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  1. Colloid administration normalizes resuscitation ratio and ameliorates "fluid creep".

    PubMed

    Lawrence, Amanda; Faraklas, Iris; Watkins, Holly; Allen, Ashlee; Cochran, Amalia; Morris, Stephen; Saffle, Jeffrey

    2010-01-01

    Although colloid was a component of the original Parkland formula, it has been omitted from standard Parkland resuscitation for over 30 years. However, some burn centers use colloid as "rescue" therapy for patients who exhibit progressively increasing crystalloid requirements, a phenomenon termed "fluid creep." We reviewed our experience with this procedure. With Institutional Review Board approval, we reviewed all adult patients with > or =20%TBSA burns admitted from January 1, 2005, through December 31, 2007, who completed formal resuscitation. Patients were resuscitated using the Parkland formula, adjusted to maintain urine output of 30 to 50 ml/hr. Patients who required greater amounts of fluid than expected were given a combination of 5% albumin and lactated Ringer's until fluid requirements normalized. Results were expressed as an hourly ratio (I/O ratio) of fluid infusion (ml/kg/%TBSA/hr) to urine output (ml/kg/hr). Predicted values for this ratio vary for individual patients but are usually less than 0.5 to 1.0. Fifty-two patients were reviewed, of whom 26 completed resuscitation using crystalloid alone, and the remaining 26 required albumin supplementation (AR). The groups were comparable in age, gender, weight, mortality, and time between injury and admission. AR patients had larger total and full-thickness burns and more inhalation injuries. Patients managed with crystalloid alone maintained mean resuscitation ratios from 0.13 to 0.40, whereas AR patients demonstrated progressively increasing ratios to a maximum mean of 1.97, until albumin was started. Administration of albumin produced a dramatic and precipitous return of ratios to within predicted ranges throughout the remainder of resuscitation. No patient developed abdominal compartment syndrome. Measuring hourly I/O ratios is an effective means of expressing and tracking fluid requirements. The addition of colloid to Parkland resuscitation rapidly reduces hourly fluid requirements, restores normal

  2. Intermittent administration of brain-derived neurotrophic factor ameliorates glucose metabolism in obese diabetic mice.

    PubMed

    Ono, M; Itakura, Y; Nonomura, T; Nakagawa, T; Nakayama, C; Taiji, M; Noguchi, H

    2000-01-01

    We have previously shown that brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, interacts with the endocrine system in obese diabetic mice, and systemic peripheral administration of BDNF regulates glucose metabolism in this model. Results from the present study show that the hypoglycemic effect induced by 2 weeks' daily administration of BDNF (20 mg/kg/d) to db/db mice lasts for several weeks after treatment cessation, irrespective of food reduction. On the other hand, the antidiabetic agent, metformin had no lasting effect. This duration of the BDNF hypoglycemic action prompted us to examine the efficacy of BDNF intermittent administration on glucose metabolism. BDNF administered once or twice per week (70 mg/kg/wk) to db/db mice for 3 weeks significantly reduced blood glucose concentrations and hemoglobin A(1c), (HbA(1c)) as compared with ad libitum-fed phosphate-buffered saline (PBS)-treated and pair-fed PBS-treated groups. This suggests that BDNF not only temporarily reduced blood glucose concentrations but also ameliorated systemic glucose balance in this obese diabetic mouse model during the experimental period. Our results indicate that BDNF could be a novel hypoglycemic agent with an exceptional ability to normalize glucose metabolism even with treatment as infrequently as once per week. PMID:10647076

  3. Curculigo orchioides Gaertn Effectively Ameliorates the Uro- and Nephrotoxicities Induced by Cyclophosphamide Administration in Experimental Animals.

    PubMed

    Murali, Vishnu Priya; Kuttan, Girija

    2016-06-01

    Background Curculigo orchioides Gaertn is an ancient medicinal plant (Family: Amaryllidaceae), well known for its immunomodulatory and rejuvenating effects. Cyclophosphamide (CPA) is an alkylating agent widely used for treating a variety of human malignancies, but associated with different toxicities too. Our previous reports regarding the hemoprotective and hepatoprotective effects of the plant against CPA toxicities provide the background for the present study, which is designed to analyze the ameliorative effect of the methanolic extract of C orchioides on the urotoxicity and nephrotoxicity induced by CPA. Methods CPA was administered to male Swiss albino mice at a single dose of 1.5 mmol/kg body weight to induce urotoxicity after 5 days of prophylactic treatment with C orchioides extract (20 mg/kg body weight). Mesna (2-mercaptoethanesulfonate) was used as a control drug. Serum, tissue, and urine levels of kidney function markers and antioxidant levels were checked along with the serum cytokine levels. Results The plant extract was found to be effective in ameliorating the urotoxic and nephrotoxic side effects of CPA. Upregulation of serum interferon-γ and interleukin-2 levels were observed with C orchioides treatment, which was decreased by CPA administration. Besides these, serum tumor necrosis factor-α level was also downregulated by C orchioides treatment. Conclusion Curculigo orchioides was found to be effective against the CPA-induced bladder and renal toxicities by its antioxidant capability and also by regulating the pro-inflammatory cytokine levels. PMID:26424815

  4. Alcohol-induced vascular damage of brain can be ameliorated by administration of magnesium

    SciTech Connect

    Altura, B.M.; Altura, B.T.; Gebrewold, A.

    1986-03-01

    Long-term as well as short-term administration of alcohol can cause neuronal and vascular damage in the brain. The authors have reported that acute administration of ethyl alcohol (ALC), either directly into the rat brain, IV or locally, can produce concentration-dependent spasms of cerebral arterioles, venules, arteries and veins followed by irreversible rupture of capillaries and veins followed by irreversible rupture of capillaries and venules. Several experiments have suggested that administration of magnesium ions (Mg/sup 2 +/) can modify vascular tone. Whether Mg/sup 2 +/ can exert direct actions on the intact cerebral microcirculation is not known. Using the above intact rat brain model, and TV-image intensification, the authors determine whether administration of Mg/sup 2 +/ : 1) exerts actions on cerebral (coritical) arterioles (A) and venules (V) (12-40..mu..m); 2) directly into the brain alters arterial blood pressure (BP); and 3) could ameliorate or prevent some of the detrimental cerebral-vascular actions ALC exerts in the brain. The data show that infusion of Mg/sup 7 +/ : 1) into the rat brain result in a rapid dose-dependent lowering of systolic and diastolic and BP; 2) IV or intra-arterially (IA) produces dose-dependent vaso-dilation of A and V; 3) IV or IA prevents spasms and rupture of A and V induced by 10% ALC. The cerebral vascular actions of Mg/sup 2 +/ may prove to be useful in treatment and prevention of ALC-induced brain damage.

