Aged MIP-CCK mice have increased β-cell area. MIP-CCK mice are resistant to streptozotocin-induced diabetes and exhibit reduced β-cell apoptosis. Directed CCK overexpression in cultured β-cells also protects from cytokine-induced apoptosis. We have identified an important new paracrine/autocrine effect of CCK in protection of β-cells from apoptotic stress. Understanding the role of β-cell CCK adds to the emerging knowledge of classic gut peptides in intraislet signaling. CCK receptor agonists are being investigated as therapeutics for obesity and diabetes. While these agonists clearly have beneficial effects on body weight and insulin sensitivity in peripheral tissues, they may also directly protect β-cells from apoptosis. PMID:26394663

  5. Insulinotropic and β-cell protective action of cuminaldehyde, cuminol and an inhibitor isolated from Cuminum cyminum in streptozotocin-induced diabetic rats.

    PubMed

    Patil, Swapnil B; Takalikar, Shreehari S; Joglekar, Madhav M; Haldavnekar, Vivek S; Arvindekar, Akalpita U

    2013-10-01

    Cuminum cyminum, a commonly used spice, is known to have anti-diabetic action. The present study aims towards the isolation of bioactive components from C. cyminum and the evaluation of their insulin secretagogue potential with the probable mechanism and β-cell protective action. The anti-diabetic activity was detected in the petroleum ether (pet ether) fraction of the C. cyminum distillate and studied through in vivo and in vitro experiments. Bioactive components were identified through GC-MS, Fourier transform infrared spectroscopy and NMR analysis. The isolated components were evaluated for their insulin secretagogue action using rat pancreatic islets. Further, the probable mechanism of stimulation of islets was evaluated through in vitro studies using diazoxide, nifedipine and 3-isobutyl-1-methylxanthine. β-Cell protection was evaluated using the (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan) (MTT) assay, the alkaline comet assay and nitrite production. The administration of the pet ether fraction for 45 d to streptozotocin-induced diabetic rats revealed an improved lipid profile. Cuminaldehyde and cuminol were identified as potent insulinotrophic components. Cuminaldehyde and cuminol (25 μg/ml) showed 3·34- and 3·85-fold increased insulin secretion, respectively, than the 11·8 mm-glucose control. The insulinotrophic action of both components was glucose-dependent and due to the closure of the ATP-sensitive K (K⁺-ATP) channel and the increase in intracellular Ca²⁺ concentration. An inhibitor of insulin secretion with potent β-cell protective action was also isolated from the same pet ether fraction. In conclusion, C. cyminum was able to lower blood glucose without causing hypoglycaemia or β-cell burn out. Hence, the commonly used spice, C. cyminum, has the potential to be used as a novel insulinotrophic therapy for prolonged treatment of diabetes. PMID:23507295

  6. Effects of Hydro-Alcoholic Extract of Rhus coriaria (Sumac) Seeds on Reproductive Complications of Nicotinamide-Streptozotocin Induced Type-2 Diabetes in Male Mice

    PubMed Central

    Ahangarpour, Akram; Heidari, Hamid; Ehsan, Ghaedi; Rashidi Nooshabadi, Mohammad Reza

    2014-01-01

    Purpose The purpose of this study was to investigate the effects of the hydro-alcoholic extract of Rhus coriaria seeds on the reproductive system of nicotinamide-streptozotocin-induced type-2 diabetic mice. Materials and Methods In this experimental study, 56 male Naval Medical Research Institute mice were randomly divided into seven groups (n=8): control; diabetic mice; diabetic mice administered glibenclamide (0.25 mg/kg); diabetic mice who received the hydro-alcoholic extract of R. coriaria seeds (200 and 400 mg/kg groups); and normal mice who received this extract (200 and 400 mg/kg groups). Diabetes was induced by intraperitoneal administration of streptozotocin (65 mg/kg) 15 minutes after an injection of nicotinamide (120 mg/kg). Then, glibenclamide and the above mentioned extract were administered orally for 28 consecutive days. Twenty-four hours after the last treatment, serum samples, the testes, and the cauda epididymis were removed immediately for hormonal, testis morphology, and sperm parameter assessments. Results Body and testicular weight, sperm count and viability, and serum luteinizing hormone, follicle-stimulating hormone and testosterone levels were significantly lower in the diabetic mice (p<0.05). The diabetic mice treated with 400 mg/kg of the hydro-alcoholic extract of R. coriaria seeds recovered from these reductions (p<0.05). Further, glibenclamide alleviated hormonal and sperm count depletion in diabetes-induced mice (p<0.05). Conclusions The present results indicated that the hydro-alcoholic extract of R. coriaria seeds has anti-infertility effects in diabetic males. PMID:25606564

  7. A mixture of extracts from Peruvian plants (black maca and yacon) improves sperm count and reduced glycemia in mice with streptozotocin-induced diabetes.

    PubMed

    Gonzales, Gustavo F; Gonzales-Castañeda, Cynthia; Gasco, Manuel

    2013-09-01

    We investigated the effect of two extracts from Peruvian plants given alone or in a mixture on sperm count and glycemia in streptozotocin-diabetic mice. Normal or diabetic mice were divided in groups receiving vehicle, black maca (Lepidium meyenii), yacon (Smallanthus sonchifolius) or three mixtures of extracts black maca/yacon (90/10, 50/50 and 10/90%). Normal or diabetic mice were treated for 7 d with each extract, mixture or vehicle. Glycemia, daily sperm production (DSP), epididymal and vas deferens sperm counts in mice and polyphenol content, and antioxidant activity in each extract were assessed. Black maca (BM), yacon and the mixture of extracts reduced glucose levels in diabetic mice. Non-diabetic mice treated with BM and yacon showed higher DSP than those treated with vehicle (p < 0.05). Diabetic mice treated with BM, yacon and the mixture maca/yacon increased DSP, and sperm count in vas deferens and epididymis with respect to non-diabetic and diabetic mice treated with vehicle (p < 0.05). Yacon has 3.05 times higher polyphenol content than in maca, and this was associated with higher antioxidant activity. The combination of two extracts improved glycemic levels and male reproductive function in diabetic mice. Streptozotocin increased 1.43 times the liver weight that was reversed with the assessed plants extracts. In summary, streptozotocin-induced diabetes resulted in reduction in sperm counts and liver damage. These effects could be reduced with BM, yacon and the BM+yacon mixture. PMID:23489070

  8. Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration.

    PubMed

    Ali, Sumia; Driscoll, Heather E; Newton, Victoria L; Gardiner, Natalie J

    2014-11-01

    Minocycline is an inhibitor of matrix metalloproteinases (MMPs) and has been shown to have analgesic effects. Whilst increased expression of MMPs is associated with neuropathic pain, MMPs also play crucial roles in Wallerian degeneration and nerve regeneration. In this study we examined the expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1/-2 in the sciatic nerve of control and streptozotocin-induced diabetic rats treated with either vehicle or minocycline by quantitative PCR and gelatin zymography. We assessed the effects of minocycline on nerve conduction velocity and intraepidermal nerve fibre (IENF) deficits in diabetic neuropathy and investigated the effects of minocycline or MMP-2 on neurite outgrowth from primary cultures of dissociated adult rat sensory neurons. We show that MMP-2 is expressed constitutively in the sciatic nerve in vivo and treatment with minocycline or diabetes leads to downregulation of MMP-2 expression and activity. The functional consequence of this is IENF deficits in minocycline-treated nondiabetic rats and an unsupportive microenvironment for regeneration in diabetes. Minocycline reduces levels of MMP-2 mRNA and nerve growth factor-induced neurite outgrowth. Furthermore, in vivo minocycline treatment reduces preconditioning-induced in vitro neurite outgrowth following a sciatic nerve crush. In contrast, the addition of active MMP-2 facilitates neurite outgrowth in the absence of neurotrophic support and pre-treatment of diabetic sciatic nerve substrata with active MMP-2 promotes a permissive environment for neurite outgrowth. In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using

  9. Cardioprotection from emulsified isoflurane postconditioning is lost in rats with streptozotocin-induced diabetes due to the impairment of Brg1/Nrf2/STAT3 signalling.

    PubMed

    Wang, Yan; Li, Haobo; Huang, Huansen; Liu, Shiming; Mao, Xiaowen; Wang, Sheng; Wong, Stanley Sau-Ching; Xia, Zhengyuan; Irwin, Michael G

    2016-05-01

    Isoflurane postconditioning (IsoPostC) attenuates myocardial ischaemia/reperfusion injury (IRI). Signal transducer and activator of transcription-3 (STAT3) is critical in ischaemic postconditioning cardioprotection, which can be regulated by the Brahma-related gene (Brg1) and nuclear factor-erythroid 2-related factor 2 (Nrf2), although they are both reduced in diabetic hearts. We hypothesized that reduced Brg1/Nrf2 and STAT3 activation may jeopardize IsoPostC-mediated cardioprotection in diabetic hearts. In the present study, Langendorff-perfused, non-diabetic (control) and 8-week-old streptozotocin-induced Type 1 diabetic rat hearts were subjected to 30 min of global ischaemia and 120 min of reperfusion without or with IsoPostC, which was achieved by administering emulsified isoflurane (2.0%, v/v) in Krebs-Henseleit (KH) solution immediately at the onset of reperfusion for 10 min and switching to KH solution perfusion alone thereafter. Cultured H9C2 cells were exposed to normal glucose (NG, 5.5 mM) or high glucose (HG, 30 mM) and subjected to hypoxia/reoxygenation (HR) in the presence or absence of IsoPostC. Diabetic rats displayed larger post-ischaemic myocardial infarction and more severe haemodynamic dysfunction, associated with increased myocardial oxidative stress and reduced cardiac Brg1, Nrf2 and STAT3 phosphorylation/activation (p-STAT3), compared with controls. These changes were reversed/prevented by IsoPostC in control but not in diabetic rats. In H9C2 cells exposed to NG but not HG, IsoPostC significantly attenuated HR-induced cellular injury and superoxide anion production with increased Brg1, Nrf2 and p-STAT3. These beneficial effects of IsoPostC were abolished by Brg1, Nrf2 or STAT3 gene knockdown. Brg1 or Nrf2 gene knockdown abolished IsoPostC-induced STAT3 activation. N-acetylcysteine restored Brg1, Nrf2 and p-STAT3, and IsoPostC-induced protection in H9C2 cells exposed to HG and HR. In conclusion, IsoPostC confers cardioprotection through

  10. Oxidative Stress Parameters and Erythrocyte Membrane Adenosine Triphosphatase Activities in Streptozotocin-induced Diabetic Rats Administered Aqueous Preparation of Kalanchoe Pinnata Leaves

    PubMed Central

    Menon, Nikhil; Sparks, Jean; Omoruyi, Felix O.

    2016-01-01

    Background: Diabetes mellitus is a chronic metabolic disease that according to the World Health Organization affects more than 382 million people. The rise in diabetes mellitus coupled with the lack of an effective treatment has led many to investigate medicinal plants to identify a viable alternative. Objective: To evaluate red blood cell (RBC) membrane adenosine triphosphatase (ATPase) activities and antioxidant levels in streptozotocin-induced diabetic rats administered aqueous preparation of Kalanchoe pinnata leaves. Materials and Methods: Diabetes mellitus was induced in rats by a single administration of streptozotocin (60 mg/kg). Diabetic rats were then treated with aqueous K. pinnata preparation (three mature leaves ~ 9.96 g/70 kg body weight or about 0.14 g/kg body weight/day) for 30 days. Serum glucose, RBC membrane ATPase activities, and antioxidant levels were determined. Results: We noted weight loss and reduced food consumption in the treated diabetic group. Serum glucose levels were reduced in the treated diabetic group compared to the other groups. Superoxide dismutase activity and glutathione levels were not significantly elevated in the treated group compared to the diabetic group. However, serum catalase activity was significantly (P < 0.05) increased in the treated diabetic group compared to the other groups. Serum thiobarbituric acid reactive substances were not significantly altered among the groups. There was a significant (P < 0.05) increase in Mg2+ ATPase activity and a nonsignificant increase in Na+/K+ ATPase activity in the RBC membrane of the treated diabetic group compared to the diabetic group. Conclusion: The consumption of aqueous preparation of K. pinnata may accrue benefits in the management of diabetes by lowering oxidative stress often associated with the disease and improving the availability of cellular magnesium through an increase in the magnesium ATPase pump in the RBC membrane for increased cellular metabolism of glucose

  11. Effect of Telmisartan or Insulin on the Expression of Adiponectin and its Receptors in the Testis of Streptozotocin-Induced Diabetic Rats.

    PubMed

    Guo, Z; Yan, X; Wang, L; Wu, J; Jing, X; Liu, J

    2016-06-01

    This study investigated the effect of insulin and telmisartan on the expression of adiponectin and its receptors, oxidative stress, and inflammatory cytokines in the testis of streptozotocin-induced diabetic rats. Male Wistar rats were randomly divided into control (C, n=8), diabetic (D, n=8), diabetic treated with insulin (DI, n=8), and diabetic treated with telmisartan (DT, n=8). Diabetic was induced by the peritoneal injection of a single dose of streptozotocin. Eight weeks later, bilateral testes were immediately removed after the rat was sacrificed. Epididymis was harvested to prepare sperm suspension. Plasma adiponectin, testicular interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA). The mRNA or protein expression of testicular adiponectin receptor 1 (adipoR1) and 2 (adipoR2), p22phox, transcription factor NF-E2 associated factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), AMPK-α, Akt, and eNOS was assayed by real-time fluorescence quantitative PCR or Western blot. There were significant pathological changes in the testes of diabetic rats. The levels of testicular weight, sperm number and motility, serum and testicular testosterone, plasma insulin and adiponectin, testicular adiponectin and its receptor 1, Nrf2, NQO1, HO-1, and phosphorylated-AMPK were significantly decreased in diabetic rats. The levels of blood glucose and lipids, and the levels of testicular p22phox, IL-6, TNF-α, phosphorylated-AKT, e-NOS, and nitric oxide (NO) were significantly increased in diabetic rats. These changes could be significantly reversed by insulin treatment. Similar results were observed with telmisartan treatment except for NQO1 mRNA and phosphorylated-AMPK. There was no significant difference in the expression of testicular adiponectin receptor 2 among 4 groups. The decreased adiponectin and its receptors, and the increased oxidative stress and inflammatory cytokines may

  12. Evaluation of low-level laser therapy on skeletal muscle ischemia-reperfusion in streptozotocin-induced diabetic rats by assaying biochemical markers and histological changes.

    PubMed

    Takhtfooladi, Hamed Ashrafzadeh; Asghari, Ahmad; Amirkamali, Sahar; Hoseinzadeh, Hesam Aldin; Takhtfooladi, Mohammad Ashrafzadeh

    2016-08-01

    The purpose of the present study was to assess the effects of low-level laser therapy (LLLT) on skeletal muscle ischemia-reperfusion (IR) injuries in streptozotocin-induced diabetic rats. Twenty male Wistar rats were randomly assigned into two experimental groups, as follows: the diabetic IR group (G1, n = 10) and the diabetic IR + LLLT group (G2, n = 10). Ischemia was induced in anesthetized rats from the right femoral artery clipping for 2 h, followed by a reperfusion for 24 h. Then, the laser irradiation (K30 handheld probe, AZOR, Technica, Russia, 650 nm, 30 mW, surface area = 1 cm(2), energy density = 1.8 J/cm(2)) was carried out by irradiating the rats over a unique point on the skin over the middle region of the right gastrocnemius muscle belly three times (every 8 h), starting after initiating the reperfusion for 3 min. At the end of the reperfusion period, rats were anaesthetized and blood samples were collected and used for the estimation of pO2, pCO2, pH, HCO3, serum creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Subsequently, the right gastrocnemius muscle samples were taken for wet/dry weight ratio assessment and histological/biochemical examination. The pO2, pCO2, HCO3, and pH levels were similar for both groups (P > 0.05). The serum LDH and CPK levels were significantly lower (P < 0.05) for G2 compared to G1. In comparison to G1, tissue malondialdehyde level in G2 was significantly decreased (P < 0.05). In G2, superoxide dismutase activity was significantly increased compared to G1 (P < 0.05). Unlike G2, a significant decrease in the activity of catalase was observed in G1 (P < 0.05). The wet/dry ratio in G1 was significantly higher than that of G2 (P < 0.05). Histological examination confirmed that the extent of muscle changes in G1 was higher than G2 (P < 0.05). Finally, according to this study, LLLT has a beneficial effect on the IR muscle injury treatment in the diabetic rats

  13. Extracts of black bean peel and pomegranate peel ameliorate oxidative stress-induced hyperglycemia in mice.

    PubMed

    Wang, Jian-Yun; Zhu, Chuang; Qian, Tian-Wei; Guo, Hao; Wang, Dong-Dong; Zhang, Fan; Yin, Xiaoxing

    2015-01-01

    Oxidative stress has a central role in the progression of diabetes mellitus (DM), which can directly result in the injury of islet β cells and consequent hyperglycemia. The aim of the present study was to evaluate the possible protective effects of black bean peel extract (BBPE), pomegranate peel extract (PPE) and a combination of the two (PPE + BBPE) on streptozotocin-induced DM mice. Oxidative stress was assessed by the levels of total antioxidative capability and glutathione in the serum. Fasting blood glucose and insulin levels, as well as the pancreas weight index and the histological changes in the pancreas, were also determined. The results showed that, after fours weeks of treatment with PPE, BBPE or PPE + BBPE, DM mice showed, to different degrees, a decrease in blood glucose, increases in insulin secretion and the pancreas weight index, and an increase in antioxidative activity. These changes were particularly evident in the DM mice subjected to the combined intervention strategy of PPE + BBPE. The histological findings indicated that the injury to the pancreatic islets in DM mice was also ameliorated following treatment. In conclusion, PPE and BBPE, particularly the combination of the two, have the ability to ameliorate hyperglycemia by inhibiting oxidative stress-induced pancreatic damage; this finding may be useful in the prevention and treatment of DM. PMID:25452774

  14. Diazoxide preconditioning of endothelial progenitor cells from streptozotocin-induced type 1 diabetic rats improves their ability to repair diabetic cardiomyopathy.

    PubMed

    Ali, Muhammad; Mehmood, Azra; Anjum, Muhammad Sohail; Tarrar, Moazzam Nazir; Khan, Shaheen N; Riazuddin, Sheikh

    2015-12-01

    Type 1 diabetes mellitus (DM) is a strong risk factor for the development of diabetic cardiomyopathy (DCM) which is the leading cause of morbidity and mortality in the type 1 diabetic patients. Stem cells may act as a therapeutic agent for the repair of DCM. However, deteriorated functional abilities and survival of stem cells derived from type 1 diabetic subjects need to be overcome for obtaining potential outcome of the stem cell therapy. Diazoxide (DZ) a highly selective mitochondrial ATP-sensitive K(+) channel opener has been previously shown to improve the ability of mesenchymal stem cells for the repair of heart failure. In the present study, we evaluated the effects of DZ preconditioning in improving the ability of streptozotocin-induced type 1 diabetes affected bone marrow-derived endothelial progenitor cells (DM-EPCs) for the repair of DCM in the type 1 diabetic rats. DM-EPCs were characterized by immunocytochemistry, flow cytometry, and reverse transcriptase PCR for endothelial cell-specific markers like vWF, VE cadherin, VEGFR2, PECAM, CD34, and eNOS. In vitro studies included preconditioning of DM-EPCs with 200 μM DZ for 30 min followed by exposure to either 200 μM H2O2 for 2 h (for oxidative stress induction) or 30 mM glucose media (for induction of hyperglycemic stress) for 48 h. Non-preconditioned EPCs with and without exposure to H2O2 and 30 mM high glucose served as controls. These cells were then evaluated for survival (by MTT and XTT cell viability assays), senescence, paracrine potential (by ELISA for VEGF), and alteration in gene expression [VEGF, stromal derived factor-1α (SDF-1α), HGF, bFGF, Bcl2, and Caspase-3]. DZ preconditioned DM-EPCs demonstrated significantly increased survival and VEGF release while reduced cell injury and senescence. Furthermore, DZ preconditioned DM-EPCs exhibited up-regulated expression of prosurvival genes (VEGF, SDF-1α, HGF, bFGF, and Bcl2) on exposure to H2O2, and VEGF and Bcl2 on exposure to hyperglycemia

  15. Guizhi-Fuling-Wan, a Traditional Chinese Herbal Medicine, Ameliorates Memory Deficits and Neuronal Apoptosis in the Streptozotocin-Induced Hyperglycemic Rodents via the Decrease of Bax/Bcl2 Ratio and Caspase-3 Expression.

    PubMed

    Wu, Kuo-Jen; Chen, Yuh-Fung; Tsai, Huei-Yann; Wu, Chi-Rei; Wood, W Gibson

    2012-01-01

    Brain neuronal apoptosis and cognitive impairment are associated with hyperglycemia and diabetes mellitus. The present study determined if the Chinese herbal medicine Guizhi-Fuling-Wan (GFW) would reduce memory loss and neuronal apoptosis in streptozotocin- (STZ-) induced hyperglycemic rodents. Two weeks after STZ induction, GFW was orally administered once daily for 7 days. GFW significantly improved spatial memory deficits in STZ-induced hyperglycemic mice. GFW decreased TUNEL-positive cells and caspase-3 positive cells in STZ-induced hyperglycemic rats. It also was found that GFW treatment reduced caspase-3 protein levels and increased levels of the antiapoptotic protein Bcl-2 that were indicative of neuroprotection. The protective therapeutic effects of GFW on neuronal apoptosis and cognition deficits caused by STZ-induced hyperglycemia may be due in part to inhibition of the cellular apoptosis pathway. GFW may have therapeutic effects in patients with diabetes-mellitus-induced neuropathology. PMID:23304209

  16. Angelica sinensis polysaccharide regulates glucose and lipid metabolism disorder in prediabetic and streptozotocin-induced diabetic mice through the elevation of glycogen levels and reduction of inflammatory factors.

    PubMed

    Wang, Kaiping; Cao, Peng; Shui, Weizhi; Yang, Qiuxiang; Tang, Zhuohong; Zhang, Yu

    2015-03-01

    The present study was designed to evaluate the potential hypoglycemic and hypolipidemic effects of Angelica sinensis polysaccharide (ASP), purified from the fresh roots of Angelica sinensis (AS), in prediabetic and streptozotocin (STZ)-induced diabetic BALB/c mice. It was observed that fasting blood glucose (FBG) levels in both models were reduced after a 4-week oral administration of ASP or metformin, and abnormal fasting serum insulin (FINS) concentrations were ameliorated as well. Moreover, the homeostasis model assessment-insulin resistance (HOMA-IR) index was decreased strikingly and body weight (BW) was reduced significantly in prediabetic mice after treatment with ASP. In addition, ASP also contributed to improving the dyslipidemia conditions. Elevated serum total cholesterol (TC) or triglyceride (TG) concentrations were reduced after treatment with ASP in prediabetic mice or STZ-induced diabetic mice. Meanwhile, hepatic glycogen (HG) and muscle glycogen (MG) concentrations were increased while insulin resistance (IR)-related inflammatory factors IL-6 and TNF-α in serum were reduced in STZ-induced diabetic mice. Histopathological examination indicated that the impaired pancreatic/hepatic tissues or adipose tissues were effectively restored in STZ-induced diabetic mice or prediabetic mice after the ASP treatment. Taken together, these results revealed that ASP efficiently exerted hypoglycemic and hypolipidemic benefits, and its potential effect was associated with the amelioration of IR. ASP can be applied in the prevention and treatment of diabetes. PMID:25630053

  17. Autophagy ameliorates cognitive impairment through activation of PVT1 and apoptosis in diabetes mice.

    PubMed

    Li, Zhigui; Hao, Shuang; Yin, Hongqiang; Gao, Jing; Yang, Zhuo

    2016-05-15

    The underlying mechanisms of cognitive impairment in diabetes remain incompletely characterized. Here we show that the autophagic inhibition by 3-methyladenine (3-MA) aggravates cognitive impairment in streptozotocin-induced diabetic mice, including exacerbation of anxiety-like behaviors and aggravation in spatial learning and memory, especially the spatial reversal memory. Further neuronal function identification confirmed that both long term potentiation (LTP) and depotentiation (DPT) were exacerbated by autophagic inhibition in diabetic mice, which indicating impairment of synaptic plasticity. However, no significant change of pair-pulse facilitation (PPF) was recorded in diabetic mice with autophagic suppression compared with the diabetic mice, which indicated that presynaptic function was not affected by autophagic inhibition in diabetes. Subsequent hippocampal neuronal cell death analysis showed that the apoptotic cell death, but not the regulated necrosis, significantly increased in autophagic suppression of diabetic mice. Finally, molecular mechanism that may lead to cell death was identified. The long non-coding RNA PVT1 (plasmacytoma variant translocation 1) expression was analyzed, and data revealed that PVT1 was decreased significantly by 3-MA in diabetes. These findings show that PVT1-mediated autophagy may protect hippocampal neurons from impairment of synaptic plasticity and apoptosis, and then ameliorates cognitive impairment in diabetes. These intriguing findings will help pave the way for exciting functional studies of autophagy in cognitive impairment and diabetes that may alter the existing paradigms. PMID:26971628

  18. The Protective Effect of Beraprost Sodium on Diabetic Nephropathy by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats.

    PubMed

    Peng, Li; Li, Jie; Xu, Yixing; Wang, Yangtian; Du, Hong; Shao, Jiaqing; Liu, Zhimin

    2016-01-01

    Background. p38 mitogen-activated protein kinase (MAPK) plays a crucial role in regulating signaling pathways implicated in inflammatory processes leading to diabetic nephropathy (DN). This study aimed to examine p38 MAPK activation in DN and determine whether beraprost sodium (BPS) ameliorates DN by inhibiting inflammation and p38 MAPK signaling pathway in diabetic rats. Methods. Forty male Sprague Dawley (SD) rats were randomly divided into the normal control group, type 2 diabetic group, and BPS treatment group. At the end of the 8-week experiment, we measured renal pathological changes and the activation of the p38 MAPK signaling pathway and inflammation. Result. After BPS treatment, renal function, 24-hour urine protein, lipid profiles, and blood glucose level were improved significantly; meanwhile, inflammation and the expression of p38 MAPK signaling pathway in the diabetic kidney were attenuated. Conclusions. BPS significantly prevented type 2 diabetes induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms are complicated but may be mainly attributed to the inhibition of the p38 MAPK signaling pathway and inflammation in the diabetic kidney. PMID:27212945

  19. Extract of Polygonum cuspidatum Attenuates Diabetic Retinopathy by Inhibiting the High-Mobility Group Box-1 (HMGB1) Signaling Pathway in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Sohn, Eunjin; Kim, Junghyun; Kim, Chan-Sik; Lee, Yun Mi; Kim, Jin Sook

    2016-03-01

    High-mobility group box-1 (HMGB1) is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE) on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day) was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE) and the activity of nuclear factor-kappa B (NF-κB) in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes. PMID:26950148

  20. Extract of Polygonum cuspidatum Attenuates Diabetic Retinopathy by Inhibiting the High-Mobility Group Box-1 (HMGB1) Signaling Pathway in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Sohn, Eunjin; Kim, Junghyun; Kim, Chan-Sik; Lee, Yun Mi; Kim, Jin Sook

    2016-01-01

    High-mobility group box-1 (HMGB1) is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE) on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day) was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE) and the activity of nuclear factor-kappa B (NF-κB) in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes. PMID:26950148

  1. The Protective Effect of Beraprost Sodium on Diabetic Nephropathy by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Peng, Li; Li, Jie; Xu, Yixing; Wang, Yangtian; Du, Hong; Shao, Jiaqing; Liu, Zhimin

    2016-01-01

    Background. p38 mitogen-activated protein kinase (MAPK) plays a crucial role in regulating signaling pathways implicated in inflammatory processes leading to diabetic nephropathy (DN). This study aimed to examine p38 MAPK activation in DN and determine whether beraprost sodium (BPS) ameliorates DN by inhibiting inflammation and p38 MAPK signaling pathway in diabetic rats. Methods. Forty male Sprague Dawley (SD) rats were randomly divided into the normal control group, type 2 diabetic group, and BPS treatment group. At the end of the 8-week experiment, we measured renal pathological changes and the activation of the p38 MAPK signaling pathway and inflammation. Result. After BPS treatment, renal function, 24-hour urine protein, lipid profiles, and blood glucose level were improved significantly; meanwhile, inflammation and the expression of p38 MAPK signaling pathway in the diabetic kidney were attenuated. Conclusions. BPS significantly prevented type 2 diabetes induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms are complicated but may be mainly attributed to the inhibition of the p38 MAPK signaling pathway and inflammation in the diabetic kidney. PMID:27212945

  2. The antidiabetic effect of low doses of Moringa oleifera Lam. seeds on streptozotocin induced diabetes and diabetic nephropathy in male rats.

    PubMed

    Al-Malki, Abdulrahman L; El Rabey, Haddad A

    2015-01-01

    The antidiabetic activity of two low doses of Moringa seed powder (50 and 100 mg/kg body weight, in the diet) on streptozotocin (STZ) induced diabetes male rats was investigated. Forty rats were divided into four groups. The diabetic positive control (STZ treated) group showed increased lipid peroxide, increased IL-6, and decreased antioxidant enzyme in the serum and kidney tissue homogenate compared with that of the negative control group. Immunoglobulins (IgA, IgG), fasting blood sugar, and glycosylated hemoglobin (HbA1c) were also increased as a result of diabetes in G2 rats. Moreover albumin was decreased, and liver enzymes and α-amylase were not affected. In addition, the renal functions and potassium and sodium levels in G2 were increased as a sign of diabetic nephropathy. Urine analysis showed also glucosuria and increased potassium, sodium, creatinine, uric acid, and albumin levels. Kidney and pancreas tissues showed also pathological alteration compared to the negative control group. Treating the diabetic rats with 50 or 100 mg Moringa seeds powder/kg body weight in G3 and G4, respectively, ameliorated the levels of all these parameters approaching the negative control values and restored the normal histology of both kidney and pancreas compared with that of the diabetic positive control group. PMID:25629046

  3. The Antidiabetic Effect of Low Doses of Moringa oleifera Lam. Seeds on Streptozotocin Induced Diabetes and Diabetic Nephropathy in Male Rats

    PubMed Central

    Al-Malki, Abdulrahman L.; El Rabey, Haddad A.

    2015-01-01

    The antidiabetic activity of two low doses of Moringa seed powder (50 and 100 mg/kg body weight, in the diet) on streptozotocin (STZ) induced diabetes male rats was investigated. Forty rats were divided into four groups. The diabetic positive control (STZ treated) group showed increased lipid peroxide, increased IL-6, and decreased antioxidant enzyme in the serum and kidney tissue homogenate compared with that of the negative control group. Immunoglobulins (IgA, IgG), fasting blood sugar, and glycosylated hemoglobin (HbA1c) were also increased as a result of diabetes in G2 rats. Moreover albumin was decreased, and liver enzymes and α-amylase were not affected. In addition, the renal functions and potassium and sodium levels in G2 were increased as a sign of diabetic nephropathy. Urine analysis showed also glucosuria and increased potassium, sodium, creatinine, uric acid, and albumin levels. Kidney and pancreas tissues showed also pathological alteration compared to the negative control group. Treating the diabetic rats with 50 or 100 mg Moringa seeds powder/kg body weight in G3 and G4, respectively, ameliorated the levels of all these parameters approaching the negative control values and restored the normal histology of both kidney and pancreas compared with that of the diabetic positive control group. PMID:25629046

  4. The hydrogen sulfide releasing compounds ATB-346 and diallyl trisulfide attenuate streptozotocin-induced cognitive impairment, neuroinflammation, and oxidative stress in rats: involvement of asymmetric dimethylarginine.

    PubMed

    Mostafa, Dalia K; El Azhary, Nesrine M; Nasra, Rasha A

    2016-07-01

    Hydrogen sulfide (H2S) has attracted interest as a gaseous mediator involved in diverse processes in the nervous system, particularly with respect to learning and memory. However, its therapeutic potential in Alzheimer disease (AD) is not fully explored. Therefore, the effects of H2S-releasing compounds against AD-like behavioural and biochemical abnormalities were investigated. Memory deficit was induced by intracerberoventicular injection of streptozotocin (STZ, 3 mg·kg(-1)). Animals were randomly assigned into 5 groups (12 rats each): normal control, STZ treated, and 3 drug-treated groups receiving naproxen, H2S-releasing naproxen (ATB-346), and diallyl trisulfide in 20, 32, 40 mg·kg(-1)·day(-1), respectively. Memory function was assessed by passive avoidance and T-maze tasks. After 21 days, hippocampal IL-6, malondialdehyde, reduced glutathione (GSH), asymmetric dimethylarginine (ADMA), and acetylcholinestrase activity were determined. ATB-346 and diallyl trisulfide ameliorated behavioural performance and reduced malondialdehyde, ADMA, and acetylcholinestrase activity while increasing GSH. This study demonstrates the beneficial effects of H2S release in STZ-induced memory impairment by modulation of neuroinflammation, oxidative stress, and cholinergic function. It also delineates the implication of ADMA to the cognitive impairment induced by STZ. These findings draw the attention to H2S-releasing compounds as new candidates for treating neurodegenerative disorders that have prominent oxidative and inflammatory components such as AD. PMID:27088818

  5. Antidiabetic Potentiality of the Aqueous-Methanolic Extract of Seed of Swietenia mahagoni (L.) Jacq. in Streptozotocin-Induced Diabetic Male Albino Rat: A Correlative and Evidence-Based Approach with Antioxidative and Antihyperlipidemic Activities

    PubMed Central

    De, Debasis; Chatterjee, Kausik; Ali, Kazi Monjur; Bera, Tushar Kanti; Ghosh, Debidas

    2011-01-01

    Antidiabetic, antioxidative, and antihyperlipidemic activities of aqueous-methanolic (2 : 3) extract of Swietenia mahagoni (L.) Jacq. (family Meliaceae) seed studied in streptozotocin-induced diabetic rats. Feeding with seed extract (25 mg 0.25 mL distilled water−1100 gm b.w.−1rat−1 day−1) for 21 days to diabetic rat lowered the blood glucose level as well as the glycogen level in liver. Moreover, activities of antioxidant enzymes like catalase, peroxidase, and levels of the products of free radicals like conjugated diene and thiobarbituric acid reactive substances in liver, kidney, and skeletal muscles were corrected towards the control after this extract treatment in this model. Furthermore, the seed extract corrected the levels of serum urea, uric acid, creatinine, cholesterol, triglyceride, and lipoproteins towards the control level in this experimental diabetic model. The results indicated the potentiality of the extract of S. mahagoni seed for the correction of diabetes and its related complications like oxidative stress and hyperlipidemia. The extract may be a good candidate for developing a safety, tolerable, and promising neutraceutical treatment for the management of diabetes. PMID:20981322

  6. Synthesis, Spectral Characterization, and Biochemical Evaluation of Antidiabetic Properties of a New Zinc-Diosmin Complex Studied in High Fat Diet Fed-Low Dose Streptozotocin Induced Experimental Type 2 Diabetes in Rats

    PubMed Central

    Gopalakrishnan, Veerasamy; Iyyam Pillai, Subramanian; Subramanian, Sorimuthu Pillai

    2015-01-01

    In view of the established antidiabetic properties of zinc, the present study was aimed at evaluating the hypoglycemic properties of a new zinc-diosmin complex in high fat diet fed-low dose streptozotocin induced experimental type 2 diabetes in rats. Zinc-diosmin complex was synthesized and characterized by various spectral studies. The complexation between zinc ions and diosmin was further evidenced by pH-potentiometric titrations and Job's plot. Diabetic rats were orally treated with zinc-diosmin complex at a concentration of 20 mg/kg b.w./rat/day for 30 days. At the end of the experimental period, the rats were subjected to oral glucose tolerance test. In addition, HOMA-IR and various biochemical parameters related to glucose homeostasis were analyzed. Treatment with zinc-diosmin complex significantly improved the glucose homeostasis in diabetic rats. Treatment with zinc-diosmin complex significantly improved insulin sensitivity, at least in part, through enhancing protein metabolism and alteration in the levels of muscle and liver glycogen. The assay of clinical marker enzymes revealed the nontoxic nature of the complex. Determination of renal tissue markers such as blood urea and serum creatinine indicates the renoprotective nature of the complex. These findings suggest that zinc-diosmin complex is nontoxic and has complimentary potential to develop as an antihyperglycemic agent for the treatment of diabetes mellitus. PMID:26783461

  7. Effects of vitamin A, C and E, or omega-3 fatty acid supplementation on the level of paraoxonase and arylesterase activity in streptozotocin-induced diabetic rats: an investigation of activities in plasma, and heart and liver homogenates

    PubMed Central

    Zarei, Mahnaz; Fakher, Shima; Tabei, Seyed Mohammad Bagher; Javanbakht, Mohammad Hassan; Derakhshanian, Hoda; Farahbakhsh-Farsi, Payam; Sadeghi, Mohammad Reza; Mostafavi, Ebrahim; Djalali, Mahmoud

    2016-01-01

    INTRODUCTION This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. METHODS A total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. RESULTS Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors. CONCLUSION Vitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications. PMID:26996784

  8. Synthesis, Spectral Characterization, and Biochemical Evaluation of Antidiabetic Properties of a New Zinc-Diosmin Complex Studied in High Fat Diet Fed-Low Dose Streptozotocin Induced Experimental Type 2 Diabetes in Rats.

    PubMed

    Gopalakrishnan, Veerasamy; Iyyam Pillai, Subramanian; Subramanian, Sorimuthu Pillai

    2015-01-01

    In view of the established antidiabetic properties of zinc, the present study was aimed at evaluating the hypoglycemic properties of a new zinc-diosmin complex in high fat diet fed-low dose streptozotocin induced experimental type 2 diabetes in rats. Zinc-diosmin complex was synthesized and characterized by various spectral studies. The complexation between zinc ions and diosmin was further evidenced by pH-potentiometric titrations and Job's plot. Diabetic rats were orally treated with zinc-diosmin complex at a concentration of 20 mg/kg b.w./rat/day for 30 days. At the end of the experimental period, the rats were subjected to oral glucose tolerance test. In addition, HOMA-IR and various biochemical parameters related to glucose homeostasis were analyzed. Treatment with zinc-diosmin complex significantly improved the glucose homeostasis in diabetic rats. Treatment with zinc-diosmin complex significantly improved insulin sensitivity, at least in part, through enhancing protein metabolism and alteration in the levels of muscle and liver glycogen. The assay of clinical marker enzymes revealed the nontoxic nature of the complex. Determination of renal tissue markers such as blood urea and serum creatinine indicates the renoprotective nature of the complex. These findings suggest that zinc-diosmin complex is nontoxic and has complimentary potential to develop as an antihyperglycemic agent for the treatment of diabetes mellitus. PMID:26783461

  9. Effects of acute and chronic hyperglycemia on the neurochemical profiles in the rat brain with streptozotocin-induced diabetes detected using in vivo 1H MR spectroscopy at 9.4 T

    PubMed Central

    Wang, Wen-Tung; Lee, Phil; Yeh, Hung-Wen; Smirnova, Irina V.; Choi, In-Young

    2012-01-01

    Chronic hyperglycemia could lead to cerebral metabolic alterations and CNS injury. However, findings of metabolic alterations in poorly managed diabetes in humans and animal models are rather inconsistent. We have characterized the cerebral metabolic consequences of untreated hyperglycemia from the onset to the chronic stage in a streptozotocin-induced rat model of diabetes. In vivo 1H magnetic resonance spectroscopy (MRS) was used to measure over 20 neurochemicals longitudinally. Upon the onset of hyperglycemia (acute state), increases in brain glucose levels were accompanied by increases in osmolytes and ketone bodies, all of which remained consistently high through the chronic state of over 10 weeks of hyperglycemia. Only after over 4 weeks of hyperglycemia, the levels of other neurochemicals including N-acetylaspartate and glutathione were significantly reduced and these alterations persisted into the chronic stage. However, glucose transport was not altered in chronic hyperglycemia of over 10 weeks. When glucose levels were acutely restored to euglycemia, some neurochemical changes were irreversible, indicating the impact of prolonged uncontrolled hyperglycemia on the CNS. Furthermore, progressive changes in neurochemical levels from control to acute and chronic conditions demonstrated the utility of 1H MRS as a noninvasive tool in monitoring the disease progression in diabetes. PMID:22353009

  10. Treadmill exercise alleviates impairment of spatial learning ability through enhancing cell proliferation in the streptozotocin-induced Alzheimer’s disease rats

    PubMed Central

    Sim, Young-Je

    2014-01-01

    Alzheimer’s disease is the most common cause of dementia. This disease is a progressive and irreversible brain disorder accompanied with severe learning and memory impairment. Exercise increases cognitive ability, attenuates motor deficits, increases new neuron formation, and ameliorates neurological impairments in several neurodegenerative diseases. This study investigated the effects of treadmill exercise on spatial learning ability in relation with cell proliferation in the hippocampus. The rat model of Alzheimer’s disease was induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) using a stereotaxic instrument. The rats in the exercise groups were forced to run on a treadmill for once 30 min daily for 28 consecutive days starting at 3 days after the ICV injection of STZ. Radial 8-arm maze test was conducted for the spatial learning ability. New neuron formation in the hippocampus was detected by 5-bromo-2’-deoxyuridine (BrdU) immunohistochemistry. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions were examined by western blot analysis. The present results show that ICV injection of STZ impaired spatial learning ability. Decreased cell proliferation with decrement of BDNF and TrkB expressions in the hippocampus were observed in the STZ-induced Alzheimer’s disease rats. However, treadmill exercise alleviated deficits of spatial learning ability. Treadmill exercise enhanced cell proliferation and increased BDNF and TrkB expressions in the rats with ICV injection of STZ. The present study suggests that treadmill exercise can be a useful strategy for treating memory impairment induced by several neurodegenerative diseases. PMID:24877042

  11. Preventive Effect of Garlic (Allium sativum L.) on Serum Biochemical Factors and Histopathology of Pancreas and Liver in Streptozotocin- Induced Diabetic Rats

    PubMed Central

    Masjedi, Fatemeh; Gol, Ali; Dabiri, Shahriar

    2013-01-01

    Antidiabetic action of garlic is established in animal studies. Since all of the pervious studies have focused on the therapeutic role of garlic, this study investigated the preventive effect of garlic juice on biochemical factors and histological features in Streptozotocin (STZ)- induced diabetic rats. Forty male rats were divided into five groups (n = 8): 1-Normal group (N), 2-Normal+Garlic group (N+G) received garlic juice (1 mL/100g BW) for 6 weeks, 3-Diabetic group (D) was injected with STZ (60 mg/kg, IP), 4-Diabetic+Garlic-before group (D+Gb) received garlic juice for 3 weeks before STZ injection and continued for another 3 weeks, 5-Diabetic+Garlic-after group (D+Ga), three days after STZ injection, they received garlic juice for 3 weeks. Serum biochemical factors were measured by the enzymatic methods and H&E stained sections of pancreas and liver were prepared for light microscopy. In diabetic rats, elevated levels of glucose, cholesterol and triglycerides, the increment of the activities of ALT and AST, increased food and water consumption were observed. The abnormal increases were significantly (p < 0.05) decreased in D+Gb groups compared to D group. In D group, scattered degeneration of the hepatocytes with lymphocytic infiltration in the portal areas, decrease of pancreatic islets numbers and diameter, atrophy of pancreatic islets were observed. These abnormal histological signs were dramatically ameliorated in D+Gb group compared to D group. In D+Ga group compared to D+Gb group slighter effects of garlic juice on histopathological and biochemical changes were seen. These results indicate that garlic juice may help in the prevention of the complications of diabetes. PMID:24250639

  12. Effects of Cichorium intybus linn on blood glucose, lipid constituents and selected oxidative stress parameters in streptozotocin-induced diabetic rats.

    PubMed

    Samarghandian, Saeed; Borji, Abasalt; Tabasi, Seyed Hidar

    2013-12-01

    The efficacy of herbal medicine has been confirmed in treatment of diabetes mellitus (DM) by amelioration of oxidative stress. The present study was designed to investigate protective effects of Cichorium intybus extract (CIE) against oxidative damage in diabetic rats. In this study, the rats were divided into the control (C), diabetic (D), D + CIE- treated (125 mg/kg/day) groups. Male Sprague-Dawley rats aged 9 weeks (160 ± 15 g) were administered with streptozotocin (STZ, 60 mg/kg) intraperitoneally (ip) to induce experimental diabetes. From 3 days after STZ administration to the end of the study (4 weeks) the ethanolic extract of CIE was administered (i.p) to diabetic rats. Body weight and blood glucose were measured weekly. At the end of the 4-week period, blood was drawn for biochemical assay, in order to determine the changes of cellular antioxidant defense system, serum oxidative damage and serum lipid were measured profile. CIE injection to diabetic rats resulted in significant reduction in blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels and significant elevation high density lipoprotein cholesterol (HDL-C) level as well as increase in the body weight as compared with the rats treated with STZ alone. In the treated diabetic group, we also observed the significant increase in reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) with decline in malondialdehyde (MDA) level compared with the non-treated diabetic group. These results suggest that the Cichorium intybus extract has antioxidant properties and prevents diabetes complications by modulation of oxidative stress system. PMID:24304233

  13. Curcumin regulates gene expression of insulin like growth factor, B-cell CLL/lymphoma 2 and antioxidant enzymes in streptozotocin induced diabetic rats

    PubMed Central

    2013-01-01

    Background The effects of curcumin on the activities and gene expression of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (G-ST), B-cell CLL/lymphoma 2 (Bcl-2) and insulin like growth factor-1 (IGF-1) in diabetic rats were studied. Methods Twenty four rats were assigned to three groups (8 rats for each). Rats of first group were non diabetic and rats of the second group were rendered diabetic by streptozotocin (STZ). Both groups received vehicle, corn oil only (5 ml/kg body weight) and served as negative and positive controls, respectively. Rats of the third group were rendered diabetic and received oral curcumin dissolved in corn oil at a dose of 15 mg/5 ml/kg body weight for 6 weeks. Results Diabetic rats showed significant increase of blood glucose, thiobarbituric acid reactive substances (TBARS) and activities of all antioxidant enzymes with significant reduction of reduced glutathione (GSH) compare to the control non diabetic group. Gene expression of Bcl2, SOD, CAT, GPX and GST was increased significantly in diabetic untreated rats compare to the control non diabetic group. The administration of curcumin to diabetic rats normalized significantly their blood sugar level and TBARS values and increased the activities of all antioxidant enzymes and GSH concentration. In addition, curcumin treated rats showed significant increase in gene expression of IGF-1, Bcl2, SOD and GST compare to non diabetic and diabetic untreated rats. Conclusion Curcumin was antidiabetic therapy, induced hypoglycemia by up-regulation of IGF-1 gene and ameliorate the diabetes induced oxidative stress via increasing the availability of GSH, increasing the activities and gene expression of antioxidant enzymes and Bcl2. Further studies are required to investigate the actual mechanism of action of curcumin regarding the up regulation of gene expression of examined parameters. PMID:24364912

  14. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    PubMed Central

    Oguntibeju, Oluwafemi O.; Meyer, Samantha; Aboua, Yapo G.; Goboza, Mediline

    2016-01-01

    Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ-) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue. PMID:27403200

  15. Extract of Rhizoma Polygonum cuspidatum reduces early renal podocyte injury in streptozotocin-induced diabetic rats and its active compound emodin inhibits methylglyoxal-mediated glycation of proteins

    PubMed Central

    SOHN, EUNJIN; KIM, JUNGHYUN; KIM, CHAN SIK; JO, KYUHYUNG; KIM, JIN SOOK

    2015-01-01

    Podocyte injury contributes to renal damage and, eventually, to the occurrence of proteinuria in diabetic nephropathy. The aim of the present study was to investigate the effect of an ethanol extract from Rhizoma Polygonum cuspidatum (P. cuspidatum) on proteinuria and podocyte injury, and elucidate the underlying mechanism for streptozotocin (STZ)-induced diabetic nephropathy. The protective effects of P. cuspidatum extract (PCE) on renal podocytes in STZ-induced diabetic rats were also investigated. PCE (100 or 350 mg/kg/day) was administered to STZ-induced diabetic rats for 16 weeks, and blood glucose levels, body weight and proteinuria were measured. A double labeling technique with the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed and synaptopodin expression was observed. In addition, cleaved caspase-3, methylglyoxal (MGO) and 8-hydroxydeoxyguanosine (8-OHdG) expression levels were measured. STZ-induced diabetic rats developed hyperglycemia and proteinuria. Increased apoptosis of the podocytes and increased cleaved caspase-3, MGO and 8-OHdG expression levels, as well as decreased synaptopodin expression were detected in the glomeruli of STZ-induced diabetic rats. However, treatment with PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and apoptosis. Levels of caspase-3 and MGO expression, as well as oxidative stress were ameliorated by PCE treatment. In addition, emodin, a biologically active ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO-derived advanced glycation end-product formation. These findings indicate that PCE may be administered to prevent proteinuria and podocyte loss in STZ-induced diabetic rats partly by inhibiting podocyte apoptosis and cleaved caspase-3 expression, and by restoring the balance of oxidative stress and MGO expression. PMID:26299942

  16. Anti-diabetic effects of ethanol extract of Bryonia laciniosa seeds and its saponins rich fraction in neonatally streptozotocin-induced diabetic rats

    PubMed Central

    Patel, Sandip B.; Santani, Devdas; Patel, Veena; Shah, Mamta

    2015-01-01

    Context: Bryonia laciniosa Linn. (Cucurbitaceae) seed is used in traditional medicine for a number of ailments including metabolic disorders. Aim: This study evaluated the anti-diabetic action of the ethanol extract of B. laciniosa seeds and saponin fraction of it through its effect on hyperglycemia, dyslipidaemia and oxidative stress in neonatally streptozotocin (n-STZ)-induced diabetic rats (n-STZ diabetic rats). Materials and Methods: Ethanol extract (250 and 500 mg/kg; p.o.), saponin fraction (100 and 200 mg/kg; p.o.) and standard drug glibenclamide (3 mg/kg; p.o.) were administered to diabetic rats when the rats were 6 weeks old and continued for 10 consecutive weeks. Effects of ethanol extract and saponin fraction on various biochemical parameters were studied in diabetic rats. Results: The treatment with ethanol extract and saponin fraction for 10 weeks decrease in the levels of glucose, triglycerides, cholesterol, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, serum urea, serum creatinine and diminished activities of aspartate transaminase, and alanine transaminase. The anti-hyperglycemic nature of B. laciniosa is probably brought about by the extra- the pancreatic mechanism as evidenced from unchanged levels of plasma insulin. B. laciniosa modulated effect of diabetes on the liver malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity. Administration of ethanol extract and saponin fraction to diabetic rats showed a significant reversal of disturbed antioxidant status. Significant increase in SOD, CAT, and levels of GSH was observed in treated n-STZ diabetic rats. Conclusion: The present study reveals the efficacy of B. laciniosa seed extract and its saponin fraction in the amelioration of n-STZ diabetic rats. PMID:25598641

  17. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats.

    PubMed

    Oguntibeju, Oluwafemi O; Meyer, Samantha; Aboua, Yapo G; Goboza, Mediline

    2016-01-01

    Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ-) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue. PMID:27403200

  18. Garlic Attenuates Plasma and Kidney ACE-1 and AngII Modulations in Early Streptozotocin-Induced Diabetic Rats: Renal Clearance and Blood Pressure Implications

    PubMed Central

    Al-Qattan, Khaled K.; Jayasree, Divya; Ali, Muslim

    2016-01-01

    Raw garlic aqueous extract (GE) has ameliorative actions on the renin-angiotensin system in type-1 diabetes mellitus (DM); however its effects on plasma and kidney angiotensin I converting enzyme type-1 (ACE-1) and angiotensin II (AngII) require further elucidation. This study investigated the effect of GE on plasma and kidney ACE-1 and AngII concentrations and in relation to systemic and renal clearance indicators significant to blood pressure (BP) homeostasis in early streptozotocin- (STZ-) induced type-1 DM. Normal rats (n = 10) received 0.5 mL normal saline (NR/NS), diabetic rats (n = 10) received 0.5 mL NS (DR/NS), and treated diabetic rats (n = 10) received 50 mg/0.1 mL/100 g body weight GE (DR/GE) as daily intraperitoneal injections for 8 weeks. Compared to NR/NS, DR/NS showed a significant increase in plasma ACE-1 and AngII and conversely a decrease in kidney ACE-1 and AngII. These changes were associated with an increase in BP and clearance functions. Alternatively and compared to DR/NS, DR/GE showed normalization or attenuation in plasma and kidney ACE-1 and AngII. These GE induced rectifications were associated with moderation in BP elevation and renal clearance functions. Garlic attenuates modulations in plasma and kidney ACE-1 and AngII, in addition to BP and renal clearance function in type-1 DM. PMID:27293465

  19. Hypoglycemic effect of deoxynojirimycin-polysaccharide on high fat diet and streptozotocin-induced diabetic mice via regulation of hepatic glucose metabolism.

    PubMed

    Li, You-gui; Ji, Dong-feng; Zhong, Shi; Lin, Tian-bao; Lv, Zhi-qiang

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is currently considered a worldwide epidemic and finding effective therapeutic strategies against this disease is highly important. A deoxynojirimycin-polysaccharide mixture (DPM) has previously been shown to exert hypoglycemic effects on alloxan- or streptozotocin (STZ)-induced diabetic mice. The purpose of the present study was to evaluate the therapeutic effects and underlying mechanism(s) of DPM on T2DM induced by high fat diet following low-dose STZ treatment in mice. After daily oral treatment of diabetic mice with DPM (150 mg/kg b.w.) for 90 d, significant decline in blood glucose, pyruvate, triglyceride (TG), aspartate transaminase (AST), alanine transaminase (ALT), creatinine (Cr), lipid peroxide (LPO) and malondialdehyde (MDA) levels as well as evident increases in high density lipoprotein (HDL-c) and hepatic glycogen concentrations were observed. In the first stage, in which DPM was administered for 60 d, blood insulin levels did not undergo significant change but a significant decrease in the HOMA-IR index was detected. By contrast, the HOMA-IR index increased significantly in T2MD controls. In the second stage, in which DPM treatment was continued for another 30 d, insulin levels significantly increased in DPM-treated mice in comparison with T2DM controls. These results indicate that insulin resistance in the pre-diabetic period and the dysfunction of pancreatic β-cells are ameliorated by DPM treatment. DPM also down-regulated protein levels of insulin receptor (IR) and gluconeogenic enzymes (pyruvate carboxylase, fructose-1, 6-bisphosphatase, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in peripheral tissues (liver and/or muscle), but enhanced the expressions of insulin in pancreas, lipoprotein lipase (LPL) and glycolysis enzymes (glucokinase, phosphofructokinase, private kinase and pyruvate decarboxylase E1) in the liver. Furthermore, deoxynojirimycin (DNJ) and polysaccharide (P) were found to increase

  20. Validation of the Antidiabetic and Hypolipidemic Effects of Clitocybe nuda by Assessment of Glucose Transporter 4 and Gluconeogenesis and AMPK Phosphorylation in Streptozotocin-Induced Mice

    PubMed Central

    Shih, Chun-Ching; Chen, Mei-Hsing; Lin, Cheng-Hsiu

    2014-01-01

    The study was designed to investigate the effects of extract of Clitocybe nuda (CNE) on type 1 diabetes mellitus and dyslipidemia in streptozotocin- (STZ-) induced diabetic mice. Diabetes was induced by injection of STZ. Diabetic mice were randomly divided into five groups and given orally CNE (C1: 0.2, C2: 0.5, and C3: 1.0 g/kg body weight) or metformin (Metf) or vehicle for 4 weeks. STZ induction decreased in the levels of insulin, body weight, and the weight of skeletal muscle, whereas the levels of blood glucose, hemoglobin nonenzymatically (percent HbA1c), and circulating triglyceride (P < 0.001, P < 0.001, and P < 0.01, resp.) were increased. CNE decreased the levels of blood glucose, HbA1c, and triglyceride levels, whereas it increased the levels of insulin and leptin compared with the vehicle-treated STZ group. STZ induction caused a decrease in the protein contents of skeletal muscular and hepatic phosphorylation of AMP-activated protein kinase (phospho-AMPK) and muscular glucose transporter 4 (GLUT4). Muscular phospho-AMPK contents were increased in C2-, C3-, and Metf-treated groups. CNE and Metf significantly increased the muscular proteins of GLUT4. Liver phospho-AMPK showed an increase in all CNE- and Metf-treated groups combined with the decreased hepatic glucose production by decreasing phosphenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and 11beta hydroxysteroid dehydroxygenase (11β-HSD1) gene, which contributed to attenuating diabetic state. The study indicated that the hypoglycemic properties of CNE were related to both the increased muscular glucose uptake and the reduction in hepatic gluconeogenesis. CNE exerts hypolipidemic effect by increasing gene expressions of peroxisome proliferator-activated receptor α (PPARα) and decreasing expressions of fatty acid synthesis, including acyl-coenzyme A: diacylglycerol acyltransferase (DGAT) 2. Therefore, amelioration of diabetic and dyslipidemic state by CNE in STZ

  1. Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function

    PubMed Central

    Izumoto-Akita, Takako; Tsunekawa, Shin; Yamamoto, Akihito; Uenishi, Eita; Ishikawa, Kota; Ogata, Hidetada; Iida, Atsushi; Ikeniwa, Makoto; Hosokawa, Kaori; Niwa, Yasuhiro; Maekawa, Ryuya; Yamauchi, Yuichiro; Seino, Yusuke; Hamada, Yoji; Hibi, Hideharu; Arima, Hiroshi; Ueda, Minoru; Oiso, Yutaka

    2015-01-01

    Objective Many studies have reported that stem cell transplantation promotes propagation and protection of pancreatic β-cells in streptozotocin (STZ)-induced diabetic mice without the differentiation of transplanted cells into pancreatic β-cells, suggesting that the improvement is due to a paracrine effect of the transplanted cells. We investigated the effects of factors secreted by dental pulp stem cells from human exfoliated deciduous teeth (SHED) on β-cell function and survival. Research design and methods Conditioned medium from SHED (SHED-CM) was collected 48 h after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM). The insulin levels in SHED-CM and serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (BM-CM) were undetectable. STZ-induced diabetic male C57B/6J mice were injected with DMEM as a control, SHED-CM, exendin-4 (Ex-4), or BM-CM for 14 days. Mouse pancreatic β-cell line MIN6 cells were incubated with different concentrations of STZ with SHED-CM, DMEM, Ex-4, or BM-CM for 6 h. Results Administration of 1 mL of SHED-CM twice a day improved glucose intolerance in STZ-induced diabetic mice and the effect continued for 20 days after the end of treatment. SHED-CM treatment increased pancreatic insulin content and β-cell mass through proliferation and an intraperitoneal glucose tolerance test revealed enhanced insulin secretion. Incubation of MIN6 cells (a mouse pancreatic β-cell line) with SHED-CM enhanced insulin secretion in a glucose concentration-dependent manner and reduced STZ-induced cell death, indicating that the amelioration of hyperglycemia was caused by the direct effects of SHED-CM on β-cell function and survival. These effects were more pronounced than with the use of Ex-4, a conventional incretin-based drug, and BM-CM, which is a medium derived from other stem cells. Conclusions These findings suggest that SHED-CM provides direct protection and encourages the propagation of

  2. Anti-diabetic activity of the semi-purified fractions of Averrhoa bilimbi in high fat diet fed-streptozotocin-induced diabetic rats.

    PubMed

    Tan, Benny Kwong Huat; Tan, Chee Hong; Pushparaj, Peter Natesan

    2005-04-29

    The present study was designed to investigate the hypoglycemic and hypolipidemic activities of the semi-purified fractions of an ethanolic leaf extract of Averrhoa bilimbi (ABe) in high fat diet (HFD)-streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats aged 10 weeks (200-250 g) were fed with a high fat diet obtained from Glen Forrest stock feeders (Western Australia) for 2 weeks prior to intraperitoneal injection with streptozotocin (STZ, 50 mg/kg). The leaves of A.bilimbi were exhaustively extracted with 80% ethanol, concentrated at 40 degrees C using a rotavapor and partitioned successively with butanol, ethylacetate and hexane to get aqueous (AF), butanol (BuF), ethylacetate (EF), and hexane fractions (HF). The fractions were freeze-dried to obtain powders of each. To investigate the effect of long term administration of the hypoglycemic fractions, diabetic animals were treated with vehicle (distilled water), AF (125 mg/kg), or BuF (125 mg/kg), twice a day for 14 days. The long term administration of AF and BuF at a dose of 125 mg/kg significantly (P < 0.05) lowered blood glucose and triglyceride concentrations when compared to the vehicle. The hepatic glycogen content was significantly higher (P < 0.05) in AF-treated rats when compared to diabetic control, however no change was found in the BuF-treated rats. Moreover, AF as well as BuF did not cause any significant change in the total cholesterol and HDL-cholesterol. There was also no difference in liver thiobarbituric acid reactive substances (TBARS) and cytochrome P450 values between AF, BuF and vehicle-treated control rats. In conclusion, the results indicate that AF is more potent than BuF in the amelioration of hyperglycemia and hyperlipidemia in HFD fed-STZ diabetic rats. Hence, AF is a potential source for the isolation of active principle(s) for oral anti-diabetic therapy. PMID:15808883

  3. Glutamate (mGluR-5) gene expression in brain regions of streptozotocin induced diabetic rats as a function of age: role in regulation of calcium release from the pancreatic islets in vitro

    PubMed Central

    2009-01-01

    Metabotrophic glutamate receptors (mGluRs) modulate cellular activities involved in the processes of differentiation and degeneration. In this study, we have analysed the expression pattern of group-I metabotropic glutamate receptor (mGlu-5) in cerebral cortex, corpus striatum, brainstem and hippocampus of streptozotocin induced and insulin treated diabetic rats (D+I) as a function of age. Also, the functional role of glutamate receptors in intra cellular calcium release from the pancreatic islets was studied in vitro. The gene expression studies showed that mGlu-5 mRNA in the cerebral cortex increased siginficantly in 7 weeks old diabetic rats whereas decreased expression was observed in brainstem, corpus striatum and hippocampus when compared to control. 90 weeks old diabetic rats showed decreased expression in cerebral cortex, corpus striatum and hippocampus whereas in brainstem the expression increased significantly compared to their respective controls. In 7 weeks old D+I group, mGlu-5 mRNA expression was significantly decreased in cerebral cortex and corpus striatum whereas the expression increased significantly in brainstem and hippocampus. 90 weeks old D+I group showed an increased expression in cerebral cortex, while it was decreased significantly in corpus striatum, brainstem and hippocampus compared to their respective controls. In vitro studies showed that glutamate at lower concentration (10-7 M) stimulated calcium release from the pancreatic islets. Our results suggest that mGlu-5 receptors have differential expression in brain regions of diabetes and D+I groups as a function of age. This will have clinical significance in management of degeneration in brain function and memory enhancement through glutamate receptors. Also, the regulatory role of glutamate receptors in calcium release has immense therapeutic application in insulin secretion and function. PMID:19903331

  4. Effects of Hydro-alcoholic Extract from Arctium lappa L. (Burdock) Root on Gonadotropins, Testosterone, and Sperm Count and Viability in Male Mice with Nicotinamide/ Streptozotocin-Induced Type 2 Diabetes

    PubMed Central

    AHANGARPOUR, Akram; OROOJAN, Ali Akbar; HEIDARI, Hamid; GHAEDI, Ehsan; TAHERKHANI, Reza

    2015-01-01

    Background: Reproductive dysfunction is a complication of diabetes. Arctium lappa (burdock) root has hypoglycemic and antioxidative properties, which are traditionally used for treatment of impotence and sterility. Therefore, the aim of this study is to investigate the effects of its hydro alcoholic extract on gonadotropin, testosterone, and sperm parameters in nicotinamide/ streptozotocin-induced diabetic mice. Methods: In this experimental study, 56 adult male Naval Medical Research Institute (NMRI) mice (30–35 g) were randomly divided into seven groups: control, diabetes, diabetes + glibenclamide (0.25 mg/kg), diabetes + extract (200 or 300 mg/kg), and extract (200 or 300 mg/kg). Diabetes was induced with intraperitoneal injection of nicotinamide (NA) and streptozotocin (STZ). Twenty-four hours after the last extract and drug administration, serum samples, testes, and cauda epididymis were removed immediately for experimental assessment. Results: Body weight, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone levels, and sperm count (P < 0.05) and viability (P < 0.01) decreased in diabetic mice. Administration of glibenclamide significantly improved these reductions in diabetic animals (P < 0.05). However, the hydro alcoholic extract (300 mg/kg) enhanced sperm viability only in diabetic mice (P < 0.01). In addition, this dose of extract increased sperm count, LH, FSH, and testosterone in nondiabetic animals compared with the control group (P < 0.05). Conclusion: The results indicate that applied burdock root extract has anti-infertility effects in nondiabetic mice. Hence, this part of the A. lappa plant has an effect on the health of the reproductive system in order to improve diabetic conditions. PMID:26023292

  5. Hyperoside reduces albuminuria in diabetic nephropathy at the early stage through ameliorating renal damage and podocyte injury.

    PubMed

    Zhang, Jisheng; Fu, Haiyan; Xu, Yan; Niu, Yunfei; An, Xiaofei

    2016-10-01

    Diabetic nephropathy (DN) is one of the major microvascular complications in diabetes. Podocyte injury such as slit diaphragm effacement is regarded as a determinant in the occurrence and development of albuminuria in DN. In this study, we examined the effect of hyperoside, an active flavonoid glycoside, on proteinuria and renal damage in a streptozotocin-induced DN mouse model at the early stage. The results showed that oral administration of hyperoside (30 mg/kg/day for 4 weeks could significantly decrease urinary microalbumin excretion and glomerular hyperfiltration in DN mice, but did not affect the glucose and lipid metabolism. Periodic acid-Schiff staining and transmission electron microscopy showed that glomerular mesangial matrix expansion and podocyte process effacement in DN mice were significantly improved by hyperoside. Further investigations via immunofluorescence staining, real-time reverse transcription polymerase chain reaction and Western blot analysis showed that the decreased slit diaphragm protein nephrin and podocin mRNA expression and protein levels in DN mice were restored by hyperoside treatment. Collectively, these findings demonstrated that hyperoside could decrease albuminuria at the early stage of DN by ameliorating renal damage and podocyte injury. PMID:27255369

  6. N-hydroxycinnamide derivatives of osthole ameliorate hyperglycemia through activation of AMPK and p38 MAPK.

    PubMed

    Lee, Wei-Hwa; Wu, Hsueh-Hsia; Huang, Wei-Jan; Li, Yi-Ning; Lin, Ren-Jye; Lin, Shyr-Yi; Liang, Yu-Chih

    2015-01-01

    Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes. Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor

  7. Efficacy of a single high dose versus multiple low doses of LLLT on wounded skin fibroblasts

    NASA Astrophysics Data System (ADS)

    Hawkins, Denise H.; Abrahamse, Heidi

    2007-07-01

    Background/purpose: In vivo studies have demonstrated that phototherapy accelerates wound healing in the clinical environment; however the exact mechanism is still not completely understood. The main focus of this study was to use in vitro laboratory results to establish an effective treatment regimen that may be practical and applicable to the clinical environment. This in vitro study aimed to compare the cellular responses of wounded fibroblasts following a single exposure of 5 J/cm2 or multiple exposures of low doses (2.5 J/cm2 or 5 J/cm2) on one day of the week to a single application of a higher dose (16 J/cm2) on day 1 and day 4. Methodology: Cellular responses to Helium-Neon (632.8 nm) laser irradiation were evaluated by measuring changes in cell morphology, cell viability, cell proliferation, membrane integrity and DNA damage. Results: Wounded cells exposed to 5 J/cm2 on day 1 and day 4 showed an increase in cell viability, increase in the release of bFGF, increase in cell density, decrease in ALP enzyme activity and decrease in caspase 3/7 activity indicating a stimulatory effect. Wounded cells exposed to three doses of 5 J/cm2 on day 1 showed a decrease in cell viability and cell proliferation and an increase in LDH cytotoxicity and DNA damage indicating an inhibitory effect. Conclusion: Results indicate that cellular responses are influenced by the combination of dose administered, number of exposures and time between exposures. Single doses administered with sufficient time between exposures is more beneficial to restoring cell function than multiple doses within a short period. Although this work confirms previous reports on the cumulative effect of laser irradiation it provides essential information for the initiation of in vivo clinical studies.

  8. Aqueous Extract from Hibiscus sabdariffa Linnaeus Ameliorate Diabetic Nephropathy via Regulating Oxidative Status and Akt/Bad/14-3-3γ in an Experimental Animal Model

    PubMed Central

    Wang, Shou-Chieh; Lee, Shiow-Fen; Wang, Chau-Jong; Lee, Chao-Hsin; Lee, Wen-Chin; Lee, Huei-Jane

    2011-01-01

    Several studies point out that oxidative stress maybe a major culprit in diabetic nephropathy. Aqueous extract of Hibiscus sabdariffa L. (HSE) has been demonstrated as having beneficial effects on anti-oxidation and lipid-lowering in experimental studies. This study aimed at investigating the effects of Hibiscus sabdariffa L. on diabetic nephropathy in streptozotocin induced type 1 diabetic rats. Our results show that HSE is capable of reducing lipid peroxidation, increasing catalase and glutathione activities significantly in diabetic kidney, and decreasing the plasma levels of triglyceride, low-density lipoprotein (LDL) and increasing high-density lipoprotein (HDL) value. In histological examination, HSE improves hyperglycemia-caused osmotic diuresis in renal proximal convoluted tubules (defined as hydropic change) in diabetic rats. The study also reveals that up-regulation of Akt/Bad/14-3-3γ and NF-κB-mediated transcription might be involved. In conclusion, our results show that HSE possesses the potential effects to ameliorate diabetic nephropathy via improving oxidative status and regulating Akt/Bad/14-3-3γ signaling. PMID:19965962

  9. Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway.

    PubMed

    Gandhi, Gopalsamy Rajiv; Jothi, Gnanasekaran; Antony, Poovathumkal James; Balakrishna, Kedike; Paulraj, Michael Gabriel; Ignacimuthu, Savarimuthu; Stalin, Antony; Al-Dhabi, Naif Abdullah

    2014-12-15

    In this study, the therapeutic efficacy of gallic acid from Cyamopsis tetragonoloba (L.) Taub. (Fabaceae) beans was examined against high-fat diet fed-streptozotocin-induced experimental type 2 diabetic rats. Molecular-dockings were done to determine the putative binding modes of gallic acid into the active sites of key insulin-signaling markers. Gallic acid (20 mg/kg) given to high-fat diet fed-streptozotocin-induced rats lowered body weight gain, fasting blood glucose and plasma insulin in diabetic rats. It further restored the alterations of biochemical parameters to near normal levels in diabetic treated rats along with cytoprotective action on pancreatic β-cell. Histology of liver and adipose tissues supported the biochemical findings. Gallic acid significantly enhanced the level of peroxisome proliferator-activated receptor γ (PPARγ) expression in the adipose tissue of treated rat compared to untreated diabetic rat; it also slightly activated PPARγ expressions in the liver and skeletal muscle. Consequently, it improved insulin-dependent glucose transport in adipose tissue through translocation and activation of glucose transporter protein 4 (GLUT4) in phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (p-Akt) dependent pathway. Gallic acid docked with PPARγ; it exhibited promising interactions with the GLUT4, glucose transporter protein 1 (GLUT1), PI3K and p-Akt. These findings provided evidence to show that gallic acid could improve adipose tissue insulin sensitivity, modulate adipogenesis, increase adipose glucose uptake and protect β-cells from impairment. Hence it can be used in the management of obesity-associated type 2 diabetes mellitus. PMID:25445038

  10. Enhanced autophagy ameliorates cardiac proteinopathy

    PubMed Central

    Bhuiyan, Md. Shenuarin; Pattison, J. Scott; Osinska, Hanna; James, Jeanne; Gulick, James; McLendon, Patrick M.; Hill, Joseph A.; Sadoshima, Junichi; Robbins, Jeffrey

    2013-01-01

    Basal autophagy is a crucial mechanism in cellular homeostasis, underlying both normal cellular recycling and the clearance of damaged or misfolded proteins, organelles and aggregates. We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). To increase levels of basal autophagy, we generated an inducible Tg mouse expressing autophagy-related 7 (Atg7), a critical and rate-limiting autophagy protein. Hearts from these mice had enhanced autophagy, but normal morphology and function. We crossed these mice with CryABR120G mice, a model of DRC in which autophagy is significantly attenuated in the heart, to test the functional significance of autophagy activation in a proteotoxic model of heart failure. Sustained Atg7-induced autophagy in the CryABR120G hearts decreased interstitial fibrosis, ameliorated ventricular dysfunction, decreased cardiac hypertrophy, reduced intracellular aggregates and prolonged survival. To determine whether different methods of autophagy upregulation have additive or even synergistic benefits, we subjected the autophagy-deficient CryABR120G mice and the Atg7-crossed CryABR120G mice to voluntary exercise, which also upregulates autophagy. The entire exercised Atg7-crossed CryABR120G cohort survived to 7 months. These findings suggest that activating autophagy may be a viable therapeutic strategy for improving cardiac performance under proteotoxic conditions. PMID:24177425

  11. Dietary Amelioration of Helicobacter Infection

    PubMed Central

    Fahey, Jed W.; Stephenson, Katherine K.; Wallace, Alison J.

    2015-01-01

    We review herein the basis for using dietary components to treat and/or prevent Helicobacter pylori infection, with emphasis on: (a) work reported in the last decade, (b) dietary components for which there is mechanism-based plausibility, and (c) components for which clinical results on H. pylori amelioration are available. There is evidence that a diet-based treatment may reduce the levels and/or the virulence of H. pylori colonization without completely eradicating the organism in treated individuals. This concept was endorsed a decade ago by the participants in a small international consensus conference held in Honolulu, Hawaii, USA, and interest in such a diet-based approach has increased dramatically since then. This approach is attractive in terms of cost, treatment, tolerability and cultural acceptability. This review therefore highlights specific foods, food components, and food products, grouped as follows: bee products (e.g. honey and propolis), probiotics, dairy products, vegetables, fruits, oils, essential oils, and herbs, spices and other plants. A discussion of the small number of clinical studies that are available is supplemented by supportive in vitro and animal studies. This very large body of in vitro and pre-clinical evidence must now be followed up with rationally designed, unambiguous human trials. PMID:25799054

  12. Dietary amelioration of Helicobacter infection.

    PubMed

    Fahey, Jed W; Stephenson, Katherine K; Wallace, Alison J

    2015-06-01

    We review herein the basis for using dietary components to treat and/or prevent Helicobacter pylori infection, with emphasis on (a) work reported in the last decade, (b) dietary components for which there is mechanism-based plausibility, and (c) components for which clinical results on H pylori amelioration are available. There is evidence that a diet-based treatment may reduce the levels and/or the virulence of H pylori colonization without completely eradicating the organism in treated individuals. This concept was endorsed a decade ago by the participants in a small international consensus conference held in Honolulu, Hawaii, USA, and interest in such a diet-based approach has increased dramatically since then. This approach is attractive in terms of cost, treatment, tolerability, and cultural acceptability. This review, therefore, highlights specific foods, food components, and food products, grouped as follows: bee products (eg, honey and propolis); probiotics; dairy products; vegetables; fruits; oils; essential oils; and herbs, spices, and other plants. A discussion of the small number of clinical studies that are available is supplemented by supportive in vitro and animal studies. This very large body of in vitro and preclinical evidence must now be followed up with rationally designed, unambiguous human trials. PMID:25799054

  13. Evaluation of multiple low doses of copper oxide wire particles compared with levamisole for control of Haemonchus contortus in lambs.

    PubMed

    Burke, J M; Miller, J E

    2006-06-30

    High levels of anthelmintic resistance in gastrointestinal nematodes (GIN) of small ruminants have created the need for alternative approaches to parasite control. Copper oxide wire particles (COWP; 2g) have proven effective in decreasing GIN infection in lambs. However, the risk of copper toxicity has limited the usefulness of this approach. Recently, smaller doses (0.5 and 1g) have proven effective in GIN control, reducing the risk of toxicity. The objective of this study was to examine the effectiveness and risk of toxicity using multiple small doses of COWP for GIN control in lambs between weaning and market weight. Dorper crossbred ram lambs were orally administered levamisole (Levasol, 8.0mg/kg; n=8), 0.5g (n=9), or 1g COWP (n=9) at weaning (Day 0; 118+/-2 days of age; late May 2005) and again at 6-week intervals for a total of four treatments. A pooled fecal culture determined that Haemonchus contortus was the predominant gastrointestinal parasite at weaning. Lambs grazed bermudagrass pastures and were supplemented with up to 500g corn/soybean meal and free choice trace mineralized salt. Fecal egg counts (FEC), packed cell volume (PCV), and plasma aspartate aminotransferase (AST) activity were determined every 14 days and lambs weighed every 28 days. GIN infection reached a peak at Day 42 (high FEC, low PCV). COWP effectively reduced FEC on Days 0 and 42 compared with the previous week, but did not reduce FEC on Days 84 and 126 (treatment by time interaction, P<0.005). Plasma AST activity and weight gains were similar among treatment groups throughout the study period. Concentrations of copper in the liver on Day 155 were greater in COWP-treated lambs (P<0.001), but all concentrations were normal. Multiple doses of COWP were as effective as levamisole for control of H. contortus without risk of copper toxicity. PMID:16574324

  14. Fucoidan Extracts Ameliorate Acute Colitis.

    PubMed

    Lean, Qi Ying; Eri, Rajaraman D; Fitton, J Helen; Patel, Rahul P; Gueven, Nuri

    2015-01-01

    Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are an important cause of morbidity and impact significantly on quality of life. Overall, current treatments do not sustain a long-term clinical remission and are associated with adverse effects, which highlight the need for new treatment options. Fucoidans are complex sulphated, fucose-rich polysaccharides, found in edible brown algae and are described as having multiple bioactivities including potent anti-inflammatory effects. Therefore, the therapeutic potential of two different fucoidan preparations, fucoidan-polyphenol complex (Maritech Synergy) and depyrogenated fucoidan (DPF) was evaluated in the dextran sulphate sodium (DSS) mouse model of acute colitis. Mice were treated once daily over 7 days with fucoidans via oral (Synergy or DPF) or intraperitoneal administration (DPF). Signs and severity of colitis were monitored daily before colons and spleens were collected for macroscopic evaluation, cytokine measurements and histology. Orally administered Synergy and DPF, but not intraperitoneal DPF treatment, significantly ameliorated symptoms of colitis based on retention of body weight, as well as reduced diarrhoea and faecal blood loss, compared to the untreated colitis group. Colon and spleen weight in mice treated with oral fucoidan was also significantly lower, indicating reduced inflammation and oedema. Histological examination of untreated colitis mice confirmed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and oedema, while all aspects of this pathology were alleviated by oral fucoidan. Importantly, in this model, the macroscopic changes induced by oral fucoidan correlated significantly with substantially decreased production of at least 15 pro-inflammatory cytokines by the colon tissue. Overall, oral fucoidan preparations significantly reduce the inflammatory pathology associated with DSS-induced colitis and could therefore represent

  15. Anatabine ameliorates experimental autoimmune thyroiditis.

    PubMed

    Caturegli, Patrizio; De Remigis, Alessandra; Ferlito, Marcella; Landek-Salgado, Melissa A; Iwama, Shintaro; Tzou, Shey-Cherng; Ladenson, Paul W

    2012-09-01

    Tobacco smoking favorably influences the course of Hashimoto thyroiditis, possibly through the antiinflammatory proprieties of nicotine. In this study we tested anatabine, another tobacco alkaloid, in a model of experimental autoimmune thyroiditis. Experimental autoimmune thyroiditis was induced by different doses of thyroglobulin, to produce a disease of low, moderate, or high severity, in 88 CBA/J female mice: 43 drank anatabine supplemented water and 45 regular water. Mice were bled after immunization and killed to assess thyroid histopathology, thyroglobulin antibodies, T(4), and thyroid RNA expression of 84 inflammatory genes. We also stimulated in vitro a macrophage cell line with interferon-γ or lipopolysaccharide plus or minus anatabine to quantitate inducible nitric oxide synthase and cyclooxygenase 2 protein expression. Anatabine reduced the incidence and severity of thyroiditis in the moderate disease category: only 13 of 21 mice (62%) developed thyroid infiltrates when drinking anatabine as compared with 22 of 23 (96%) controls (relative risk 0.59, P = 0.0174). The median thyroiditis severity was 0.5 and 2.0 in anatabine and controls, respectively (P = 0.0007 by Wilcoxon rank sum test). Anatabine also reduced the antibody response to thyroglobulin on d 14 (P = 0.029) and d 21 (P = 0.045) after immunization and improved the recovery of thyroid function on d 21 (P = 0.049). In the thyroid transcriptome, anatabine restored expression of IL-18 and IL-1 receptor type 2 to preimmunization levels. Finally, anatabine suppressed in a dose-dependent manner macrophage production of inducible nitric oxide synthase and cyclooxygenase 2. Anatabine ameliorates disease in a model of autoimmune thyroiditis, making the delineation of its mechanisms of action and potential clinical utility worthwhile. PMID:22807490

  16. Fucoidan Extracts Ameliorate Acute Colitis

    PubMed Central

    Lean, Qi Ying; Eri, Rajaraman D.; Fitton, J. Helen; Patel, Rahul P.; Gueven, Nuri

    2015-01-01

    Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease, are an important cause of morbidity and impact significantly on quality of life. Overall, current treatments do not sustain a long-term clinical remission and are associated with adverse effects, which highlight the need for new treatment options. Fucoidans are complex sulphated, fucose-rich polysaccharides, found in edible brown algae and are described as having multiple bioactivities including potent anti-inflammatory effects. Therefore, the therapeutic potential of two different fucoidan preparations, fucoidan-polyphenol complex (Maritech Synergy) and depyrogenated fucoidan (DPF) was evaluated in the dextran sulphate sodium (DSS) mouse model of acute colitis. Mice were treated once daily over 7 days with fucoidans via oral (Synergy or DPF) or intraperitoneal administration (DPF). Signs and severity of colitis were monitored daily before colons and spleens were collected for macroscopic evaluation, cytokine measurements and histology. Orally administered Synergy and DPF, but not intraperitoneal DPF treatment, significantly ameliorated symptoms of colitis based on retention of body weight, as well as reduced diarrhoea and faecal blood loss, compared to the untreated colitis group. Colon and spleen weight in mice treated with oral fucoidan was also significantly lower, indicating reduced inflammation and oedema. Histological examination of untreated colitis mice confirmed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and oedema, while all aspects of this pathology were alleviated by oral fucoidan. Importantly, in this model, the macroscopic changes induced by oral fucoidan correlated significantly with substantially decreased production of at least 15 pro-inflammatory cytokines by the colon tissue. Overall, oral fucoidan preparations significantly reduce the inflammatory pathology associated with DSS-induced colitis and could therefore

  17. 27 CFR 24.178 - Amelioration.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... is calculated as tartaric acid for grapes, malic acid for apples, and citric acid for other fruit... natural wine from juice having a fixed acid level exceeding 5.0 grams per liter, the winemaker may adjust the fixed acid level by adding ameliorating material (water, sugar, or a combination of both)...