  5. IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

    PubMed Central

    Murdocca, Michela; Malgieri, Arianna; Luchetti, Andrea; Saieva, Luciano; Dobrowolny, Gabriella; de Leonibus, Elvira; Filareto, Antonio; Quitadamo, Maria Chiara; Novelli, Giuseppe; Musarò, Antonio; Sangiuolo, Federica

    2012-01-01

    Spinal muscular atrophy (SMA) is an inherited neurodegenerative disorder and the first genetic cause of death in childhood. SMA is caused by low levels of survival motor neuron (SMN) protein that induce selective loss of α-motor neurons (MNs) in the spinal cord, resulting in progressive muscle atrophy and consequent respiratory failure. To date, no effective treatment is available to counteract the course of the disease. Among the different therapeutic strategies with potential clinical applications, the evaluation of trophic and/or protective agents able to antagonize MNs degeneration represents an attractive opportunity to develop valid therapies. Here we investigated the effects of IPLEX (recombinant human insulinlike growth factor 1 [rhIGF-1] complexed with recombinant human IGF-1 binding protein 3 [rhIGFBP-3]) on a severe mouse model of SMA. Interestingly, molecular and biochemical analyses of IGF-1 carried out in SMA mice before drug administration revealed marked reductions of IGF-1 circulating levels and hepatic mRNA expression. In this study, we found that perinatal administration of IPLEX, even if does not influence survival and body weight of mice, results in reduced degeneration of MNs, increased muscle fiber size and in amelioration of motor functions in SMA mice. Additionally, we show that phenotypic changes observed are not SMN-dependent, since no significant SMN modification was addressed in treated mice. Collectively, our data indicate IPLEX as a good therapeutic candidate to hinder the progression of the neurodegenerative process in SMA. PMID:22669476

  6. Administration of Lactobacillus casei and Bifidobacterium bifidum Ameliorated Hyperglycemia, Dyslipidemia, and Oxidative Stress in Diabetic Rats

    PubMed Central

    Sharma, Poonam; Bhardwaj, Priyanka; Singh, Rambir

    2016-01-01

    Background: The present work was planned to evaluate the antihyperglycemic, lipid-lowering, and antioxidant effect of Lactobacillus casei and Bifidobacterium bifidum in streptozotocin (STZ)-induced diabetic rats. Methods: Single daily dose of 1 × 107 cfu/ml of L. casei and B. bifidum alone and in combination of both was given to Wistar rats orally by gavaging for 28 days. Glucose tolerance test, fasting blood glucose (FBG), lipid profile, and glycosylated hemoglobin (HbA1c) were measured from blood. Glycogen from thigh muscles and liver and oxidative stress parameters from pancreas were analyzed. Results: Administration of L. casei and B. bifidum alone and in combination of both to diabetic rats decreased serum FBG (60.47%, 55.89%, and 56.49%, respectively), HbA1c (28.11%, 28.61%, and 28.28%), total cholesterol (171.69%, 136.47%, and 173.58%), triglycerides (9.935%, 8.58%, and 7.91%), low-density lipoproteins (53.27%, 53.35%, and 52.91%) and very low-density lipoproteins (10%, 8.58%, and 11.15%, respectively) and increased high-density lipoproteins (13.73%, 15.47%, and 15.47%), and insulin (19.50%, 25.80%, and 29.47%, respectively). The treatment also resulted in increase in muscle (171.69%, 136.47%, and 173.58%) and liver (25.82%, 6.63%, and 4.02%) glycogen level. The antioxidant indexes in pancreas of diabetic rats returned to normal level with reduction in lipid peroxidation (30.89%, 46.46%, and 65.36%) and elevation in reduced glutathione (104.5%, 161.34%, and 179.04%), superoxide dismutase (38.65%, 44.32%, and 53.35%), catalase (13.08%, 27%, and 31.52%), glutathione peroxidase (55.56%, 72.23%, and 97.23%), glutathione reductase (49.27%, 88.40%, and 110.86%), and glutathione-S-transferase (140%, 220%, and 246.6%, respectively) on treatment with L. casei, B. bifidum, and combination treatment. Conclusions: Administration of L. casei and B. bifidum alone and in combination of both ameliorated hyperglycemia, dyslipidemia, and oxidative stress in STZ

  7. Intratracheal Administration of Prostacyclin Analogue–incorporated Nanoparticles Ameliorates the Development of Monocrotaline and Sugen-Hypoxia-induced Pulmonary Arterial Hypertension

    PubMed Central

    Matsubara, Hiromi; Kondo, Megumi; Miura, Daiji; Matoba, Tetsuya; Egashira, Kensuke; Ito, Hiroshi

    2016-01-01

    Abstract: Nanoparticles (NPs) have been used as novel drug delivery systems. Drug-incorporated NPs for local delivery might optimize the efficacy and minimize the side effects of drugs. Intravenous prostacyclin improves long-term survival in patients with pulmonary arterial hypertension (PAH), but it causes serious side effects such as catheter-related infections. We investigated the efficacy and safety of intratracheal administration of a prostacyclin analogue, beraprost (BPS), incorporated NPs in Sugen-hypoxia-normoxia and monocrotaline rat models of PAH and in human PAH pulmonary arterial smooth muscle cells (PASMCs). After a single administration, BPS NPs significantly decreased right ventricular pressure, right ventricular hypertrophy, and pulmonary artery muscularization in the 2 rat models. BPS NPs significantly improved the survival rate in the monocrotaline rat model. No infiltration of inflammatory cells, hemorrhage, or fibrosis was found in the liver, kidney, spleen, and heart after the administration of BPS NPs. No liver or kidney dysfunction was found in the blood examinations. BPS and BPS NPs significantly inhibited the proliferation of human PAH PASMCs after 24 hours of treatment. BPS NPs significantly continued to inhibit the proliferation of human PAH PASMCs at 24 hours after the removal of BPS NPs. BPS NPs significantly induced apoptosis in PAH PASMCs compared to that in non-PAH PASMCs. Intratracheal administration of BPS NPs ameliorates pulmonary hypertension in PAH rat models by a sustained antiproliferative effect and a proapoptotic effect on PAH PASMCs. PMID:26745002

  8. Mucosal Administration of Collagen V Ameliorates the Atherosclerotic Plaque Burden by Inducing Interleukin 35-dependent Tolerance.

    PubMed

    Park, Arick C; Huang, Guorui; Jankowska-Gan, Ewa; Massoudi, Dawiyat; Kernien, John F; Vignali, Dario A; Sullivan, Jeremy A; Wilkes, David S; Burlingham, William J; Greenspan, Daniel S

    2016-02-12

    We have shown previously that collagen V (col(V)) autoimmunity is a consistent feature of atherosclerosis in human coronary artery disease and in the Apoe(-/-) mouse model. We have also shown sensitization of Apoe(-/-) mice with col(V) to markedly increase the atherosclerotic burden, providing evidence of a causative role for col(V) autoimmunity in atherosclerotic pathogenesis. Here we sought to determine whether induction of immune tolerance to col(V) might ameliorate atherosclerosis, providing further evidence for a causal role for col(V) autoimmunity in atherogenesis and providing insights into the potential for immunomodulatory therapeutic interventions. Mucosal inoculation successfully induced immune tolerance to col(V) with an accompanying reduction in plaque burden in Ldlr(-/-) mice on a high-cholesterol diet. The results therefore demonstrate that inoculation with col(V) can successfully ameliorate the atherosclerotic burden, suggesting novel approaches for therapeutic interventions. Surprisingly, tolerance and reduced atherosclerotic burden were both dependent on the recently described IL-35 and not on IL-10, the immunosuppressive cytokine usually studied in the context of induced tolerance and amelioration of atherosclerotic symptoms. In addition to the above, using recombinant protein fragments, we were able to localize two epitopes of the α1(V) chain involved in col(V) autoimmunity in atherosclerotic Ldlr(-/-) mice, suggesting future courses of experimentation for the characterization of such epitopes. PMID:26721885

  9. Oral administration of polyamines ameliorates liver ischemia/reperfusion injury and promotes liver regeneration in rats.

    PubMed

    Okumura, Shinya; Teratani, Takumi; Fujimoto, Yasuhiro; Zhao, Xiangdong; Tsuruyama, Tatsuaki; Masano, Yuki; Kasahara, Naoya; Iida, Taku; Yagi, Shintaro; Uemura, Tadahiro; Kaido, Toshimi; Uemoto, Shinji

    2016-09-01

    Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD. PMID:27102080

  10. S-Nitrosoglutathione administration ameliorates cauda equina compression injury in rats

    PubMed Central

    Shunmugavel, Anandakumar; Khan, Mushfiquddin; Martin, Marcus M; Copay, Anne G; Subach, Brian R; Schuler, Thomas C; Singh, Inderjit

    2012-01-01

    Lumbar spinal stenosis (LSS) causes ischemia, inflammation, demyelination and results in dysfunction of the cauda equina (CE), leading to pain and locomotor functional deficits. We investigated whether exogenous administration of S-nitrosoglutathione (GSNO), an endogenous redox modulating anti-neuroinflammatory agent, hastens functional recovery in a CE compression (CEC) rat model. CEC was induced in adult female rats by the surgical implantation of two silicone blocks within the epidural spaces of L4-L6 vertebrae. GSNO (50 μg/kg body weight) was administered by gavage 1 h after the injury, and the treatment was continued daily thereafter. GSNO induced change in the pain threshold was evaluated for four days after the compression. Tissue analyses and locomotor function evaluation were carried out at two weeks and four weeks after the CEC respectively. GSNO significantly improved motor function in CEC rats as evidenced by an increased latency on rotarod compared with vehicle-treated CEC rats. CEC induced hyperalgesia was decreased by GSNO. GSNO also increased the expression of VEGF, reduced cellular infiltration (H&E staining) and apoptotic cell death (TUNEL assay), and hampered demyelination (LFB staining and g-ratio). These data demonstrate that administration of GSNO after CEC decreased inflammation, hyperalgesia and cell death leading to improved locomotor function of CEC rats. The therapeutic potential of GSNO observed in the present study with CEC rats suggests that GSNO is a candidate drug to test in LSS patients. PMID:23997981

  11. Single administration of a novel γ-secretase modulator ameliorates cognitive dysfunction in aged C57BL/6J mice.

    PubMed

    Hayama, Tatsuya; Murakami, Koji; Watanabe, Tomomichi; Maeda, Ryota; Kamata, Makoto; Kondo, Shinichi

    2016-02-15

    Mutations in presenilin 1 (PS1) and presenilin 2 (PS2) are known to cause early onset of Alzheimer's disease (AD). These proteins comprise the catalytic domain of γ-secretase, which catalyzes the cleavage of β-amyloid (Aβ) from amyloid precursor protein (APP). In recent reports, PS1 and PS2 were linked to the modulation of intracellular calcium ion (Ca(2+)) dynamics, a key regulator of synaptic function. Ca(2+) dysregulation and synaptic dysfunction are leading hypothesis of cognitive dysfunctions during aging and AD progression. Accordingly, manipulations of presenilins by small molecules may have therapeutic potential for the treatment of cognitive dysfunction. In an accompanying report, we showed that chronic treatment with compound-1, a novel γ-secretase modulator (GSM), reduced Aβ production and ameliorated cognitive dysfunction in Tg2576 APP transgenic mice. Accordingly, in the present study we showed that single oral administration of compound-1 at 1 and 3mg/kg ameliorated cognitive dysfunction in aged non-transgenic mice. Moreover, compound-1 enhanced synaptic plasticity in hippocampal slices from aged C57BL/6J mice and increased messenger RNA (mRNA) expression of the immediate early gene c-fos, which has been shown to be related to synaptic plasticity in vivo. Finally, compound-1 modulated Ca(2+) signals through PS1 in mouse embryonic fibroblast cells. Taken together, compound-1 ameliorates both Aβ pathology and age-related cognitive dysfunctions. Hence, compound-1 may have potential as an early intervention for the cognitive declines that are commonly diagnosed in aged subjects, such as mild cognitive impairment (MCI) and prodromal AD. PMID:26707406

  12. CRTH2 antagonism significantly ameliorates airway hyperreactivity and downregulates inflammation-induced genes in a mouse model of airway inflammation.

    PubMed

    Lukacs, Nicholas W; Berlin, Aaron A; Franz-Bacon, Karin; Sásik, Roman; Sprague, L James; Ly, Tai Wei; Hardiman, Gary; Boehme, Stefen A; Bacon, Kevin B

    2008-11-01

    Prostaglandin D(2), the ligand for the G protein-coupled receptors DP1 and CRTH2, has been implicated in the pathogenesis of the allergic response in diseases such as asthma, rhinitis, and atopic dermatitis. This prostanoid also fulfills a number of physiological, anti-inflammatory roles through its receptor DP1. We investigated the role of PGD(2) and CRTH2 in allergic pulmonary inflammation by using a highly potent and specific antagonist of CRTH2. Administration of this antagonist ameliorated inflammation caused by either acute or subchronic sensitization using the cockroach egg antigen. Gene expression and ELISA analysis revealed that there was reduced proinflammatory cytokine mRNA or protein produced, as well as a wide array of genes associated with the Th2-type proinflammatory response. Importantly, the CRTH2 antagonist reduced antigen-specific IgE, IgG1, and IgG2a antibody levels as well as decreased mucus deposition and leukocyte infiltration in the large airways. Collectively, these findings suggest that the PGD(2)-CRTH2 activation axis has a pivotal role in mediating the inflammation and the underlying immune response in a T cell-driven model of allergic airway inflammation. PMID:18757520

  13. Systemic Administration of Human Bone Marrow-Derived Mesenchymal Stromal Cell Extracellular Vesicles Ameliorates Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation in Immunocompetent Mice

    PubMed Central

    Cruz, Fernanda F.; Borg, Zachary D.; Goodwin, Meagan; Sokocevic, Dino; Wagner, Darcy E.; Coffey, Amy; Antunes, Mariana; Robinson, Kristen L.; Mitsialis, S. Alex; Kourembanas, Stella; Thane, Kristen; Hoffman, Andrew M.; McKenna, David H.; Rocco, Patricia R.M.

    2015-01-01

    An increasing number of studies demonstrate that administration of either conditioned media (CM) or extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) derived from bone marrow and other sources are as effective as the MSCs themselves in mitigating inflammation and injury. The goal of the current study was to determine whether xenogeneic administration of CM or EVs from human bone marrow-derived MSCs would be effective in a model of mixed Th2/Th17, neutrophilic-mediated allergic airway inflammation, reflective of severe refractory asthma, induced by repeated mucosal exposure to Aspergillus hyphal extract (AHE) in immunocompetent C57Bl/6 mice. Systemic administration of both CM and EVs isolated from human and murine MSCs, but not human lung fibroblasts, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE-provoked increases in airway hyperreactivity (AHR), lung inflammation, and the antigen-specific CD4 T-cell Th2 and Th17 phenotype. Notably, both CM and EVs from human MSCs (hMSCs) were generally more potent than those from mouse MSCs (mMSCs) in most of the outcome measures. The weak cross-linking agent 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride was found to inhibit release of both soluble mediators and EVs, fully negating effects of systemically administered hMSCs but only partly inhibited the ameliorating effects of mMSCs. These results demonstrate potent xenogeneic effects of CM and EVs from hMSCs in an immunocompetent mouse model of allergic airway inflammation and they also show differences in mechanisms of action of hMSCs versus mMSCs to mitigate AHR and lung inflammation in this model. Significance There is a growing experience demonstrating benefit of mesenchymal stromal cell (MSC)-based cell therapies in preclinical models of asthma. In the current study, conditioned media (CM) and, in particular, the extracellular vesicle fraction obtained from the CM were as potent as the