  18. 27 CFR 24.178 - Amelioration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... is calculated as tartaric acid for grapes, malic acid for apples, and citric acid for other fruit... natural wine from juice having a fixed acid level exceeding 5.0 grams per liter, the winemaker may adjust the fixed acid level by adding ameliorating material (water, sugar, or a combination of both)...

  19. 27 CFR 24.178 - Amelioration.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... is calculated as tartaric acid for grapes, malic acid for apples, and citric acid for other fruit... natural wine from juice having a fixed acid level exceeding 5.0 grams per liter, the winemaker may adjust the fixed acid level by adding ameliorating material (water, sugar, or a combination of both)...

  20. 27 CFR 24.178 - Amelioration.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... natural wine from juice having a fixed acid level exceeding 5.0 grams per liter, the winemaker may adjust... acid level of the juice or wine by 0.1 gram per liter (the fixed acid level of the juice or wine may not be less than 5.0 gram per liter after the addition of ameliorating material). (b) Limitations....

  1. 27 CFR 24.178 - Amelioration.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... natural wine from juice having a fixed acid level exceeding 5.0 grams per liter, the winemaker may adjust... acid level of the juice or wine by 0.1 gram per liter (the fixed acid level of the juice or wine may not be less than 5.0 gram per liter after the addition of ameliorating material). (b) Limitations....

  2. Amelioration of Hyperglycemia with a Sodium-Glucose Cotransporter 2 Inhibitor Prevents Macrophage-Driven Atherosclerosis through Macrophage Foam Cell Formation Suppression in Type 1 and Type 2 Diabetic Mice

    PubMed Central

    Terasaki, Michishige; Hiromura, Munenori; Mori, Yusaku; Kohashi, Kyoko; Nagashima, Masaharu; Kushima, Hideki; Watanabe, Takuya; Hirano, Tsutomu

    2015-01-01

    Direct associations between hyperglycemia and atherosclerosis remain unclear. We investigated the association between the amelioration of glycemia by sodium-glucose cotransporter 2 inhibitors (SGLT2is) and macrophage-driven atherosclerosis in diabetic mice. We administered dapagliflozin or ipragliflozin (1.0 mg/kg/day) for 4-weeks to apolipoprotein E-null (Apoe−/−) mice, streptozotocin-induced diabetic Apoe−/− mice, and diabetic db/db mice. We then determined aortic atherosclerosis, oxidized low-density lipoprotein (LDL)-induced foam cell formation, and related gene expression in exudate peritoneal macrophages. Dapagliflozin substantially decreased glycated hemoglobin (HbA1c) and glucose tolerance without affecting body weight, blood pressure, plasma insulin, and lipids in diabetic Apoe−/− mice. Aortic atherosclerotic lesions, atheromatous plaque size, and macrophage infiltration in the aortic root increased in diabetic Apoe−/− mice; dapagliflozin attenuated these changes by 33%, 27%, and 20%, respectively. Atherosclerotic lesions or foam cell formation highly correlated with HbA1c. Dapagliflozin did not affect atherosclerosis or plasma parameters in non-diabetic Apoe−/− mice. In db/db mice, foam cell formation increased by 4-fold compared with C57/BL6 mice, whereas ipragliflozin decreased it by 31%. Foam cell formation exhibited a strong correlation with HbA1c. Gene expression of lectin-like ox-LDL receptor-1 and acyl-coenzyme A:cholesterol acyltransferase 1 was upregulated, whereas that of ATP-binding cassette transporter A1 was downregulated in the peritoneal macrophages of both types of diabetic mice. SGLT2i normalized these gene expressions. Our study is the first to demonstrate that SGLT2i exerts anti-atherogenic effects by pure glucose lowering independent of insulin action in diabetic mice through suppressing macrophage foam cell formation, suggesting that foam cell formation is highly sensitive to glycemia ex vivo. PMID:26606676

  3. Amelioration of Hyperglycemia with a Sodium-Glucose Cotransporter 2 Inhibitor Prevents Macrophage-Driven Atherosclerosis through Macrophage Foam Cell Formation Suppression in Type 1 and Type 2 Diabetic Mice.

    PubMed

    Terasaki, Michishige; Hiromura, Munenori; Mori, Yusaku; Kohashi, Kyoko; Nagashima, Masaharu; Kushima, Hideki; Watanabe, Takuya; Hirano, Tsutomu

    2015-01-01

    Direct associations between hyperglycemia and atherosclerosis remain unclear. We investigated the association between the amelioration of glycemia by sodium-glucose cotransporter 2 inhibitors (SGLT2is) and macrophage-driven atherosclerosis in diabetic mice. We administered dapagliflozin or ipragliflozin (1.0 mg/kg/day) for 4-weeks to apolipoprotein E-null (Apoe-/-) mice, streptozotocin-induced diabetic Apoe-/- mice, and diabetic db/db mice. We then determined aortic atherosclerosis, oxidized low-density lipoprotein (LDL)-induced foam cell formation, and related gene expression in exudate peritoneal macrophages. Dapagliflozin substantially decreased glycated hemoglobin (HbA1c) and glucose tolerance without affecting body weight, blood pressure, plasma insulin, and lipids in diabetic Apoe-/- mice. Aortic atherosclerotic lesions, atheromatous plaque size, and macrophage infiltration in the aortic root increased in diabetic Apoe-/- mice; dapagliflozin attenuated these changes by 33%, 27%, and 20%, respectively. Atherosclerotic lesions or foam cell formation highly correlated with HbA1c. Dapagliflozin did not affect atherosclerosis or plasma parameters in non-diabetic Apoe-/- mice. In db/db mice, foam cell formation increased by 4-fold compared with C57/BL6 mice, whereas ipragliflozin decreased it by 31%. Foam cell formation exhibited a strong correlation with HbA1c. Gene expression of lectin-like ox-LDL receptor-1 and acyl-coenzyme A:cholesterol acyltransferase 1 was upregulated, whereas that of ATP-binding cassette transporter A1 was downregulated in the peritoneal macrophages of both types of diabetic mice. SGLT2i normalized these gene expressions. Our study is the first to demonstrate that SGLT2i exerts anti-atherogenic effects by pure glucose lowering independent of insulin action in diabetic mice through suppressing macrophage foam cell formation, suggesting that foam cell formation is highly sensitive to glycemia ex vivo. PMID:26606676

  4. Electrophysiological changes in optic neuropathy of streptozotocin induced diabetic rats

    PubMed Central

    Ghita, AM; Parvu, D; Sava, R; Georgescu, L; Zagrean, L

    2013-01-01

    The visually evoked potentials are electrical signals generated by the occipital cortex due to electrical stimulus. The clinical importance of VEP is to diagnose the functional changes of the optic nerve in different diseases such as diabetic mellitus. Our study sought latency of VEP changes depending on glycemic value and duration of diabetes in Wistar rats. Methods: this study evaluated the VEP of 25 rats in three groups: control group, diabetic group 1 with glycemic values between 200-400mg/dl and diabetic group 2 with glycemic values between 400 and 600mg/dl. These rats from diabetic group 2 were followed for 4 months and the ones in control group and diabetic group 1 for 5 months. Results: the latency of VEP shows slight changes without any statistical significance in the control group. In diabetic group 1 and 2 similar changes occurred, with statistical significance and the amplitude of the changes was proportional with the glycemic value. The rats had a rapid increase of VEP latency after the induction of diabetes and returned to a normal range in the first month. After a time, when the latencies of VEP were in normal range, a new growth appeared faster and larger as the glycemic values were higher. Conclusion: diabetes brings changes to the visual signal transmission and to the central processing, this being revealed by the examination of the visually evoked potential. Increased VEP latency is statistically correlated with the changes that occur at the level of the values of glucose in blood. A rapid growth in blood sugar lowers the visual signal transmission. This change is temporary despite the persistence of elevated blood glucose values, probably by adjusting to the new condition. However, maintaining high glycemic values remotely produces a progressive increase of the delay of the visual signal. This progressive increase is faster as blood glucose levels are higher. PMID:24155786

  5. Auditory neuropathy in streptozotocin-induced diabetic mouse.

    PubMed

    Hong, Bin Na; Kang, Tong Ho

    2008-02-01

    An investigation of the mechanism of damage to the peripheral nervous system and central nervous system in diabetes mellitus (DM) is highly important in current neurological research. Auditory neuropathy is a hearing disorder in which the auditory brainstem evoked potential is absent or severely abnormal. This study investigated auditory neuropathy caused by streptozotocin in mouse model. In order to assess diabetic auditory neuropathy, we evaluated auditory brainstem response (ABR) for the evaluation of sensorineural function in peripheral auditory nerve. Auditory middle latency response (AMLR) was employed to assess the middle response in the midbrain. STZ groups significantly increased the absolute latencies IV and the interpeak latencies I-III and I-IV of ABR compared with STZ 0 group. Pa latency of AMLR also significantly increased in proportion to STZ dosage. Taken together, our results demonstrate that STZ-induced DM may impair the auditory pathway from peripheral auditory nerve to midbrain in the mouse model. We suggest that the STZ-induced diabetic mouse model may be useful for the evaluation of auditory pathway impairment by using ABR and AMLR tests. PMID:18164131

  6. Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice

    PubMed Central

    Lee, Young-Sun; Eun, Hyuk Soo; Kim, So Yeon; Jeong, Jong-Min; Seo, Wonhyo; Byun, Jin-Seok; Jeong, Won-Il; Yi, Hyon-Seung

    2016-01-01

    Emerging evidence revealed that diabetes induces abnormal immune responses that result in serious complications in organs. However, the effect of hyperglycemia on hepatic immunity remains obscure. We evaluated the population and function of hepatic immune cells in streptozotocin (STZ)-induced hyperglycemic mice. CC chemokine receptor 2 (CCR2)-knockout mice and mice with a depletion of regulatory T cells (DEREG) were used to investigate the migration and role of regulatory T cells (Tregs) in hyperglycemic mice. The inflammatory cytokines and hepatic transaminase levels were significantly increased in the hyperglycemic mice. The population and number of infiltrating monocytes, granulocytes, and Tregs were enhanced in the livers of the hyperglycemic mice. Hepatic monocytes other than macrophages showed the increased expression of inflammatory cytokines and chemokines in the hyperglycemic mice. The CCR2 knockout and DEREG chimeric mice exhibited increased populations of activated T cells and neutrophils compared to the WT chimeric mice, which promoted hepatic inflammation in the hyperglycemic mice. The migration of CCR2 knockout Tregs into the liver was significantly reduced compared to the WT Tregs. We demonstrated that hyperglycemia contributes to increase in infiltrating monocytes and Tregs, which are associated with hepatic immune dysfunction in mice. CCR2-mediated migration of Tregs regulates hyperglycemia-induced hepatic inflammation. PMID:27464894

  7. Efficiency of noopept in streptozotocin-induced diabetes in rats.

    PubMed

    Ostrovskaya, R U; Ozerova, I V; Gudascheva, T A; Kapitsa, I G; Ivanova, E A; Voronina, T A; Seredenin, S B

    2013-01-01

    We studied the effects of new nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) in various dosage regimens on the dynamics of glycemia, body weight, and pain sensitivity in rats receiving diabetogenic toxin streptozotocin. In experimental diabetic rats, Noopept alleviated glycemia and weight loss and normalized enhanced pain sensitivity. The normalizing effect of Noopept was most pronounced when it was administered as a preventive agent prior to injection of the toxin. Both preventive and therapeutic administration of Noopept (delayed injections included) significantly weakened the examined metabolic effects of diabetogenic toxin. Possible mechanisms of the antidiabetic action of Noopept are analyzed. PMID:23484194

  8. Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice

    SciTech Connect

    Kang, Seong-Il; Jin, Young-Jun; Ko, Hee-Chul; Choi, Soo-Youn; Hwang, Joon-Ho; Whang, Ilson; Kim, Moo-Han; Shin, Hye-Sun; Jeong, Hyung-Bok; Kim, Se-Jae

    2008-08-22

    The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPAR{gamma} luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes.

  9. Black Ginseng Extract Counteracts Streptozotocin-Induced Diabetes in Mice

    PubMed Central

    Kim, Jun Ho; Pan, Jeong Hoon; Cho, Hyung Taek; Kim, Young Jun

    2016-01-01

    Black ginseng, a new type of processed ginseng that has a unique ginsenoside profile, has been shown to display potent pharmacological activities in in vitro and in vivo models. Although red ginseng is considered beneficial for the prevention of diabetes, the relationship between black ginseng and diabetes is unknown. Therefore, this study was designed to evaluate the anti-diabetic potential of black ginseng extract (BGE) in streptozotocin (STZ)-induced insulin-deficient diabetic mice, in comparison with red ginseng extract (RGE). HPLC analyses showed that BGE has a different ginsenoside composition to RGE; BGE contains Rg5 and compound k as the major ginsenosides. BGE at 200 mg/kg reduced hyperglycemia, increased the insulin/glucose ratio and improved islet architecture and β-cell function in STZ-treated mice. The inhibition of β-cell apoptosis by BGE was associated with suppression of the cytokine—induced nuclear factor–κB—mediated signaling pathway in the pancreas. Moreover, these anti-diabetic effects of BGE were more potent than those of RGE. Collectively, our data indicate that BGE, in part by suppressing cytokine—induced apoptotic signaling, protects β-cells from oxidative injury and counteracts diabetes in mice. PMID:26751692

  10. Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Li; Deng, Yuanxiong; Yu, Sen; Lu, Shousi; Xie, Lin; Liu, Xiaodong

    2008-05-01

    Previous studies demonstrated anti-diabetic effects of berberine. However, the facts that berberine had low bioavailability and poor absorption through the gut wall indicated that berberine might exert its antihyperglycaemic effect in the intestinal tract before absorption. The purpose of this study was to investigate whether berberine attenuates disaccharidase activities and beta-glucuronidase activity in the small intestine of streptozotocin (STZ)-induced diabetic rats. Two groups of STZ-induced diabetic rats were treated with protamine zinc insulin (10 U/Kg) subcutaneously twice daily and berberine (100 mg/Kg) orally once daily for 4 weeks, respectively. Both age-matched normal rats and diabetic control rats received physiological saline only. Fasting blood glucose levels, body weight, intestinal disaccharidase and beta-glucuronidase activities in duodenum, jejunum and ileum were assessed for changes. Our findings suggested that berberine treatment significantly decreases the activities of intestinal disaccharidases and beta-glucuronidase in STZ-induced diabetic rats. The results demonstrated that the inhibitory effect on intestinal disaccharidases and beta-glucuronidase of berberine might be one of the mechanisms for berberine as an antihyperglycaemic agent. PMID:18557425

  11. Black Ginseng Extract Counteracts Streptozotocin-Induced Diabetes in Mice.

    PubMed

    Kim, Jun Ho; Pan, Jeong Hoon; Cho, Hyung Taek; Kim, Young Jun

    2016-01-01

    Black ginseng, a new type of processed ginseng that has a unique ginsenoside profile, has been shown to display potent pharmacological activities in in vitro and in vivo models. Although red ginseng is considered beneficial for the prevention of diabetes, the relationship between black ginseng and diabetes is unknown. Therefore, this study was designed to evaluate the anti-diabetic potential of black ginseng extract (BGE) in streptozotocin (STZ)-induced insulin-deficient diabetic mice, in comparison with red ginseng extract (RGE). HPLC analyses showed that BGE has a different ginsenoside composition to RGE; BGE contains Rg5 and compound k as the major ginsenosides. BGE at 200 mg/kg reduced hyperglycemia, increased the insulin/glucose ratio and improved islet architecture and β-cell function in STZ-treated mice. The inhibition of β-cell apoptosis by BGE was associated with suppression of the cytokine-induced nuclear factor-κB-mediated signaling pathway in the pancreas. Moreover, these anti-diabetic effects of BGE were more potent than those of RGE. Collectively, our data indicate that BGE, in part by suppressing cytokine-induced apoptotic signaling, protects β-cells from oxidative injury and counteracts diabetes in mice. PMID:26751692

  12. Ergosterol Alleviates Kidney Injury in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Ang, Li; Yuguang, Liu; Liying, Wang; Shuying, Zhang; Liting, Xu; Shumin, Wang

    2015-01-01

    Ergosterol (ERG) has been widely used in the development of novel drugs due to its unique physiological function. However, little is known about the protective effects of ERG on diabetes. Hence, the current study was designed to evaluate the positive role of ergosterol on streptozotocin- (STZ-) induced diabetes in mice. Oral glucose tolerance test (OGTT) was carried out to assess blood glucose level. Biochemical parameters such as uric acid, creatinine, serum insulin, triglycerides (TG), and total cholesterol (TC) were also measured. Pathological condition of kidney was examined by hematoxylin-eosin (H&E) staining. The expressions of PI3K, p-PI3K, Akt, p-Akt, NF-κBp65, p-NF-κBp65, IκBα, and p-IκBα were analyzed by western blot. ERG significantly reduced the concentrations of blood glucose, uric acid, creatinine, TG, and TC. Serum insulin was elevated with ERG treatment. In addition, renal pathologic changes of diabetes mice were also alleviated by ERG. Obtained data revealed that ERG restored the levels of PI3K/Akt/NF-κB signaling-related proteins in comparison with diabetes mice. Above all, it could be assumed that ERG might play a positive role in regulating STZ-induced diabetes through suppressing PI3K/Akt/NF-κB pathway. PMID:26664454

  13. Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice.

    PubMed

    Lee, Young-Sun; Eun, Hyuk Soo; Kim, So Yeon; Jeong, Jong-Min; Seo, Wonhyo; Byun, Jin-Seok; Jeong, Won-Il; Yi, Hyon-Seung

    2016-01-01

    Emerging evidence revealed that diabetes induces abnormal immune responses that result in serious complications in organs. However, the effect of hyperglycemia on hepatic immunity remains obscure. We evaluated the population and function of hepatic immune cells in streptozotocin (STZ)-induced hyperglycemic mice. CC chemokine receptor 2 (CCR2)-knockout mice and mice with a depletion of regulatory T cells (DEREG) were used to investigate the migration and role of regulatory T cells (Tregs) in hyperglycemic mice. The inflammatory cytokines and hepatic transaminase levels were significantly increased in the hyperglycemic mice. The population and number of infiltrating monocytes, granulocytes, and Tregs were enhanced in the livers of the hyperglycemic mice. Hepatic monocytes other than macrophages showed the increased expression of inflammatory cytokines and chemokines in the hyperglycemic mice. The CCR2 knockout and DEREG chimeric mice exhibited increased populations of activated T cells and neutrophils compared to the WT chimeric mice, which promoted hepatic inflammation in the hyperglycemic mice. The migration of CCR2 knockout Tregs into the liver was significantly reduced compared to the WT Tregs. We demonstrated that hyperglycemia contributes to increase in infiltrating monocytes and Tregs, which are associated with hepatic immune dysfunction in mice. CCR2-mediated migration of Tregs regulates hyperglycemia-induced hepatic inflammation. PMID:27464894

  14. Cacao polyphenols ameliorate autoimmune myocarditis in mice.

    PubMed

    Zempo, Hirofumi; Suzuki, Jun-Ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2016-04-01

    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress. PMID:26657007

  15. Means for limiting and ameliorating electrode shorting

    DOEpatents

    Van Konynenburg, Richard A.; Farmer, Joseph C.

    1999-01-01

    A fuse and filter arrangement for limiting and ameliorating electrode shorting in capacitive deionization water purification systems utilizing carbon aerogel, for example. This arrangement limits and ameliorates the effects of conducting particles or debonded carbon aerogel in shorting the electrodes of a system such as a capacitive deionization water purification system. This is important because of the small interelectrode spacing and the finite possibility of debonding or fragmentation of carbon aerogel in a large system. The fuse and filter arrangement electrically protect the entire system from shutting down if a single pair of electrodes is shorted and mechanically prevents a conducting particle from migrating through the electrode stack, shorting a series of electrode pairs in sequence. It also limits the amount of energy released in a shorting event. The arrangement consists of a set of circuit breakers or fuses with one fuse or breaker in the power line connected to one electrode of each electrode pair and a set of screens of filters in the water flow channels between each set of electrode pairs.

  16. Acetylcholinesterase inhibition ameliorates deficits in motivational drive

    PubMed Central

    2012-01-01

    Background Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS) protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes. Methods We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes. Results CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens. Conclusions Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive. PMID:22433906

  17. ANTIOXIDANTS AMELIORATION OF ARSENICAL-INDUCED EFFECTS IN VIVO

    EPA Science Inventory

    Antioxidant amelioration of arsenical-induced effects in vivo. ES Hunter and EH Rogers. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC.

    Antioxidants have been reported to ameliorate the effects of many developmental toxicants. We tested the hypothesis that oxi...

  18. Ameliorated GA approach for base station planning

    NASA Astrophysics Data System (ADS)

    Wang, Andong; Sun, Hongyue; Wu, Xiaomin

    2011-10-01

    In this paper, we aim at locating base station (BS) rationally to satisfy the most customs by using the least BSs. An ameliorated GA is proposed to search for the optimum solution. In the algorithm, we mesh the area to be planned according to least overlap length derived from coverage radius, bring into isometric grid encoding method to represent BS distribution as well as its number and develop select, crossover and mutation operators to serve our unique necessity. We also construct our comprehensive object function after synthesizing coverage ratio, overlap ratio, population and geographical conditions. Finally, after importing an electronic map of the area to be planned, a recommended strategy draft would be exported correspondingly. We eventually import HongKong, China to simulate and yield a satisfactory solution.

  19. Erythropoietin ameliorates hyperglycemia in type 1-like diabetic rats

    PubMed Central

    Niu, Ho-Shan; Chang, Chin-Hong; Niu, Chiang-Shan; Cheng, Juei-Tang; Lee, Kung-Shing

    2016-01-01

    Background Erythropoietin (EPO) is widely used in diabetic patients receiving hemodialysis. The role of EPO in glucose homeostasis remains unclear. Therefore, we investigated the effect of EPO on hyperglycemia in rats with type 1-like diabetes. Methods Rats with streptozotocin-induced type 1-like diabetes (STZ rats) were used to estimate the blood glucose-lowering effects of EPO, and changes in the expression levels of glucose transporter 4 (GLUT4) and the hepatic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were identified by Western blot analysis. Results EPO attenuated the hyperglycemia in the STZ rats in a dose-dependent manner without altering the hematopoietic parameters, including the hematocrit and number of red blood cells. The involvement of the EPO receptor (EPOR) was identified using EPOR-specific antibodies. In addition, injection of EPO enhanced the glucose utilization, which was assessed using an intravenous glucose tolerance test in rats. However, blood insulin was not changed by EPO in this assay, showing the insulinotropic action of EPO. Moreover, EPO treatment increased the insulin sensitivity. Western blots indicated that the phosphorylation of AMP-activated protein kinase was enhanced by EPO to support the signaling caused by EPOR activation. Furthermore, the decrease in the GLUT4 level in skeletal muscle was reversed by EPO, and the increase in the PEPCK expression in liver was reduced by EPO, as shown in STZ rats. Conclusion Taken together, the results show that EPO injection may reduce hyperglycemia in diabetic rats through activation of EPO receptors. Therefore, EPO is useful for managing diabetic disorders, particularly hyperglycemia-associated changes. In addition, EPO receptor will be a good target for the development of antihyperglycemic agent(s) in the future. PMID:27350742

  20. siRNA-Based Therapy Ameliorates Glomerulonephritis

    PubMed Central

    Shimizu, Hideki; Hori, Yuichi; Kaname, Shinya; Yamada, Koei; Nishiyama, Nobuhiro; Matsumoto, Satoru; Miyata, Kanjiro; Oba, Makoto; Yamada, Akira; Kataoka, Kazunori

    2010-01-01

    RNA interference by short interfering RNAs (siRNAs) holds promise as a therapeutic strategy, but use of siRNAs in vivo remains limited. Here, we developed a system to target delivery of siRNAs to glomeruli via poly(ethylene glycol)-poly(l-lysine)-based vehicles. The siRNA/nanocarrier complex was approximately 10 to 20 nm in diameter, a size that would allow it to move across the fenestrated endothelium to access to the mesangium. After intraperitoneal injection of fluorescence-labeled siRNA/nanocarrier complexes, we detected siRNAs in the blood circulation for a prolonged time. Repeated intraperitoneal administration of a mitogen-activated protein kinase 1 (MAPK1) siRNA/nanocarrier complex suppressed glomerular MAPK1 mRNA and protein expression in a mouse model of glomerulonephritis; this improved kidney function, reduced proteinuria, and ameliorated glomerular sclerosis. Furthermore, this therapy reduced the expression of the profibrotic markers TGF-β1, plasminogen activator inhibitor-1, and fibronectin. In conclusion, we successfully silenced intraglomerular genes with siRNA using nanocarriers. This technique could aid the investigation of molecular mechanisms of renal disease and has potential as a molecular therapy of glomerular diseases. PMID:20203158

  1. Resveratrol Pretreatment Ameliorates TNBS Colitis in Rats

    PubMed Central

    Yildiz, Gulserap; Yildiz, Yuksel; Ulutas, Pinar A.; Yaylali, Aslı; Ural, Muruvvet

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease in humans constituting a major health concern today whose prevalence has been increasing over the world. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in IBD subjects have been reported. Antioxidants may play a significant role in IBD treatment. This study aimed at evaluating ameliorative effects of intraperitoneal resveratrol pretreatment on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Thirty five Wistar-Albino female rats were divided equally into five groups. Inflammation was induced by the intrarectal administration of TNBS under anesthesia. Intraperitoneal administration of resveratrol (RSV) at a concentration of 10mg/kg/day for 5 days before the induction of colitis significantly reduced microscopy score and malondialdehyde (MDA) levels and increased glutathione peroxidase (GSH Px) activity compared to TNBS and vehicle groups. Also an insignificant increase in catalase (CAT) activity was observed in the RSV treated group compared to TNBS and vehicle groups. In this paper, the most recent patent on the identification and treatment of IBD was indicated. In conclusion, antioxidant RSV proved to have a beneficial effect on TNBS colitis in rats. In light of these advantageous results, the RSV can be considered as adjuvant agent in IBD treatments. PMID:26246013

  2. Resveratrol Pretreatment Ameliorates TNBS Colitis in Rats.

    PubMed

    Yildiz, Gulserap; Yildiz, Yuksel; Ulutas, Pinar A; Yaylali, Asl; Ural, Muruvvet

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease in humans constituting a major health concern today whose prevalence has been increasing over the world. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in IBD subjects have been reported. Antioxidants may play a significant role in IBD treatment. This study aimed at evaluating ameliorative effects of intraperitoneal resveratrol pretreatment on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Thirty five Wistar-Albino female rats were divided equally into five groups. Inflammation was induced by the intrarectal administration of TNBS under anesthesia. Intraperitoneal administration of resveratrol (RSV) at a concentration of 10mg/kg/day for 5 days before the induction of colitis significantly reduced microscopy score and malondialdehyde (MDA) levels and increased glutathione peroxidase (GSH Px) activity compared to TNBS and vehicle groups. Also an insignificant increase in catalase (CAT) activity was observed in the RSV treated group compared to TNBS and vehicle groups. In this paper, the most recent patent on the identification and treatment of IBD was indicated. In conclusion, antioxidant RSV proved to have a beneficial effect on TNBS colitis in rats. In light of these advantageous results, the RSV can be considered as adjuvant agent in IBD treatments. PMID:26246013

  3. Characterization of prefrontal cortex microstructure and antioxidant status in a rat model of neurodegeneration induced by aluminium chloride and multiple low-dose streptozotocin.

    PubMed

    Akinola, Oluwole B; Biliaminu, Sikiru A; Adediran, Rianat A; Adeniye, Kehinde A; Abdulquadir, Fatimah C

    2015-12-01

    Diabetes mellitus (DM) is a risk factor for Alzheimer's disease (AD), and several individuals with AD are diabetic. Most non-transgenic animal models of AD make use of oral treatment with aluminium chloride (AlCl(3)) to induce brain lesions pathognomonic of the disease. Moreover, streptozotocin (STZ) can induce pathological features of either AD or DM depending on the mode of treatment. In the present study, we characterised prefrontal microanatomy and antioxidant defence system in a rat model of AD confounded by DM, with the objective of assessing the suitability of this model in the study of sporadic AD with DM co-morbidity. Adult Wistar rats were randomly assigned to receive either intraperitoneal STZ (30 mg/kg/day for 3 days; to induce DM), oral AlCl(3) (500 mg/kg/day for 4 weeks; to induce some brain lesions characteristic of AD); or both STZ and AlCl(3) (to induce AD with DM co-morbidity). Untreated rats served as controls. During treatment, blood glucose levels and body weights were evaluated repeatedly in all rats. At euthanasia, prefrontal cortex was homogenized in phosphate buffer solution and the supernatants assayed for some antioxidant enzymes (catalase, CAT; superoxide dismutase, SOD; and reduced glutathione, GSH). Moreover, following perfusion-fixation of the brain, frontal lobes were processed by the haematoxylin and eosin (H&E) or Congo red technique. Our findings showed that in rats co-administered AlCl(3) and STZ (AD + DM rats), prefrontal levels of GSH reduced significantly (p < 0.05), while reductions in SOD and CAT were not significant (p > 0.05) compared with the controls. Moreover, in this model of AD with DM co-morbidity, extensive neuronal cell loss was observed in the prefrontal cortex, but Congophilic deposits were not present. The neurodegenerative lesions and antioxidant deficits characteristic of this AlCl(3) + STZ (AD + DM) rat model were more pronounced than similar lesions associated with mono-treatment with either STZ (DM) or AlCl(3) (AD) alone; and this makes the AlCl(3) + STZ model a suitable option for the study of neurodegenerative diseases (such as AD) with DM co-morbidity. PMID:26307418

  4. Using Community-Based Participatory Research to Ameliorate Cancer Disparities

    ERIC Educational Resources Information Center

    Gehlert, Sarah; Coleman, Robert

    2010-01-01

    Although much attention has been paid to health disparities in the past decades, interventions to ameliorate disparities have been largely unsuccessful. One reason is that the interventions have not been culturally tailored to the disparity populations whose problems they are meant to address. Community-engaged research has been successful in…

  5. Social buffering ameliorates conditioned fear responses in female rats.

    PubMed

    Ishii, Akiko; Kiyokawa, Yasushi; Takeuchi, Yukari; Mori, Yuji

    2016-05-01

    The stress experienced by an animal is ameliorated when the animal is exposed to distressing stimuli along with a conspecific animal(s). This is known as social buffering. Previously, we found that the presence of an unfamiliar male rat induced social buffering and ameliorated conditioned fear responses of a male rat subjected to an auditory conditioned stimulus (CS). However, because our knowledge of social buffering is highly biased towards findings in male subjects, analyses using female subjects are crucial for comprehensively understanding the social buffering phenomenon. In the present studies, we assessed social buffering of conditioned fear responses in female rats. We found that the estrus cycle did not affect the intensity of the rats' fear responses to the CS or their degree of vigilance due to the presence of a conspecific animal. Based on these findings, we then assessed whether social buffering ameliorated conditioned fear responses in female rats without taking into account their estrus cycles. When fear conditioned female rats were exposed to the CS without the presence of a conspecific, they exhibited behavioral responses, including freezing, and elevated corticosterone levels. By contrast, the presence of an unfamiliar female rat suppressed these responses. Based on these findings, we conclude that social buffering can ameliorate conditioned fear responses in female rats. PMID:27060333

  6. XANES of Chromium in Sludges Used as Soil Ameliorants

    SciTech Connect

    Naftel, S.J.; Martin, R.R.; Sham, T.K.; Hart, B.; Powell, M.A.

    2010-12-01

    Samples of sewage sludges proposed for use as soil ameliorants in an Indo-Canadian project were tested for chromium content. Standard aqua regia extractions found one sludge to have excessive amounts of Cr. X-ray absorption near-edge structure (XANES) spectroscopy, however, indicated that the Cr was present in the relatively benign Cr(III) oxidation state in all the sludge samples.

  7. Evaluation of Soil Salinity Amelioration Technologies in Timpaki, Crete

    NASA Astrophysics Data System (ADS)

    Panagea, Ioanna; Daliakopoulos, Ioannis; Tsanis, Ioannis; Schwilch, Gudrun

    2015-04-01

    Salinization is a soil threat that adversely affects ecosystem services and diminishes soil functions in many arid and semi-arid regions. Soil salinity management depends on a range of factors, and can be complex expensive and time demanding. Besides taking no action, possible management strategies include amelioration and adaptation measures. The WOCAT Technologies Questionnaire is a standardized methodology for monitoring, evaluating and documenting sustainable land management practices through interaction with the stakeholders. Here we use WOCAT for the systematic analysis and evaluation of soil salinization amelioration measures, for the RECARE project Case Study in Greece, the Timpaki basin, a semi-arid region in south-central Crete where the main land use is horticulture in greenhouses irrigated by groundwater. Excessive groundwater abstractions have resulted in a drop of the groundwater level in the coastal part of the aquifer, thus leading to seawater intrusion and in turn to soil salinization due to irrigation with brackish water. Amelioration technologies that have already been applied in the case study by the stakeholders are examined and classified depending on the function they promote and/or improve. The documented technologies are evaluated for their impacts on ecosystem services, cost and input requirements. Preliminary results show that technologies which promote maintaining existing crop types while enhancing productivity and decreasing soil salinity such as composting, mulching, rain water harvesting and seed biopriming are preferred by the stakeholders. Further work will include result validation using qualitative approaches. Keywords: soil salinity; salinization; evaluation of soil salinization amelioration techniques; WOCAT; RECARE FP7 project; Timpaki Crete

  8. Biochar from commercially cultivated seaweed for soil amelioration

    NASA Astrophysics Data System (ADS)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-04-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum - brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma - red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.

  9. Biochar from commercially cultivated seaweed for soil amelioration.

    PubMed

    Roberts, David A; Paul, Nicholas A; Dworjanyn, Symon A; Bird, Michael I; de Nys, Rocky

    2015-01-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum--brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma--red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity. PMID:25856799

  10. Biochar from commercially cultivated seaweed for soil amelioration

    PubMed Central

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-01-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum – brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma – red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity. PMID:25856799

  11. Restoration of Na+/H+ exchanger NHE3-containing macrocomplexes ameliorates diabetes-associated fluid loss

    PubMed Central

    He, Peijian; Zhao, Luqing; Zhu, Lixin; Weinman, Edward J.; De Giorgio, Roberto; Koval, Michael; Srinivasan, Shanthi; Yun, C. Chris

    2015-01-01

    Diarrhea is one of the troublesome complications of diabetes, and the underlying causes of this problem are complex. Here, we investigated whether altered electrolyte transport contributes to diabetic diarrhea. We found that the expression of Na+/H+ exchanger NHE3 and several scaffold proteins, including NHE3 regulatory factors (NHERFs), inositol trisphosphate (IP3) receptor-binding protein released with IP3 (IRBIT), and ezrin, was decreased in the intestinal brush border membrane (BBM) of mice with streptozotocin-induced diabetes. Treatment of diabetic mice with insulin restored intestinal NHE3 activity and fluid absorption. Molecular analysis revealed that NHE3, NHERF1, IRBIT, and ezrin form macrocomplexes, which are perturbed under diabetic conditions, and insulin administration reconstituted these macrocomplexes and restored NHE3 expression in the BBM. Silencing of NHERF1 or IRBIT prevented NHE3 trafficking to the BBM and insulin-dependent NHE3 activation. IRBIT facilitated the interaction of NHE3 with NHERF1 via protein kinase D2–dependent phosphorylation. Insulin stimulated ezrin phosphorylation, which enhanced the interaction of ezrin with NHERF1, IRBIT, and NHE3. Additionally, oral administration of lysophosphatidic acid (LPA) increased NHE3 activity and fluid absorption in diabetic mice via an insulin-independent pathway. Together, these findings indicate the importance of NHE3 in diabetic diarrhea and suggest LPA administration as a potential therapeutic strategy for management of diabetic diarrhea. PMID:26258413

  12. Potential of carnuba wax in ameliorating brittle fracture during tableting.

    PubMed

    Uhumwangho, M U; Okor, R S; Adogah, J T

    2009-01-01

    Carnuba wax (as binder) forms hard tablets even at low compression load attributable to its high plasticity. The aim of the present study is to investigate its potential in ameliorating brittle fracture (i.e., lamination and capping) a problem often encountered during tableting. Granules of paracetamol (test drug) were made by triturating the drug powder with the melted wax or starch mucilage (20%w/v). Resulting granules were separated into different size fractions which were separately compressed into tablets with and without a centre hole (as in- built defect) using different compression loads. The tablets were evaluated for tensile strength and the data used to calculate the brittle fracture index (BFI), using the expression: BFI = 0.5(T/T(0)-1) where T0 and T are the tensile strength of tablets with and without a centre hole respectively. The BFI values were significantly lower (p<0.05) in tablets made with carnuba wax compared with tablets made with maize starch as binders. Increase in particle size of the granules or lowering of the compression load further ameliorated the brittle fracture tendency of the tablets. Using granules with the larger particle size (850microm) and applying the lowest unit of load (6 arbitrary unit on the load scale of the tableting machine) the BFI values were 0.03 (carnuba wax tablets) and 0.11 (maize starch tablets). When the conditions were reversed (i.e., a highest load, 8 units and the smallest particle size, 212microm) the BFI values now became 0.17 (carnuba wax tablets) and 0.26 (maize starch tablets). The indication is that the use of large granules and low compression loads to form tablets can further enhance the potential of carnuba wax in ameliorating brittle fracture tendency of tablets during their manufacture. PMID:19168422

  13. Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis

    PubMed Central

    Jiang, Zhao-Xin; Qiu, Suo; Lou, Bing-Sheng; Yang, Yao; Wang, Wen-Cong; Lin, Xiao-Feng

    2016-01-01

    Neutrophils have been recognized as critical response cells during the pathogenesis of endotoxin-induced uveitis (EIU). Apoptosis of neutrophils induced by roscovitine has previously been demonstrated to ameliorate inflammation in several in vivo models. The present study aimed to assess whether roscovitine ameliorates EIU. EIU was induced in female C57BL/6 mice by a single intravitreal injection of lipopolysaccharide (LPS; 250 ng). The mice were divided into three groups as follows: LPS alone, LPS plus vehicle, LPS plus roscovitine (50 mg/kg). The mice were euthanized 12, 24, 48 and 72 h after LPS-induced uveitis. Accumulation of inflammatory cells in the vitreous body was confirmed by immunohistochemistry, and quantified following hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was performed to detect of apoptotic cells. The mRNA levels of inflammatory cytokines were analyzed by reverse transcription-quantitative polymerase chain reaction and the changes in protein levels were analyzed by western blotting. Inflammatory cells accumulated in the vitreous near the optic nerve head and the quantity peaked at 24 h after LPS injection. Immunohistochemistry revealed that the majority of the inflammatory cells were neutrophils. The number of infiltrating cells was similar in the LPS and LPS plus vehicle groups, while there were significantly less in the roscovitine group at 24 h. Apoptosis of neutrophils was observed between 12 and 48 h after roscovitine injection, while no apoptosis was observed in the other groups. The mRNA expression levels of GMCSF, CINC-1 and ICAM-1 peaked at 12 h after LPS injection, and decreased to normal levels at 72 h. This trend in mRNA expression was similar in the LPS and LPS plus vehicle groups; however, the expression levels decreased more quickly in the roscovitine group at 24 and 48 h. Following roscovitine administration, upregulated cleaved caspase 3 expression levels and downregulated Mcl-1

  14. Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis.

    PubMed

    Jiang, Zhao-Xin; Qiu, Suo; Lou, Bing-Sheng; Yang, Yao; Wang, Wen-Cong; Lin, Xiao-Feng

    2016-08-01

    Neutrophils have been recognized as critical response cells during the pathogenesis of endotoxin‑induced uveitis (EIU). Apoptosis of neutrophils induced by roscovitine has previously been demonstrated to ameliorate inflammation in several in vivo models. The present study aimed to assess whether roscovitine ameliorates EIU. EIU was induced in female C57BL/6 mice by a single intravitreal injection of lipopolysaccharide (LPS; 250 ng). The mice were divided into three groups as follows: LPS alone, LPS plus vehicle, LPS plus roscovitine (50 mg/kg). The mice were euthanized 12, 24, 48 and 72 h after LPS‑induced uveitis. Accumulation of inflammatory cells in the vitreous body was confirmed by immunohistochemistry, and quantified following hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick‑end labeling was performed to detect of apoptotic cells. The mRNA levels of inflammatory cytokines were analyzed by reverse transcription‑quantitative polymerase chain reaction and the changes in protein levels were analyzed by western blotting. Inflammatory cells accumulated in the vitreous near the optic nerve head and the quantity peaked at 24 h after LPS injection. Immunohistochemistry revealed that the majority of the inflammatory cells were neutrophils. The number of infiltrating cells was similar in the LPS and LPS plus vehicle groups, while there were significantly less in the roscovitine group at 24 h. Apoptosis of neutrophils was observed between 12 and 48 h after roscovitine injection, while no apoptosis was observed in the other groups. The mRNA expression levels of GMCSF, CINC‑1 and ICAM‑1 peaked at 12 h after LPS injection, and decreased to normal levels at 72 h. This trend in mRNA expression was similar in the LPS and LPS plus vehicle groups; however, the expression levels decreased more quickly in the roscovitine group at 24 and 48 h. Following roscovitine administration, upregulated cleaved caspase 3 expression levels

  15. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms

    PubMed Central

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-01-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)—a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  16. Guanfacine ameliorates hypobaric hypoxia induced spatial working memory deficits.

    PubMed

    Kauser, H; Sahu, S; Kumar, S; Panjwani, U

    2014-01-17

    Hypobaric hypoxia (HH) observed at high altitude causes mild cognitive impairment specifically affecting attention and working memory. Adrenergic dysregulation and neuronal damage in prefrontal cortex (PFC) has been implicated in hypoxia induced memory deficits. Optimal stimulation of alpha 2A adrenergic receptor in PFC facilitates the spatial working memory (SWM) under the conditions of adrenergic dysregulation. Therefore the present study was designed to test the efficacy of alpha 2A adrenergic agonist, Guanfacine (GFC), to restore HH induced SWM deficits and PFC neuronal damage. The rats were exposed to chronic HH equivalent to 25,000ft for 7days in an animal decompression chamber and received daily treatment of GFC at a dose of 1mg/kg body weight via the intramuscular route during the period of exposure. The cognitive performance was assessed by Delayed Alternation Task (DAT) using T-Maze and PFC neuronal damage was studied by apoptotic and neurodegenerative markers. Percentage of correct choice decreased significantly while perseverative errors showed a significant increase after 7days HH exposure, GFC significantly ameliorated the SWM deficits and perseveration. There was a marked and significant increase in chromatin condensation, DNA fragmentation, neuronal pyknosis and fluoro Jade positive cells in layer II of the medial PFC in hypoxia exposed group, administration of GFC significantly reduced the magnitude of these changes. Modulation of adrenergic mechanisms by GFC may serve as an effective countermeasure in amelioration of prefrontal deficits and neurodegenerative changes during HH. PMID:24184415

  17. The ameliorative effects of a hypnotic bromvalerylurea in sepsis.

    PubMed

    Kikuchi, Satoshi; Nishihara, Tasuku; Kawasaki, Shun; Abe, Naoki; Kuwabara, Jun; Choudhury, Mohammed E; Takahashi, Hisaaki; Yano, Hajime; Nagaro, Takumi; Watanabe, Yuji; Aibiki, Mayuki; Tanaka, Junya

    2015-04-01

    Sepsis is a severe pathologic event, frequently causing death in critically ill patients. However, there are no approved drugs to treat sepsis, despite clinical trials of many agents that have distinct targets. Therefore, a novel effective treatment should be developed based on the pathogenesis of sepsis. We recently observed that an old hypnotic drug, bromvalerylurea (BU) suppressed expression of many kinds of pro- and anti-inflammatory mediators in LPS- or interferon-γ activated alveolar and peritoneal macrophages (AMs and PMs). Taken the anti-inflammatory effects of BU on macrophages, we challenged it to septic rats that had been subjected to cecum-ligation and puncture (CLP). BU was subcutaneously administered to septic rats twice per day. Seven days after CLP treatment, 85% of septic rats administrated vehicle had died, whereas administration of BU reduce the rate to 50%. Septic rats showed symptoms of multi-organ failure; respiratory, circulatory and renal system failures as revealed by histopathological analyses, blood gas test and others. BU ameliorated these symptoms. BU also prevented elevated serum-IL-6 level as well as IL-6 mRNA expression in septic rats. Collectively, BU might be a novel agent to ameliorate sepsis by preventing the onset of MOF. PMID:25732089

  18. Oxidative Stress in Lead and Cadmium Toxicity and Its Amelioration

    PubMed Central

    Patra, R. C.; Rautray, Amiya K.; Swarup, D.

    2011-01-01

    Oxidative stress has been implicated to play a role, at least in part, in pathogenesis of many disease conditions and toxicities in animals. Overproduction of reactive oxygen species and free radicals beyond the cells intrinsic capacity to neutralize following xenobiotics exposure leads to a state of oxidative stress and resultant damages of lipids, protein, and DNA. Lead and cadmium are the common environmental heavy metal pollutants and have widespread distribution. Both natural and anthropogenic sources including mining, smelting, and other industrial processes are responsible for human and animal exposure. These pollutants, many a times, are copollutants leading to concurrent exposure to living beings and resultant synergistic deleterious health effects. Several mechanisms have been explained for the damaging effects on the body system. Of late, oxidative stress has been implicated in the pathogenesis of the lead- and cadmium-induced pathotoxicity. Several ameliorative measures to counteract the oxidative damage to the body system aftermath or during exposure to these toxicants have been assessed with the use of antioxidants. The present review focuses on mechanism of lead- and cadmium-induced oxidate damages and the ameliorative measures to counteract the oxidative damage and pathotoxicity with the use of supplemented antioxidants for their beneficial effects. PMID:21547215

  19. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms.

    PubMed

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-09-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)-a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  20. Curcumin ameliorates experimental autoimmune myasthenia gravis by diverse immune cells.

    PubMed

    Wang, Shan; Li, Heng; Zhang, Min; Yue, Long-Tao; Wang, Cong-Cong; Zhang, Peng; Liu, Ying; Duan, Rui-Sheng

    2016-07-28

    Curcumin is a traditional Asian medicine with diverse immunomodulatory properties used therapeutically in the treatment of many autoimmune diseases. However, the effects of curcumin on myasthenia gravis (MG) remain undefined. Here we investigated the effects and potential mechanisms of curcumin in experimental autoimmune myasthenia gravis (EAMG). Our results demonstrated that curcumin ameliorated the clinical scores of EAMG, suppressed the expression of T cell co-stimulatory molecules (CD80 and CD86) and MHC class II, down-regulated the levels of pro-inflammatory cytokines (IL-17, IFN-γ and TNF-α) and up-regulated the levels of the anti-inflammatory cytokine IL-10, shifted the balance from Th1/Th17 toward Th2/Treg, and increased the numbers of NKR-P1(+) cells (natural killer cell receptor protein 1 positive cells, including NK and NKT cells). Moreover, the administration of curcumin promoted the differentiation of B cells into a subset of B10 cells, increased the anti-R97-166 peptide IgG1 levels and decreased the relative affinity indexes of anti-R97-116 peptide IgG. In summary, curcumin effectively ameliorate EAMG, indicating that curcumin may be a potential candidate therapeutic agent for MG. PMID:27181511

  1. 18 CFR 2.23 - Use of reserved authority in hydropower licenses to ameliorate cumulative impacts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... authority in hydropower licenses to ameliorate cumulative impacts. 2.23 Section 2.23 Conservation of Power... § 2.23 Use of reserved authority in hydropower licenses to ameliorate cumulative impacts. The... opportunity for hearing by the licensee and all interested parties. Hydropower licenses also contain...

  2. 18 CFR 2.23 - Use of reserved authority in hydropower licenses to ameliorate cumulative impacts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... authority in hydropower licenses to ameliorate cumulative impacts. 2.23 Section 2.23 Conservation of Power... § 2.23 Use of reserved authority in hydropower licenses to ameliorate cumulative impacts. The... opportunity for hearing by the licensee and all interested parties. Hydropower licenses also contain...

  3. 18 CFR 2.23 - Use of reserved authority in hydropower licenses to ameliorate cumulative impacts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... authority in hydropower licenses to ameliorate cumulative impacts. 2.23 Section 2.23 Conservation of Power... § 2.23 Use of reserved authority in hydropower licenses to ameliorate cumulative impacts. The... opportunity for hearing by the licensee and all interested parties. Hydropower licenses also contain...

  4. 18 CFR 2.23 - Use of reserved authority in hydropower licenses to ameliorate cumulative impacts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... authority in hydropower licenses to ameliorate cumulative impacts. 2.23 Section 2.23 Conservation of Power... § 2.23 Use of reserved authority in hydropower licenses to ameliorate cumulative impacts. The... opportunity for hearing by the licensee and all interested parties. Hydropower licenses also contain...

  5. Effects of metformin on inflammation and short-term memory in streptozotocin-induced diabetic mice.

    PubMed

    Oliveira, Wilma Helena; Nunes, Ana Karolina; França, Maria Eduarda Rocha; Santos, Laise Aline; Lós, Deniele Bezerra; Rocha, Sura Wanessa; Barbosa, Karla Patrícia; Rodrigues, Gabriel Barros; Peixoto, Christina Alves

    2016-08-01

    The aim of the present study was to analyze the action of metformin on short-term memory, glial cell activation and neuroinflammation caused by experimental diabetic encephalopathy in C57BL/6 mice. Diabetes was induced by the intraperitoneal injection of a dose of 90mg/kg of streptozotocin on two successive days. Mice with blood glucose levels ≥200dl/ml were considered diabetic and were given metformin hydrochloride at doses of 100mg/kg and 200mg/kg (by gavage, twice daily) for 21 days. On the final day of treatment, the mice underwent a T-maze test. On the 22nd day of treatment all the animals were anesthetized and euthanized. Diabetic animals treated with metformin had a higher spatial memory score. The hippocampus of the diabetic animals presented reactive gliosis, neuronal loss, NF-kB signaling activation, and high levels of IL-1 and VEGF. In addition, the T-maze test scores of these animals were low. Treatment with metformin reduced the expression of GFAP, Iba-1 (astrocyte and microglial markers) and the inflammation markers (p-IKB, IL-1 and VEGF), while enhancing p-AMPK and eNOS levels and increasing neuronal survival (Fox-1 and NeuN). Treatment with metformin also improved the spatial memory scores of diabetic animals. In conclusion, the present study showed that metformin can significantly reduce neuroinflammation and can decrease the loss of neurons in the hippocampus of diabetic animals, which can subsequently promote improvements in spatial memory. PMID:27174003

  6. Antidepressant-like Effect of Insulin in Streptozotocin-induced Type 2 Diabetes Mellitus Rats.

    PubMed

    Sestile, Caio C; Maraschin, Jhonatan C; Rangel, Marcel P; Cuman, Roberto K N; Audi, Elisabeth A

    2016-09-01

    This study evaluated the antidepressant-like effect of insulin compared to sertraline and a combination of insulin and sertraline in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats submitted to the forced swim test (FST). Male Wistar rats were daily treated for 21 days with insulin (1 or 2 IU/kg, i.p.), with the selective serotonin reuptake inhibitor (SSRI), sertraline (10 mg/kg, i.p.), or with a combination of insulin (1 or 2 IU/kg, i.p.) and sertraline (10 mg/kg, i.p.) and submitted to the FST. We also evaluated the water and food intake, urine volume and weight gain of the rats. Rats treated with STZ showed impaired glucose tolerance. Chronic treatment with sertraline showed an antidepressant-like effect in non-diabetic and diabetic rats. Furthermore, sertraline promoted lower weight gain in diabetic rats. Insulin reduced the immobility behaviour in T2DM rats with impaired glucose tolerance. In conclusion, our results showed that insulin has an antidepressant-like effect comparable to that of sertraline. Sertraline is effective as an antidepressant and reduces weight gain, which reinforces its superiority over other SSRIs in the treatment of major depression disorder in patients with T2DM. PMID:26857652

  7. Effect of diabetic duration on hemorheological properties and platelet aggregation in streptozotocin-induced diabetic rats

    PubMed Central

    Yeom, Eunseop; Byeon, Hyeokjun; Lee, Sang Joon

    2016-01-01

    Diabetes mellitus with abnormal glucose concentration is associated with changes in hemorheological properties, endothelial function, and platelets hyperactivity. Disturbances may significantly be responsible for diabetes-related vascular complications. In this study, hemorheological and hemodynamic properties were measured according to diabetic duration after streptozotocin treatment in rats. For ex vivo measurements, an extracorporeal model was adopted. Flow rate and blood viscosity were measured using a microfluidic device. Erythrocyte aggregation and morphological parameters of erythrocytes were measured by modified erythrocyte sedimentation rate and the phase-contrast holography under in vitro conditions. The platelet aggregation and mean pressure in the femoral artery were estimated under ex vivo conditions. Hemorheological properties including blood viscosity, erythrocyte aggregation and shape parameters for the control group are significantly different with those for diabetic groups. The changes with respect to diabetic duration were relatively unnoticeable. However, the platelet aggregation is strongly dependent on the diabetic duration. Based on these results, hyperglycemia exposure may induce hemorheological variations in early stages of diabetes mellitus. High platelet aggregation may become more pronounced according to the diabetic duration caused by variations in hemorheological properties resulting in endothelial dysfunction. This study would be helpful in understanding the effects of diabetic duration on biophysical properties. PMID:26898237

  8. Antioxidant and anti-inflammatory effect of conjugated linolenic acid isomers against streptozotocin-induced diabetes.

    PubMed

    Saha, Siddhartha S; Ghosh, Mahua

    2012-09-28

    The present study was undertaken to evaluate the effect of α-eleostearic acid and punicic acid, two isomers of conjugated linolenic acid (CLnA) present in bitter gourd (Momordica charantia) and snake gourd oil (Trichosanthes anguina), respectively, against oxidative stress, inflammatory challenge and aberration in erythrocyte morphology due to streptozotocin (STZ)-induced diabetes. Male albino rats were divided into four groups consisting of eight animals in each group. The first group served as control and diabetes was induced in rats in groups 2-4 by a single intraperitoneal injection of STZ. Moreover, rats in groups 3 and 4 were treated with 0·5 % of α-eleostearic acid and 0·5 % of punicic acid of the total lipid given, respectively, by oral administration once per d. After administration, CLnA isomers had significantly reduced oxidative stress, lipid peroxidation and restored antioxidant and pro-inflammatory enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, reduced glutathione, NO synthase level in pancreas, blood and erythrocyte lysate. The ferric reducing antioxidant power (FRAP) assay of plasma showed that CLnA treatment caused improvement in the FRAP value which was altered after STZ treatment due to an increased level of free radicals. Expression of inflammatory cytokines such as TNF-α and IL-6 in blood and expression of hepatic NF-κB (p65) increased significantly after STZ treatment due to increased inflammation which was restored with the administration of CLnA isomers. From the obtained results, it could be concluded that α-eleostearic acid and punicic acid showed potent antioxidant and anti-inflammatory activity with varying effectivity. PMID:22182422

  9. Effect of dietary intake of freeze dried bitter gourd (Momordica charantia) in streptozotocin induced diabetic rats.

    PubMed

    Platel, K; Srinivasan, K

    1995-01-01

    Consumption of bitter gourd (Momordica charantia) by diabetic patients is a common practice in India, with the belief that it has an useful hypoglycemic potential. In the absence of conclusive information on the hypoglycemic influence of continuous intake of bitter gourd, in the present investigation, we have examined the hypoglycemic potency of dietary bitter gourd in experimentally induced diabetic rats. Wistar rats rendered hyperglycemic by streptozotocin (50 mg/kg b.w., i.p.) were maintained on a semi-synthetic diet containing freeze dried bitter gourd powder at 0.5% level for 6 weeks. The excretion of glucose, protein, urea and creatinine was monitored during the experimental period. Plasma glucose, albumin, urea and cholesterol were analysed at the end of the experimental regime. Dietary bitter gourd did not show any beneficial hypoglycemic influence as evidenced by the blood glucose levels as well as the excretion of diabetes related metabolites. PMID:7477242

  10. Evaluation of Anti-diabetic Property on Streptozotocin-Induced Diabetic Rats.

    PubMed

    2016-01-01

    The diabetes-inducing agent streptozotocin (STZ) is a glucosamine-nitrosourea compound produced by Streptomyces achromogenes, which specifically induces DNA strand breakage in β-cells causing diabetes mellitus. The destruction of pancreatic β-cells by STZ is associated with a huge release of insulin in their first phase, and then in the second phase, the destruction has lead to deficiency of insulin causes hyperglycaemia. A detailed method on selection of diabetic animals, investigation of blood glucose levels, body weight, biochemical and histopathological parameters is presented in this chapter. PMID:26939281

  11. Streptozotocin induced diabetes as a model of phrenic nerve neuropathy in rats.

    PubMed

    Rodrigues Filho, Omar Andrade; Fazan, Valéria Paula Sassoli

    2006-03-15

    Phrenic neuropathies are increasingly recognized in peripheral neuropathies but reports on experimental models of the phrenic nerves diabetic neuropathy are scanty. In the present study, we investigated the phrenic nerve neuropathy, due to experimental diabetes induced by streptozotocin (STZ) and the evolution of this neuropathy in diabetic rats treated with insulin. Proximal and distal segments of the left and right phrenic nerves were morphologically and morphometrically evaluated, from rats rendered diabetic for 12 weeks, by injection of STZ. Control rats received vehicle. Treated rats received a single subcutaneous injection of insulin on a daily basis. The nerves were prepared for light microcopy study by means of conventional techniques. Morphometry was carried out with the aid of computer software. The phrenic nerves of diabetic rats showed smaller myelinated axon diameters compared to controls. The g ratio was significantly smaller for myelinated fibers from diabetic rats compared to controls. Insulin treatment prevented these alterations. Histograms of size distribution for myelinated fibers and axons from control rats were bimodal. For diabetic animals, the myelinated fiber histogram was bimodal while the axon distribution turned to be unimodal. Insulin treatment also prevented these alterations. Our results confirm the phrenic nerve neuropathy in this experimental model of diabetes and suggest that conventional insulin treatment was able to prevent and/or correct the myelinated axon commitment by diabetes. PMID:16125783

  12. Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation

    PubMed Central

    Kesavan, Suresh K.; Bhat, Shweta; Golegaonkar, Sandeep B.; Jagadeeshaprasad, Mashanipalya G.; Deshmukh, Arati B.; Patil, Harshal S.; Bhosale, Santosh D.; Shaikh, Mahemud L.; Thulasiram, Hirekodathakallu V.; Boppana, Ramanamurthy; Kulkarni, Mahesh J.

    2013-01-01

    The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine. Hydralazine down regulated the expression of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and super oxide dismutase (SOD). These findings will provide a new dimension for developing intervention strategies for the treatment of glycation associated diseases such as diabetes complications, atherosclerosis, and aging. PMID:24126953

  13. Melatonin Reduces Cataract Formation and Aldose Reductase Activity in Lenses of Streptozotocin-induced Diabetic Rat

    PubMed Central

    Khorsand, Marjan; Akmali, Masoumeh; Sharzad, Sahab; Beheshtitabar, Mojtaba

    2016-01-01

    Background: The relationship between the high activity of aldose reductase (AR) and diabetic cataract formation has been previously investigated. The purpose of the present study was to determine the preventing effect of melatonin on streptozotocin (STZ)-induced diabetic cataract in rats. Methods: 34 adult healthy male Sprague-Dawely rats were divided into four groups. Diabetic control and diabetic+melatonin received a single dose of STZ (50 mg/kg, intraperitoneally), whereas the normal control and normal+melatonin received vehicle. The melatonin groups were gavaged with melatonin (5 mg/kg) daily for a period of 8 weeks, whereas the rats in the normal control and diabetic control groups received only the vehicle. The rats’ eyes were examined every week and cataract formation scores (0-4) were determined by slit-lamp microscope. At the end of the eighth week, the rats were sacrificed and markers of the polyol pathway and antioxidative (Glutathione, GSH) in their lens were determined. The levels of blood glucose, HbA1c and plasma malondialdhyde (MDA), as a marker of lipid peroxidation, were also measured. Results: Melatonin prevented STZ-induced hyperglycemia by decreased blood glucose and HbA1c levels. Slit lamp examination indicated that melatonin delayed cataract progression in diabetic rats. The results revealed that melatonin feeding increased the GSH levels, decreased the activities of AR and sorbitol dehydrogenase (SDH) and sorbitol formation in catractous lenses as well as plasma MDA content. Conclusion: In summary, for the first time we demonstrated that melatonin delayed the formation and progression of cataract in diabetic rat lenses. PMID:27365552

  14. Vasodilator effects of adenosine on retinal arterioles in streptozotocin-induced diabetic rats.

    PubMed

    Nakazawa, Taisuke; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2008-02-01

    Adenosine is a potent vasodilator of retinal blood vessels and is implicated to be a major regulator of retinal blood flow during metabolic stress, but little is known about the impact of diabetes on the role of adenosine in regulation of retinal hemodynamics. Therefore, we examined how diabetes affects adenosine-induced vasodilation of retinal arterioles. Male Wistar rats were treated with streptozotocin (80 mg/kg, intraperitoneally), and experiments were performed 6-8 weeks later. Rats were treated with tetrodotoxin (50 microg/kg, intravenously [i.v.]) to eliminate any nerve activity and prevent movement of the eye and infused with methoxamine continuously to maintain adequate systemic circulation. Fundus images were captured with a digital camera that was equipped with a special objective lens, and diameters of retinal arterioles were measured. Adenosine increased diameters of retinal arterioles and decreased systemic blood pressure. These responses were significantly attenuated by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg, i.v.) and the adenosine triphosphate-dependent K+ (K(ATP)) channel blocker glibenclamide (20 mg/kg, i.v.). The depressor responses to adenosine were reduced in diabetic rats, whereas diabetes did not alter vasodilation of retinal arterioles to adenosine. In contrast, both depressor response and vasodilation of retinal arteriole to acetylcholine were reduced in diabetic rats. The retinal vasodilator responses to adenosine and acetylcholine observed in diabetic rats were diminished by N(G)-nitro-L-arginine methyl ester. There were no differences in the responses to pinacidil, a K(ATP) channel opener, between the diabetic and nondiabetic rats. These results suggest that both the activation of nitric oxide synthase and opening of K(ATP) channels contribute to the vasodilator effects of adenosine in rats in vivo. However, diabetes has no significant impact on the vasodilation mediated by these mechanisms in the retinal circulation. PMID:18092153

  15. Icariside II, a novel phosphodiesterase-5 inhibitor, attenuates streptozotocin-induced cognitive deficits in rats.

    PubMed

    Yin, Caixia; Deng, Yuanyuan; Gao, Jianmei; Li, Xiaohui; Liu, Yuangui; Gong, Qihai

    2016-07-22

    Beta-amyloid (Aβ) deposition and neuroinflammation are involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive deficits. Phosphodiesterase-5 (PDE5) inhibitors have recently been studied as a potential target for cognitive enhancement by reducing inflammatory responses and Aβ levels. The present study was designed to investigate the effects of icariside II (ICS II), a novel PDE5 inhibitor derived from the traditional Chinese herb Epimedium brevicornum, on cognitive deficits, Aβ levels and neuroinflammation induced by intracerebroventricular-streptozotocin (ICV-STZ) in rats. The results demonstrated that ICV-STZ exhibited cognitive deficits and neuronal morphological damage, along with Aβ increase and neuroinflammation in the rat hippocampus. ICS II improved cognitive deficits, attenuated neuronal death, and decreased the levels of Aβ1-40, Aβ1-42 and PDE5 in the hippocampus of STZ rats. Furthermore, administration of ICS II at the dose of 10mg/kg for 21days significantly suppressed the expression of beta-amyloid precursor protein (APP), beta-secretase1 (BACE1) and increased the expressions of neprilysin (NEP) together with inhibited interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, cyclooxygenase-2 (COX-2) and transforming growth factor-β1 (TGF-β1) levels. In addition, ICS II exerted a beneficial effect on inhibition of IκB-α degradation and NF-κB activation induced by STZ. Taken together, the present study demonstrated that ICS II was a potential therapeutic agent for AD treatment. PMID:27109920

  16. Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes.

    PubMed

    Dogné, Sophie; Rath, Géraldine; Jouret, François; Caron, Nathalie; Dessy, Chantal; Flamion, Bruno

    2016-09-01

    Hyaluronic acid (HA) is a major component of the glycocalyx involved in the vascular wall and endothelial glomerular permeability barrier. Endocytosed hyaluronidase HYAL1 is known to degrade HA into small fragments in different cell types, including endothelial cells. In diabetes, the size and permeability of the glycocalyx are altered. In addition, patients with type 1 diabetes present increased plasma levels of both HA and HYAL1. To investigate the potential implication of HYAL1 in the development of diabetes-induced endothelium dysfunction, we measured endothelial markers, endothelium-dependent vasodilation, arteriolar glycocalyx size, and glomerular barrier properties in wild-type and HYAL1 knockout (KO) mice with or without streptozotocin (STZ)-induced diabetes. We observed that 4 weeks after STZ injections, the lack of HYAL1 1) prevents diabetes-induced increases in soluble P-selectin concentrations and limits the impact of the disease on endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation; 2) increases glycocalyx thickness and maintains glycocalyx structure and HA content during diabetes; and 3) prevents diabetes-induced glomerular barrier dysfunction assessed using the urinary albumin-to-creatinine ratio and urinary ratio of 70- to 40-kDa dextran. Our findings suggest that HYAL1 contributes to endothelial and glycocalyx dysfunction induced by diabetes. HYAL1 inhibitors could be explored as a new therapeutic approach to prevent vascular complications in diabetes. PMID:27246914

  17. Attenuation of erythrocyte membrane oxidative stress by Sesbania grandiflora in streptozotocin-induced diabetic rats.

    PubMed

    Sureka, Chandrabose; Ramesh, Thiyagarajan; Begum, Vavamohaideen Hazeena

    2015-08-01

    The aim of the present study was to investigate the protective effects of Sesbania grandiflora flower (SGF) extract on erythrocyte membrane in Streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 190-220 g, were made diabetic by an intraperitonial administration of STZ (45 mg/kg). Normal and diabetic rats were treated with SGF, and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In this study plasma insulin and haemoglobin levels were decreased and blood glucose, glycosylated haemoglobin, protein oxidation, lipid peroxidation markers, and osmotic fragility levels were increased in diabetic rats. Moreover, erythrocytes antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxide, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities and non-enzymatic antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), and oxidized glutathione (GSSG) levels were altered. Similarly, the activities of total ATPases, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase were also decreased in the erythrocytes of diabetic rats. Administration of SGF to STZ-induced diabetic rats reduced blood glucose and glycosylated haemoglobin levels with increased levels of insulin and haemoglobin. Moreover, SGF reversed the protein and lipid peroxidation markers, osmotic fragility, membrane-bound ATPases activities, and antioxidant status in STZ-induced diabetic rats. These results suggest that SGF could provide a protective effect on diabetes by decreasing oxidative stress-associated diabetic complications. PMID:26176361

  18. Protective Action of Carica papaya on β-Cells in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Miranda-Osorio, Pedro H.; Castell-Rodríguez, Andrés E.; Vargas-Mancilla, Juan; Tovilla-Zárate, Carlos A.; Ble-Castillo, Jorge L.; Aguilar-Domínguez, Dora E.; Juárez-Rojop, Isela E.; Díaz-Zagoya, Juan C.

    2016-01-01

    The aim of the present study was to investigate the effect of C. papaya L. leaf extract (CPLE) on pancreatic islets in streptozotocin (STZ)-induced diabetic rats, as well as on cultured normal pancreatic cells with STZ in the medium. CPLE (3–125 mg/Kg) was administered orally for 20 days, while a group of diabetic rats received 5 IU/Kg/day of insulin. At the end of the treatment the rats were sacrificed. Blood was obtained to assess glucose and insulin levels. The pancreas was dissected to evaluate β cells by immunohistochemistry. In addition, normal pancreatic cells were cultured in a medium that included CPLE (3–12 mg). One half of the cultured cells received simultaneously CPLE and STZ (6 mg), while the other half received CPLE and five days later the STZ. After three days of incubation, insulin was assayed in the incubation medium. The CPLE administered to diabetic rats improved the fasting glycemia and preserved the number and structure of pancreatic islets. However, when CPLE was added to pancreatic cells in culture along with STZ, the insulin concentration was higher in comparison with the cells that only received STZ. In conclusion, the CPLE preserves the integrity of pancreatic islets, improves the basal insulin secretion and protects cultured cells from the adverse effects of STZ. PMID:27128930

  19. Hypoglycaemic effect of Berberis vulgaris L. in normal and streptozotocin-induced diabetic rats

    PubMed Central

    Meliani, Nawel; Dib, Mohamed El Amine; Allali, Hocine; Tabti, Boufeldja

    2011-01-01

    Objective To achieve a primary pharmacological screening contained in the aqueous extract of Berberis vulgaris (B. vulgaris) and to examine the hypoglycaemic effect and biochemical parameters of aqueous and saponins extract on groups of rats rendered diabetic by injection of streptozotocin. Methods The phytochemical tests to detect the presence of different compounds were based on the visual observation of color change or formation of precipitate after the addition of specific reagents. Diabetes was induced in rats by intraperitoneal (i.p.) injection of streptozotocin (STZ) at a dose of 65 mg/kg bw. The fasting blood glucose levels were estimated by glucose oxidase-peroxidase reactive strips (Dextrostix, Bayer Diagnostics). Blood samples were taken by cutting the tip of the tail. Serum cholesterol and serum triglycerides were estimated by enzymatic DHBS colorimetric method. Results Administration of 62.5 and 25.0 mg/kg of saponins and aqueous extract respectively in normal rats group shows a significant hypoglycemic activity (32.33% and 40.17% respectively) during the first week. However, diabetic group treated with saponin extract produced a maximum fall of 73.1% and 76.03% at day 1 and day 21 compared to the diabetics control. Also, blood glucose levels of the diabetic rats treated with aqueous extract showed decrease of 78.79% on the first day and the effect remains roughly constant during 3 week. Both extracts also declined significantly biochemical parameters (20.77%-49.00%). The control in the loss of body weight was observed in treated diabetic rats as compared to diabetic controls. Conclusions These results demonstrated significant antidiabetic effects and showed that serum cholesterol and serum triglycerides levels were decreased, significantly, consequently this plant might be of value in diabetes treatment. PMID:23569815

  20. Protective Action of Carica papaya on β-Cells in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Miranda-Osorio, Pedro H; Castell-Rodríguez, Andrés E; Vargas-Mancilla, Juan; Tovilla-Zárate, Carlos A; Ble-Castillo, Jorge L; Aguilar-Domínguez, Dora E; Juárez-Rojop, Isela E; Díaz-Zagoya, Juan C

    2016-01-01

    The aim of the present study was to investigate the effect of C. papaya L. leaf extract (CPLE) on pancreatic islets in streptozotocin (STZ)-induced diabetic rats, as well as on cultured normal pancreatic cells with STZ in the medium. CPLE (3-125 mg/Kg) was administered orally for 20 days, while a group of diabetic rats received 5 IU/Kg/day of insulin. At the end of the treatment the rats were sacrificed. Blood was obtained to assess glucose and insulin levels. The pancreas was dissected to evaluate β cells by immunohistochemistry. In addition, normal pancreatic cells were cultured in a medium that included CPLE (3-12 mg). One half of the cultured cells received simultaneously CPLE and STZ (6 mg), while the other half received CPLE and five days later the STZ. After three days of incubation, insulin was assayed in the incubation medium. The CPLE administered to diabetic rats improved the fasting glycemia and preserved the number and structure of pancreatic islets. However, when CPLE was added to pancreatic cells in culture along with STZ, the insulin concentration was higher in comparison with the cells that only received STZ. In conclusion, the CPLE preserves the integrity of pancreatic islets, improves the basal insulin secretion and protects cultured cells from the adverse effects of STZ. PMID:27128930

  1. Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Aseer, Kanikkai Raja; Kim, Sang Woo; Choi, Myung-Sook; Yun, Jong Won

    2015-01-01

    Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates several cellular events, including inflammation and tissue remodelling. In this study, we investigated the tissue-specific expression of SPARC in streptozotocin (STZ)-induced diabetes, and found that SPARC was significantly up-regulated in the liver while down-regulated in the pancreas of STZ-induced diabetic rats. Chronic inflammation occurred in the diabetic pancreas accompanied by up-regulation of CCAAT/enhancer-binding protein beta (C/EBPβ) and its targets (TNFα, Il6, CRP, and Fn1) as well as myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2). Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis. PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver. On the contrary, CD95-dependent apoptosis was not observed in the diabetic pancreas due to up-regulation of PARP-1 and ATP depletion, resulting in necrosis. The cytoprotective machinery was damaged by pancreatic inflammation, whereas adequate antioxidant capacity indicates low oxidative stress in the diabetic liver. High and low cellular insulin content was found in the diabetic liver and pancreas, respectively. Furthermore, we identified six novel interacting partner proteins of SPARC by co-immunoprecipitation in the diabetic liver and pancreas, and their interactions with SPARC were predicted by bioinformatics tools. Taken together, opposite expression of SPARC in the diabetic liver and pancreas may be related to inflammation and immune cell infiltration, degrees of apoptosis and fibrosis, cytoprotective machinery, and cellular insulin levels. PMID:26110898

  2. Antihyperlipidemic Effect of a Polyherbal Mixture in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Shafiee-Nick, Reza; Rakhshandeh, Hassan; Borji, Abasalt

    2013-01-01

    The effects of a polyherbal mixture containing Allium sativum, Cinnamomum zeylanicum, Citrullus colocynthis, Juglans regia, Nigella sativa, Olea europaea, Punica granatum, Salvia officinalis, Teucrium polium, Trigonella foenum, Urtica dioica, and Vaccinium arctostaphylos were tested on biochemical parameters in diabetic rats. The animals were randomized into three groups: (1) normal control, (2) diabetic control, and (3) diabetic rats which received diet containing 15% (w/w) of this mixture for 4 weeks. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg). At the end of experiment, the mixture had no significant effect on serum hepatic enzymes, aspartate aminotransferase, and alanine aminotransferase activities. However, the level of fasting blood glucose, water intake, and urine output in treated group was lower than that in diabetic control rats (P < 0.01). Also, the levels of triglyceride and total cholesterol in polyherbal mixture treated rats were significantly lower than those in diabetic control group (P < 0.05). Our results demonstrated that this polyherbal mixture has beneficial effects on blood glucose and lipid profile and it has the potential to be used as a dietary supplement for the management of diabetes. PMID:24383002

  3. Improved peripheral nerve regeneration in streptozotocin-induced diabetic rats by oral lumbrokinase.

    PubMed

    Lee, Han-Chung; Hsu, Yuan-Man; Tsai, Chin-Chuan; Ke, Cherng-Jyh; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2015-01-01

    We assessed the therapeutic effects of lumbrokinase, a group of enzymes extracted from the earthworm, on peripheral-nerve regeneration using well-defined sciatic nerve lesion paradigms in diabetic rats induced by the injection of streptozotocin (STZ). We found that lumbrokinase therapy could improve the rats' circulatory blood flow and promote the regeneration of axons in a silicone rubber conduit after nerve transection. Lumbrokinase treatment could also improve the neuromuscular functions with better nerve conductive performances. Immunohistochemical staining showed that lumbrokinase could dramatically promote calcitonin gene-related peptide (CGRP) expression in the lamina I-II regions in the dorsal horn ipsilateral to the injury and cause a marked increase in the number of macrophages recruited within the distal nerve stumps. In addition, the lumbrokinase could stimulate the secretion of interleukin-1 (IL-1), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) in dissected diabetic sciatic nerve segments. In conclusion, the administration of lumbrokinase after nerve repair surgery in diabetic rats was found to have remarkable effects on promoting peripheral nerve regeneration and functional recovery. PMID:25787300

  4. Short- and Longterm Glycemic Control of Streptozotocin-Induced Diabetic Rats Using Different Insulin Preparations.

    PubMed

    Luippold, Gerd; Bedenik, Jessica; Voigt, Anke; Grempler, Rolf

    2016-01-01

    The chemical induction of diabetes with STZ has gained popularity because of the relative ease of rendering normal animals diabetic. Insulin substitution is required in STZ-rats in long-term studies to avoid ketoacidosis and consequently loss of animals. Aim of the present studies was to test different insulin preparations and different ways of administration in their ability to reduce blood glucose in STZ-induced diabetic rats. Single dosing of the long-acting insulin analogue glargine was able to dose-dependently reduce blood glucose over 4 h towards normoglycemia in STZ-treated rats. However, this effect was not sustained until 8 h post injection. A more sustained glucose-lowering effect was achieved using insulin-releasing implants. In STZ-rats, 1 insulin implant moderately lowered blood glucose levels 10 days after implantation, while 2 implants induced normoglycemia over the whole day. According to the glucose-lowering effect 1 as well as 2 insulin implants significantly reduced HbA1c measured after 26 days of implantation. In line with the improved glucose homeostasis due to the implants, urinary glucose excretion was also blunted in STZ-treated rats with 2 implants. Since diabetic nephropathy is one of the complications of longterm diabetes, renal function was characterized in the STZ-rat model. Increases in creatinine clearance and urinary albumin excretion resemble early signs of diabetic nephropathy. These functional abnormalities of the kidney could clearly be corrected with insulin-releasing implants 27 days after implantation. The data show that diabetic STZ-rats respond to exogenous insulin with regard to glucose levels as well as kidney parameters and a suitable dose of insulin implants for glucose control was established. This animal model together with the insulin dosing regimen is suitable to address diabetes-induced early diabetic nephropathy and also to study combination therapies with insulin for the treatment of type 1 diabetes. PMID:27253523

  5. Antihyperglycemic Effect of Methanol Extract of Syzygium polyanthum (Wight.) Leaf in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Widyawati, Tri; Yusoff, Nor Adlin; Asmawi, Mohd Zaini; Ahmad, Mariam

    2015-09-01

    Syzygium polyanthum (S. polyanthum), a plant belonging to Myrtaceae, is widely used in Indonesian and Malaysian cuisines. Diabetic patients in Indonesia also commonly use it as a traditional medicine. Hence, this study was conducted to investigate the antihyperglycemic effect of the methanol extract (ME) of S. polyanthum leaf and its possible mechanisms of action. To test for hypoglycemic activity, ME was administered orally to normal male Sprague Dawley rats after a 12-h fast. To further test for antihyperglycemic activity, the same treatment was administered to glucose-loaded (intraperitoneal glucose tolerance test, IPGTT) and streptozotocin (STZ)-induced diabetic rats, respectively. Hypoglycemic test in normal rats did not show significant reduction in blood glucose levels (BGLs) by the extract. Furthermore, IPGTT conducted on glucose-loaded normal rats also did not show significant reduction of BGLs. However, repeated administration of metformin and three doses of ME (250, 500 and 1000 mg/kg) for six days caused significant reduction of fasting BGLs in STZ-induced diabetic rats. The possible mechanisms of action of S. polyanthum antihyperglycemic activity were assessed by measurement of intestinal glucose absorption and glucose uptake by isolated rat abdominal muscle. It was found that the extract not only inhibited glucose absorption from the intestine but also significantly increased glucose uptake in muscle tissue. A preliminary phytochemical qualitative analysis of ME indicated the presence of tannins, glycosides, flavonoids, alkaloids and saponins. Additionally, Gas Chromatography-Mass Spectrometry (GC-MS) analysis detected squalene. In conclusion, S. polyanthum methanol leaf extract exerts its antihyperglycemic effect possibly by inhibiting glucose absorption from the intestine and promoting glucose uptake by the muscles. PMID:26389944

  6. Aquaporin 4 knockdown exacerbates streptozotocin-induced diabetic retinopathy through aggravating inflammatory response.