  14. Oral administration of acarbose ameliorates imiquimod-induced psoriasis-like dermatitis in a mouse model.

    PubMed

    Chen, Hsin-Hua; Chao, Ya-Hsuan; Chen, Der-Yuan; Yang, Deng-Ho; Chung, Ting-Wen; Li, Yi-Rong; Lin, Chi Chen

    2016-04-01

    Psoriasis is a chronic autoimmune disease of undefined etiology that involves dysregulated interplay between immune cells and keratinocytes. Acarbose was found to decrease inflammatory parameters in diabetic patients in addition to its anti-diabetic effects. Here, we report that imiquimod (IMQ)-induced epidermal hyperplasia and psoriasis like-inflammation were significantly inhibited by acarbose treatment. Real-time PCR showed that mRNA levels of the cytokines TNF-α, IL-6, IL-1β IL-17A, and IL-22 in skin were also decreased significantly by acarbose. In addition, we found that acarbose reduced infiltration of CD3(+) T cells and GR-1(+) neutrophils in lesional skin and also reduced the percentage of IL-17-producing CD4(+) T cells (Th17) and IL-17- and IL-22-producing γδ T cells in the spleen. In contrast, acarbose increased the frequency of IL-10-producing CD4(+) regulator Tr1 T cells in the spleen and small intestine. These results indicate that oral administration of acarbose can attenuate the severity of imiquimod-induced psoriasis with local and systemic anti-inflammatory and immune modulation effects, thus suggesting that acarbose is an effective therapeutic strategy for psoriasis regulation. PMID:26874324

  15. Oral Administration of Ginseng Ameliorates Cyclosporine-Induced Pancreatic Injury in an Experimental Mouse Model

    PubMed Central

    Lim, Sun Woo; Doh, Kyoung Chan; Jin, Long; Piao, Shang Guo; Heo, Seong Beom; Zheng, Yu Fen; Bae, Soo Kyung; Chung, Byung Ha; Yang, Chul Woo

    2013-01-01

    Background This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury. Methods Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously) and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage) for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measurements of serum insulin level, β cell area, macrophage infiltration, and apoptosis. Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line. Oxidative stress was measured by the concentration of 8-hydroxy-2′-deoxyguanosine in serum, tissue sections, and culture media. Results Four weeks of cyclosporine treatment increased blood glucose levels and decreased insulin levels, but cotreatment with ginseng ameliorated the cyclosporine-induced glucose intolerance and hyperglycemia. Pancreatic β cell area was also greater with ginseng cotreatment compared with cyclosporine monotherapy. The production of proinflammatory molecules, such as induced nitric oxide synthase and cytokines, and the level of apoptotic cell death also decreased in pancreatic β cell with ginseng treatment. Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death. These in vivo and in vitro changes were accompanied by decreases in the levels of 8-hydroxy-2′-deoxyguanosine in pancreatic β cell in tissue section, serum, and culture media during cotreatment of ginseng with cyclosporine. Conclusions The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress. PMID:24009697

  16. Mild ischemic Injury Leads to Long-Term Alterations in the Kidney: Amelioration by Spironolactone Administration

    PubMed Central

    Barrera-Chimal, Jonatan; Pérez-Villalva, Rosalba; Ortega, Juan Antonio; Sánchez, Andrea; Rodríguez-Romo, Roxana; Durand, Marta; Jaisser, Frederic; Bobadilla, Norma A.

    2015-01-01

    Administration of the mineralocorticoid receptor antagonist spironolactone prevents the development of chronic kidney disease (CKD) after a severe ischemic injury. However, whether brief periods of ischemia lead to CKD and whether spironolactone administration after ischemia may be a useful therapeutic strategy to prevent the gradual deterioration of structure and function remains unexplored. Nineteen male Wistar rats were divided into four groups: rats that underwent renal bilateral ischemia for 10, 20, or 45 min were compared with sham operated rats. Additionally, thirteen male Wistar rats that underwent renal bilateral ischemia for 20 min were divided into an untreated ischemic group (I) and two groups receiving spironolactone, 20 mg/kg by gavage, at either 0 (Sp0) or 1.5-h after ischemia (Sp1.5). The rats were followed up and studied after 9 months. Mild (20 min) and severe (45 min) ischemia induced a progressive increase in proteinuria at varying magnitudes, whereas minor ischemia (10 min) did not modify proteinuria. CKD induced by moderate ischemia was characterized by renal hypertrophy and tubulointerstitial fibrosis. These effects were associated with activation of the transforming growth factor β (TGFβ) signaling pathway and up-regulation of endothelin receptor A (ETA) and alpha smooth muscle actin (αSMA). Spironolactone treatment immediately or 1.5-h after the ischemic insult prevented the onset of these disorders. Our results show that moderate ischemic insult leads to long-term structural and molecular changes that may compromise renal function in later stages. Additionally, we demonstrate that spironolactone administration after mild ischemia prevents this detrimental effect. PMID:26157344

  17. Mild ischemic injury leads to long-term alterations in the kidney: amelioration by spironolactone administration.

    PubMed

    Barrera-Chimal, Jonatan; Pérez-Villalva, Rosalba; Ortega, Juan Antonio; Sánchez, Andrea; Rodríguez-Romo, Roxana; Durand, Marta; Jaisser, Frederic; Bobadilla, Norma A

    2015-01-01

    Administration of the mineralocorticoid receptor antagonist spironolactone prevents the development of chronic kidney disease (CKD) after a severe ischemic injury. However, whether brief periods of ischemia lead to CKD and whether spironolactone administration after ischemia may be a useful therapeutic strategy to prevent the gradual deterioration of structure and function remains unexplored. Nineteen male Wistar rats were divided into four groups: rats that underwent renal bilateral ischemia for 10, 20, or 45 min were compared with sham operated rats. Additionally, thirteen male Wistar rats that underwent renal bilateral ischemia for 20 min were divided into an untreated ischemic group (I) and two groups receiving spironolactone, 20 mg/kg by gavage, at either 0 (Sp0) or 1.5-h after ischemia (Sp1.5). The rats were followed up and studied after 9 months. Mild (20 min) and severe (45 min) ischemia induced a progressive increase in proteinuria at varying magnitudes, whereas minor ischemia (10 min) did not modify proteinuria. CKD induced by moderate ischemia was characterized by renal hypertrophy and tubulointerstitial fibrosis. These effects were associated with activation of the transforming growth factor β (TGFβ) signaling pathway and up-regulation of endothelin receptor A (ETA) and alpha smooth muscle actin (αSMA). Spironolactone treatment immediately or 1.5-h after the ischemic insult prevented the onset of these disorders. Our results show that moderate ischemic insult leads to long-term structural and molecular changes that may compromise renal function in later stages. Additionally, we demonstrate that spironolactone administration after mild ischemia prevents this detrimental effect. PMID:26157344