    PubMed

    Cui, Bei; Sun, Jin-Hua; Xiang, Fen-Fen; Liu, Lin; Li, Wen-Jie

    2012-05-01

    Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Diabetes is known to alter the amount of retinal expression of the water-selective channels aquaporin 4 (AQP4). However, the function and impact of AQP4 in diabetic retinopathy is not well understood. In the present work, diabetes was induced by intraperitoneal injection of streptozotocin in Sprague-Dawley rats. Two weeks later, AQP4 shRNA (r) lentiviral particles or negative lentiviral particles were delivered by intravitreal injection to the eyes. Gene delivery was confirmed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting analysis. Eight weeks later, BRB breakdown was measured using Evans blue dye. Images of retinal sections were obtained and the thicknesses of the retinas were determined. Retinal leukostasis measurement was performed using acridine orange leukocyte fluorography. The mRNA levels of IL-1β, IL-6, intercellular adhesion molecule 1 (ICAM-1), glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined using qRT-PCR method. AQP4 shRNA (r) lentiviral particles or negative lentiviral particles were transfected into rMC-1 cells to investigate its effect on inflammation induced by high glucose. Incubation with IL-1β or IL-6 was performed to test their effect on AQP4 expression in rMC-1 cells. In the current work, it was found that AQP4 expression was enhanced in the retina of diabetic rats. AQP4 knockdown led to exacerbation of retinopathy including enhancing retinal vascular permeability, retinal thickness, pro-inflammatory factors expression, and VEGF and GFAP expression in retinas of diabetic rats. AQP4 knockdown enhanced the expression of pro-inflammatory cytokines induced by high glucose in rMC-1 cells. In addition, AQP4 knockdown enhanced the release of IL-6 and VEGF from rMC-1 cells into the medium. Moreover, it was found that incubation with IL-1β or IL-6 suppressed AQP4 expression in rMC-1 cells. These results suggested that streptozotocin injection induced diabetes resulted in compensatory increases of AQP4 expression, and downregulation of AQP4 exacerbated diabetic retinopathy through aggravating inflammatory response, at last in part. Therefore, regulation of retinal function by AQP4 may attenuate diabetic retinopathy, offering a promising therapeutic strategy for diabetic retinopathy. PMID:22449442

  7. Dendrobium officinale Prevents Early Complications in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Hou, Shao-Zhen; Liang, Chu-Yan; Liu, Hua-Zhen; Zhu, Dong-Mei; Wu, Ya-Yun; Liang, Jian; Zhao, Ya; Guo, Jian-Ru; Huang, Song; Lai, Xiao-Ping

    2016-01-01

    Background. Dendrobium officinale (DO) Kimura et Migo is a precious Chinese herb that is considered beneficial for health due to its antioxidant and antidiabetes properties, and so on. In this research, we try to determine the preventive effect of DO on the early complications of STZ-induced diabetic rats. Methods. Type 1 diabetic rats were produced with a single intraperitoneal injection of STZ (50 mg/kg). DO (1 g/kg/day) was then orally administered for 5 weeks. Blood glucose, TC, TG, BUN, CREA, and GSH-PX levels were determined, and electroretinographic activity and hypoalgesia were investigated. Pathological sections of the eyes, hearts, aortas, kidneys, and livers were analyzed. Results. Treatment with DO significantly attenuated the serum levels of TC, TG, BUN, and CREA, markedly increased the amplitudes of ERG a- and b-waves and Ops, and reduced the hypoalgesia and histopathological changes of vital organs induced by hyperglycemia. The protective effect of DO in diabetic rats may be associated with its antioxidant activity, as evidenced by the marked increase in the serum level of glutathione peroxidase. However, DO had no significant effect on blood glucose levels and bodyweight of diabetic rats. Conclusions. DO supplementation is an effective treatment to prevent STZ-induced diabetic complications. PMID:27034693

  8. Dietary supplementation with fermented legumes modulate hyperglycemia and acetylcholinesterase activities in Streptozotocin-induced diabetes.

    PubMed

    Ademiluyi, Adedayo O; Oboh, Ganiyu; Boligon, Aline A; Athayde, Margareth L

    2015-12-01

    The study investigated the hypoglycemic and anticholinesterase activities of some fermented legumes (bambara groundnut and locust bean) in Streptozotocin (STZ)-induced diabetic rats. The rats were made diabetic by intraperitoneal administration of STZ (35mg/kg b.w.) and were fed diets containing fermented legumes (10% inclusion) for 14 days. The effect of the diets on blood glucose, pancreatic glutathione peroxidase (GPx) activity, reduced glutathione (GSH) and malondialdehyde (MDA) contents, α-amylase, intestinal α-glucosidase and acetylcholinesterase activities were studied. Significant (P<0.05) increase in blood glucose, pancreatic MDA, α-amylase, intestinal α-glucosidase and acetylcholinesterase activities with concomitant decrease in pancreatic GPx and GSH contents were observed in diabetic rats. However, this trend was reversed in rats fed fermented legumes supplemented diets for 14 days. The HPLC-DAD finger printing revealed the presence of gallic acid, catechin, caffeic acid, epicatechin, rutin, isoquercitrin, quercitrin, quercetin and kaempferol as the dominant phenolic compounds of the fermented legumes. However, possible contributing role of some bioactive peptides could not be ruled out. Hence, the hypoglycemic and antiacetylcholinesterase activities of the fermented legume condiments could be attributed to their constituent phytochemicals. PMID:26349771

  9. Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats.

    PubMed

    Jang, Y Y; Song, J H; Shin, Y K; Han, E S; Lee, C S

    2000-10-01

    Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. Several antioxidants have been described as beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1, 10-dimethoxyaporphine) is a major alkaloid found in the leaves and bark of boldo (Peumus boldus Molina), and has been shown to possess antioxidant activity and anti-inflammatory effects. From this point of view, the possible anti-diabetic effect of boldine and its mechanism were evaluated. The experiments were performed on male rats divided into four groups: control, boldine (100 mg kg(-1), daily in drinking water), diabetic [single dose of 80 mg kg(-1)of streptozotocin (STZ), i.p.] and diabetic simultaneously fed with boldine for 8 weeks. Diabetic status was evaluated periodically with changes of plasma glucose levels and body weight in rats. The effect of boldine on the STZ-induced diabetic rats was examined with the formation of malondialdehydes and carbonyls and the activities of endogenous antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in mitochondria of the pancreas, kidney and liver. The scavenging action of boldine on oxygen free radicals and the effect on mitochondrial free-radical production were also investigated. The treatment of boldine attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. The levels of malondialdehyde (MDA) and carbonyls in liver, kidney and pancreas mitochondria were significantly increased in STZ-treated rats and decreased after boldine administration. The activities of mitochondrial manganese superoxide dismutase (MnSOD) in the liver, pancreas and kidney were significantly elevated in STZ-treated rats. Boldine administration decreased STZ-induced elevation of MnSOD activity in kidney and pancreas mitochondria, but not in liver mitochondria. In the STZ-treated group, glutathione peroxidase activities decreased in liver mitochondria, and were elevated in pancreas and kidney mitochondria. The boldine treatment restored the altered enzyme activities in the liver and pancreas, but not the kidney. Boldine attenuated both STZ- and iron plus ascorbate-induced MDA and carbonyl formation and thiol oxidation in the pancreas homogenates. Boldine decomposed superoxide anions, hydrogen peroxides and hydroxyl radicals in a dose-dependent manner. The alkaloid significantly attenuated the production of superoxide anions, hydrogen peroxide and nitric oxide caused by liver mitochondria. The results indicate that boldine may exert an inhibitory effect on STZ-induced oxidative tissue damage and altered antioxidant enzyme activity by the decomposition of reactive oxygen species and inhibition of nitric oxide production and by the reduction of the peroxidation-induced product formation. Boldine may attenuate the development of STZ-induced diabetes in rats and interfere with the role of oxidative stress, one of the pathogeneses of diabetes mellitus. PMID:10987997

  10. Antidiabetic Activity of Aqueous Leaves Extract of Sesbania sesban (L) Merr. in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Pandhare, Ramdas B.; Sangameswaran, B.; Mohite, Popat B.; Khanage, Shantaram G.

    2011-01-01

    The aqueous leaves extract of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its antidiabetic potential on normal and streptozotocin (STZ)-induced diabetic rats. In the chronic model, the aqueous extract was administered to normal and STZ- induced diabetic rats at the doses of 250 and 500 mg/kg body weight (b.w.) p.o. per day for 30 days. The fasting Blood Glucose Levels (BGL), serum insulin level and biochemical data such as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were evaluated and all were compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data indicated significant increase in the body weight, liver glycogen, serum insulin and HDL levels and decrease in blood glucose, glycosylated hemoglobin, total cholesterol and serum triglycerides when compared with glibenclamide. Thus the aqueous leaves extract of Sesbania sesban had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced diabetic rats. PMID:23407749

  11. Beneficial Effects of Sarpogrelate and Rosuvastatin in High Fat Diet/Streptozotocin-Induced Nephropathy in Mice

    PubMed Central

    Ku, Sae-Kwang; Park, Jeong-hyeon; Oh, Euichaul; Kwak, Mi-Kyoung

    2016-01-01

    Chronic kidney disease (CKD) is a major complication of metabolic disorders such as diabetes mellitus, obesity, and hypertension. Comorbidity of these diseases is the factor exacerbating CKD progression. Statins are commonly used in patients with metabolic disorders to decrease the risk of cardiovascular complications. Sarpogrelate, a selective antagonist of 5-hydroxytryptamine (5-HT) 2A receptor, inhibits platelet aggregation and is used to improve peripheral circulation in diabetic patients. Here, we investigated the effects of sarpogrelate and rosuvastatin on CKD in mice that were subjected to a high fat diet (HFD) for 22 weeks and a single low dose of streptozotocin (STZ, 40 mg/kg). When mice were administrated sarpogrelate (50 mg/kg, p.o.) for 13 weeks, albuminuria and urinary cystatin C excretion were normalized and histopathological changes such as glomerular mesangial expansion, tubular damage, and accumulations in lipid droplets and collagen were significantly improved. Sarpogrelate treatment repressed the HFD/STZ-induced CD31 and vascular endothelial growth factor receptor-2 expressions, indicating the attenuation of glomerular endothelial proliferation. Additionally, sarpogrelate inhibited interstitial fibrosis by suppressing the increases in transforming growth factor-β1 (TGF-β1) and plasminogen activator inhibitor-1 (PAI-1). All of these functional and histological improvements were also seen in rosuvastatin (20 mg/kg) group and, notably, the combinatorial treatment with sarpogrelate and rosuvastatin showed additive beneficial effects on histopathological changes by HFD/STZ. Moreover, sarpogrelate reduced circulating levels of PAI-1 that were elevated in the HFD/STZ group. As supportive in vitro evidence, sarpogrelate incubation blocked TGF-β1/5-HT-inducible PAI-1 expression in murine glomerular mesangial cells. Taken together, sarpogrelate and rosuvastatin may be advantageous to control the progression of CKD in patients with comorbid metabolic disorders, and particularly, the use of sarpogrelate as adjunctive therapy with statins may provide additional benefits on CKD. PMID:27097221

  12. Protective Effects of Red Guava on Inflammation and Oxidative Stress in Streptozotocin-Induced Diabetic Mice.

    PubMed

    Li, Pei-Ying; Hsu, Cheng-Chin; Yin, Mei-Chin; Kuo, Yueh-Hsiung; Tang, Feng-Yao; Chao, Che-Yi

    2015-01-01

    Diabetes is an important chronic disease and the 4th leading cause of death in Taiwan. Hyperglycemia-induced oxidative and inflammatory damage are the main causes of chronic complications in diabetic patients. The red guava (red-fleshed guava cultivar of Psidium guajava L.) is a tropical fruit belonging to the Myrtaceae family and an important commercial crop in Taiwan. In this study, the protective effects of a diet containing red guava on inflammation and oxidative stress in streptozotocin (STZ)-induced diabetic mice were examined. The experimental group was divided into seven subgroups: normal (N), diabetes mellitus (DM), diabetes + red guava 1% (L), 2% (M), and 5% (H), diabetes + 5% red guava + anti-diabetic rosiglitazone (HR), and diabetes + anti-diabetic rosiglitazone (R). The mice were fed for 8 weeks and sacrificed by decapitation. Compared with the DM group, the experimental groups with diets containing red guava as well as rosiglitazone all showed significant improvements in blood glucose control, insulin resistance, creatinine, blood urea nitrogen, triglycerides, non-esterified fatty acids, cholesterol, c-reactive protein, TNF-α, and IL-10. Furthermore, the expression of inflammatory proteins, such as iNOS and NF-κB, was suppressed via activated PPARγ, and the expression levels of GPx3 and ACO increased. In summary, red guava can significantly suppress inflammatory and oxidative damage caused by diabetes and alleviate diabetic symptoms; thus, it exerts protective effects and has potential applications for the development of a dietary supplement. PMID:26703532

  13. Nigella sativa seed decreases endothelial dysfunction in streptozotocin-induced diabetic rat aorta

    PubMed Central

    Abbasnezhad, Abbasali; Niazmand, Saeed; Mahmoudabady, Maryam; Soukhtanloo, Mohammad; Rezaee, Seyed Abdolrahim; Mousavi, Seyed Mojtaba

    2016-01-01

    Objective: Diabetes is an important risk factor for cardiovascular events. The great percent of morbidity in patients with diabetes is due to endothelial dysfunction. The present study investigated the effects of hydroalcholic extract of Nigella sativa (N. sativa) on contractile and dilatation response of isolated aorta in streptozotocin (STZ)-induced diabetic rat. Materials and Methods: Rats were divided into six experimental groups (control, untreated STZ-diabetic, and N. sativa hydroalcholic extract or metformin-treated diabetic rats). Treated rats received N. sativa extract (100, 200, and 400 mg/kg) or metformin (300 mg/kg) by gavage, daily for 6 weeks. Isolated rat thoracic rings were mounted in an organ bath system then contractile and dilatation responses induced by phenylephrine (PE), acetylcholine (ACh), potassium chloride (KCl), and sodium nitroprusside (SNP) were evaluated in different situations. Results: The lower concentrations of N. sativa seed extract (DE 100 and DE 200) and metformin significantly reduced the contractile responses to higher concentrations of PE (10-6 - 10-5 M) compared to diabetic group (p<0.05 to p<0.01). The relaxation response to Ach 10-8 M, was increased in DE 200 and metformin groups compared to diabetic group (p<0.05). The relaxation responses to Ach 10-7 - 10-5 M were significantly higher in all treated groups compared to diabetic group (p<0.05 to p<0.001). Conclusion: Chronic administration of N. sativa seed extract has a significant hypoglycemic effect and improves aortic reactivity to vasoconstrictor and vasodilator agents in STZ-induced diabetic rats. PMID:27247923

  14. The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats.

    PubMed

    Kong, Wei-Yuan; Tong, Li-Quan; Zhang, Hai-Jun; Cao, Yong-Gang; Wang, Gong-Chen; Zhu, Jin-Zhi; Zhang, Feng; Sun, Xue-Ying; Zhang, Tie-Hui; Zhang, Lin-Lin

    2016-01-01

    Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg-1 ) in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg-1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg-1 ), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men. PMID:26387585

  15. Regional enzymatic analysis of UV-B and streptozotocin induced diabetic cataract lens.

    PubMed

    Kojima, M

    1990-01-01

    As the UV-B cataract and early stages of diabetic cataract in rats only touches the epithelium and anterior superficial cortex, a whole lens analysis is not meaningful, but a regional analysis with the freeze-sectioning device has to be performed. Scheimpflug photography with microdensitometric image analysis enables the scientist to discern in vivo single layers along the optical axis of the lens. UV-B cataracts (0.2 J/cm2, every 2nd day) and diabetic cataracts (Streptozotocin (STZ), 70 mg/kg BW) were induced in Brown-Norway rats. The stages of lens opacification were documented by Scheimpflug photography. 8 weeks after start of UV-B treatment and at several dates before onset of visible diabetic cataractous changes, the animals were sacrificed. The lenses were divided reproducibly into 4 or 7 parts such as an equatorial ring and several layers of the central cylinder from anterior to posterior part. The enzyme activity spectrum shows highly region related pattern that would not have been found in a whole lens analysis. Aldose reductase was activated before appearance of visible cataractous changes due to diabetes compared to normal lenses. In contrast Fructose-1,6-biphosphate-aldolase activity was lower before onset of visible changes than in normal lenses, but only within the 1st section where later visible cataractous changes of UV-B cataract could be detected. PMID:1966039

  16. Berberine Nanosuspension Enhances Hypoglycemic Efficacy on Streptozotocin Induced Diabetic C57BL/6 Mice

    PubMed Central

    Wang, Zhiping; Wu, Junbiao; Zhou, Qun; Wang, Yifei; Chen, Tongsheng

    2015-01-01

    Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg) treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC) and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg). These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes. PMID:25866534

  17. Hypoglycemic activity of Ailanthus excelsa leaves in normal and streptozotocin-induced diabetic rats.

    PubMed

    Cabrera, W; Genta, S; Said, A; Farag, A; Rashed, K; Sánchez, S

    2008-03-01

    The hypoglycemic activity of a 70% methanol extract from the leaves of Ailanthus excelsa Roxb. (Simaroubaceae) was studied in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Oral administration of the extract at doses of 14, 70 and 350 mg/kg body weight caused no significant changes in fasting blood glucose levels of normal rats. In an oral glucose tolerance test, the extract produced a significant decrease in glycemia 90 min after the glucose pulse. Daily administration of A. excelsa extract for 60 days produced a significant hypoglycemic effect in diabetic animals. In addition, this treatment improved the altered renal function observed in diabetic control rats. This study suggests that Ailanthus leaf extract could be potentially useful for post-prandial hyperglycemia treatment. PMID:18058975

  18. Urtica dioica modulates hippocampal insulin signaling and recognition memory deficit in streptozotocin induced diabetic mice.

    PubMed

    Patel, Sita Sharan; Gupta, Sahil; Udayabanu, Malairaman

    2016-06-01

    Diabetes mellitus has been associated with functional abnormalities in the hippocampus and performance of cognitive function. Urtica dioica (UD) has been used in the treatment of diabetes. In our previous report we observed that UD extract attenuate diabetes mediated associative and spatial memory dysfunction. The present study aimed to evaluate the effect of UD extract on mouse model of diabetes-induced recognition memory deficit and explore the possible mechanism behind it. Streptozotocin (STZ) (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes followed by UD extract (50 mg/kg, oral) or rosiglitazone (ROSI) (5 mg/kg, oral) administration for 8 weeks. STZ induced diabetic mice showed significant decrease in hippocampal insulin signaling and translocation of glucose transporter type 4 (GLUT4) to neuronal membrane resulting in cognitive dysfunction and hypolocomotion. UD treatment effectively improved hippocampal insulin signaling, glucose tolerance and recognition memory performance in diabetic mice, which was comparable to ROSI. Further, diabetes mediated oxidative stress and inflammation was reversed by chronic UD or ROSI administration. UD leaves extract acts via insulin signaling pathway and might prove to be effective for the diabetes mediated central nervous system complications. PMID:26767366

  19. Serum concentrations and hypoglycemic effect of gliclazide: crosspovidone solid dispersion on streptozotocin induced diabetic rats.

    PubMed

    Adibkia, K; Babaei, H; Asnaashari, S; Andalib, S; Khorrami, A; Ghavimi, H; Jadidinia, V; Hajiloo, H; Barzegar-Jalali, M

    2013-02-01

    Gliclazide is practically insoluble in water and its GI absorption is limited by its dissolution rate. Our previously published works indicated that preparing gliclazide-crosspovidone solid dispersion in the drug/ carrier ratio of 1:1 using cogrinding technique is able to enhance drug dissolution rate. The coground of gliclazide-crosspovidone was administrated to the rats and the hypoglycemic effects of pure drug, a physical mixture and the coground were considered in 3 groups of rats weighing 200-250 g (n=6). The rats were made diabetic by single intravenous administration of streptozotocin (60 mg/kg). Each of the rats received a single dose of gliclazide (equivalent to 40 mg/kg) as pure drug, physical mixture and coground in an aqueous suspension. Glucose level was assessed via glucometer after collecting the blood samples from tail vein. Gliclazide concentration in plasma was assessed applying high pressure liquid chromatography. According to 1-way ANOVA, Student-Newman-Keuls test, the coground revealed enhanced hypoglycemic effects as well as higher serum gliclazide concentration relative to pure drug and its corresponding physical mixture in the all sampling times. The area under serum glucose concentration curve vs. time for the pure gliclazide, physical mixture and coground formulations were 3 090.5±79, 3 018.8±96 and 2 374.0±73 mg.h/dl, respectively. Correspondingly, their area under serum gliclazide concentration curve vs. time were 1 171.8±156.8, 1 379.5±96.2 and 4 827.7±637.5 μg.h/ml. It follows that; formulation of gliclazide-crosspovidone coground is able to improve oral absorption of the drug. PMID:23427050

  20. Antihyperglycemic activity of Catharanthus roseus leaf powder in streptozotocin-induced diabetic rats

    PubMed Central

    Rasineni, Karuna; Bellamkonda, Ramesh; Singareddy, Sreenivasa Reddy; Desireddy, Saralakumari

    2010-01-01

    Catharanthus roseus Linn (Apocynaceae), is a traditional medicinal plant used to control diabetes, in various regions of the world. In this study we evaluated the possible antidiabetic and hypolipidemic effect of C. roseus (Catharanthus roseus) leaf powder in diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 55 mg/kg body wt) to male Wistar rats. The animals were divided into four groups: Control, control-treated, diabetic, and diabetic-treated group. Diabetic-treated and control-treated rats were treated with C. roseus leaf powder suspension in 2 ml distilled water, orally (100 mg/kg body weight/day/60 days). In diabetic rats (D-group) the plasma glucose was increased and the plasma insulin was decreased gradually. In the diabetic-treated group lowering of plasma glucose and an increase in plasma insulin were observed after 15 days and by the end of the experimental period the plasma glucose had almost reached the normal level, but insulin had not. The significant enhancement in plasma total cholesterol, triglycerides, LDL and VLDL-cholesterol, and the atherogenic index of diabetic rats were normalized in diabetic-treated rats. Decreased hepatic and muscle glycogen content and alterations in the activities of enzymes of glucose metabolism (glycogen phosphorylase, hexokinase, phosphofructokinase, pyruvate kinase, and glucose-6-phosphate dehydrogenase), as observed in the diabetic control rats, were prevented with C. roseus administration. Our results demonstrated that C. roseus with its antidiabetic and hypolipidemic properties could be a potential herbal medicine in treating diabetes. PMID:21808566

  1. Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Akkoç, Tolga; Eraslan, Muhsin; Şahin, Özlem; Özkara, Selvinaz; Vardar Aker, Fugen; Subaşı, Cansu; Karaöz, Erdal; Akkoç, Tunç

    2016-01-01

    Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ) in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP) labelled bone marrow derived stem cells (BMSC) and left eyes with balanced salt solution (Sham). Animals were grouped as Baseline (n = 51), Diabetic (n = 45), Diabetic+BMSC (n = 45 eyes), Diabetic+Sham (n = 45 eyes), Healthy+BMSC (n = 6 eyes), Healthy+Sham (n = 6 eyes). Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function. PMID:27300133

  2. Insulin secretion enhancing activity of roselle calyx extract in normal and streptozotocin-induced diabetic rats

    PubMed Central

    Wisetmuen, Eamruthai; Pannangpetch, Patchareewan; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Yutanawiboonchai, Wiboonchai; Itharat, Arunporn

    2013-01-01

    Background and Objective: Our recent study revealed the antihyperglycemic activity of an ethanolic extract of roselle calyxes (Hibiscus sabdariffa) in diabetic rats. The present study had, therefore, an objective to investigate the mechanism underlying this activity. Materials and Methods: Male Sprague Dawley rats were induced to be diabetes by intraperitoneal injection of 45 mg/kg streptozotocin (STZ). Normal rats as well as diabetic rats were administered with the ethanolic extract of H. sabdariffa calyxes (HS-EE) at 0.1 and 1.0 g/kg/day, respectively, for 6 weeks. Then, blood glucose and insulin levels, at basal and glucose-stimulated secretions, were measured. The pancreas was dissected to examine histologically. Results: HS-EE 1.0 g/kg/day significantly decreased the blood glucose level by 38 ± 12% in diabetic rats but not in normal rats. In normal rats, treatment with 1.0 g/kg HS-EE increased the basal insulin level significantly as compared with control normal rats (1.28 ± 0.25 and 0.55 ± 0.05 ng/ml, respectively). Interestingly, diabetic rats treated with 1.0 g/kg HS-EE also showed a significant increase in basal insulin level as compared with the control diabetic rats (0.30 ± 0.05 and 0.15 ± 0.01 ng/ml, respectively). Concerning microscopic histological examination, HS-EE 1.0 g/kg significantly increased the number of islets of Langerhans in both normal rats (1.2 ± 0.1 and 2.0 ± 0.1 islet number/10 low-power fields (LPF) for control and HS-EE treated group, respectively) and diabetic rats (1.0 ± 0.3 and 3.9 ± 0.6 islet number/10 LPF for control and HS-EE treated group, respectively). Conclusion: The antidiabetic activity of HS-EE may be partially mediated via the stimulating effect on insulin secretion. PMID:23798879

  3. Dimethyl fumarate attenuates intracerebroventricular streptozotocin-induced spatial memory impairment and hippocampal neurodegeneration in rats.

    PubMed

    Majkutewicz, Irena; Kurowska, Ewelina; Podlacha, Magdalena; Myślińska, Dorota; Grembecka, Beata; Ruciński, Jan; Plucińska, Karolina; Jerzemowska, Grażyna; Wrona, Danuta

    2016-07-15

    Intracerebroventricular (ICV) injection of streptozotocin (STZ) is a widely-accepted animal model of sporadic Alzheimer's disease (sAD). The present study evaluated the ability of dimethyl fumarate (DMF), an agent with antioxidant and anti-inflammatory properties, to prevent spatial memory impairments and hippocampal neurodegeneration mediated by ICV injection of STZ in 4-month-old rats. Rodent chow containing DMF (0.4%) or standard rodent chow was made available on day 0. Rat body weight and food intake were measured daily for whole the experiment (21days). STZ or vehicle (SHAM) ICV injections were performed on days 2 and 4. Spatial reference and working memory were evaluated using the Morris water maze on days 14-21. Cells containing Fluoro-Jade B (neurodegeneration marker), IL-6, IL-10 were quantified in the hippocampus and choline acetyltransferase (ChAT) in the basal forebrain. The disruption of spatial memory and a high density of hippocampal CA1-3 cells labeled with Fluoro-Jade B or containing IL-6 or IL-10 were observed in the STZ group but not in the STZ+DMF group, as compared to the SHAM or SHAM+DMF groups. STZ vs. STZ+DMF differences were found: worse reference memory acquisition, fewer ChAT-positive neurons in the medial septum (Ch1), more Fluoro-Jade-positive CA1 hippocampal cells in STZ rats. DMF therapy in a rodent model of sAD prevented the disruption of spatial reference and working memory, loss of Ch1 cholinergic cells and hippocampal neurodegeneration as well as the induction of IL-6 and IL-10 in CA1. These beneficial cognitive and molecular effects validate the anti-inflammatory and neuroprotective properties of DMF in the hippocampus. PMID:27083302

  4. Increased intrinsic mitochondrial respiratory capacity in skeletal muscle from rats with streptozotocin-induced hyperglycemia

    PubMed Central

    Larsen, Steen; Scheede-Bergdahl, Celena; Whitesell, Thomas; Boushel, Robert; Bergdahl, Andreas

    2015-01-01

    Type I diabetes mellitus (T1DM) is a chronic disorder, characterized by an almost or complete insulin deficiency. Widespread tissue dysfunction and deleterious diabetes-complications are associated with long-term elevations of blood glucose. The aim of this study was to investigate the effects of type I diabetes, as induced by streptozotocin, on the mitochondria in skeletal muscles that predominantly consist of either slow or fast twitch fibers. Soleus (primarily slow twitch fiber type) and the plantaris muscle (mainly fast twitch fiber type) were removed in order to measure mitochondrial protein expression and integrated mitochondrial respiratory function. Mitochondrial capacity for oxidative phosphorylation (OXPHOS) was found to be higher in the slow (more oxidative) soleus muscle from STZ rats when evaluating lipid and complex I linked OXPHOS capacity, whereas no difference was detected between the groups when evaluating the more physiological complex I and II linked OXPHOS capacity. These findings indicate that chronic hyperglycemia results in an elevated intrinsic mitochondrial respiratory capacity in both soleus and, at varying degree, plantaris muscle, findings that are consistent with human T1DM patients. PMID:26197936

  5. Antihyperglycemic, antihyperlipidemic and antioxidant effects of Dihar, a polyherbal ayurvedic formulation in streptozotocin induced diabetic rats.

    PubMed

    Patel, Snehal S; Shah, Rajendra S; Goyal, Ramesh K

    2009-07-01

    Present investigation was undertaken to evaluate antihyperglycemic, antihyperlipidemic and antioxidant activities of Dihar, a polyherbal formulation containing drugs from eight different herbs viz., Syzygium cumini, Momordica charantia, Emblica officinalis, Gymnema sylvestre, Enicostemma littorale, Azadirachta indica, Tinospora cordifolia and Curcuma longa in streptozotocin (STZ, 45 mg/kg iv single dose) induced type 1 diabetic rats. STZ produced a significant increase in serum glucose, cholesterol, triglyceride, very low density lipoprotein, low density lipoprotein, creatinine, and urea levels in diabetic rat. Treatment with Dihar (100 mg/kg) for 6 weeks produced decrease in STZ induced serum glucose and lipids levels and increased insulin levels as compared to control. Dihar produced significant decrease in serum creatinine and urea levels in diabetic rats. There was a significant decrease in reduced glutathione, superoxide dismutase, catalase levels and increase in thiobarbituiric acid reactive species levels in the liver of STZ-induced diabetic rats. Administration of Dihar to diabetic rats significantly reduced the levels of lipid paroxidation and increased the activities of antioxidant enzymes. The results suggest Dihar to be beneficial for the treatment of type 1 diabetes. PMID:19761040

  6. Hyperactivity of ON-type retinal ganglion cells in streptozotocin-induced diabetic mice.

    PubMed

    Yu, Jun; Wang, Lu; Weng, Shi-Jun; Yang, Xiong-Li; Zhang, Dao-Qi; Zhong, Yong-Mei

    2013-01-01

    Impairment of visual function has been detected in the early stage of diabetes but the underlying neural mechanisms involved are largely unknown. Morphological and functional alterations of retinal ganglion cells, the final output neurons of the vertebrate retina, are thought to be the major cause of visual defects in diabetes but direct evidence to support this notion is limited. In this study we investigated functional changes of retinal ganglion cells in a type 1-like diabetic mouse model. Our results demonstrated that the spontaneous spiking activity of ON-type retinal ganglion cells was increased in streptozotocin-diabetic mice after 3 to 4 months of diabetes. At this stage of diabetes, no apoptotic signals or cell loss were detected in the ganglion cell layer of the retina, suggesting that the functional alterations in ganglion cells occur prior to massive ganglion cell apoptosis. Furthermore, we found that the increased activity of ON-type ganglion cells was mainly a result of reduced inhibitory signaling to the cells in diabetes. This novel mechanism provides insight into how visual function is impaired in diabetic retinopathy. PMID:24069457

  7. Effect of diabetic duration on hemorheological properties and platelet aggregation in streptozotocin-induced diabetic rats.

    PubMed

    Yeom, Eunseop; Byeon, Hyeokjun; Lee, Sang Joon

    2016-01-01

    Diabetes mellitus with abnormal glucose concentration is associated with changes in hemorheological properties, endothelial function, and platelets hyperactivity. Disturbances may significantly be responsible for diabetes-related vascular complications. In this study, hemorheological and hemodynamic properties were measured according to diabetic duration after streptozotocin treatment in rats. For ex vivo measurements, an extracorporeal model was adopted. Flow rate and blood viscosity were measured using a microfluidic device. Erythrocyte aggregation and morphological parameters of erythrocytes were measured by modified erythrocyte sedimentation rate and the phase-contrast holography under in vitro conditions. The platelet aggregation and mean pressure in the femoral artery were estimated under ex vivo conditions. Hemorheological properties including blood viscosity, erythrocyte aggregation and shape parameters for the control group are significantly different with those for diabetic groups. The changes with respect to diabetic duration were relatively unnoticeable. However, the platelet aggregation is strongly dependent on the diabetic duration. Based on these results, hyperglycemia exposure may induce hemorheological variations in early stages of diabetes mellitus. High platelet aggregation may become more pronounced according to the diabetic duration caused by variations in hemorheological properties resulting in endothelial dysfunction. This study would be helpful in understanding the effects of diabetic duration on biophysical properties. PMID:26898237

  8. Isoflurane anesthesia aggravates cognitive impairment in streptozotocin-induced diabetic rats

    PubMed Central

    Yang, Chun; Zhu, Bin; Ding, Jie; Wang, Zhi-Gang

    2014-01-01

    Several lines of evidence demonstrate that isoflurane anesthesia would be a great risk factor for the patients undergoing surgeries to suffer from postoperative cognitive dysfunction (POCD). Additionally, diabetes is also an important pathogenic factor for the emergence of cognitive dysfunction. If patient is suffering from diabetes, the incidence of cognitive dysfunction greatly increased. We therefore aimed to investigate the effects of isoflurane anesthesia on cognitive dysfunction in a diabetic rat model induced by a single injection of streptozotocin (STZ). Wistar rats received 2 h of 2% isoflurane or oxygen exposure 1 month after a single intraperitoneal injection of 60 mg/kg of STZ or the vehicle. The results showed that isoflurane anesthesia significantly aggravates STZ-induced an increase of the latency to the platform and a decrease of the proportion of time spent in the target quadrant of rats in Morris water maze test. In addition to the expression of amyloid-β (Aβ), superoxide dismutase (SOD), malonyldialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), isoflurane anesthesia significantly increased as compared with a single injection of STZ. However, isoflurane anesthesia had no effect on the blood glucose and leptin. In conclusion, our results suggested that isoflurane anesthesia aggravating cognitive impairment induced by STZ is probably related to the activation of oxidative stress and inflammatory response in rat hippocampus. PMID:24955160

  9. Favorable effects of vildagliptin on metabolic and cognitive dysfunctions in streptozotocin-induced diabetic rats.

    PubMed

    El Batsh, Maha M; El Batch, Manal M; Shafik, Noha M; Younos, Ibrahim H

    2015-12-15

    Progression of diabetes mellitus is accompanied by metabolic disorders together with psychological deficits including cognitive dysfunctions. Herein, we used a murine streptozotocin (STZ)-induced diabetes to investigate the beneficial effects of vildagliptin not only on metabolic abnormalities, but also on diabetes-induced cognitive decline. Sixty rats were divided randomly and equally into 2 groups; one remains normal and the other serves as STZ- induced diabetic. Both groups were further divided equally into 2 groups; one received vehicle and the other received oral vildagliptin for 8 weeks. Cognitive behavior was assessed using novel object recognition test. Blood samples were collected to measure metabolic parameters and dipeptidyl peptidase (DPP)-IV activity. Brains were removed and investigated for the levels of inflammatory and oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-α (TNF-α), in addition to brain-derived neurotrophic factor (BDNF) and relative expression of nuclear factor kappa B (NF-κB)/p65. Treatment of STZ-induced diabetic rats with vildagliptin increased their body weight and corrected diabetes-induced memory and learning impairment. Moreover, vildagliptin significantly decreased serum levels of glucose and lipids (except high density lipoprotein) together with brain MDA, TNF-α, serum DPP-IV activities and NF-κB/p65 gene expression. On the other hand, vildagliptin significantly increased brain BDNF, SOD as well as serum insulin. Results suggested that vildagliptin has a protective role in counteracting both metabolic abnormalities and memory deficits in diabetic rats, possibly via its anti-hyperglycemic, anti-inflammatory, antioxidant effects, together with reduction of brain NF-κB/p65 over expression. PMID:26607467

  10. Different Profile of mRNA Expression in Sinoatrial Node from Streptozotocin-Induced Diabetic Rat

    PubMed Central

    Ferdous, Zannatul; Qureshi, Muhammad Anwar; Jayaprakash, Petrilla; Parekh, Khatija; John, Annie; Oz, Murat; Raza, Haider; Dobrzynski, Halina; Adrian, Thomas Edward; Howarth, Frank Christopher

    2016-01-01

    Background Experiments in isolated perfused heart have shown that heart rate is lower and sinoatrial node (SAN) action potential duration is longer in streptozotocin (STZ)–induced diabetic rat compared to controls. In sino-atrial preparations the pacemaker cycle length and sino-atrial conduction time are prolonged in STZ heart. To further clarify the molecular basis of electrical disturbances in the diabetic heart the profile of mRNA encoding a wide variety of proteins associated with the generation and transmission of electrical activity has been evaluated in the SAN of STZ-induced diabetic rat heart. Methodology/Principal Findings Heart rate was measured in isolated perfused heart with an extracellular suction electrode. Expression of mRNA encoding a variety of intercellular proteins, intracellular Ca2+-transport and regulatory proteins, cell membrane transport proteins and calcium, sodium and potassium channel proteins were measured in SAN and right atrial (RA) biopsies using real-time reverse transcription polymerase chain reaction techniques. Heart rate was lower in STZ (203±7 bpm) compared to control (239±11 bpm) rat. Among many differences in the profile of mRNA there are some worthy of particular emphasis. Expression of genes encoding some proteins were significantly downregulated in STZ-SAN: calcium channel, Cacng4 (7-fold); potassium channel, Kcnd2 whilst genes encoding some other proteins were significantly upregulated in STZ-SAN: gap junction, Gjc1; cell membrane transport, Slc8a1, Trpc1, Trpc6 (4-fold); intracellular Ca2+-transport, Ryr3; calcium channel Cacna1g, Cacna1h, Cacnb3; potassium channels, Kcnj5, Kcnk3 and natriuretic peptides, Nppa (5-fold) and Nppb (7-fold). Conclusions/Significance Collectively, this study has demonstrated differences in the profile of mRNA encoding a variety of proteins that are associated with the generation, conduction and regulation of electrical signals in the SAN of STZ-induced diabetic rat heart. Data from this study will provide a basis for a substantial range of future studies to investigate whether these changes in mRNA translate into changes in electrophysiological function. PMID:27096430

  11. SEXUAL BEHAVIOUR, SPERM QUANTITY AND QUALITY AFTER SHORT-TERM STREPTOZOTOCIN-INDUCED HYPERGLYCAEMIA IN RATS.

    EPA Science Inventory

    Studies of diabetes mellitus in the streptozotocin rat model suggest that sexual dysfunctions may result from diabetes-induced alterations of the neuroendocrine-reproductive tract axis. Our investigation was performed to better define the effects of short-term hyperglycemia on ra...

  12. Effect of Cordyceps sinensis and taurine either alone or in combination on streptozotocin induced diabetes.

    PubMed

    El Zahraa Z El Ashry, Fatma; Mahmoud, Mona F; El Maraghy, Nabila N; Ahmed, Ahmed F

    2012-03-01

    The present study aimed to investigate the antidiabetic effects of Cordyceps sinensis, taurine and their combination in comparison with glibenclamide both in vivo and in vitro using streptozotocin rat model. The diabetic rats were orally given glibenclamide, C. sinensis, taurine or Cordyceps and taurine combination for 21 days. Their effects were studied both in vivo and in vitro. Oral administration of Cordyceps, taurine and their combination decreased serum glucose, fructosamine, total cholesterol, triglycerides levels, insulin resistance index and pancreatic malondialdehyde content. Cordyceps significantly increased serum insulin, HDL-cholesterol, total antioxidant capacity levels, β cell function percent, and pancreatic reduced glutathione (GSH) content. However, taurine was unable to elevate pancreatic GSH level to a significant level. These natural products and their combinations were more effective than glibenclamide in reducing insulin resistance index and they had stronger antioxidant properties. Cordyceps and taurine significantly enhanced glucose uptake by diaphragms of normal and diabetic rats in absence and presence of insulin. In conclusion, Cordyceps and taurine either alone or in combination have less potent hypoglycemic effects than glibenclamide; however, they have more ability to reduce insulin resistance and stronger antioxidant properties. PMID:22226943

  13. Antihyperglycemic effect of thymoquinone and oleuropein, on streptozotocin-induced diabetes mellitus in experimental animals

    PubMed Central

    Sangi, Sibghatullah Muhammad Ali; Sulaiman, Mansour Ibrahim; El-wahab, Mohammed Fawzy Abd; Ahmedani, Elsamoual Ibrahim; Ali, Soad Shaker

    2015-01-01

    Background: Diabetes mellitus is one of the most important diseases related with endocrines. Its main manifestation includes abnormal metabolism of carbohydrates and lipids and inappropriate hyperglycemia that is caused by absolute or relative insulin deficiency. It affects humankind worldwide. Objectives: Our research was aimed to observe antihyperglycemic activity of thymoquinone and oleuropein. Materials and Methods: In this study, rats were divided into six groups, 6 rats in each. Diabetes was inducted by streptozotocin (STZ). The level of fasting blood glucose was determined for each rats during the experiment, doses of thymoquinone and oleuropein (3 mg/kg and 5 mg/kg) for both, were injected intraperitoneal. Pancreatic tissues were investigated to compare β-cells in diabetic and treated rats. Result and Conclusion: It was found that thymoquinone and oleuropein significantly decrease serum Glucose levels in STZ induced diabetic rats. PMID:26664013

  14. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats

    PubMed Central

    Mansouri, Esrafil; Khorsandi, Layasadat; Abdollahzade Fard, Amin

    2015-01-01

    Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg-1 body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes. PMID:26261706

  15. Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Ghasemi, Mohsen; Zendehbad, Bamdad; Zabihi, Hoda; Hosseini, Mahmoud; Hadjzadeh, Mousa Al Reza; Hayatdavoudi, Parichehr

    2016-01-01

    Background: Diabetes mellitus is a chronic disease which may be accompanied by cognitive impairments. The expression of the obesity gene (ob) is decreased in insulin-deficient diabetic animals and increased after the administration of insulin or leptin. Plasma leptin levels are reduced in the streptozotocin (STZ)-induced diabetic rats. Therefore, the deleterious effects of diabetes on memory may be due to the reduction of leptin. Aims: Investigate the effect of subcutaneous injection of leptin on spatial learning and memory in STZ-induced diabetic rats. Study Design: Animal experimentation. Methods: The rats were divided into three groups: 1-control, 2- diabetic, and 3- diabetic-leptin. Diabetes was induced in groups 2 and 3 by STZ injection (55 mg/kg) intraperitoneally (i.p). The animals received leptin (0.1 mg/kg) or saline subcutaneously (s.c) for 10 days before behavioral studies. Then, they were examined in the Morris water maze over 3 blocks after 3 days of the last injection of leptin. Results: The travelled path length and time spent to reach the platform significantly increased in the diabetic group (p<0.001) and decreased with leptin treatment (p<0.01 & p<0.001 respectively); also, a significant increase in path length and time was observed between the diabetic-leptin group and the diabetic group (p<0.01, p<0.001, respectively) in the probe test. Conclusion: Leptin can exert positive effects on memory impairments in diabetic rats. PMID:26966625

  16. The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats

    PubMed Central

    Kong, Wei-Yuan; Tong, Li-Quan; Zhang, Hai-Jun; Cao, Yong-Gang; Wang, Gong-Chen; Zhu, Jin-Zhi; Zhang, Feng; Sun, Xue-Ying; Zhang, Tie-Hui; Zhang, Lin-Lin

    2016-01-01

    Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg−1) in Wistar rats. Animals then received GdCl3 (an agonist of CaSR, 8.67 mg kg−1), NPS-2390 (an antagonist of CaSR, 0.20 g kg−1), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH2-terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl3, but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men. PMID:26387585

  17. Assessment of antidiabetogenic potential of fermented soybean extracts in streptozotocin-induced diabetic rat.

    PubMed

    Lim, Kyu Hee; Han, Ji-Hui; Lee, Jae Yeon; Park, Young Shik; Cho, Yong Seok; Kang, Kyung-Don; Yuk, Won Jeong; Hwang, Kyo Yeol; Seong, Su-Il; Kim, Bumseok; Kwon, JungKee; Kang, Chang-Won; Kim, Jong-Hoon

    2012-11-01

    Most of the available drugs for the treatment of diabetes mellitus (DM) produce detrimental side effects, which has prompted an ongoing search for plant with the antidiabetic potential. The present study investigated the effect of soybean extracts fermented with Bacillus subtilis MORI, fermented soybean extracts (BTD-1) was investigated in streptozotocin (STZ)-induced diabetic rats. The possible effects of BTD-1 against hyperglycemia and free radical-mediated oxidative stress was investigated by assaying the plasma glucose level and the activity of enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA). A significant increase in the levels of both plasma glucose and reactive oxygen species (ROS) was observed in the diabetic rats when compared to normal control group. After administration of BTD-1 (500 and 1000 mg/kg/day), the elevated plasma glucose level was significantly reduced while the plasma insulin level and the activities of SOD, GSH-Px, CAT and MDA were significantly increased. The results suggest that administration of BTD-1 can inhibit hyperglycemia and free radical-mediated oxidative stress. The administration of BTD-1 also inhibited the contractile response by norepinephrine (10(-10)-10(-5) M) in the presence of endothelium, and caused significant relaxation by carbachol (10(-8)-10(-5) M) in rat aorta. These findings indicate that BTD-1 improves vascular functions on STZ-induced diabetic rats. Therefore, subchronic administration of BTD-1 could prevent the functional changes in vascular reactivity in STZ-induced diabetic rats. The collective findings support that administration of BTD-1 may prevent some diabetes-related changes in vascular reactivity directly and/or indirectly due to its hypoglycaemic effect and inhibition of production of ROS. PMID:22943971

  18. Antidiabetic effect of aqueous extract of seed of Tamarindus indica in streptozotocin-induced diabetic rats.

    PubMed

    Maiti, R; Jana, D; Das, U K; Ghosh, D

    2004-05-01

    In Indian traditional system of medicine, herbal remedies are prescribed for the treatment of diseases including diabetes mellitus. In recent years, plants are being effectively tried in a variety of pathophysiological states. Tamarindus indica Linn. is one of them. In the present study, aqueous extract of seed of Tamarindus indica Linn. was found to have potent antidiabetogenic activity that reduces blood sugar level in streptozotocin (STZ)-induced diabetic male rat. Supplementation of this aqueous extract by gavage at the dose of 80 mg/0.5 ml distilled water/100 g body weight per day in STZ-induced diabetic rat resulted a significant diminution of fasting blood sugar level after 7 days. Continuous supplementation of this extract for 14 days resulted no significant difference in this parameter from control level. Moreover, this supplementation produced a significant elevation in liver and skeletal muscle glycogen content, activity of liver glucose-6-phosphate dehydrogenase in respect to diabetic group. Activities of liver glucose-6-phosphatase, liver and kidney glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities were decreased significantly in the aqueous extract supplemented group in respect to diabetic group. All these parameters were not resettled to the controlled level after 7 days of this extract supplementation but after 14 days of this supplementation, all the above mentioned parameters were restored to the control level. PMID:15099853

  19. Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats

    PubMed Central

    2012-01-01

    Background Traditional plant treatment for diabetes has shown a surging interest in the last few decades. Therefore, the purpose of this study was to assess the hypoglycemic effect of the aqueous extract of C. papaya leaves in diabetic rats. Several studies have reported that some parts of the C. papaya plant exert hypoglycemic effects in both animals and humans. Methods Diabetes was induced in rats by intraperitoneal administration of 60 mg/kg of streptozotocin (STZ). The aqueous extract of C. papaya was administered in three different doses (0.75, 1.5 and 3 g/100 mL) as drinking water to both diabetic and non-diabetic animals during 4 weeks. Results The aqueous extract of Carica papaya (0.75 g and 1.5 g/100 mL) significantly decreased blood glucose levels (p<0.05) in diabetic rats. It also decreased cholesterol, triacylglycerol and amino-transferases blood levels. Low plasma insulin levels did not change after treatment in diabetic rats, but they significantly increased in non-diabetic animals. Pancreatic islet cells were normal in non-diabetic treated animals, whereas in diabetic treated rats, C. papaya could help islet regeneration manifested as preservation of cell size. In the liver of diabetic treated rats, C. papaya prevented hepatocyte disruption, as well as accumulation of glycogen and lipids. Finally, an antioxidant effect of C. papaya extract was also detected in diabetic rats. Conclusions This study showed that the aqueous extract of C. papaya exerted a hypoglycemic and antioxidant effect; it also improved the lipid profile in diabetic rats. In addition, the leaf extract positively affected integrity and function of both liver and pancreas. PMID:23190471

  20. Antihyperglycemic effect of Hypericum perforatum ethyl acetate extract on streptozotocin-induced diabetic rats

    PubMed Central

    Arokiyaraj, S; Balamurugan, R; Augustian, P

    2011-01-01

    Objective To evaluate the antihyperglycemic activity of ethyl acetate extract of Hypericum perforatum (H. perforatum) in streptozotocin (STZ)-induced diabetic rats. Methods Acute toxicity and oral glucose tolerance test were performed in normal rats. Male albino rats were rendered diabetic by STZ (40 mg/kg, intraperitoneally). H. perforatum ethyl acetate extract was orally administered to diabetic rats at 50, 100 and 200 mg/kg doses for 15 days to determine the antihyperglycemic activity. Biochemical parameters were determined at the end of the treatment. Results H. perforatum ethyl acetate extract showed dose dependant fall in fasting blood glucose (FBG). After 30 min of extract administration, FBG was reduced significantly when compared with normal rats. H. perforatum ethyl acetate extract produced significant reduction in plasma glucose level, serum total cholesterol, triglycerides, glucose-6-phosphatase levels. Tissue glycogen content, HDL-cholesterol, glucose-6-phosphate dehydrogenase were significantly increased compared with diabetic control. No death or lethal effect was observed in the toxic study. Conclusions The results demonstrate that H. perforatum ethyl acetate extract possesses potent antihyperglycemic activity in STZ induced diabetic rats. PMID:23569798

  1. Prophylactic protective effects and its potential mechanisms of IcarisideII on streptozotocin induced spermatogenic dysfunction.

    PubMed

    Xu, Yongde; Lei, Hongen; Guan, Ruili; Gao, Zhezhu; Li, Huixi; Wang, Lin; Hui, Yu; Zhou, Feng; Xin, Zhongcheng

    2014-01-01

    The aim of this study was to investigate the effects of IcarisideII(ICAII) on the prevention of streptozotocin (STZ) induced spermatogenic dysfunction. Forty male Sprague-Dawley rats received intraperitoneal injection of STZ (55 mg/kg) and were equally randomized to gavage feeding of vehicle (the vehicle group) or ICAII (0.5, 1.5 or 4.5 mg/kg/day, respectively). Ten normal rats received vehicle and served as control. Four weeks later, sperm parameters, histopathological changes, testicular lipid peroxidation, antioxidant enzyme activities, and apoptosis index (AI) were evaluated. Results showed that ICAII treatment resulted in a significant recovery of sperm parameters and histopathological changes relative to the vehicle group (p<0.05). In the vehicle group, antioxidant enzyme activities and the expression of Sertoli cell Vimentin filaments obviously decreased, while lipid peroxidation and AI significantly increased as compared with the control group (p<0.05). Following ICAII treatment, corrective effects on these items towards normal levels were observed. The results suggested that ICAII has beneficial effect on the preservation of spermatogenic function in the STZ-induced diabetic rats. The mechanisms might be related to its improvement of antioxidant enzyme activities, preservation of the protein expression and apical extensions of Vimentin filaments, and anti-apoptosis capability. PMID:25216341

  2. Antihyperglycemic Effect of Ganoderma Lucidum Polysaccharides on Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Li, Fenglin; Zhang, Yiming; Zhong, Zhijian

    2011-01-01

    The current study evaluated the glucose-lowering effect of ganoderma lucidum polysaccharides (Gl-PS) in streptozotocin (STZ)-induced diabetic mice. The diabetic mice were randomly divided into four groups (8 mice per group): diabetic control group, low-dose Gl-PS treated group (50 mg/kg, Gl-PS), high-dose Gl-PS treated group (150 mg/kg, Gl-PS) and positive drug control treated group (glibenclamide, 4 mg/kg), with normal mice used as the control group. Body weights, fasting blood glucose (FBG), serum insulin and blood lipid levels of mice were measured. After 28 days of treatment with Gl-PS, body weights and serum insulin levels of the Gl-PS treated groups was significantly higher than that of the diabetic control group, whereas FBG levels was significantly lower. Moreover, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) levels of the Gl-PS treated groups had dropped, whereas the high density lipoprotein cholesterol (HDL-C) levels had increased. In addition, according to acute toxicity studies, Gl-PS did not cause behavioral changes and any death of mice. These data suggest that Gl-PS has an antihyperglycemic effect. Furthermore, considering the Gl-PS effects on lipid profile, it may be a potential hypolipidaemic agent, which will be a great advantage in treating diabetic conditions associated with atherosclerosis or hyperlipidemia. PMID:22016649

  3. Beneficial Effects of Sarpogrelate and Rosuvastatin in High Fat Diet/Streptozotocin-Induced Nephropathy in Mice.

    PubMed

    Kim, Dong-Hyun; Choi, Bo-Hyun; Ku, Sae-Kwang; Park, Jeong-Hyeon; Oh, Euichaul; Kwak, Mi-Kyoung

    2016-01-01

    Chronic kidney disease (CKD) is a major complication of metabolic disorders such as diabetes mellitus, obesity, and hypertension. Comorbidity of these diseases is the factor exacerbating CKD progression. Statins are commonly used in patients with metabolic disorders to decrease the risk of cardiovascular complications. Sarpogrelate, a selective antagonist of 5-hydroxytryptamine (5-HT) 2A receptor, inhibits platelet aggregation and is used to improve peripheral circulation in diabetic patients. Here, we investigated the effects of sarpogrelate and rosuvastatin on CKD in mice that were subjected to a high fat diet (HFD) for 22 weeks and a single low dose of streptozotocin (STZ, 40 mg/kg). When mice were administrated sarpogrelate (50 mg/kg, p.o.) for 13 weeks, albuminuria and urinary cystatin C excretion were normalized and histopathological changes such as glomerular mesangial expansion, tubular damage, and accumulations in lipid droplets and collagen were significantly improved. Sarpogrelate treatment repressed the HFD/STZ-induced CD31 and vascular endothelial growth factor receptor-2 expressions, indicating the attenuation of glomerular endothelial proliferation. Additionally, sarpogrelate inhibited interstitial fibrosis by suppressing the increases in transforming growth factor-β1 (TGF-β1) and plasminogen activator inhibitor-1 (PAI-1). All of these functional and histological improvements were also seen in rosuvastatin (20 mg/kg) group and, notably, the combinatorial treatment with sarpogrelate and rosuvastatin showed additive beneficial effects on histopathological changes by HFD/STZ. Moreover, sarpogrelate reduced circulating levels of PAI-1 that were elevated in the HFD/STZ group. As supportive in vitro evidence, sarpogrelate incubation blocked TGF-β1/5-HT-inducible PAI-1 expression in murine glomerular mesangial cells. Taken together, sarpogrelate and rosuvastatin may be advantageous to control the progression of CKD in patients with comorbid metabolic disorders, and particularly, the use of sarpogrelate as adjunctive therapy with statins may provide additional benefits on CKD. PMID:27097221

  4. Protective effect of polysaccharides from Opuntia dillenii Haw. fruits on streptozotocin-induced diabetic rats.

    PubMed

    Gao, Jie; Han, Yu-Lu; Jin, Zheng-Yu; Xu, Xue-Ming; Zha, Xue-Qiang; Chen, Han-Qing; Yin, Yan-Yan

    2015-06-25

    In this study, a novel water-soluble polysaccharide fraction with molecular weight of 6479.1kDa was isolated from the fruits of Opuntia dillenii Haw., which consisted of rhamnose, xylose, mannose and glucose in the molar ratio of 14.99:1.14:1.00:6.47. The protective effect of O. dillenii Haw. fruits polysaccharide (ODFP) against oxidative damage in streptozotocin (STZ)-induced diabetic rats was investigated. The results showed that oral administration of ODFP significantly decreased food intake, water intake, urine production, organ weights and blood glucose level, and increased body weight in STZ-induced diabetic rats. ODFP also significantly increased the activities of SOD, GPx and CAT, and decreased malondialdehyde level in serum, liver, kidney, and pancreas in STZ-induced diabetic rats. Moreover, histopathological examination showed that ODFP could markedly improve the structure integrity of pancreatic islet tissue in STZ-induced diabetic rats. These results suggest that ODFP have hypoglycemic and antioxidant properties and can protect rats from STZ-induced oxidative damage. PMID:25839790

  5. Clock gene expression in the liver of streptozotocin-induced and spontaneous type 1 diabetic rats.

    PubMed

    Hofmann, K; Schönerstedt, U; Mühlbauer, E; Wedekind, D; Peschke, E

    2013-09-01

    Several investigations have shown a relation between diabetes and alterations of the liver circadian clock. We investigated the diurnal expression of clock genes and clock-controlled genes (CCGs) in 3-hour intervals for a 24-h period in the livers of male streptozotocin (STZ)-treated rats, male spontaneous type 1 diabetic LEW.1AR1-iddm (Iddm) rats, and Iddm rats treated for 10 days with insulin. Hepatic mRNA was extracted, and the relative expression of clock genes (Per1, Per2, Bmal1, Clock, Cry1), as well as CCGs (Dbp, E4bp4, RevErbα, Rorα, Pparγ), was analyzed by reverse transcription followed by real-time polymerase chain reaction. Diabetic STZ and Iddm rats, as well as insulin-substituted Iddm rats, exhibited a significant diurnal expression pattern of clock genes as determined by Cosinor analysis; however, the MESOR (midline estimating statistic of rhythm) of Bmal1, Per2, and Clock transcript expression was altered in Iddm and insulin-substituted Iddm rats. The hepatic expression of the CCGs Dbp and RevErbα revealed a diurnal rhythm in all investigated groups. Insulin administration to Iddm rats normalized the enhanced MESOR in the expression of Dbp, RevErbα, and E4bp4 to the levels of normoglycemic controls. Cosinor analysis indicated no diurnal rhythm of Pparγ expression in the livers of diabetic STZ or Iddm rats or in those of insulin-substituted Iddm rats. Also, insulin substitution could not reverse the decreased MESOR of Pparγ expression in Iddm rats. In consequence of the diabetic disease, changes in the expression of clock genes and CCGs suggest alterations in the hepatic peripheral clock mechanism. PMID:23632905

  6. 1-deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism in streptozotocin-induced diabetic mice

    PubMed Central

    Li, You-Gui; Ji, Dong-Feng; Zhong, Shi; Lin, Tian-Bao; Lv, Zhi-Qiang; Hu, Gui-Yan; Wang, Xin

    2013-01-01

    We investigated the role of 1-deoxynojirimycin (DNJ) on glucose absorption and metabolism in normal and diabetic mice. Oral and intravenous glucose tolerance tests and labeled 13C6-glucose uptake assays suggested that DNJ inhibited intestinal glucose absorption in intestine. We also showed that DNJ down-regulated intestinal SGLT1, Na+/K+-ATP and GLUT2 mRNA and protein expression. Pretreatment with DNJ (50 mg/kg) increased the activity, mRNA and protein levels of hepatic glycolysis enzymes (GK, PFK, PK, PDE1) and decreased the expression of gluconeogenesis enzymes (PEPCK, G-6-Pase). Assays of protein expression in hepatic cells and in vitro tests with purified enzymes indicated that the increased activity of glucose glycolysis enzymes was resulted from the relative increase in protein expression, rather than from direct enzyme activation. These results suggest that DNJ inhibits intestinal glucose absorption and accelerates hepatic glucose metabolism by directly regulating the expression of proteins involved in glucose transport systems, glycolysis and gluconeogenesis enzymes. PMID:23536174

  7. Response of thymus lymphocytes to streptozotocin-induced diabetes and exogenous vitamin C administration in rats.

    PubMed

    Ozerkan, Dilşad; Ozsoy, Nesrin; Cebesoy, Suna

    2014-12-01

    Diabetes causes oxidative stress, which in turn generates excessive free radicals resulting in cellular damage. Vitamin C is an antioxidant that protects tissues and organs from oxidative stress. The thymus is one of the most important lymphoid organs, which regulates T-lymphocyte proliferation and maturation. The aim of this study is to investigate the protective effects of vitamin C on the thymus of streptozotocin (STZ)-induced diabetic rats. The mitotic activity and cell integrity of thymic lymphocytes were explored. Wistar Albino rats were divided into three groups: control (Group 1), STZ-diabetes (Group 2) and vitamin C-treated STZ-diabetics (Group 3). Rats received a single intraperitoneal injection of 45 mg/kg STZ to induce diabetes. Vitamin C (20 mg/kg) was administered intragastrically. Semithin and ultrathin sections were examined under a light or an electron microscope, respectively. Considerable numbers of mitotic lymphocytes were observed in the thymus of control rats. In the diabetic rats, however, numbers of mitotic lymphocytes decreased to ∼57% of controls, and cell division abnormalities were observed. Additionally, diabetic rats showed degeneration in the structure of the thymus including trabecular thickening, accumulation of lipid vacuoles, heterochromatic nuclei and loss of mitochondrial cristae. Degradation of medullar and cortical integrity was also detected. In the vitamin C-treated STZ-diabetic group, the structure of the thymus and mitotic activity of the lymphocytes were similar to the control group. These results suggest that vitamin C protects the thymus against injury caused by diabetes and restores thymocyte mitotic activity. PMID:25145646

  8. Prospective evaluation of aminopeptidase activities in plasma and peripheral organs of streptozotocin-induced diabetic rats.

    PubMed

    Zambotti-Villela, L; Yamasaki, S C; Villarroel, J S; Alponti, R F; Silveira, P F

    2008-06-01

    The cleavage of peptides by aminopeptidase enzyme types could be among the mechanisms related to certain disruptions on mediator and modulatory functions in diabetes mellitus. In order to examine this hypothesis, we measured representative aminopeptidase activities in tissues of peripheral organs of control and streptozotocin-diabetic rats. None of the examined aminopeptidase activities differed between diabetics and controls in plasma, ileum, stomach or lung. Soluble and membrane-associated alanyl, and membrane-associated cystyl aminopeptidase activities were higher in the kidney of diabetics. Decreased activity was observed in soluble and membrane-associated aspartyl and soluble dipeptidyl-peptidase IV, while increased activity was observed in soluble alanyl, arginyl, and cystyl aminopeptidases in the pancreas of diabetics. In the jejunum, soluble cystyl aminopeptidase increased in diabetics. Soluble arginyl and type-1-pyroglutamyl aminopeptidase and membrane-associated dipeptidyl-peptidase IV activities increased in the liver of diabetics. Membrane-associated dipeptidyl-peptidase IV and alanyl aminopeptidase activities in the spleen were higher in diabetics than in controls. Membrane-associated alanyl aminopeptidase activity also increased in the heart of diabetics. All these changes in streptozotocin-treated rats were avoided by the administration of insulin. Our comparative analysis of a diverse array of aminopeptidase activities supported the proposal that the regulation of peptide cleavage by these enzyme types is associated with the effects of streptozotocin-diabetes mellitus on peripheral organs. PMID:18591879

  9. Antihyperglycemic and hypolipidemic effects of Melothria maderaspatana and Coccinia indica in Streptozotocin induced diabetes in rats

    PubMed Central

    Balaraman, Ashok Kumar; Singh, Jagadish; Dash, Sasmita; Maity, Tapan Kumar

    2010-01-01

    Antihyperglycemic and hypolipidemic effects of ethanol extract of aerial parts of Melothria maderaspatana and Coccinia indica were evaluated in STZ induced diabetes in Sprague–Dawley rats. The rats were concurrently treated with 100 or 200 mg/kg b.w. p.o. for 14 days. The changes in fasting blood glucose level and body weight were measured in 5 days interval. After 14 days experimental period, rats were sacrificed by cervical decapitation, blood and liver samples were collected. Biochemical estimation of plasma glucose, cholesterol, triglycerides, LDL, HDL, SGOT, SGPT and ALP were done from blood sample. The liver glycogen content was estimated using standard procedure from homogenized liver sample. Administration of EEMm or EECi to STZ-diabetic rats caused significant antihyperglycemic and hypolipidemic effects (p < 0.001). The extracts were also found to be significantly effective (p < 0.001; p < 0.05) on recovery of altered biochemical parameters and decreased body weight in treated animals. Glibenclamide (0.5 mg/kg b.w.) was used as standard in present study. PMID:23964177

  10. Bacterial Flora Changes in Conjunctiva of Rats with Streptozotocin-Induced Type I Diabetes

    PubMed Central

    Qin, Yali; Luo, Dan; Yang, Shufei; Kou, Xinyun; Zi, Yingxin; Deng, Tingting; Jin, Ming

    2015-01-01

    Background The microbiota of both humans and animals plays an important role in their health and the development of disease. Therefore, the bacterial flora of the conjunctiva may also be associated with some diseases. However, there are no reports on the alteration of bacterial flora in conjunctiva of diabetic rats in the literature. Therefore, we investigated the changes in bacterial flora in bulbar conjunctiva of rats with streptozotocin (STZ)-induced type I diabetes. Methods A high dose of STZ (60 mg/kg, i.p.) was injected into Sprague-Dawley (SD) rats to induce type I diabetes mellitus (T1DM). The diabetic rats were raised in the animal laboratory and at 8 months post-injection of STZ swab samples were taken from the bulbar conjunctiva for cultivation of aerobic bacteria. The bacterial isolates were identified by Gram staining and biochemical features. The identified bacteria from both diabetic and healthy rats were then compared. Results The diabetic and healthy rats had different bacterial flora present in their bulbar conjunctiva. In total, 10 and 8 bacterial species were found in the STZ and control groups, respectively, with only three species (Enterococcus faecium, Enterococcus gallinarum and Escherichia coli) shared between the two groups. Gram-positive bacteria were common in both groups and the most abundant was Enterococcus faecium. However, after the development of T1DM, the bacterial flora in the rat bulbar conjunctiva changed considerably, with a reduced complexity evident. Conclusions STZ-induced diabetes caused alterations of bacterial flora in the bulbar conjunctiva in rats, with some bacterial species disappearing and others emerging. Our results indicate that the conjunctival bacterial flora in diabetic humans should be surveyed for potential diagnostic markers or countermeasures to prevent eye infections in T1DM patients. PMID:26176548

  11. Antidiabetic activity of zinc oxide and silver nanoparticles on streptozotocin-induced diabetic rats.

    PubMed

    Alkaladi, Ali; Abdelazim, Aaser Mohamed; Afifi, Mohamed

    2014-01-01

    The use of nanoparticles in medicine is an attractive proposition. In the present study, zinc oxide and silver nanoparticles were evaluated for their antidiabetic activity. Fifty male albino rats with weight 120 ± 20 and age 6 months were used. Animals were grouped as follows: control; did not receive any type of treatment, diabetic; received a single intraperitoneal dose of streptozotocin (100 mg/kg), diabetic + zinc oxide nanoparticles (ZnONPs), received single daily oral dose of 10 mg/kg ZnONPs in suspension, diabetic + silver nanoparticles (SNPs); received a single daily oral dose of SNP of 10 mg/kg in suspension and diabetic + insulin; received a single subcutaneous dose of 0.6 units/50 g body weight. Zinc oxide and silver nanoparticles induce a significant reduced blood glucose, higher serum insulin, higher glucokinase activity higher expression level of insulin, insulin receptor, GLUT-2 and glucokinase genes in diabetic rats treated with zinc oxide, silver nanoparticles and insulin. In conclusion, zinc oxide and sliver nanoparticles act as potent antidiabetic agents. PMID:24477262

  12. Hypoglycemic effect of Hibiscus rosa sinensis L. leaf extract in glucose and streptozotocin induced hyperglycemic rats.

    PubMed

    Sachdewa, A; Nigam, R; Khemani, L D

    2001-03-01

    Investigations were carried out to evaluate the effect of aqueous extract of H. rosa sinensis leaves on blood glucose level and glucose tolerance using Wistar rats. Repeated administration of the extract (once a day for seven consecutive days), at an oral dose equivalent to 250 mg kg(-1), significantly improved glucose tolerance in rats. The peak blood glucose level was obtained at 30 min of glucose load (2 g kg(-1)), thereafter a decreasing trend was recorded up to 120 min. The data exhibit that repeated ingestion of the reference drug tolbutamide, a sulphonylurea and the extract brings about 2-3 fold decrease in blood glucose concentration as compared to single oral treatment. The results clearly indicate that tolbutamide improves the glucose tolerance by 91% and extract does so only by 47%. At 250 mg kg(-1), the efficacy of the extract was 51.5% of tolbutamide (100mg kg(-1)). In streptozotocin diabetic rats, no significant effect was observed with the extract, while glibenclamide significantly lowered the glucose level up to 7 hr. These data suggest that hypoglycemic activity of H. rosa sinensis leaf extract is comparable to tolbutamide and not to glibenclamide treatment. PMID:11495291

  13. Augmented insulin effects on plasma glucose by cranberry procyanidins in streptozotocin-induced diabetic rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives of this study were to determine if cranberry proanthocyanidins (CPACs) had an antihyperglycemic effect in the presence or absence of insulin in male diabetic Sprague-Dawley rats. Rats (approximately 250 g)(n=6-10/ trt) were given a single intraperitoneal (ip) injection of freshly prepared...

  14. Antidiabetic Activity of Artemisia amygdalina Decne in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Ganai, Bashir A.; Akbar, Seema; Mubashir, Khan; Dar, Showkat Ahmad; Dar, Mohammad Younis; Tantry, Mudasir A.

    2014-01-01

    Artemisia species have been extensively used for the management of diabetes in folklore medicine. The current study was designed to investigate the antidiabetic and antihyperlipidemic effects of Artemisia amygdalina. Petroleum ether, ethyl acetate, methanol, and hydroethanolic extracts of Artemisia amygdalina were tested for their antidiabetic potentials in diabetic rats. The effect of extracts was observed by checking the biochemical, physiological, and histopathological parameters in diabetic rats. The hydroethanolic and methanolic extracts each at doses of 250 and 500 mg/kg b. w significantly reduced glucose levels in diabetic rats. The other biochemical parameters like cholesterol, triglycerides, low density lipoproteins (LDL), serum creatinine, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), and alkaline phosphatise (ALP), were found to be reduced by the hydroethanolic and methanolic extracts. The extracts also showed reduction in the feed and water consumption of diabetic rats when compared with the diabetic control. The histopathological results of treated groups showed the regenerative/protective effect on β-cells of pancreas in diabetic rats. The current study revealed the antidiabetic potential of Artemisia amygdalina being effective in hyperglycemia and that it can effectively protect against other metabolic aberrations caused by diabetes in rats, which seems to validate its therapeutic traditional use. PMID:24967338

  15. Dendrobium officinale Prevents Early Complications in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Hou, Shao-zhen; Liang, Chu-yan; Liu, Hua-zhen; Zhu, Dong-mei; Wu, Ya-yun; Liang, Jian; Zhao, Ya; Guo, Jian-ru; Huang, Song; Lai, Xiao-Ping

    2016-01-01

    Background. Dendrobium officinale (DO) Kimura et Migo is a precious Chinese herb that is considered beneficial for health due to its antioxidant and antidiabetes properties, and so on. In this research, we try to determine the preventive effect of DO on the early complications of STZ-induced diabetic rats. Methods. Type 1 diabetic rats were produced with a single intraperitoneal injection of STZ (50 mg/kg). DO (1 g/kg/day) was then orally administered for 5 weeks. Blood glucose, TC, TG, BUN, CREA, and GSH-PX levels were determined, and electroretinographic activity and hypoalgesia were investigated. Pathological sections of the eyes, hearts, aortas, kidneys, and livers were analyzed. Results. Treatment with DO significantly attenuated the serum levels of TC, TG, BUN, and CREA, markedly increased the amplitudes of ERG a- and b-waves and Ops, and reduced the hypoalgesia and histopathological changes of vital organs induced by hyperglycemia. The protective effect of DO in diabetic rats may be associated with its antioxidant activity, as evidenced by the marked increase in the serum level of glutathione peroxidase. However, DO had no significant effect on blood glucose levels and bodyweight of diabetic rats. Conclusions. DO supplementation is an effective treatment to prevent STZ-induced diabetic complications. PMID:27034693

  16. Combination therapies prevent the neuropathic, proinflammatory characteristics of bone marrow in streptozotocin-induced diabetic rats.

    PubMed

    Dominguez, James M; Yorek, Mark A; Grant, Maria B

    2015-02-01

    We previously showed that peripheral neuropathy of the bone marrow was associated with loss of circadian rhythmicity of stem/progenitor cell release into the circulation. Bone marrow neuropathy results in dramatic changes in hematopoiesis that lead to microvascular complications, inflammation, and reduced endothelial repair. This series of events represents early pathogenesis before development of diabetic retinopathy. In this study we characterized early alterations within the bone marrow of streptozotocin (STZ)-induced diabetic rats following treatments that prevent experimental peripheral neuropathy. We asked whether bone marrow neuropathy and the associated bone marrow pathology were reversed with treatments that prevent peripheral neuropathy. Three strategies were tested: inhibition of neutral endopeptidase, inhibition of aldose reductase plus lipoic acid supplementation, and insulin therapy with antioxidants. All strategies prevented loss of nerve conduction velocity resulting from STZ-induced diabetes and corrected the STZ-induced diabetes-associated increase of immunoreactivity of neuropeptide Y, tyrosine hydroxylase, and somatostatin. The treatments also reduced concentrations of interleukin-1β, granulocyte colony-stimulating factor, and matrix metalloproteinase 2 in STZ-induced diabetic bone marrow supernatant and decreased the expression of NADPH oxidase 2, nitric oxide synthase 2, and nuclear factor-κB1 mRNA in bone marrow progenitor cells. These therapies represent novel approaches to attenuate the diabetic phenotype within the bone marrow and may constitute an important therapeutic strategy for diabetic microvascular complications. PMID:25204979

  17. Modulation of celecoxib- and streptozotocin-induced experimental dementia of Alzheimer's disease by pitavastatin and donepezil.

    PubMed

    Sharma, Bhupesh; Singh, Nirmal; Singh, Manjeet

    2008-03-01

    Present study was designed to investigate modulation of experimental dementia by Pitavastatin and donepezil. Learning and memory of the swiss albino mice were studied on Morris water-maze. Celecoxib orally (p.o.)/Streptozotocin (STZ) intracerebroventricular administrations were used to induce experimental dementia. Brain acetyl cholinesterase activity was measured by EllMann's method to assess cholinergic activity of the brain. Brain thio barbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively, to assess total oxidative stress in brain. Total serum cholesterol level was measured by Allain's method. Celecoxib/STZ treatments produced a significant loss of learning and memory. Pitavastatin/Donepezil successfully attenuated this Celecoxib/STZ induced dementia. Higher levels of brain acetyl-cholinesterase (AChE) activity, TBARS and lower level of GSH were observed in Celecoxib/STZ treated animals, which were significantly attenuated by Donepezil. Pitavastatin also attenuated the Celecoxib/STZ induced high levels of TBARS & low levels of GSH without effecting AChE activity and total serum cholesterol levels. Celecoxib induced dementia noted in the present study may be attributed to its stimulatory effect on amyloid beta-42, brain AChE activity, and oxidative stress. Sub-diabetogenic STZ induced memory deficits closely related to Alzheimer's disease. Reversal of Celecoxib/STZ induced memory deficits by Pitavastatin may be due to its antioxidative, anti beta amyloid aggregatory property, and by Donepezil, due to its anticholinesterase and neuroprotective actions. PMID:18208924

  18. Astaxanthin Inhibits Expression of Retinal Oxidative Stress and Inflammatory Mediators in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Yeh, Po-Ting; Huang, Hsin-Wei; Yang, Chung-May; Yang, Wei-Shiung; Yang, Chang-Hao

    2016-01-01

    Purpose We evaluated whether orally administered astaxanthin (AST) protects against oxidative damage in the ocular tissues of streptozotocin (STZ)-induced diabetic rats. Methods and Results Fifty 6-week-old female Wistar rats were randomly assigned to receive an injection of STZ to induce diabetes (n = 40) or to remain uninduced (n = 10). The diabetic rats were randomly selected into four groups and they were separately administered normal saline, 0.6 mg/kg AST, 3 mg/kg AST, or 0.5 mg/kg lutein daily for eight weeks. Retinal functions of each group were evaluated by electroretinography. The expression of oxidative stress and inflammatory mediators in the ocular tissues was then assessed by immunohistochemistry, western blot analysis, ELISA, RT-PCR, and electrophoretic mobility shift assay (EMSA). Retinal functions were preserved by AST and lutein in different levels. Ocular tissues from AST- and lutein-treated rats had significantly reduced levels of oxidative stress mediators (8-hydroxy-2'-deoxyguanosine, nitrotyrosine, and acrolein) and inflammatory mediators (intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and fractalkine), increased levels of antioxidant enzymes (heme oxygenase-1 and peroxiredoxin), and reduced activity of the transcription factor nuclear factor-kappaB (NF-κB). Conclusion The xanthophyll carotenoids AST and lutein have neuroprotective effects and reduce ocular oxidative stress, and inflammation in the STZ diabetic rat model, which may be mediated by downregulation of NF-κB activity. PMID:26765843

  19. Involvement of Spinal Angiotensin II System in Streptozotocin-Induced Diabetic Neuropathic Pain in Mice.

    PubMed

    Ogata, Yoshiki; Nemoto, Wataru; Nakagawasai, Osamu; Yamagata, Ryota; Tadano, Takeshi; Tan-No, Koichi

    2016-09-01

    Renin-angiotensin system (RAS) activity increases under hyperglycemic states, and is thought to be involved in diabetic complications. We previously demonstrated that angiotensin (Ang) II, a main bioactive component of the RAS, might act as a neurotransmitter and/or neuromodulator in the transmission of nociceptive information in the spinal cord. Here, we examined whether the spinal Ang II system is responsible for diabetic neuropathic pain induced by streptozotocin (STZ). Tactile allodynia was observed concurrently with an increase in blood glucose levels the day after mice received STZ (200 mg/kg, i.v.) injections. Tactile allodynia on day 14 was dose-dependently inhibited by intrathecal administration of losartan, an Ang II type 1 (AT1) receptor antagonist, but not by PD123319, an AT2 receptor antagonist. In the lumbar dorsal spinal cord, the expression of Ang II, Ang converting enzyme (ACE), and phospho-p38 mitogen-activated protein kinase (MAPK) were all significantly increased on day 14 after STZ injection compared with vehicle-treated controls, whereas no differences were observed among AT1 receptors or angiotensinogen levels. Moreover, the increase in phospho-p38 MAPK was significantly inhibited by intrathecal administration of losartan. These results indicate that the expression of spinal ACE increased in STZ-induced diabetic mice, which in turn led to an increase in Ang II levels and tactile allodynia. This increase in spinal Ang II was accompanied by the phosphorylation of p38 MAPK, which was shown to be mediated by AT1 receptors. PMID:27401876

  20. Minocycline Attenuates Kidney Injury in a Rat Model of Streptozotocin-Induced Diabetic Nephropathy.

    PubMed

    Yuan, Hongping; Zhang, Xiaoxuan; Zheng, Wei; Zhou, Hui; Zhang, Bo-Yin; Zhao, Dongxu

    2016-01-01

    The effects of minocycline on the development of diabetic nephropathy (DN) in streptozotocin (STZ) induced diabetic rats were evaluated in this study. The diabetes rats with DN were induced by STZ (55 mg/kg) injection. The experiment included 5 groups 1) normal, 2) normal plus minocycline for 16 weeks, 3) DN plus vehicle, 4) DN plus minocycline 16 weeks and 5) DN plus minocycline for 8 weeks. The pathological changes were analyzed by hematoxylin and eosin (H&E) staining and the apoptotic cells were stained by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. The mRNA expression of caspase-3, Bax and Bcl-2 in the kidney tissues was detected by quantitative RT-PCR. The biochemical parameters of blood and urine were determined by biochemical analyzer. Treatment with minocycline reduced the urine volume, 24-h urine protein, serum creatinine (Scr), blood urea nitrogen (BUN) but not blood alanine aminotransferase (ALT) in the DN rats. Furthermore, treatment with minocycline improved the pathological score of STZ-injured kidney and reduced the numbers of apoptotic cells in the kidney of DN rats. Moreover, minocycline mitigated the expression of caspase-3 and Bax mRNA, but increased Bcl-2 expression in the kidney of DN rats. These data indicated that minocycline improved the STZ-induced kidney damages, at least partially by protection form long-term hyperglycemia-induced kidney cell apoptosis. PMID:27476934

  1. Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis.