  18. Thymoquinone ameliorates testicular tissue inflammation induced by chronic administration of oral sodium nitrite.

    PubMed

    Alyoussef, A; Al-Gayyar, M M H

    2016-06-01

    Although sodium nitrite has been widely used as food preservative, building bases of scientific evidence about nitrite continues to oppose the general safety in human health. Moreover, thymoquinone (TQ) has therapeutic potential as antioxidant, anti-inflammatory, antibacterial and anticancer. Therefore, we investigated the effects of both sodium nitrite and TQ on testicular tissues of rats. Forty adult male Sprague Dawley rats were used. They received either 80 mg kg(-1) sodium nitrite or 50 mg kg(-1) TQ daily for twelve weeks. Serum testosterone was measured. Testis were weighed and the testicular tissue homogenates were used for measurements of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-6, IL10, caspase-3, caspase-8 and caspase-9. Sodium nitrite resulted in significant reduction in serum testosterone concentration and elevation in testis weight and Gonado-Somatic Index. We found significant reduction in testicular tissues levels of IL-4 and IL-10 associated with elevated levels of TNF-α, IL-1β, IL-6, caspase-3, caspase-8 and caspase-9. In conclusion, chronic oral sodium nitrite induced changes in the weight of rat testis accompanied by elevation in the testicular tissue level of oxidative stress markers and inflammatory cytokines. TQ attenuated sodium nitrite-induced testicular tissue damage through blocking oxidative stress, restoration of normal inflammatory cytokines balance and blocking of apoptosis. PMID:26260072

  19. Recombinant AAV9-TLK1B Administration Ameliorates Fractionated Radiation-Induced Xerostomia

    PubMed Central

    Shanmugam, Prakash Srinivasan Timiri; Dayton, Robert D.; Palaniyandi, Senthilnathan; Abreo, Fleurette; Caldito, Gloria; Klein, Ronald L.

    2013-01-01

    Abstract Salivary glands are highly susceptible to radiation, and patients with head and neck cancer treated with radiotherapy invariably suffer from its distressing side effect, salivary hypofunction. The reduction in saliva disrupts oral functions, and significantly impairs oral health. Previously, we demonstrated that adenoviral-mediated expression of Tousled-like kinase 1B (TLK1B) in rat submandibular glands preserves salivary function after single-dose ionizing radiation. To achieve long-term transgene expression for protection of salivary gland function against fractionated radiation, this study examines the usefulness of recombinant adeno-associated viral vector for TLK1B delivery. Lactated Ringers or AAV2/9 with either TLK1B or GFP expression cassette were retroductally delivered to rat submandibular salivary glands (1011 vg/gland), and animals were exposed, or not, to 20 Gy in eight fractions of 2.5 Gy/day. AAV2/9 transduced predominantly the ductal cells, including the convoluted granular tubules of the submandibular glands. Transgene expression after virus delivery could be detected within 5 weeks, and stable gene expression was observed till the end of study. Pilocarpine-stimulated saliva output measured at 8 weeks after completion of radiation demonstrated >10-fold reduction in salivary flow in saline- and AAV2/9-GFP-treated animals compared with the respective nonirradiated groups (90.8% and 92.5% reduction in salivary flow, respectively). Importantly, there was no decrease in stimulated salivary output after irradiation in animals that were pretreated with AAV2/9-TLK1B (121.5% increase in salivary flow; p<0.01). Salivary gland histology was better preserved after irradiation in TLK1B-treated group, though not significantly, compared with control groups. Single preemptive delivery of AAV2/9-TLK1B averts salivary dysfunction resulting from fractionated radiation. Although AAV2/9 transduces mostly the ductal cells of the gland, their protection

  20. Oral Administration of N-Acetyl-seryl-aspartyl-lysyl-proline Ameliorates Kidney Disease in Both Type 1 and Type 2 Diabetic Mice via a Therapeutic Regimen

    PubMed Central

    Nitta, Kyoko; Shi, Sen; Nagai, Takako; Kanasaki, Megumi; Kitada, Munehiro; Srivastava, Swayam Prakash; Haneda, Masakazu; Kanasaki, Keizo; Koya, Daisuke

    2016-01-01

    Kidney fibrosis is the final common pathway of progressive kidney diseases including diabetic nephropathy. Here, we report that the endogenous antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), the substrate of angiotensin-converting enzyme (ACE), is an orally available peptide drug used to cure kidney fibrosis in diabetic mice. We utilized two mouse models of diabetic nephropathy, streptozotocin- (STZ-) induced type 1 diabetic CD-1 mice and type 2 diabetic nephropathy model db/db mice. Intervention with the ACE inhibitor imidapril, oral AcSDKP, or imidapril + oral AcSDKP combination therapy increased urine AcSDKP levels. AcSDKP levels were significantly higher in the combination group compared to those of the other groups. AcSDKP oral administration, either AcSDKP alone or in addition to imidapril, ameliorated glomerulosclerosis and tubulointerstitial fibrosis. Plasma cystatin C levels were higher in both models, at euthanasia, and were restored by all the treatment groups. The levels of antifibrotic miRs, such as miR-29 or let-7, were suppressed in the kidneys of both models; all treatments, especially the combination of imidapril + oral AcSDKP, restored the antifibrotic miR levels to a normal value or even higher. AcSDKP may be an oral antifibrotic peptide drug that would be relevant to combating fibroproliferative kidney diseases such as diabetic nephropathy. PMID:27088094

  1. Oral administration of heat-killed Lactobacillus brevis SBC8803 ameliorates alcoholic liver disease in ethanol-containing diet-fed C57BL/6N mice.

    PubMed

    Segawa, Shuichi; Wakita, Yoshihisa; Hirata, Hiroshi; Watari, Junji

    2008-12-10

    We examined the effect of heat-killed Lactobacillus brevis (L. brevis) SBC8803 on the development of alcoholic liver disease using ethanol-containing diet-fed mice. Heat-killed L. brevis was orally administered at a dose of 100 or 500 mg/kg once a day for 35 days. Alcoholic liver injury was examined by measuring the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a serum, and the alcoholic fatty liver was assessed from the content of triglyceride (TG) and total cholesterol in the liver. Quantitative RT-PCR was used to examine mRNA expression of tumor necrosis factor (TNF)-alpha, sterol regulatory element-binding protein (SREBP)-1, SREBP-2, and peroxisome proliferator-activated receptor alpha (PPARalpha) in the liver, as well as E-cadherin, Zonula occludens 1 (ZO-1), and heat shock protein (Hsp) 25 in the small intestine. Oral administration of L. brevis significantly inhibited an increase in the level of serum ALT and AST, as well as the content of TG and total cholesterol in the liver caused by ethanol intake. L. brevis supplementation suppressed the overexpression of TNF-alpha, SREBP-1, and SREBP-2 mRNA in the liver induced by ethanol intake and up-regulated the expression of Hsp25 mRNA in the small intestine. These results suggest that L. brevis ameliorated the ethanol-induced liver injury and the fatty liver by suppressing the up-regulation of TNF-alpha and SREBPs in the liver. We speculate that the inhibition of TNF-alpha and SREBPs up-regulation by L. brevis is due to the inhibition of gut-derived endotoxin migration into the liver through the enhancement of intestinal barrier function by the induction of cytoprotective Hsps. PMID:18976829

  2. Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice.