    PubMed

    Kutlu, O; Karaguzel, E; Gurgen, S G; Okatan, A E; Kutlu, S; Bayraktar, C; Kazaz, I O; Eren, H

    2016-05-01

    We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-β1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions. PMID:26276507

  2. Mineral contents of aloe vera leaf gel and their role on streptozotocin-induced diabetic rats.

    PubMed

    Rajasekaran, S; Sivagnanam, K; Subramanian, S

    2005-01-01

    The role of some inorganic elements like vanadium, zinc, sodium, potassium, calcium, copper, manganese, and traces of chromium in the improvement of impaired glucose tolerance and their indirect role in the management of diabetes mellitus are being increasingly recognized. In traditional methods, medicinal plants are being used, which contain both organic and inorganic constituents. In the present study, an attempt has been made to analyze the inorganic elements present in Aloe vera leaf gel and their role on diabetes-related biochemical alterations in experimental rats. Special emphasis was given to the inorganic parts by carefully preparing ash of the leaf gel. The results clearly indicate the presence of several hypoglycemic-activity-possessing elements in the gel. The ash treatment also resulted in hypoglycemic action. In conclusion, the presence of various inorganic trace elements in the gel might account for the hypoglycemic nature of the plant. PMID:16327071

  3. Short- and Longterm Glycemic Control of Streptozotocin-Induced Diabetic Rats Using Different Insulin Preparations

    PubMed Central

    Luippold, Gerd; Bedenik, Jessica; Voigt, Anke; Grempler, Rolf

    2016-01-01

    The chemical induction of diabetes with STZ has gained popularity because of the relative ease of rendering normal animals diabetic. Insulin substitution is required in STZ-rats in long-term studies to avoid ketoacidosis and consequently loss of animals. Aim of the present studies was to test different insulin preparations and different ways of administration in their ability to reduce blood glucose in STZ-induced diabetic rats. Single dosing of the long-acting insulin analogue glargine was able to dose-dependently reduce blood glucose over 4 h towards normoglycemia in STZ-treated rats. However, this effect was not sustained until 8 h post injection. A more sustained glucose-lowering effect was achieved using insulin-releasing implants. In STZ-rats, 1 insulin implant moderately lowered blood glucose levels 10 days after implantation, while 2 implants induced normoglycemia over the whole day. According to the glucose-lowering effect 1 as well as 2 insulin implants significantly reduced HbA1c measured after 26 days of implantation. In line with the improved glucose homeostasis due to the implants, urinary glucose excretion was also blunted in STZ-treated rats with 2 implants. Since diabetic nephropathy is one of the complications of longterm diabetes, renal function was characterized in the STZ-rat model. Increases in creatinine clearance and urinary albumin excretion resemble early signs of diabetic nephropathy. These functional abnormalities of the kidney could clearly be corrected with insulin-releasing implants 27 days after implantation. The data show that diabetic STZ-rats respond to exogenous insulin with regard to glucose levels as well as kidney parameters and a suitable dose of insulin implants for glucose control was established. This animal model together with the insulin dosing regimen is suitable to address diabetes-induced early diabetic nephropathy and also to study combination therapies with insulin for the treatment of type 1 diabetes. PMID:27253523

  4. Hyperactivity of ON-Type Retinal Ganglion Cells in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Yu, Jun; Wang, Lu; Weng, Shi-Jun; Yang, Xiong-Li; Zhang, Dao-Qi; Zhong, Yong-Mei

    2013-01-01

    Impairment of visual function has been detected in the early stage of diabetes but the underlying neural mechanisms involved are largely unknown. Morphological and functional alterations of retinal ganglion cells, the final output neurons of the vertebrate retina, are thought to be the major cause of visual defects in diabetes but direct evidence to support this notion is limited. In this study we investigated functional changes of retinal ganglion cells in a type 1-like diabetic mouse model. Our results demonstrated that the spontaneous spiking activity of ON-type retinal ganglion cells was increased in streptozotocin-diabetic mice after 3 to 4 months of diabetes. At this stage of diabetes, no apoptotic signals or cell loss were detected in the ganglion cell layer of the retina, suggesting that the functional alterations in ganglion cells occur prior to massive ganglion cell apoptosis. Furthermore, we found that the increased activity of ON-type ganglion cells was mainly a result of reduced inhibitory signaling to the cells in diabetes. This novel mechanism provides insight into how visual function is impaired in diabetic retinopathy. PMID:24069457

  5. Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic mice.

    PubMed

    Peng, Jia; Hui, Kang; Hao, Chen; Peng, Zhao; Gao, Qian Xing; Jin, Qi; Lei, Guo; Min, Jiang; Qi, Zhou; Bo, Chen; Dong, Qian Nian; Bing, Zhou Han; Jia, Xu You; Fu, Deng Lian

    2016-07-01

    It is known that type 1 diabetes (T1D) reduces bone mass and increases the risk for fragility fractures, an effect that has been largely ascribed to decreased bone formation. However, the potential role of decreased angiogenesis as a factor in osteogenesis reduction has not been extensively studied. Furthermore, there is controversy surrounding the effect of T1D on bone resorption. This study characterized bone microstructure, bone strength, and bone turnover of streptozotocin (STZ)-induced diabetic mice (T1D mice) and explored the role of angiogenesis in the pathogenesis of T1D-induced osteoporosis. Results demonstrate that T1D deteriorated trabecular microarchitecture and led to reduced bone strength. Furthermore, T1D mice showed reduced osteoblast number/bone surface (N.Ob/BS), mineral apposition rate, mineral surface/BS, and bone formation rate/BS, suggesting attenuated bone formation. Decreased angiogenesis was shown by a reduced number of blood vessels in the femur and decreased expression of platelet endothelial cell adhesion molecule (CD31), nerve growth factor, hypoxia-inducible factor-1α, and vascular endothelial growth factor was observed. On the other hand, reduced bone resorption, an effect that could lead to impaired osteogenesis, was demonstrated by lower osteoclast number/BS and decreased tartrate-resistant acid phosphatase and cathepsin K mRNA levels. Reduced number of osteoblasts and decreased expression of receptor activator for nuclear factor-κB ligand could be responsible for compromised bone resorption in T1D mice. In conclusion, T1D mice display reduced bone formation and bone resorption, suggesting decreased bone turnover. Furthermore, this study points to impairments in angiogenesis as a pivotal cause of decreased bone formation. PMID:27028715

  6. Magnetic resonance imaging (MRI) and pathophysiology of the rat kidney in streptozotocin-induced diabetes

    SciTech Connect

    Lohr, J.; Mazurchuk, R.J.; Acara, M.A.; Nickerson, P.A.; Fiel, R.J. )

    1991-01-01

    Proton magnetic resonance imaging was performed on rats before induction of diabetes with streptozotocin (STZ) and at 2 and 12 days postinduction. Images revealed an increase in maximal longitudinal and axial dimensions of the kidneys at 2 days and a further increase at 12 days. Similarly, an increase in the size of the remaining kidney was seen in a rat which underwent uninephrectomy as a positive control. Two major differences were observed between the kidney undergoing compensatory hypertrophy and those developing diabetic nephropathy: (i) Expansion of the renal vasculature was seen only in images of the diabetic rat; (ii) A loss in conspicuity of the normal corticomedullary junction was seen in the T2-weighted images of the diabetic rat but not in the uninephrectomized rat. Histologic examination revealed that the medulla increased to a size greater than the cortex during diabetic nephropathy whereas the medullary volume was less than that of the cortex during compensatory hypertrophy. In vitro T1 relaxation times in cortex, outer medulla and inner medulla of kidneys from control rats were measured and compared with the same respective regions in diabetic rats. When these values were correlated with tissue water content, a linear increase in relaxation rate versus percent water content from cortex to inner medulla was found in the control kidneys, but this correlation was absent in diabetic nephropathy. These studies demonstrate that MRI is an effective noninvasive tool for studying the course of renal hypertrophy and hydration changes in the development of renal disease in STZ-induced diabetes in the rat.

  7. Hypolipidaemic activity of Helicteres isora L. bark extracts in streptozotocin induced diabetic rats.

    PubMed

    Kumar, G; Murugesan, A G

    2008-02-28

    In this study, the hypolipidaemic effect of an aqueous extract of the bark of Helicteres isora was investigated in streptozotocin (STZ)-induced diabetic rats. Administration of the bark extract of Helicteres isora (100 and 200 mg/kgb.w.) for 21 days resulted in significant reduction in serum and tissue cholesterol, phospholipids, free fatty acids and triglycerides in STZ diabetic rats. In addition to that, significant (p<0.05) decrease in high-density lipoprotein (HDL) whereas significant increase (p<0.05) low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) were observed in STZ diabetic rats, which were normalized after 21 days of bark extract treatment. The bark extract at a dose of 200 mg/kgb.w. showed much significant hypolipidaemic effect than at the dose of 100 mg/kgb.w. PMID:18191354

  8. Anti-diabetic Effect of Friedelan Triterpenoids in Streptozotocin Induced Diabetic Rat.

    PubMed

    Mandal, Amitava; Das, Vaskar; Ghosh, Pranab; Ghosh, Shilpi

    2015-10-01

    We herein report the anti-diabetic effect of the natural friedelan tritepenoid, 4-oxa-3, 4-secofriedelan (cerin), isolated from cork tissue of Quercus suber L. and its oxygenated derivative, 4-oxa-3, 4-secofriedelan-3-oic acid (cerin(ox)) in streptozotocin (STZ)-induced diabetic rat. Male Sprague Dawley rats were randomized into four groups: non-diabetic control (Group I), STZ-induced diabetic rats (Group II), STZ-induced diabetic rats treated with cerin (Group III), and STZ-induced diabetic rats treated with cerin(ox), (Group IV). Administration of cerin (3 mg/kg) and cerin(ox), (3 mg/kg) orally to STZ-diabetic rats for three weeks improved the body weight, reduced serum glucose level and activities of alkaline phosphatase, acid phosphatase, glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase, and restored liver antioxidant status. PMID:26669102

  9. Hypoglycemic Effect of Jicama (Pachyrhizus erosus) Extract on Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Park, Chan Joo; Han, Ji-Sook

    2015-01-01

    The purpose of this research was to investigate the inhibitory effect of jicama extract on α-glucosidase activity, α-amylase activity, and postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. Jicama extract showed prominent inhibitory effects against α-glucosidase and α-amylase. The IC50 values of jicama extract against α-glucosidase and α-amylase were 0.083±0.004 and 0.091±0.017 mg/mL, respectively. The increase in postprandial blood glucose levels was more significantly suppressed in the jicama extract-administered group than in the control group of both STZ-induced diabetic and normal mice. Blood glucose levels of the control group increased to 383.75±11.54 and 402.50±15.32 mg/dL at 30 and 60 min after a meal and decreased to 349.67±11.62 mg/dL at 120 min. However, postprandial blood glucose levels were significantly decreased, when diabetic mice were fed with jicama extract (342.00±15.73, 367.00±13.00, and 329.67±12.43 mg/dL at 30, 60, and 120 min, respectively). Furthermore, the area under the curve was significantly decreased with jicama extract administration in diabetic mice (P<0.05). Therefore, these results indicate that jicama extract may help decrease postprandial blood glucose level by inhibiting α-glucosidase. PMID:26175995

  10. Hypoglycemic Effect of Jicama (Pachyrhizus erosus) Extract on Streptozotocin-Induced Diabetic Mice.

    PubMed

    Park, Chan Joo; Han, Ji-Sook

    2015-06-01

    The purpose of this research was to investigate the inhibitory effect of jicama extract on α-glucosidase activity, α-amylase activity, and postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. Jicama extract showed prominent inhibitory effects against α-glucosidase and α-amylase. The IC50 values of jicama extract against α-glucosidase and α-amylase were 0.083±0.004 and 0.091±0.017 mg/mL, respectively. The increase in postprandial blood glucose levels was more significantly suppressed in the jicama extract-administered group than in the control group of both STZ-induced diabetic and normal mice. Blood glucose levels of the control group increased to 383.75±11.54 and 402.50±15.32 mg/dL at 30 and 60 min after a meal and decreased to 349.67±11.62 mg/dL at 120 min. However, postprandial blood glucose levels were significantly decreased, when diabetic mice were fed with jicama extract (342.00±15.73, 367.00±13.00, and 329.67±12.43 mg/dL at 30, 60, and 120 min, respectively). Furthermore, the area under the curve was significantly decreased with jicama extract administration in diabetic mice (P<0.05). Therefore, these results indicate that jicama extract may help decrease postprandial blood glucose level by inhibiting α-glucosidase. PMID:26175995

  11. Hypolipidemic Activity of Eryngium carlinae on Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Noriega-Cisneros, Ruth; Ortiz-Ávila, Omar; Esquivel-Gutiérrez, Edgar; Clemente-Guerrero, Mónica; Manzo-Avalos, Salvador; Salgado-Garciglia, Rafael; Cortés-Rojo, Christian; Boldogh, Istvan; Saavedra-Molina, Alfredo

    2012-01-01

    Diabetes mellitus (DM) is a significant risk factor for the development of cardiovascular complications. This study was undertaken to investigate the effect of chronic administration of ethanolic extract of Eryngium carlinae on glucose, creatinine, uric acid, total cholesterol, and triglycerides levels in serum of streptozotocin- (STZ-) induced diabetic rats. Triglycerides, total cholesterol, and uric acid levels increased in serum from diabetic rats. The treatment with E. carlinae prevented these changes. The administration of E. carlinae extract reduced the levels of creatinine, uric acid, total cholesterol, and triglycerides. Thus administration of E. carlinae is able to reduce hyperlipidemia related to the cardiovascular risk in diabetes mellitus. PMID:22162811

  12. Resveratrol, an activator of SIRT1, restores erectile function in streptozotocin-induced diabetic rats

    PubMed Central

    Yu, Wen; Wan, Zan; Qiu, Xue-Feng; Chen, Yun; Dai, Yu-Tian

    2013-01-01

    The high incidence of erectile dysfunction (ED) in diabetes highlights a need for effective treatment strategies. Resveratrol, an activator of silent information regulator 2-related enzymes 1 (sirtuin1, SIRT1), has received attention for its valuable effects in cancer, neurodegenerative diseases, longevity and cardiovascular disease. To explore the effects of resveratrol in diabetes-induced ED, resveratrol was administered to rats with streptozocin (65 mg kg−1)-induced diabetes. Erectile function, cavernous structure, tissue protein expression of silent information regulator 2-related enzymes 1 (sirtuin1, SIRT1), p53 and forkhead transcription factor O 3a (FOXO3a), superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in the corpora cavernosa were studied. We found that SIRT1 was expressed in cavernosal tissue, and it was downregulated in the corpora of diabetic rats. The administration of resveratrol upregulated the expression of SIRT1 and restored erectile function. In contrast, resveratrol downregulated the expression of p53 and FOXO3a, which regulate apoptosis and oxidative stress. Furthermore, the resveratrol-treated group showed an improvement in smooth muscle content, SOD activity and MDA levels when compared with the diabetic group. Therefore, the ability of resveratrol to improve diabetes-induced ED is likely related to its activation of SIRT1 expression, thus causing the suppression of apoptosis and resistance towards oxidative stress. PMID:23792339

  13. Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: Protective role of arjunolic acid

    SciTech Connect

    Manna, Prasenjit; Ghosh, Jyotirmoy; Das, Joydeep

    2010-04-15

    Present study investigates the beneficial role of arjunolic acid (AA) against the alteration in the cytokine levels and simultaneous activation of oxidative stress responsive signaling pathways in spleen under hyperglycemic condition. Diabetes was induced by injection of streptozotocin (STZ) (at a dose of 70 mg/kg body weight, injected in the tail vain). STZ administration elevated the levels of IL-2 as well as IFN-gamma and attenuated the level of TNF-alpha in the sera of diabetic animals. In addition, hyperglycemia is also associated with the increased production of intracellular reactive intermediates resulting with the elevation in lipid peroxidation, protein carbonylation and reduction in intracellular antioxidant defense. Investigating the oxidative stress responsive cell signaling pathways, increased expressions (immunoreactive concentrations) of phosphorylated p65 as well as its inhibitor protein phospho IkappaBalpha and phosphorylated mitogen activated protein kinases (MAPKs) have been observed in diabetic spleen tissue. Studies on isolated splenocytes revealed that hyperglycemia caused disruption of mitochondrial membrane potential, elevation in the concentration of cytosolic cytochrome c as well as activation of caspase 3 leading to apoptotic cell death. Histological examination revealed that diabetic induction depleted the white pulp scoring which is in agreement with the reduced immunological response. Treatment with AA prevented the hyperglycemia and its associated pathogenesis in spleen tissue. Results suggest that AA might act as an anti-diabetic and immunomodulatory agent against hyperglycemia.

  14. Changes in the pharmacokinetic of sildenafil citrate in rats with Streptozotocin-induced diabetic nephropathy

    PubMed Central

    2014-01-01

    Aim The present investigates deals with the change in the pharmacokinetic of Sildenafil citrate (SIL) in disease condition like diabetic nephropathy (DN). Method Diabetes was induced in rats by administering Streptozotocin i.e. STZ (60 mg/kg, IP) saline solution. Assessment of diabetes was done by GOD-POD method and conformation of DN was done by assessing the level of Creatinine, Blood Urea Nitrogen (BUN) and Albuminurea. After the conformation of DN single dose of drug SIL (2.5 mg/kg, p.o.) were given orally and Pharmacokinetic Parameters like [AUC o-t (ug.h/ml), AUC 0-∞, Cmax, Tmax, Kel, Clast] were estimated in the plasma by the help of HPLC-UV. Result There was significant increase (p < 0.01) in the Pharmacokinetic parameters of SIL in DN rat (AUC0-t, AUC0-∞, Cmax, Tmax and T1/2) compare to normal control rat and significant increase Kel in the DN rat compare to control rat. Conclusion The study concluded that there was significant (p < 0.01) increase in the bioavailability of SIL in DN. PMID:24398037

  15. The effects of photobiomodulation on healing of bone defects in streptozotocin induced diabetic rats

    NASA Astrophysics Data System (ADS)

    Martinez Costa Lino, Maíra D.; Bastos de Carvalho, Fabíola; Ferreira Moraes, Michel; Augusto Cardoso, José; Pinheiro, Antônio L. B.; Maria Pedreira Ramalho, Luciana

    2011-03-01

    Previous studies have shown positive effects of Low level laser therapy (LLLT) on the repair of bone defects, but there are only a few that associates bone healing in the presence of a metabolic disorder as Diabetes Melitus and LLLT. The aim of this study was to assess histologically the effect of LLLT (AsGaAl), 780nm, 70mW, CW, Ø~0.4mm, 16J/cm2 per session) on the repair of surgical defects created in the femur of diabetic and non-diabetic Wistar Albinus rats. Surgical bone defects were created in 60 animals divided into four groups of 15 animals each: Group C (non-diabetic - control); Group CL (non-diabetic + LLLT); Group CD (diabetic); Group CDL (diabetic + LLLT). The animals on the irradiated group received 16 J/cm2 per session divided into four points around the defect, being the first irradiation immediately after surgery and repeated every 48h for 14 days. The animals were killed 15, 21 and 30 days after surgery. The results of the present investigation showed histological evidence of improved amount of collagen fibers at early stages of the bone healing (15 days) and increased amount of well organized bone trabeculae at the end of the experimental period (30 days) on irradiated animals, (diabetic and non-diabetic) compared to non irradiated ones. It is concluded that LLLT has a positive biomodulative effect on the healing process of bone defects, even when diabetes mellitus was present.

  16. Streptozotocin Induced Neurotoxicity Involves Alzheimer's Related Pathological Markers: a Study on N2A Cells.

    PubMed

    Biswas, Joyshree; Goswami, Poonam; Gupta, Sonam; Joshi, Neeraj; Nath, Chandishwar; Singh, Sarika

    2016-07-01

    Intracerebroventricular (icv) injection of streptozotocin (STZ) in rat brain causes prolonged impairment of brain energy metabolism and oxidative damage and leads to cognitive dysfunction; however, its mechanistic specific effects on neurons are not known. The present study was conducted to investigate the STZ-induced cellular and molecular alterations in mouse neuronal N2A cells. The N2A cells were treated with STZ (10, 50, 100, 1000 μM) for 48 h, and different assays were performed. STZ treatment caused significant decrease in cell viability, choline levels, increased acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation. STZ treatment also led to low levels of glucose uptake, elevated mitochondrial stress, translocation of cytochrome c in cytosol, phosphatidylserine externalization, increased expression of caspase-3 and DNA damage. Co-treatment of clinically used drug donepezil (1 μM) offered significant protection against STZ induced neurotoxicity. Donepezil treatment significantly inhibited the STZ induced neurotoxicity, altered choline level, AChE activity, lowered glucose uptake and mitochondrial stress. However, the caspase-3 expression remains unaltered with co-treatment of donepezil. In conclusion, findings showed that STZ treated N2A cells exhibited the Alzheimer's disease (AD) related pathological markers which are attenuated with co-treatment of donepezil. Findings of the study suggested the potent use of STZ treated N2A cells as in vitro experimental test model to study the disease mechanism at cellular level. PMID:25823512

  17. Antihyperlipidemic effect of a polyherbal mixture in streptozotocin-induced diabetic rats.

    PubMed

    Ghorbani, Ahmad; Shafiee-Nick, Reza; Rakhshandeh, Hassan; Borji, Abasalt

    2013-01-01

    The effects of a polyherbal mixture containing Allium sativum, Cinnamomum zeylanicum, Citrullus colocynthis, Juglans regia, Nigella sativa, Olea europaea, Punica granatum, Salvia officinalis, Teucrium polium, Trigonella foenum, Urtica dioica, and Vaccinium arctostaphylos were tested on biochemical parameters in diabetic rats. The animals were randomized into three groups: (1) normal control, (2) diabetic control, and (3) diabetic rats which received diet containing 15% (w/w) of this mixture for 4 weeks. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg). At the end of experiment, the mixture had no significant effect on serum hepatic enzymes, aspartate aminotransferase, and alanine aminotransferase activities. However, the level of fasting blood glucose, water intake, and urine output in treated group was lower than that in diabetic control rats (P < 0.01). Also, the levels of triglyceride and total cholesterol in polyherbal mixture treated rats were significantly lower than those in diabetic control group (P < 0.05). Our results demonstrated that this polyherbal mixture has beneficial effects on blood glucose and lipid profile and it has the potential to be used as a dietary supplement for the management of diabetes. PMID:24383002

  18. The Effect of Pioglitazone on Antioxidant Levels and Renal Histopathology in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Kuru Karabas, Munire; Ayhan, Mediha; Guney, Engin; Serter, Mukadder; Meteoglu, Ibrahim

    2013-01-01

    Objective. Diabetic nephropathy is the most commonly seen cause of chronic renal failure, and oxidative stress is important in etiology. In the present study, favorable effects (if any) of the treatment with a thiazolidinedione group drug, pioglitazone, on antioxidant enzyme levels in the renal tissue, renal histopathology, and inflammatory cytokine levels have been investigated. Method. Forty male Wistar rats were divided into 4 groups as the control, diabetic control, and 10 and 30 mg pioglitazone-administered diabetic groups. After 4 weeks, antioxidant enzyme levels in renal tissues and inflammatory markers were investigated. Results. Blood glucose levels did not differ between the diabetic control and drug-administered groups. In pioglitazone-administered rats, histopathological findings such as tubular dilation, necrotic tubular epithelium, glomerular focal necrosis, and vascular consolidation were observed at a lesser extent than the diabetic control group. Any difference was not detected between the diabetic groups with respect to the levels of malondialdehyde, superoxide dismutase, catalase, glutathione, nitric oxide, interleukin-6, and tumor necrosis factor-alpha. Conclusion. Pioglitazone regressed development of histopathological lesions such as glomerular focal necrosis, tubular epithelial necrosis, tubular dilation, and vascular wall consolidation. However, any favorable effect on antioxidant enzyme levels in renal tissues and inflammation markers was not detected. PMID:23762597

  19. Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats.

    PubMed

    Phyu, Hnin Ei; Irwin, Jordon Candice; Vella, Rebecca Kate; Fenning, Andrew Stuart

    2016-06-01

    Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia. The aim of this study was to determine whether resveratrol, a polyphenol antioxidant compound, when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older, obese, diabetic rats. Diabetes was induced in 6-month old, obese, male Wistar rats via a single intravenous dose of streptozotocin (65 mg/kg). Randomly selected animals were administered resveratrol (2 mg/kg) via oral gavage daily for 8 weeks. Body weights, blood glucose levels, food intake and water consumption were monitored, and assessments of vascular reactivity, tactile allodynia and left ventricular function were performed. Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats (P<0·05). There were no significant changes in standardised vasorelaxation responses, plasma glucose concentrations, water consumption, body weight, left ventricular hypertrophy, kidney hypertrophy, heart rate or left ventricular compliance with resveratrol administration. Resveratrol-mediated improvements in vascular and nerve function in old, obese, diabetic rats were associated with its reported antioxidant effects. Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus (i.e. hyperglycaemia, polydypsia and a failure to thrive). This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus. PMID:27153202

  20. Antiperoxidative and antioxidant effects of Casearia esculenta root extract in streptozotocin-induced diabetic rats.

    PubMed Central

    Prakasam, A.; Sethupathy, S.; Pugalendi, K. V.

    2005-01-01

    Oxidative stress is currently suggested to play as a pathogenesis in the development of diabetes mellitus. The present study was designed to evaluate the effect of Casearia esculenta root extract on oxidative stress-related parameters in streptozotocin (STZ) -induced diabetic rats. Antidiabetic treatment with C. esculenta root extract (45 days) significantly (p < .05) decreased thiobarbituric acid reactive substances (TBARS) and remarkably improved tissue antioxidants status such as glutathione (GSH), ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) in liver and kidney of STZ-diabetic rats. In diabetics rats, the activities of enzymatic antioxidants such as superoxide dismutase (SOD, EC 1.11.1.1) catalase (CAT, EC 1.11.1.6) were decreased significantly while the activity of glutathione peroxidase (GPx, EC 1.11.1.9) decreased in the liver and increased in the kidney. The treatment of diabetic rats with C. esculenta root extract over a 45-day period returned these levels close to normal. These results suggest that C. esculenta root extracts exhibit antiperoxidative as well as antioxidant effects in STZ-induced diabetic rats. PMID:16197726

  1. Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract.

    PubMed

    Mediani, Ahmed; Abas, Faridah; Maulidiani, M; Khatib, Alfi; Tan, Chin Ping; Ismail, Intan Safinar; Shaari, Khozirah; Ismail, Amin; Lajis, N H

    2016-09-01

    Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus. PMID:27318080

  2. Antidiabetic effect of polysaccharides from Pleurotus ostreatus in streptozotocin-induced diabetic rats.

    PubMed

    Zhang, Yan; Hu, Tao; Zhou, Hongli; Zhang, Yang; Jin, Gang; Yang, Yu

    2016-02-01

    This study was performed to evaluate the effects of total polysaccharides extracted from Pleurotus ostreatus on type 2 diabetes. Rats were administered with high-fat diet and streptozotocin (STZ) to induce diabetes. The rats were then treated with 100, 200, and 400 mg/kg/d POP or vehicle for 4 weeks. Our experiments indicated that POP reduces hyperglycemia and hyperlipidemia levels, improves insulin resistance, and increases glycogen storage by activating GSK3 phosphorylation and GLUT4 translocation. Moreover, POP reduces the risk of oxidative damage by increasing superoxide dismutase(SOD), catalase(CAT), and glutathione peroxidase(GSH-Px) activities and decreasing malonaldehyde(MDA) level. These results suggest that POP exerts antidiabetic effect on STZ-induced diabetic rats. PMID:26627601

  3. The antioxidant effect of angiotensin II receptor blocker, losartan, in streptozotocin-induced diabetic rats.

    PubMed

    Kamper, Maria; Tsimpoukidi, Olia; Chatzigeorgiou, Antonios; Lymberi, Maria; Kamper, Elli F

    2010-07-01

    We determined the effect of a short-term angiotensin II signaling blockade on vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1), nitric oxide (NO), and malondialdehyde (MDA) (index of lipid peroxidation) levels in the systemic circulation and on peroxynitrite generation and insulitis development in the streptozotocin (STZ) diabetic rats' pancreas. Diabetes was induced in Wistar rats by intraperitoneal STZ injection. Diabetic rats were treated for 1 week with losartan (20 mg/kg/body weight/day in the drinking water), and pancreas and blood were collected for histochemical, immunohistochemical, and biochemical studies. Diabetic rats showed greater VEGF, sICAM-1, NO, and MDA levels, a high score of insulitis, increased nitrotyrosine staining, and markedly reduced pancreatic insulin content when compared with controls. Losartan treatment suppressed the excessive NO and lipid peroxidation production systemically without restoring them to that of healthy subjects and reduced VEGF levels while leaving sICAM-1 levels unchanged. The insulitis score and nitrotyrosine staining were reduced, whereas the pancreatic islets and the beta-cell area were increased significantly in the treated group, indicating the reduction of inflammation and nitrosative stress and an early regeneration of beta-cell mass in the pancreas. Conclusively, in the STZ diabetic rat model, even a short-term losartan treatment improves oxidative and nitrosative stress systemically and locally, improving the islets' environment and accelerating beta-cell regeneration. PMID:20621034

  4. Flemingia macrophylla Extract Ameliorates Experimental Osteoporosis in Ovariectomized Rats

    PubMed Central

    Ho, Hui-Ya; Wu, Jin-Bin; Lin, Wen-Chuan

    2011-01-01

    Flemingia macrophylla (Leguminosae), a native plant of Taiwan, is used as folk medicine. An in vitro study showed that a 75% ethanolic extract of F. macrophylla (FME) inhibited osteoclast differentiation of cultured rat bone marrow cells, and the active component, lespedezaflavanone A (LDF-A), was isolated. It was found that oral administration of FME for 13 weeks suppressed bone loss in ovariectomized rats, an experimental model of osteoporosis. In addition, FME decreased urinary deoxypyridinoline concentrations but did not inhibit serum alkaline phosphatase activities, indicating that it ameliorated bone loss via inhibition of bone resorption. These results suggest that FME may represent a useful remedy for the treatment of bone resorption diseases, such as osteoporosis. In addition, LDF-A could be used as a marker compound to control the quality of FME. PMID:19942664

  5. Droplet confinement and leakage: Causes, underlying effects, and amelioration strategies

    PubMed Central

    Debon, Aaron P.; Wootton, Robert C. R.

    2015-01-01

    The applicability of droplet-based microfluidic systems to many research fields stems from the fact that droplets are generally considered individual and self-contained reaction vessels. This study demonstrates that, more often than not, the integrity of droplets is not complete, and depends on a range of factors including surfactant type and concentration, the micro-channel surface, droplet storage conditions, and the flow rates used to form and process droplets. Herein, a model microfluidic device is used for droplet generation and storage to allow the comparative study of forty-four different oil/surfactant conditions. Assessment of droplet stability under these conditions suggests a diversity of different droplet failure modes. These failure modes have been classified into families depending on the underlying effect, with both numerical and qualitative models being used to describe the causative effect and to provide practical solutions for droplet failure amelioration in microfluidic systems. PMID:26015831

  6. Flemingia macrophylla Extract Ameliorates Experimental Osteoporosis in Ovariectomized Rats.

    PubMed

    Ho, Hui-Ya; Wu, Jin-Bin; Lin, Wen-Chuan

    2011-01-01

    Flemingia macrophylla (Leguminosae), a native plant of Taiwan, is used as folk medicine. An in vitro study showed that a 75% ethanolic extract of F. macrophylla (FME) inhibited osteoclast differentiation of cultured rat bone marrow cells, and the active component, lespedezaflavanone A (LDF-A), was isolated. It was found that oral administration of FME for 13 weeks suppressed bone loss in ovariectomized rats, an experimental model of osteoporosis. In addition, FME decreased urinary deoxypyridinoline concentrations but did not inhibit serum alkaline phosphatase activities, indicating that it ameliorated bone loss via inhibition of bone resorption. These results suggest that FME may represent a useful remedy for the treatment of bone resorption diseases, such as osteoporosis. In addition, LDF-A could be used as a marker compound to control the quality of FME. PMID:19942664

  7. Acetoacetate Accelerates Muscle Regeneration and Ameliorates Muscular Dystrophy in Mice.

    PubMed

    Zou, Xiaoting; Meng, Jiao; Li, Li; Han, Wanhong; Li, Changyin; Zhong, Ran; Miao, Xuexia; Cai, Jun; Zhang, Yong; Zhu, Dahai

    2016-01-29

    Acetoacetate (AA) is a ketone body and acts as a fuel to supply energy for cellular activity of various tissues. Here, we uncovered a novel function of AA in promoting muscle cell proliferation. Notably, the functional role of AA in regulating muscle cell function is further evidenced by its capability to accelerate muscle regeneration in normal mice, and it ameliorates muscular dystrophy in mdx mice. Mechanistically, our data from multiparameter analyses consistently support the notion that AA plays a non-metabolic role in regulating muscle cell function. Finally, we show that AA exerts its function through activation of the MEK1-ERK1/2-cyclin D1 pathway, revealing a novel mechanism in which AA serves as a signaling metabolite in mediating muscle cell function. Our findings highlight the profound functions of a small metabolite as signaling molecule in mammalian cells. PMID:26645687

  8. Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice

    PubMed Central

    Andoh, Tsugunobu; Ouchi, Kenji; Inatomi, Satoshi

    2014-01-01

    Pleurotus eryngii (P. eryngii) is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI). Intranasal instillation of lipopolysaccharide (LPS) (10 μg/site/mouse) induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid) as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3–1 g/kg, p.o. (HTPE)) 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection. PMID:24799939

  9. Riluzole Ameliorates Harmaline-induced Tremor in Rat

    PubMed Central

    Shourmasti, Fatemeh Rahimi; Goudarzi, Iran; Abrari, Kataneh; Salmani, Mahmoud Elahdadi; Laskarbolouki, Taghi

    2014-01-01

    Introduction Excessive olivo-cerebellar burst-firing occurs during harmaline-induced tremor. We hypothesized that antiglutamatergic agents would suppress harmaline tremor. From this point of view, the aim of the present study was to investigate the effects of riluzole on harmaline-induced tremor in rat. Methods Four groups of Wistar rats weighing 80–100 g were injected with harmaline (30 mg/ kg i.p.) for inducing experimental tremors. The rats in group 1 served as control, whereas the animals in groups 2, 3 and 4 were also given riluzole intraperitonealy at doses of 2, 4 and 8 mg/ kg 30 min before and 90 min after harmaline administration. The onset latency, intensity and duration of tremor were recorded. Results The results of this study demonstrated that riluzole could significantly increase latency period, and reduce duration and intensity of tremor. Discussion It is concluded that pretreatment of riluzole can ameliorate harmaline-induced tremor in rats. PMID:25337372

  10. Evaluation of water treatment sludge for ameliorating acid mine waste.

    PubMed

    Van Rensburg, L; Morgenthal, T L

    2003-01-01

    This study investigated the liming effect of water treatment sludge on acid mine spoils. The study was conducted with sludge from a water purification plant along the Vaal River catchments in South Africa. The optimum application rate for liming acid spoils and the speed and depth with which the sludge reacted with the mine waste were investigated. Chemical analysis indicated that the sludge is suitable as a liming agent because of its alkaline pH (8.08), high bicarbonate concentration (183.03 mg L(-1)), and low salinity (electrical conductivity = 76 mS m(-1)). The high cation exchange capacity of 15.47 cmol(c) kg(-1) and elevated nitrate concentration (73.16 mg L(-1)) also increase its value as an ameliorative material. The soluble concentrations for manganese, aluminum, lead, and selenium were high at a pH of 5 although only selenium (0.83 mg L(-1)) warranted some concern. According to experimental results, the application of 10 Mg ha(-1) of sludge to acid gold tailings increased the leach water pH from 4.5 to more than 7.5 and also increased the medium pH from 2.4 to 7.5. The addition of sludge further reduced the solubility of iron, manganese, copper, and zinc in the ameliorated gold tailings, but increased the electrical conductivity. The liming tempo was highest in the coal discard profile that had a coarse particle size distribution and took the longest to move through the gold tailings that had a fine particle size distribution. Results from this study indicate that the water treatment sludge investigated is suitable as a liming agent for rehabilitation of acid mine waste. PMID:14535306

  11. Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury

    PubMed Central

    Lempiäinen, Juha; Finckenberg, Piet; Mervaala, Elina E; Storvik, Markus; Kaivola, Juha; Lindstedt, Ken; Levijoki, Jouko; Mervaala, Eero M

    2014-01-01

    Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (α2-AR) agonist, protects against kidney I/R injury. Sprague–Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 μg/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 μg/kg). The effects of Dex postconditiong (Dex 1 or 10 μg/kg i.v. after reperfusion) as well as the effects of peripheral α2-AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen-activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre- nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning. PMID:25505591

  12. Sialic acid supplementation ameliorates puromycin aminonucleoside nephrosis in rats.

    PubMed

    Pawluczyk, Izabella Z A; Najafabadi, Maryam G; Brown, Jeremy R; Bevington, Alan; Topham, Peter S

    2015-09-01

    Defects in sialylation are known to have serious consequences on podocyte function leading to collapse of the glomerular filtration barrier and the development of proteinuria. However, the cellular processes underlying aberrant sialylation in renal disease are inadequately defined. We have shown in cultured human podocytes that puromycin aminonucleoside (PAN) downregulates enzymes involved in sialic acid metabolism and redox homeostasis and these can be rescued by co-treatment with free sialic acid. The aim of the current study was to ascertain whether sialic acid supplementation could improve renal function and attenuate desialylation in an in vivo model of proteinuria (PAN nephrosis) and to delineate the possible mechanisms involved. PAN nephrotic rats were supplemented with free sialic acid, its precursor N-acetyl mannosamine or the NADPH oxidase inhibitor apocynin. Glomeruli, urine, and sera were examined for evidence of kidney injury and therapeutic efficacy. Of the three treatment regimens, sialic acid had the broadest efficacy in attenuating PAN-induced injury. Proteinuria and urinary nephrin loss were reduced. Transmission electron microscopy revealed that podocyte ultrastructure, exhibited less severe foot process effacement. PAN-induced oxidative stress was ameliorated as evidenced by a reduction in glomerular NOX4 expression and a downregulation of urine xanthine oxidase levels. Sialylation dysfunction was improved as indicated by reduced urinary concentrations of free sialic acid, restored electrophoretic mobility of podocalyxin, and improved expression of a sialyltransferase. These data indicate that PAN induces alterations in the expression of enzymes involved in redox control and sialoglycoprotein metabolism, which can be ameliorated by sialic acid supplementation possibly via its properties as both an antioxidant and a substrate for sialylation. PMID:26121320

  13. Boldine Ameliorates Vascular Oxidative Stress and Endothelial Dysfunction: Therapeutic Implication for Hypertension and Diabetes

    PubMed Central

    Lau, Yeh Siiang; Ling, Wei Chih; Murugan, Dharmani

    2015-01-01

    Abstract: Epidemiological and clinical studies have demonstrated that a growing list of natural products, as components of the daily diet or phytomedical preparations, are a rich source of antioxidants. Boldine [(S)-2,9-dihydroxy-1,10-dimethoxy-aporphine], an aporphine alkaloid, is a potent antioxidant found in the leaves and bark of the Chilean boldo tree. Boldine has been extensively reported as a potent “natural” antioxidant and possesses several health-promoting properties like anti-inflammatory, antitumor promoting, antidiabetic, and cytoprotective. Boldine exhibited significant endothelial protective effect in animal models of hypertension and diabetes mellitus. In isolated thoracic aorta of spontaneously hypertensive rats, streptozotocin-induced diabetic rats, and db/db mice, repeated treatment of boldine significantly improved the attenuated acetylcholine-induced endothelium-dependent relaxations. The endothelial protective role of boldine correlated with increased nitric oxide levels and reduction of vascular reactive oxygen species via inhibition of the nicotinamide adenine dinucleotide phosphate oxidase subunits, p47phox and nicotinamide adenine dinucleotide phosphate oxidase 2, and angiotensin II–induced bone morphogenetic protein-4 oxidative stress cascade with downregulation of angiotensin II type 1 receptor and bone morphogenetic protein-4 expression. Taken together, it seems that boldine may exert protective effects on the endothelium via several mechanisms, including protecting nitric oxide from degradation by reactive oxygen species as in oxidative stress–related diseases. The present review supports a complimentary therapeutic role of the phytochemical, boldine, against endothelial dysfunctions associated with hypertension and diabetes mellitus by interfering with the oxidative stress–mediated signaling pathway. PMID:25469805

  14. Boldine Ameliorates Vascular Oxidative Stress and Endothelial Dysfunction: Therapeutic Implication for Hypertension and Diabetes.

    PubMed

    Lau, Yeh Siiang; Ling, Wei Chih; Murugan, Dharmani; Mustafa, Mohd Rais

    2015-06-01

    Epidemiological and clinical studies have demonstrated that a growing list of natural products, as components of the daily diet or phytomedical preparations, are a rich source of antioxidants. Boldine [(S)-2,9-dihydroxy-1,10-dimethoxy-aporphine], an aporphine alkaloid, is a potent antioxidant found in the leaves and bark of the Chilean boldo tree. Boldine has been extensively reported as a potent "natural" antioxidant and possesses several health-promoting properties like anti-inflammatory, antitumor promoting, antidiabetic, and cytoprotective. Boldine exhibited significant endothelial protective effect in animal models of hypertension and diabetes mellitus. In isolated thoracic aorta of spontaneously hypertensive rats, streptozotocin-induced diabetic rats, and db/db mice, repeated treatment of boldine significantly improved the attenuated acetylcholine-induced endothelium-dependent relaxations. The endothelial protective role of boldine correlated with increased nitric oxide levels and reduction of vascular reactive oxygen species via inhibition of the nicotinamide adenine dinucleotide phosphate oxidase subunits, p47 and nicotinamide adenine dinucleotide phosphate oxidase 2, and angiotensin II-induced bone morphogenetic protein-4 oxidative stress cascade with downregulation of angiotensin II type 1 receptor and bone morphogenetic protein-4 expression. Taken together, it seems that boldine may exert protective effects on the endothelium via several mechanisms, including protecting nitric oxide from degradation by reactive oxygen species as in oxidative stress-related diseases. The present review supports a complimentary therapeutic role of the phytochemical, boldine, against endothelial dysfunctions associated with hypertension and diabetes mellitus by interfering with the oxidative stress-mediated signaling pathway. PMID:25469805

  15. MicroRNA-29a Promotion of Nephrin Acetylation Ameliorates Hyperglycemia-Induced Podocyte Dysfunction

    PubMed Central

    Lin, Chun-Liang; Lee, Pei-Hsien; Hsu, Yung-Chien; Lei, Chen-Chou; Ko, Jih-Yang; Chuang, Pei-Chin; Huang, Yu-Ting; Wang, Shao-Yu; Wu, Shin-Long; Chen, Yu-Shan; Chiang, Wen-Chih; Reiser, Jochen

    2014-01-01

    Podocyte dysfunction is a detrimental feature in diabetic nephropathy, with loss of nephrin integrity contributing to diabetic podocytopathy. MicroRNAs (miRs) reportedly modulate the hyperglycemia-induced perturbation of renal tissue homeostasis. This study investigated whether regulation of histone deacetylase (HDAC) actions and nephrin acetylation by miR-29 contributes to podocyte homeostasis and renal function in diabetic kidneys. Hyperglycemia accelerated podocyte injury and reduced nephrin, acetylated nephrin, and miR-29a levels in primary renal glomeruli from streptozotocin-induced diabetic mice. Diabetic miR-29a transgenic mice had better nephrin levels, podocyte viability, and renal function and less glomerular fibrosis and inflammation reaction compared with diabetic wild-type mice. Overexpression of miR-29a attenuated the promotion of HDAC4 signaling, nephrin ubiquitination, and urinary nephrin excretion associated with diabetes and restored nephrin acetylation. Knockdown of miR-29a by antisense oligonucleotides promoted HDAC4 action, nephrin loss, podocyte apoptosis, and proteinuria in nondiabetic mice. In vitro, interruption of HDAC4 signaling alleviated the high glucose–induced apoptosis and inhibition of nephrin acetylation in podocyte cultures. Furthermore, HDAC4 interference increased the acetylation status of histone H3 at lysine 9 (H3K9Ac), the enrichment of H3K9Ac in miR-29a proximal promoter, and miR-29a transcription in high glucose–stressed podocytes. In conclusion, hyperglycemia impairs miR-29a signaling to intensify HDAC4 actions that contribute to podocyte protein deacetylation and degradation as well as renal dysfunction. HDAC4, via epigenetic H3K9 hypoacetylation, reduces miR-29a transcription. The renoprotective effects of miR-29a in diabetes-induced loss of podocyte integrity and renal homeostasis highlights the importance of post-translational acetylation reactions in podocyte microenvironments. Increasing miR-29a action may

  16. Probiotic BIFICO cocktail ameliorates Helicobacter pylori induced gastritis

    PubMed Central

    Yu, Hong-Jing; Liu, Wei; Chang, Zhen; Shen, Hui; He, Li-Juan; Wang, Sha-Sha; Liu, Lu; Jiang, Yuan-Ying; Xu, Guo-Tong; An, Mao-Mao; Zhang, Jun-Dong

    2015-01-01

    AIM: To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection. METHODS: Colonization of BIFICO strains in the mouse stomach was determined by counting colony-forming units per gram of stomach tissue. After treatment with or without BIFICO, inflammation and H. pylori colonization in the mouse stomach were analyzed by hematoxylin and eosin and Giemsa staining, respectively. Cytokine levels were determined by enzyme-linked immunosorbent assay and Milliplex. The activation of nuclear factor (NF)-κB and MAPK signaling in human gastric epithelial cells was evaluated by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was used to quantify TLR2, TLR4 and MyD88 mRNA expression in the mouse stomach. RESULTS: We demonstrated that BIFICO, which contains a mixture of Enterococcus faecalis, Bifidobacterium longum and Lactobacillus acidophilus, was tolerant to the mouse stomach environment and was able to survive both the 8-h and 3-d courses of administration. Although BIFICO treatment had no effect on the colonization of H. pylori in the mouse stomach, it ameliorated H. pylori-induced gastritis by significantly inhibiting the expression of cytokines and chemokines such as TNF-α, IL-1β, IL-10, IL-6, G-CSF and MIP-2 (P < 0.05). These results led us to hypothesize that BIFICO treatment would diminish the H. pylori-induced inflammatory response in gastric mucosal epithelial cells in vitro via the NF-κB and MAPK signaling pathways. Indeed, we observed a decrease in the expression of the NF-κB subunit p65 and in the phosphorylation of IκB-α, ERK and p38. Moreover, there was a significant decrease in the production of IL-8, TNF-α, G-CSF and GM-CSF (P < 0.05), and the increased expression of TLR2, TLR4 and MyD88 induced by H. pylori in the stomach was also significantly reduced following BIFICO treatment (P < 0.05). CONCLUSION: Our

  17. Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP.

    PubMed

    Han, Na-Ra; Moon, Phil-Dong; Kim, Hyung-Min; Jeong, Hyun-Ja

    2014-01-15

    Atopic dermatitis (AD) is a common skin disease that greatly worsens quality of life. Thymic stromal lymphopoietin (TSLP) plays a decisive role in the development of AD. The purpose of this study is to examine whether tryptanthrin (TR) would suppress AD through the regulation of TSLP. We analyzed the effect of TR on the level of TSLP from phorbol myristate acetate/calcium ionophore A23187-activated human mast cell line, HMC-1 cells, in 2,4-dinitrofluorobenzene-induced AD-like skin lesions of NC/Nga mice, and in anti-CD3/anti-CD28-stimulated splenocytes. TR significantly suppressed the level of intracellular calcium and the production and mRNA expression of TSLP through the blockade of receptor-interacting protein 2/caspase-1/nuclear factor-κB pathway in the activated HMC-1 cells. TR also significantly suppressed the levels of histidine decarboxylase and IL-1β. Furthermore, TR ameliorated clinical symptoms in the AD model. TR significantly reduced the levels of TSLP, IL-4, IFN-γ, IL-6, TNF-α, thymus and activation-regulated chemokine, and caspase-1 in AD skin lesions. Also, TR significantly reduced the serum levels of histamine and IL-4 in the AD model. Finally, TR significantly inhibited the production of IL-4, IFN-γ, and TNF-α from the stimulated splenocytes. Taken together, TR exhibits the potential to be a therapeutic agent for AD through down-regulation of TSLP. PMID:24295961

  18. Genetic inhibition of JNK3 ameliorates spinal muscular atrophy.

    PubMed

    Genabai, Naresh K; Ahmad, Saif; Zhang, Zhanying; Jiang, Xiaoting; Gabaldon, Cynthia A; Gangwani, Laxman

    2015-12-15

    Mutation of the Survival Motor Neuron 1 (SMN1) gene causes spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disorder that occurs in early childhood. Degeneration of spinal motor neurons caused by SMN deficiency results in progressive muscle atrophy and death in SMA. The molecular mechanism underlying neurodegeneration in SMA is unknown. No treatment is available to prevent neurodegeneration and reduce the burden of illness in SMA. We report that the c-Jun NH2-terminal kinase (JNK) signaling pathway mediates neurodegeneration in SMA. The neuron-specific isoform JNK3 is required for neuron degeneration caused by SMN deficiency. JNK3 deficiency reduces degeneration of cultured neurons caused by low levels of SMN. Genetic inhibition of JNK pathway in vivo by Jnk3 knockout results in amelioration of SMA phenotype. JNK3 deficiency prevents the loss of spinal cord motor neurons, reduces muscle degeneration, improves muscle fiber thickness and muscle growth, improves motor function and overall growth and increases lifespan of mice with SMA that shows a systemic rescue of phenotype by a SMN-independent mechanism. JNK3 represents a potential (non-SMN) therapeutic target for the treatment of SMA. PMID:26423457

  19. Mesenchymal Stem Cells Ameliorated Glucolipotoxicity in HUVECs through TSG-6

    PubMed Central

    An, Xingxing; Li, Lan; Chen, Younan; Luo, Ai; Ni, Zuyao; Liu, Jingping; Yuan, Yujia; Shi, Meimei; Chen, Bo; Long, Dan; Cheng, Jingqiu; Lu, Yanrong

    2016-01-01

    Glucolipotoxicity is one of the critical causal factors of diabetic complications. Whether mesenchymal stem cells (MSCs) have effects on glucolipotoxicity in human umbilical vein endothelial cells (HUVECs) and mechanisms involved are unclear. Thirty mM glucose plus 100 μM palmitic acid was used to induce glucolipotoxicity in HUVECs. MSCs and HUVECs were co-cultured at the ratio of 1:5 via Transwell system. The mRNA expressions of inflammatory factors were detected by RT-qPCR. The productions of reactive oxygen species (ROS), cell cycle and apoptosis were analyzed by flow cytometry. The tumor necrosis factor-α stimulated protein 6 (TSG-6) was knockdown in MSCs by RNA interference. High glucose and palmitic acid remarkably impaired cell viability and tube formation capacity, as well as increased the mRNA expression of inflammatory factors, ROS levels, and cell apoptosis in HUVECs. MSC co-cultivation ameliorated these detrimental effects in HUVECs, but no effect on ROS production. Moreover, TSG-6 was dramatically up-regulated by high glucose and fatty acid stimulation in both MSCs and HUVECs. TSG-6 knockdown partially abolished the protection mediated by MSCs. MSCs had protective effects on high glucose and palmitic acid induced glucolipotoxicity in HUVECs, and TSG-6 secreted by MSCs was likely to play an important role in this process. PMID:27043548

  20. Cellulose Supplementation Early in Life Ameliorates Colitis in Adult Mice

    PubMed Central

    Nagy-Szakal, Dorottya; Hollister, Emily B.; Luna, Ruth Ann; Szigeti, Reka; Tatevian, Nina; Smith, C. Wayne; Versalovic, James; Kellermayer, Richard

    2013-01-01

    Decreased consumption of dietary fibers, such as cellulose, has been proposed to promote the emergence of inflammatory bowel diseases (IBD: Crohn disease [CD] and ulcerative colitis [UC]) where intestinal microbes are recognized to play an etiologic role. However, it is not known if transient fiber consumption during critical developmental periods may prevent consecutive intestinal inflammation. The incidence of IBD peaks in young adulthood indicating that pediatric environmental exposures may be important in the etiology of this disease group. We studied the effects of transient dietary cellulose supplementation on dextran sulfate sodium (DSS) colitis susceptibility during the pediatric period in mice. Cellulose supplementation stimulated substantial shifts in the colonic mucosal microbiome. Several bacterial taxa decreased in relative abundance (e.g., Coriobacteriaceae [p = 0.001]), and other taxa increased in abundance (e.g., Peptostreptococcaceae [p = 0.008] and Clostridiaceae [p = 0.048]). Some of these shifts persisted for 10 days following the cessation of cellulose supplementation. The changes in the gut microbiome were associated with transient trophic and anticolitic effects 10 days following the cessation of a cellulose-enriched diet, but these changes diminished by 40 days following reversal to a low cellulose diet. These findings emphasize the transient protective effect of dietary cellulose in the mammalian large bowel and highlight the potential role of dietary fibers in amelioration of intestinal inflammation. PMID:23437211

  1. Oleuropein ameliorates arsenic induced oxidative stress in mice.

    PubMed

    Ogun, Metin; Ozcan, Ayla; Karaman, Musa; Merhan, Oguz; Ozen, Hasan; Kukurt, Abdulsamed; Karapehlivan, Mahmut

    2016-07-01

    The objective of this study is to investigate the potential preventive effect of oleuropein in an experimental arsenic toxicity in mice. For this purpose, mice were exposed to 5mg/kg/day sodium arsenite (NaAsO2) in drinking water and treated with 30mg/kg/day oleuropein for 15 days. At the end of the experiment, animals were sacrificed and selected organs were processed for biochemical and histopahtological investigations. Blood, liver, kidney and brain malondialdehyde (MDA) and nitric oxide (NO) levels were determined by colorimetric methods. Protein carbonyl content is measured by a commercial kit. Liver morphology and immunoreactivity for inducible NOS (iNOS) and endothelial NOS (eNOS) was evaluated microscopically. Level of NO was determined to decrease in blood and tissues whereas MDA increased in arsenic given mice. Tissue protein carbonyl content also increased in this group. Immunoreactivity for iNOS and eNOS was noted to increase with arsenic treatment. Oleuropein treatment had significant effects in normalizing the MDA and NO levels as well as protein carbonyl content. Immunohistochemical staining also showed reduction of the expression of iNOS and eNOS in liver. The results indicate that oleuropein ameliorates oxidative tissue damage by scavenging free radicals. PMID:27259345

  2. Triptolide ameliorates colonic fibrosis in an experimental rat model

    PubMed Central

    TAO, QINGSONG; WANG, BAOCHAI; ZHENG, YU; LI, GUANWEI; REN, JIANAN

    2015-01-01

    Triptolide is known to exert anti-inflammatory and immunomodulatory activities; however, its impact on intestinal fibrosis has not been previously examined. Based on our previous studies of the suppressive activity of triptolide on human colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide in Crohn’s disease, it was hypothesized that triptolide may have beneficial effects on intestinal fibrosis. In the present study, colonic fibrosis was induced in rats by 6 weekly repeated administration with a low-dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and was then treated with triptolide or PBS daily (control) simultaneously. Extracellular matrix (ECM) deposition in the colon was examined with image analysis of Masson Trichrome staining. Total collagen levels in colonic homogenates were measured by a Sircol assay. Collagen Iα1 transcripts and collagen I protein were measured ex vivo in the isolated colonic subepithelial myofibroblasts by reverse transcription-quantitative polymerase chain reaction and immunoblot analysis, respectively. The results indicated that triptolide decreased ECM deposition and collagen production in the colon, and inhibited collagen Iα1 transcripts and collagen I protein expression in the isolated subepithelial myofibroblasts of the rats with colonic fibrosis. In conclusion, triptolide ameliorates colonic fibrosis in the experimental rat model, suggesting triptolide may be a promising compound for inflammatory bowel disease treatment. PMID:25845760

  3. Tenuigenin ameliorates learning and memory impairments induced by ovariectomy.

    PubMed

    Cai, Zhao-Lin; Wang, Chun-Yang; Gu, Xing-Yang; Wang, Na-Jie; Wang, Jin-Jing; Liu, Wen-Xiao; Xiao, Peng; Li, Chu-Hua

    2013-06-13

    Estrogen deficiency is associated with cognitive impairment. Hormone replacement therapy (HRT) has proven to be effective in preventing and reversing the memory and learning deficiencies. However, conventional estrogenic treatment could increase the risks of breast cancer and venous thromboembolism. Tenuigenin (TEN) is putatively believed as the active component extracted from a Chinese herb Polygala tenuifolia root. Although TEN has been shown to enhance learning and memory in healthy mice, it remains unknown whether or not TEN could ameliorate learning and memory impairments. In the present study, mice were divided into four groups: sham-operated (sham), ovariectomized (OVX), OVX+estradiol benzoate (EB) and OVX+TEN groups. Step-through passive avoidance and Y-maze tests were used to assess learning and memory abilities, and the number of nitric oxide synthase (NOS) positive neurons and the synaptic measurement of hippocampal CA1 area were examined. The results showed that TEN was given orally to OVX mice, leading to the improvement of learning and memory in step-through passive avoidance and Y-maze tests. TEN could reduce the loss of NOS positive neurons and prevent the synaptic morphological changes induced by ovariectomy. Our results suggest that TEN may exert a potential therapeutic value for menopause cognitive dysfunction. PMID:23688946

  4. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    PubMed

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia. PMID:22771710

  5. An algal solution to large scale wastewater amelioration

    SciTech Connect

    Adey, W.H.

    1995-06-01

    Wastewater nutrients can be lowered to oligotrophic levels through uptake by algal biomass, while photosynthetic oxygen removes bacterial BOD, and oxygen-based ions, with UV application, can break down xenobiotic organic compounds. Algae also uptake heavy metals in cell walls, and the high pH from CO{sub 25} removal precipitates metals, earth metals and phosphorus. Algal biomass produced from many wastewaters has valuable commercial applications. Algal Turf Scrubbing (ATS) was developed as a tool to control water quality in ecosystem models, often at oligotrophic levels. ATS has routinely achieved biomass production (and water amelioration capability) of over 50 g (dry mass) m{sup -2} day{sup -1} in secondary sewage. Engineering innovations, with mechanized harvest, have brought ATS to large scale with a pilot sewage plant in central California. This is a low cost, modular unit, at 1000 cubic meters per day, and plans are underway to expand to city capacity for Tertiary-Quinary water recovery. A wide variety of wastewater applications, from agricultural, to aquacultural to industrial will be discussed.

  6. Astragaloside IV ameliorates renal injury in db/db mice.

    PubMed

    Sun, Huili; Wang, Wenjing; Han, Pengxun; Shao, Mumin; Song, Gaofeng; Du, Heng; Yi, Tiegang; Li, Shunmin

    2016-01-01

    Diabetic nephropathy is a lethal complication of diabetes mellitus and a major type of chronic kidney disease. Dysregulation of the Akt pathway and its downstream cascades, including mTOR, NFκB, and Erk1/2, play a critical role in the development of diabetic nephropathy. Astragaloside IV is a major component of Huangqi and exerts renal protection in a mouse model of type 1 diabetes. The current study was undertaken to investigate the protective effects of diet supplementation of AS-IV on renal injury in db/db mice, a type 2 diabetic mouse model. Results showed that administration of AS-IV reduced albuminuria, ameliorated changes in the glomerular and tubular pathology, and decreased urinary NAG, NGAL, and TGF-β1 in db/db mice. AS-IV also attenuated the diabetes-related activation of Akt/mTOR, NFκB, and Erk1/2 signaling pathways without causing any detectable hepatotoxicity. Collectively, these findings showed AS-IV to be beneficial to type 2 diabetic nephropathy, which might be associated with the inhibition of Akt/mTOR, NFκB and Erk1/2 signaling pathways. PMID:27585918

  7. Curcumin Ameliorates Ischemia-Induced Limb Injury Through Immunomodulation

    PubMed Central

    Liu, Yang; Chen, Lianyu; Shen, Yi; Tan, Tao; Xie, Nanzi; Luo, Ming; Li, Zhihong; Xie, Xiaoyun

    2016-01-01

    Background The prevalence of peripheral arterial disease (PAD) is increasing worldwide. Currently, there is no effective treatment for PAD. Curcumin is an ingredient of turmeric that has antioxidant, anti-inflammation, and anticancer properties. In the present study we investigated the potential effect of curcumin in protecting against ischemic limb injury. Material/Methods We used an established hindlimb ischemia mouse model in our study. Curcumin was administrated through intraperitoneal (I.P.) injection. Immunohistochemical staining and ELISA assays were performed. Treadmill training was used to evaluate skeletal muscle functions of animals. Results Our experiments using in vivo treadmill training showed that curcumin treatment improved the running capacity of animals after ischemic injury. Histological analysis revealed that curcumin treatment significantly reduced the skeletal muscle damage and fibrosis associated with ischemic injury. In order to determine the cellular and molecular mechanisms underlying curcumin-mediated tissue protection, immunohistochemical staining and ELISA assays were performed. The results showed that curcumin treatment led to less macrophage infiltration and less local inflammatory responses as demonstrated by decreasing TNF-α, IL-1, and IL-6 levels. Further immunofluorescent staining of tissue slides indicated that curcumin treatment inhibited the NF-κB signaling pathway. Finally, curcumin can inhibit NF-κB activation induced by LPS in macrophages. Conclusions Our study results show that curcumin treatment can ameliorate hindlimb injury following ischemic surgery, which suggests that curcumin could be used for PAD treatment. PMID:27302110

  8. Food Restriction Ameliorates the Development of Polycystic Kidney Disease.

    PubMed

    Warner, Gina; Hein, Kyaw Zaw; Nin, Veronica; Edwards, Marika; Chini, Claudia C S; Hopp, Katharina; Harris, Peter C; Torres, Vicente E; Chini, Eduardo N

    2016-05-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the accumulation of kidney cysts that ultimately leads to loss of renal function and kidney failure. At present, the treatment for ADPKD is largely supportive. Multiple studies have focused on pharmacologic approaches to slow the development of the cystic disease; however, little is known about the role of nutrition and dietary manipulation in PKD. Here, we show that food restriction (FR) effectively slows the course of the disease in mouse models of ADPKD. Mild to moderate (10%-40%) FR reduced cyst area, renal fibrosis, inflammation, and injury in a dose-dependent manner. Molecular and biochemical studies in these mice indicate that FR ameliorates ADPKD through a mechanism involving suppression of the mammalian target of the rapamycin pathway and activation of the liver kinase B1/AMP-activated protein kinase pathway. Our data suggest that dietary interventions such as FR, or treatment that mimics the effects of such interventions, may be potential and novel preventive and therapeutic options for patients with ADPKD. PMID:26538633

  9. Astragaloside IV ameliorates renal injury in db/db mice

    PubMed Central

    Sun, Huili; Wang, Wenjing; Han, Pengxun; Shao, Mumin; Song, Gaofeng; Du, Heng; Yi, Tiegang; Li, Shunmin

    2016-01-01

    Diabetic nephropathy is a lethal complication of diabetes mellitus and a major type of chronic kidney disease. Dysregulation of the Akt pathway and its downstream cascades, including mTOR, NFκB, and Erk1/2, play a critical role in the development of diabetic nephropathy. Astragaloside IV is a major component of Huangqi and exerts renal protection in a mouse model of type 1 diabetes. The current study was undertaken to investigate the protective effects of diet supplementation of AS-IV on renal injury in db/db mice, a type 2 diabetic mouse model. Results showed that administration of AS-IV reduced albuminuria, ameliorated changes in the glomerular and tubular pathology, and decreased urinary NAG, NGAL, and TGF-β1 in db/db mice. AS-IV also attenuated the diabetes-related activation of Akt/mTOR, NFκB, and Erk1/2 signaling pathways without causing any detectable hepatotoxicity. Collectively, these findings showed AS-IV to be beneficial to type 2 diabetic nephropathy, which might be associated with the inhibition of Akt/mTOR, NFκB and Erk1/2 signaling pathways. PMID:27585918

  10. PPARα agonist, fenofibrate, ameliorates age-related renal injury.

    PubMed

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Kim, Hyung Wook; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-08-01

    The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily. PPARα plays a major role as a transcription factor that regulates the expression of genes involved in various processes. In this study, 18-month-old male C57BL/6 mice were divided into two groups, the control group (n=7) and the fenofibrate-treated group (n=7) was fed the normal chow plus fenofibrate for 6months. The PPARα agonist, fenofibrate, improved renal function, proteinuria, histological change (glomerulosclerosis and tubular interstitial fibrosis), inflammation, and apoptosis in aging mice. This protective effect against age-related renal injury occurred through the activation of AMPK and SIRT1 signaling. The activation of AMPK and SIRT1 allowed for the concurrent deacetylation and phosphorylation of their target molecules and decreased the kidney's susceptibility to age-related changes. Activation of the AMPK-FOXO3a and AMPK-PGC-1α signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Our results suggest that activation of PPARα and AMPK-SIRT1 signaling may have protective effects against age-related renal injury. Pharmacological targeting of PPARα and AMPK-SIRT1 signaling molecules may prevent or attenuate age-related pathological changes in the kidney. PMID:27130813

  11. Amelioration of cyclosporine induced nephrotoxicity by dipeptidyl peptidase inhibitor vildagliptin.

    PubMed

    Ateyya, Hayam

    2015-09-01

    Cyclosporine A (CsA) is an immunosuppressive drug used in organ transplantation and autoimmune diseases but its clinical uses may be limited due to its dose-related nephrotoxicity. This study was carried out to evaluate the possible protective effects of vildagliptin (VLD) against CsA-induced nephrotoxicity in rats. Animals were divided into four groups treated as follows: control group (CsA & VLD vehicle); VLD group (10mg/kg/day, orally); CsA group (20mg/kg in sunflower oil, S.C.); and CsA-VLD group (CsA &VLD). Induced nephrotoxicity was evidenced by a significant elevation of serum creatinine, blood urea nitrogen (BUN), lactate dehydrogenase (LDH) and urinary micro total proteins (MTP), while serum albumin and urinary creatinine clearance were significantly decreased compared to the control group. Moreover, renal dysfunction was further confirmed by a significant increase in renal lipid peroxide that was measured as renal malondialdehyde (MDA). Renal reduced glutathione (GSH) and superoxide dismutase (SOD) were significantly decreased. Nephrotoxicity was further confirmed by renal tissue histopathology. Also, a high protein expression of Bax with decreased Bcl-2 was revealed in the renal tissue of the CsA treated group. Administration of VLD significantly ameliorated the nephrotoxic effects of CsA suggesting antioxidant, anti-inflammatory and anti-apoptotic benefits of VLD in CsA-induced nephrotoxicity. PMID:26225924

  12. Soluble CD83 ameliorates experimental colitis in mice.

    PubMed

    Eckhardt, J; Kreiser, S; Döbbeler, M; Nicolette, C; DeBenedette, M A; Tcherepanova, I Y; Ostalecki, C; Pommer, A J; Becker, C; Günther, C; Zinser, E; Mak, T W; Steinkasserer, A; Lechmann, M

    2014-07-01

    The physiological balance between pro- and anti-inflammatory processes is dysregulated in inflammatory bowel diseases (IBD) as in Crohn's disease and ulcerative colitis. Conventional therapy uses anti-inflammatory and immunosuppressive corticosteroids to treat acute-phase symptoms. However, low remission rate and strong side effects of these therapies are not satisfying. Thus, there is a high medical need for new therapeutic strategies. Soluble CD83, the extracellular domain of the transmembrane CD83 molecule, has been reported to have interesting therapeutic and immunosuppressive properties by suppressing dendritic cell (DC)-mediated T-cell activation and inducing tolerogenic DCs. However, the expression and function of CD83 in IBD is still unknown. Here, we show that CD83 expression is upregulated by different leukocyte populations in a chemical-induced murine colitis model. Furthermore, in this study the potential of sCD83 to modulate colitis using an experimental murine colitis model was investigated. Strikingly, sCD83 ameliorated the clinical disease symptoms, drastically reduced mortality, and strongly decreased inflammatory cytokine expression in mesenteric lymph nodes and colon. The infiltration of macrophages and granulocytes into colonic tissues was vigorously inhibited. Mechanistically, we could show that sCD83-induced expression of indolamine 2,3-dioxygenase is essential for its protective effects. PMID:24424524

  13. Ameliorative effects of phycocyanin against gibberellic acid induced hepatotoxicity.

    PubMed

    Hussein, Mohamed M A; Ali, Haytham A; Ahmed, Mona M

    2015-03-01

    Gibberellic acid (GA3) was used extensively unaware in agriculture in spite of its dangerous effects on human health. The current study was designed to investigate the ameliorative effects of the co-administration of phycocyanin with GA3 induced oxidative stress and histopathological changes in the liver. Forty male albino rats were randomly divided into four groups. Group I (control group) received normal saline for 6 weeks, Group II (GA3 treated group) received 3.85 mg/kg body weight GA3 once daily for 6 weeks, Group III (phycocyanin treated group) received Phycocyanin 200 mg/kg body weight/day for 6 weeks orally dissolved in distilled water and Group IV was treated with GA3 and phycocyanin at the same doses as groups 2 and 3. All treatments were given daily using intra-gastric intubation and continued for 6 weeks. Our results revealed significant downregulation of antioxidant enzyme activities and their mRNA levels (CAT, GPx and Cu-Zn, SOD) with marked elevation of liver enzymes and extensive fibrous connective tissue deposition with large biliary cells in hepatic tissue of GA3 treated rats, while treatment with phycocyanin improved the antioxidant defense system, liver enzymes and structural hepatocytes recovery in phycocyanin treated group with GA3. These data confirm the antioxidant potential of Phycocyanin and provide strong evidence to support the co-administration of Phycocyanin during using GA3. PMID:25868813

  14. Osteitis pubis ameliorated after tooth extraction: a case report.

    PubMed

    Fukushi, Jun-ichi; Nakashima, Yasuharu; Iwamoto, Yukihide

    2013-03-01

    Osteitis pubis is a non-infective inflammation of the symphysis pubis, which is known to be associated with trauma, athletic exertion, urological or gynecological surgery, or with rheumatic conditions such as seronegative spondyloarthropathies. In this report, we describe a case of osteitis pubis whose symptoms were completely ameliorated following tooth extraction attributable to periodontitis. A 57-year-old female patient developed osteitis pubis, presenting with pain in the groin area with an elevated Creactive protein (CRP; 4.4 mg/dl) and radiological erosive changes in symphysis pubis. Prednisolone (5 mg/day) and etodolac were prescribed, but the patient's symptoms improved only partially and remained persistent. One year from the patient's first visit, three teeth were extracted due to severe chronic periodontitis, which she had been suffering from for years. Soon after the above tooth extraction, her symptoms appeared completely resolved, and the patient's CRP was decreased to nearly normal levels in 4 weeks. Human leukocyte antigen (HLA)-typing analysis revealed a positive result for HLA-A11, A24, and B54. Because HLA-B54 cross-reacts with HLA-B27, the patient's osteitis pubis was considered to be a form of reactive arthritis associated with periodontitis. PMID:23599946

  15. Transcranial amelioration of inflammation and cell death after brain injury

    NASA Astrophysics Data System (ADS)

    Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.

    2014-01-01

    Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.

  16. Pathways Implicated in Tadalafil Amelioration of Duchenne Muscular Dystrophy.

    PubMed

    De Arcangelis, Valeria; Strimpakos, Georgios; Gabanella, Francesca; Corbi, Nicoletta; Luvisetto, Siro; Magrelli, Armando; Onori, Annalisa; Passananti, Claudio; Pisani, Cinzia; Rome, Sophie; Severini, Cinzia; Naro, Fabio; Mattei, Elisabetta; Di Certo, Maria Grazia; Monaco, Lucia

    2016-01-01

    Numerous therapeutic approaches for Duchenne and Becker Muscular Dystrophy (DMD and BMD), the most common X-linked muscle degenerative disease, have been proposed. So far, the only one showing a clear beneficial effect is the use of corticosteroids. Recent evidence indicates an improvement of dystrophic cardiac and skeletal muscles in the presence of sustained cGMP levels secondary to a blocking of their degradation by phosphodiesterase five (PDE5). Due to these data, we performed a study to investigate the effect of the specific PDE5 inhibitor, tadalafil, on dystrophic skeletal muscle function. Chronic pharmacological treatment with tadalafil has been carried out in mdx mice. Behavioral and physiological tests, as well as histological and biochemical analyses, confirmed the efficacy of the therapy. We then performed a microarray-based genomic analysis to assess the pattern of gene expression in muscle samples obtained from the different cohorts of animals treated with tadalafil. This scrutiny allowed us to identify several classes of modulated genes. Our results show that PDE5 inhibition can ameliorate dystrophy by acting at different levels. Tadalafil can lead to (1) increased lipid metabolism; (2) a switch towards slow oxidative fibers driven by the up-regulation of PGC-1α; (3) an increased protein synthesis efficiency; (4) a better actin network organization at Z-disk. PMID:26097015

  17. Inhibition of Neutrophil Exocytosis Ameliorates Acute Lung Injury in Rats

    PubMed Central

    Uriarte, Silvia M.; Rane, Madhavi J.; Merchant, Michael L.; Jin, Shunying; Lentsch, Alex B.; Ward, Richard A.; McLeish, Kenneth R.

    2013-01-01

    Exocytosis of neutrophil granules contributes to acute lung injury (ALI) induced by infection or inflammation, suggesting that inhibition of neutrophil exocytosis in vivo could be a viable therapeutic strategy. This study was conducted to determine the effect of a cell-permeable fusion protein that inhibits neutrophil exocytosis (TAT-SNAP-23) on ALI using an immune complex deposition model in rats. The effect of inhibition of neutrophil exocytosis by intravenous administration of TAT-SNAP-23 on ALI was assessed by albumin leakage, neutrophil infiltration, lung histology, and proteomic analysis of bronchoalveolar lavage fluid (BALf). Administration of TAT-SNAP-23, but not TAT-Control, significantly reduced albumin leakage, total protein levels in the BALf, and intra-alveolar edema and hemorrhage. Evidence that TAT-SNAP-23 inhibits neutrophil exocytosis included a reduction in plasma membrane CD18 expression by BALf neutrophils and a decrease in neutrophil granule proteins in BALf. Similar degree of neutrophil accumulation in the lungs and/or BALf suggests that TAT-SNAP-23 did not alter vascular endothelial cell function. Proteomic analysis of BALf revealed that components of the complement and coagulation pathways were significantly reduced in BALf from TAT-SNAP-23-treated animals. Our results indicate that administration of a TAT-fusion protein that inhibits neutrophil exocytosis reduces in vivo ALI. Targeting neutrophil exocytosis is a potential therapeutic strategy to ameliorate ALI. PMID:23364427

  18. Ameliorating children's reading-comprehension difficulties: a randomized controlled trial.

    PubMed

    Clarke, Paula J; Snowling, Margaret J; Truelove, Emma; Hulme, Charles

    2010-08-01

    Children with specific reading-comprehension difficulties can read accurately, but they have poor comprehension. In a randomized controlled trial, we examined the efficacy of three interventions designed to improve such children's reading comprehension: text-comprehension (TC) training, oral-language (OL) training, and TC and OL training combined (COM). Children were assessed preintervention, midintervention, postintervention, and at an 11-month follow-up. All intervention groups made significant improvements in reading comprehension relative to an untreated control group. Although these gains were maintained at follow-up in the TC and COM groups, the OL group made greater gains than the other groups did between the end of the intervention and follow-up. The OL and COM groups also demonstrated significant improvements in expressive vocabulary compared with the control group, and this was a mediator of the improved reading comprehension of the OL and COM groups. We conclude that specific reading-comprehension difficulties reflect (at least partly) underlying oral-language weaknesses that can be effectively ameliorated by suitable teaching. PMID:20585051

  19. Curcumin Ameliorates Ischemia-Induced Limb Injury Through Immunomodulation.

    PubMed

    Liu, Yang; Chen, Lianyu; Shen, Yi; Tan, Tao; Xie, Nanzi; Luo, Ming; Li, Zhihong; Xie, Xiaoyun

    2016-01-01

    BACKGROUND The prevalence of peripheral arterial disease (PAD) is increasing worldwide. Currently, there is no effective treatment for PAD. Curcumin is an ingredient of turmeric that has antioxidant, anti-inflammation, and anticancer properties. In the present study we investigated the potential effect of curcumin in protecting against ischemic limb injury. MATERIAL AND METHODS We used an established hindlimb ischemia mouse model in our study. Curcumin was administrated through intraperitoneal (I.P.) injection. Immunohistochemical staining and ELISA assays were performed. Treadmill training was used to evaluate skeletal muscle functions of animals. RESULTS Our experiments using in vivo treadmill training showed that curcumin treatment improved the running capacity of animals after ischemic injury. Histological analysis revealed that curcumin treatment significantly reduced the skeletal muscle damage and fibrosis associated with ischemic injury. In order to determine the cellular and molecular mechanisms underlying curcumin-mediated tissue protection, immunohistochemical staining and ELISA assays were performed. The results showed that curcumin treatment led to less macrophage infiltration and less local inflammatory responses as demonstrated by decreasing TNF-α, IL-1, and IL-6 levels. Further immunofluorescent staining of tissue slides indicated that curcumin treatment inhibited the NF-κB signaling pathway. Finally, curcumin can inhibit NF-kB activation induced by LPS in macrophages. CONCLUSIONS Our study results show that curcumin treatment can ameliorate hindlimb injury following ischemic surgery, which suggests that curcumin could be used for PAD treatment. PMID:27302110

  20. Transplant restoration of spinal cord inhibitory controls ameliorates neuropathic itch

    PubMed Central

    Braz, Joao M.; Juarez-Salinas, Dina; Ross, Sarah E.; Basbaum, Allan I.

    2014-01-01

    The transmission of pruritoceptive (itch) messages involves specific neural circuits within the spinal cord that are distinct from those that transmit pain messages. These itch-specific circuits are tonically regulated by inhibitory interneurons in the dorsal horn. Consistent with these findings, it has previously been reported that loss of GABAergic interneurons in mice harboring a deletion of the transcription factor Bhlhb5 generates a severe, nonremitting condition of chronic itch. Here, we tested the hypothesis that the neuropathic itch in BHLHB5-deficient animals can be treated by restoring inhibitory controls through spinal cord transplantation and integration of precursors of cortical inhibitory interneurons derived from the embryonic medial ganglionic eminence. We specifically targeted the transplants to segments of the spinal cord innervated by areas of the body that were most severely affected. BHLHB5-deficient mice that received transplants demonstrated a substantial reduction of excessive scratching and dramatic resolution of skin lesions. In contrast, the scratching persisted and skin lesions worsened over time in sham-treated mice. Together, these results indicate that cell-mediated restoration of inhibitory controls has potential as a powerful, cell-based therapy for neuropathic itch that not only ameliorates symptoms of chronic itch, but also may modify disease. PMID:25003193

  1. Antiapoptotic Effect of Simvastatin Ameliorates Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Hadi, Najah R.; Al-amran, Fadhil; Yousif, Maitham; Zamil, Suhaad T.

    2013-01-01

    Background. Myocardial ischemial reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty, and coronary bypass surgery. Injury of myocardium due to ischemial reperfusion includes cardiac contractile dysfunction, arrhythmias, and irreversible myocytes damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart. Objective. This study was undertaken to investigate the potential role of Simvastatin in the amelioration of myocardial I/R injury induced by ligation of coronary artery in a rat model. Materials and Methods. Adult male Swiss Albino r