    PubMed

    Rodgers, Jean; Bradley, Barbara; Kennedy, Peter G E; Sternberg, Jeremy M

    2015-01-01

    Invasion of the central nervous system (CNS) by African trypanosomes represents a critical step in the development of human African trypanosomiasis. In both clinical cases and experimental mouse infections it has been demonstrated that predisposition to CNS invasion is associated with a type 1 systemic inflammatory response. Using the Trypanosoma brucei brucei GVR35 experimental infection model, we demonstrate that systemic delivery of the counter-inflammatory cytokine IL-10 lowers plasma IFN-γ and TNF-α concentrations, CNS parasitosis and ameliorates neuro-inflammatory pathology and clinical symptoms of disease. The results provide evidence that CNS invasion may be susceptible to immunological attenuation. PMID:26505761

  3. Amelioration of Prallethrin-Induced Oxidative Stress and Hepatotoxicity in Rat by the Administration of Origanum majorana Essential Oil

    PubMed Central

    Mossa, Abdel-Tawab H.; Refaie, Amel A.; Ramadan, Amal; Bouajila, Jalloul

    2013-01-01

    This study was carried out to evaluate the adverse effects of exposure to prallethrin on oxidant/antioxidant status and liver dysfunction biomarkers and the protective role of Origanum majorana essential oil (EO) in rat. Male rats were divided into 4 groups: (i) received only olive oil (ii) treated with 64.0 mg/kg body weight prallethrin (1/10 LD50) in olive oil via oral route daily for 28 days, (iii) treated with 64.0 mg/kg body weight prallethrin (1/10 LD50) and EO (160 μL/kg b.wt.) in olive oil and (iv) received EO (160 μL/kg b.wt.) in olive oil via oral route twice daily for 28 days. Prallethrin treatment caused decrease in body weight gain and increase in relative liver weight. There was a significant increase in the activity of serum marker enzymes, aspartate transaminase, alanine transaminase, and alkaline phosphatase. It caused increase in thiobarbituric acid reactive substances and reduction in the activities of superoxide dismutase, catalase, and glutathione-S-transferase in liver. Consistent histological changes were found in the liver of prallethrin treatment. EO showed significant protection with the depletion of serum marker enzymes and replenishment of antioxidant status and brought all the values to near normal, indicating the protective effect of EO. We can conclude that prallethrin caused oxidative damage and liver injury in male rat and co-administration of EO attenuated the toxic effect of prallethrin. These results demonstrate that administration of EO may be useful, easy, and economical to protect human against pyrethroids toxic effects. PMID:24381944

  4. 21 CFR 10.70 - Documentation of significant decisions in administrative file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Documentation of significant decisions in administrative file. 10.70 Section 10.70 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... appropriate employees, and show all persons to whom copies were sent; (4) Avoid defamatory...

  5. Red cabbage (Brassica oleracea L.) mediates redox-sensitive amelioration of dyslipidemia and hepatic injury induced by exogenous cholesterol administration.

    PubMed

    Al-Dosari, Mohammed S

    2014-01-01

    The widely used culinary vegetable, red cabbage (Brassica oleracea L. Var. capitata f. rubra), of the Brassicaceae family contains biologically potent anthocyanins and a myriad of antioxidants. Previous studies have shown that the pharmacological effects of red cabbage in vivo are redox-sensitive. The present study explored whether red cabbage modulates various histopathological and biochemical parameters in rats administered with a cholesterol-rich diet (CRD). To this end, prolonged administration of a lyophilized-aqueous extract of red cabbage (250 and 500 mg/kg body weight) significantly blunted the imbalances in lipids, liver enzymes and renal osmolytes induced by the CRD. The effects of red cabbage were compared to simvastatin (30 mg/kg body weight) treated rats. Estimation of malondialdehyde and non-protein sulfhydryls revealed robust antioxidant properties of red cabbage. Histopathological analysis of livers from rats administered with red cabbage showed marked inhibition in inflammatory and necrotic changes triggered by CRD. Similarly, in vitro studies using a 2',7'-Dichlorofluorescein-based assay showed that red cabbage conferred cytoprotective effects in cultured HepG2 cells. In conclusion, the present study discloses the potential therapeutic effects of red cabbage in dyslipidemia as well as hepatic injury, that is at least, partly mediated by its antioxidant properties. PMID:24467544

  6. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

    PubMed Central

    Nagai, Noriaki; Yoshioka, Chiaki; Ito, Yoshimasa; Funakami, Yoshinori; Nishikawa, Hiroyuki; Kawabata, Atsufumi

    2015-01-01

    It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. PMID:26690139

  7. Voluntary exercise does not ameliorate spatial learning and memory deficits induced by chronic administration of nandrolone decanoate in rats.

    PubMed

    Tanehkar, Fatemeh; Rashidy-Pour, Ali; Vafaei, Abbas Ali; Sameni, Hamid Reza; Haghighi, Saeed; Miladi-Gorji, Hossien; Motamedi, Fereshteh; Akhavan, Maziar Mohammad; Bavarsad, Kowsar

    2013-01-01

    Chronic exposure to the anabolic androgenic steroids (AAS) nandrolone decanoate (ND) in supra-physiological doses is associated with learning and memory impairments. Given the well-known beneficial effects of voluntary exercise on cognitive functions, we examined whether voluntary exercise would improve the cognitive deficits induced by chronic administration of ND. We also investigated the effects of ND and voluntary exercise on hippocampal BDNF levels. The rats were randomly distributed into 4 experimental groups: the vehicle-sedentary group, the ND-sedentary group, the vehicle-exercise group, and the ND-exercise group. The vehicle-exercise and the ND-exercise groups were allowed to freely exercise in a running wheel for 15 days. The vehicle-sedentary and the ND-sedentary groups were kept sedentary for the same period. Vehicle or ND injections were started 14 days prior to the voluntary exercise and continued throughout the 15 days of voluntary exercise. After the 15-day period, the rats were trained and tested on a water maze spatial task using four trials per day for 5 consecutive days followed by a probe trial two days later. Exercise significantly improved performance during both the training and retention of the water maze task, and enhanced hippocampal BDNF. ND impaired spatial learning and memory, and this effect was not rescued by exercise. ND also potentiated the exercise-induced increase in hippocampal BDNF levels. These results seem to indicate that voluntary exercise is unable to improve the disruption of cognitive functions by chronic ND. Moreover, increased levels of BDNF may play a role in ND-induced impairments in learning and memory. The harmful effects of ND and other AAS on learning and memory should be taken into account when athletes decide to use AAS for performance or body image improvement. PMID:23068768

  8. Chronic administration of small nonerythropoietic peptide sequence of erythropoietin effectively ameliorates the progression of postmyocardial infarction-dilated cardiomyopathy.

    PubMed

    Ahmet, Ismayil; Tae, Hyun-Jin; Brines, Michael; Cerami, Anthony; Lakatta, Edward G; Talan, Mark I

    2013-06-01

    The cardioprotective properties of erythropoietin (EPO) in preclinical studies are well documented, but erythropoietic and prothrombotic properties of EPO preclude its use in chronic heart failure (CHF). We tested the effect of long-term treatment with a small peptide sequence within the EPO molecule, helix B surface peptide (HBSP), that possesses tissue-protective, but not erythropoietic properties of EPO, on mortality and cardiac remodeling in postmyocardial infarction-dilated cardiomyopathy in rats. Starting 2 weeks after permanent left coronary artery ligation, rats received i.p. injections of HBSP (60 µg/kg) or saline two times per week for 10 months. Treatment did not elicit an immune response, and did not affect the hematocrit. Compared with untreated rats, HBSP treatment reduced mortality by 50% (P < 0.05). Repeated echocardiography demonstrated remarkable attenuation of left ventricular dilatation (end-diastolic volume: 41 versus 86%; end-systolic volume: 44 versus 135%; P < 0.05), left ventricle functional deterioration (ejection fraction: -4 versus -63%; P < 0.05), and myocardial infarction (MI) expansion (3 versus 38%; P < 0.05). A hemodynamic assessment at study termination demonstrated normal preload independent stroke work (63 ± 5 versus 40 ± 4; P < 0.05) and arterioventricular coupling (1.2 ± 0.2 versus 2.7 ± 0.7; P < 0.05). Histologic analysis revealed reduced apoptosis (P < 0.05) and fibrosis (P < 0.05), increased cardiomyocyte density (P < 0.05), and increased number of cardiomyocytes in myocardium among HBSP-treated rats. The results indicate that HBSP effectively reduces mortality, ameliorates the MI expansion and CHF progression, and preserves systolic reserve in the rat post-MI model. There is also a possibility that HBSP promoted the increase of the myocytes number in the myocardial wall remote from the infarct. Thus, HBSP peptide merits consideration for clinical testing. PMID:23584743

  9. Neonatal oxytocin administration and supplemental milk ameliorate the weaning transition and alter hormonal expression in the gastrointestinal tract in pigs.

    PubMed

    Rault, J-L; Ferrari, J; Pluske, J R; Dunshea, F R

    2015-04-01

    The aim of this study was to investigate the influences of milk supplementation during lactation, over 1 wk after weaning, and oxytocin administration for the first 14 d of life on the pigs' response to weaning. Pigs from 20 litters were allocated to each of these 3 treatments in a randomized factorial design. Oxytocin was administered subcutaneously daily from 0 to 14 d of age at a rate of 10 I.U. per kg. The milk supplement consisted of a mixture of 25% skim milk powder offered either during lactation between 10 and 20 d of age or for the first week after weaning as a transitional diet along with dry pellets. Pigs were weaned at 21 d of age. Growth rate was measured from birth to slaughter at 140 d of age and feed intake of supplemental milk or feed from 10 to 56 d of age. Organ weights (heart, liver, stomach, and kidneys) and the gene expression of ghrelin, leptin, and glucagon-like peptides (glucagon-like peptide-1 and glucagon-like peptide-2) were measured in the stomach, ileum, and duodenum at 10, 21, and 28 d of age. Milk supplementation after weaning resulted in immediate feed intake and partially alleviated the depression in growth rate over the first 7 d postweaning (P < 0.001), but milk supplementation during lactation had no effects (P > 0.1). However, effects were only transient and disappeared once the milk liquid diet was removed. Neonatal oxytocin administration reduced weight loss over the first 2 d after weaning (P = 0.03), without affecting feed intake (P > 0.1), hence possibly reducing weaning stress. Seven days after weaning, oxytocin-treated pigs had greater stomach ghrelin and leptin expression (both P = 0.02), and pigs supplemented with milk after weaning had greater stomach leptin and glucagon-like peptide-2 expression (P = 0.02 and P = 0.05, respectively). Hence, neonatal oxytocin administration or postweaning milk supplementation are both effective means of enhancing gastric leptin expression and reducing weight loss at weaning, likely

  10. Method of Administration of PROMIS Scales Did Not Significantly Impact Score Level, Reliability or Validity

    PubMed Central

    Bjorner, Jakob B.; Rose, Matthias; Gandek, Barbara; Stone, Arthur A.; Junghaenel, Doerte U.; Ware, John E.

    2014-01-01

    Objective To test the impact of method of administration (MOA) on score level, reliability, and validity of scales developed in the Patient Reported Outcomes Measurement Information System (PROMIS). Study Design and Setting Two non-overlapping parallel forms each containing 8 items from each of three PROMIS item banks (Physical Function, Fatigue and Depression) were completed by 923 adults with COPD, depression, or rheumatoid arthritis. In a randomized cross-over design, subjects answered one form by interactive voice response (IVR) technology, paper questionnaire (PQ), personal digital assistant (PDA), or personal computer (PC) and a second form by PC, in the same administration. Method equivalence was evaluated through analyses of difference scores, intraclass correlations (ICC), and convergent/discriminant validity. Results In difference score analyses, no significant mode differences were found and all confidence intervals were within the pre-specified MID of 0.2 SD. Parallel forms reliabilities were very high (ICC=0.85-0.93). Only one across mode ICC was significantly lower than the same mode ICC. Tests of validity showed no differential effect by MOA. Participants preferred screen interface over PQ and IVR. Conclusion We found no statistically or clinically significant differences in score levels or psychometric properties of IVR, PQ or PDA administration as compared to PC. PMID:24262772

  11. Continuous administration of polyphenols from aqueous rooibos (Aspalathus linearis) extract ameliorates dietary-induced metabolic disturbances in hyperlipidemic mice.

    PubMed

    Beltrán-Debón, R; Rull, A; Rodríguez-Sanabria, F; Iswaldi, I; Herranz-López, M; Aragonès, G; Camps, J; Alonso-Villaverde, C; Menéndez, J A; Micol, V; Segura-Carretero, A; Joven, J

    2011-03-15

    The incidence of obesity and related metabolic diseases is increasing globally. Current medical treatments often fail to halt the progress of such disturbances, and plant-derived polyphenols are increasingly being investigated as a possible way to provide safe and effective complementary therapy. Rooibos (Aspalathus linearis) is a rich source of polyphenols without caloric and/or stimulant components. We have tentatively characterized 25 phenolic compounds in rooibos extract and studied the effects of continuous aqueous rooibos extract consumption in mice. The effects of this extract, which contained 25% w/w of total polyphenol content, were negligible in animals with no metabolic disturbance but were significant in hyperlipemic mice, especially in those in which energy intake was increased via a Western-type diet that increased the risk of developing metabolic complications. In these mice, we found hypolipemiant activity when given rooibos extract, with significant reductions in serum cholesterol, triglyceride and free fatty acid concentrations. Additionally, we found changes in adipocyte size and number as well as complete prevention of dietary-induced hepatic steatosis. These effects were not related to changes in insulin resistance. Among other possible mechanisms, we present data indicating that the activation of AMP-activated protein kinase (AMPK) and the resulting regulation of cellular energy homeostasis may play a significant role in these effects of rooibos extract. Our findings suggest that adding polyphenols to the daily diet is likely to help in the overall management of metabolic diseases. PMID:21211952

  12. Amelioration of Paracetamol-Induced Hepatotoxicity in Rat by the Administration of Methanol Extract of Muntingia calabura L. Leaves

    PubMed Central

    Mahmood, N. D.; Mamat, S. S.; Kamisan, F. H.; Yahya, F.; Kamarolzaman, M. F. F.; Nasir, N.; Mohtarrudin, N.; Tohid, S. F. Md.; Zakaria, Z. A.

    2014-01-01

    Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The present study is aimed at determining the hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using two models of liver injury in rats. Rats were divided into five groups (n = 6) and received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM). The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total phenolic content were also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of hepatic structure was observed in group pretreated with N-acetylcysteine and MEMC. Hepatotoxic rats pretreated with NAC or MEMC exhibited significant decrease (P < 0.05) in ALT and AST enzymes level. Moreover, the extract also exhibited good antioxidant activity. In conclusion, MEMC exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and, thus warrants further investigations. PMID:24868543

  13. Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver

    PubMed Central

    Mei, Lu; Tang, Youcai; Li, Ming; Yang, Pingchang; Liu, Zhiqiang; Yuan, Jieli; Zheng, Pengyuan

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague–Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR)-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the intestinal

  14. Antioxidant-chemoprevention diet ameliorates late effects of total-body irradiation and supplements radioprotection by MnSOD-plasmid liposome administration.

    PubMed

    Epperly, Michael W; Wang, Hong; Jones, Jeffrey A; Dixon, Tracy; Montesinos, Carlos A; Greenberger, Joel S

    2011-06-01

    Abstract Many acute and chronic effects of ionizing radiation are mediated by reactive oxygen species and reactive nitrogen species, which deplete antioxidant stores, leading to cellular apoptosis, stem cell depletion and accelerated aging. C57BL/6NHsd mice receiving intravenous MnSOD-PL prior to 9.5 Gy total-body irradiation (TBI) show increased survival from the acute hematopoietic syndrome, and males demonstrated improved long-term survival (Epperly et al., Radiat. Res. 170, 437-444, 2008). We evaluated the effect of an antioxidant-chemopreventive diet compared to a regular diet on long-term survival in female mice. Twenty-four hours before the LD(50/30) dose of 9.5 Gy TBI, subgroups of mice were injected intravenously with MnSOD-PL (100 μg plasmid DNA in 100 μl of liposomes). Mice on either diet treated with MnSOD-PL showed decreased death after irradiation compared to irradiated mice on the house diet alone (P = 0.031 for the house diet plus MnSOD-PL or 0.015 for antioxidant diet plus MnSOD-PL). The mice on the antioxidant-chemoprevention diet alone or with MnSOD-PL that survived 30 days after irradiation had a significant increase in survival compared to mice on the regular diet (P = 0.04 or 0.01, respectively). In addition, mice treated with MnSOD-PL only and surviving 30 days after radiation also had increased survival compared to those on the regular diet alone (P = 0.02). Survivors of acute ionizing radiation damage have ameliorated life shortening if they are fed an antioxidant-chemopreventive diet. PMID:21466381

  15. Antioxidant-Chemoprevention Diet Ameliorates Late Effects of Total-Body Irradiation and Supplements Radioprotection by MnSOD-Plasmid Liposome Administration

    PubMed Central

    Epperly, Michael W.; Wang, Hong; Jones, Jeffrey A.; Dixon, Tracy; Montesinos, Carlos A.; Greenberger, Joel S.

    2011-01-01

    Many acute and chronic effects of ionizing radiation are mediated by reactive oxygen species and reactive nitrogen species, which deplete antioxidant stores, leading to cellular apoptosis, stem cell depletion and accelerated aging. C57BL/6NHsd mice receiving intravenous MnSOD-PL prior to 9.5 Gy total-body irradiation (TBI) show increased survival from the acute hematopoietic syndrome, and males demonstrated improved long-term survival (Epperly et al., Radiat. Res. 170, 437–444, 2008). We evaluated the effect of an antioxidant-chemopreventive diet compared to a regular diet on long-term survival in female mice. Twenty-four hours before the LD50/30 dose of 9.5 Gy TBI, subgroups of mice were injected intravenously with MnSOD-PL (100 μg plasmid DNA in 100 μl of liposomes). Mice on either diet treated with MnSOD-PL showed decreased death after irradiation compared to irradiated mice on the house diet alone (P = 0.031 for the house diet plus MnSOD-PL or 0.015 for antioxidant diet plus MnSOD-PL). The mice on the antioxidant-chemoprevention diet alone or with MnSOD-PL that survived 30 days after irradiation had a significant increase in survival compared to mice on the regular diet (P = 0.04 or 0.01, respectively). In addition, mice treated with MnSOD-PL only and surviving 30 days after radiation also had increased survival compared to those on the regular diet alone (P = 0.02). Survivors of acute ionizing radiation damage have ameliorated life shortening if they are fed an antioxidant-chemopreventive diet. PMID:21466381

  16. Annual committee reports on significant legislative, judicial, and administrative developments in 1981: Water-Quality committee

    SciTech Connect

    Not Available

    1982-01-01

    This review of 1981 developments is divided into four basic parts. The first covers legislative, judicial, and administrative developments under the Clean Water Act (CWA); the second covers judicial and administrative developments under the Safe Drinking Water Act (SDWA); the third covers judicial developments respecting private rights of action and the federal common law of nuisance. 109 references.

  17. Annual committee report on significant legislative, judicial, and administrative developments in 1980: Water Quality Committee

    SciTech Connect

    Not Available

    1981-01-01

    This review of 1980 developments is divided into three parts. The first covers judicial and administrative developments under the Clean Water Act (CWA) such as industrial guidelines and standards; the second covers judicial administrative and legislative developments under the Safe Drinking Water Act (SDWA); and the third covers judicial developments in the areas of private rights of action and the federal common law of nuisance. 320 references.

  18. Intraperitoneal Administration of a Novel TAT-BDNF Peptide Ameliorates Cognitive Impairments via Modulating Multiple Pathways in Two Alzheimer’s Rodent Models

    PubMed Central

    Wu, Yuanyuan; Luo, Xiaobin; Liu, Xinhua; Liu, Deyi; Wang, Xiong; Guo, Ziyuan; Zhu, Lingqiang; Tian, Qing; Yang, Xifei; Wang, Jian-Zhi

    2015-01-01

    Although Alzheimer’s disease (AD) has been reported for more than 100 years, there is still a lack of effective cures for this devastating disorder. Among the various obstacles that hold back drug development, the blood-brain barrier (BBB) is one of them. Here, we constructed a novel fusion peptide by linking the active domain of brain-derived neurotrophic factor (BDNF) with an HIV-encoded transactivator of transcription (TAT) that has a strong membrane-penetrating property. After intraperitoneal injection, the eGFP-TAT could be robustly detected in different brain regions. By using scopolamine-induced rats and APPswe mice representing AD-like cholinergic deficits and amyloidosis, respectively, we found that intraperitoneal administration of the peptide significantly improved spatial memory with activation of the TrkB/ERK1/2/Akt pathway and restoration of several memory-associated proteins in both models. Administration of the peptide also modulated β-amyloid and tau pathologies in APPswe mice, and it increased the amount of M receptor with modulation of acetylcholinesterase in scopolamine-induced rats. We conclude that intraperitoneal administration of our TAT-BDNF peptide could efficiently target multiple molecular pathways in the brain and improve the cognitive functions in AD-like rodent models. PMID:26463268

  19. Annual committee reports on significant legislative, judicial, and administrative developments in 1982: Environmental Quality Committee

    SciTech Connect

    Not Available

    1983-01-01

    Judicial developments during 1982 dominated activities involving the National Environmental Policy Act (NEPA), the Federal Insecticide, Fungicide and Rotenticide Act, and Marine Sanctuaries, with some changes in administrative procedures and no legislative developments. The Endangered Species Act was amended to expedite changes to the lists and to alter exemption and international trade requirements. Several lawsuits challenged review standards and litigation claims. 231 references. (DCK)

  20. Chronic administration of the neurotrophic agent cerebrolysin ameliorates the behavioral and morphological changes induced by neonatal ventral hippocampus lesion in a rat model of schizophrenia.

    PubMed

    Vázquez-Roque, Rubén Antonio; Ramos, Brenda; Tecuatl, Carolina; Juárez, Ismael; Adame, Anthony; de la Cruz, Fidel; Zamudio, Sergio; Mena, Raúl; Rockenstein, Edward; Masliah, Eliezer; Flores, Gonzalo

    2012-01-01

    Neonatal ventral hippocampal lesion (nVHL) in rats has been widely used as a neurodevelopmental model to mimic schizophrenia-like behaviors. Recently, we reported that nVHLs result in dendritic retraction and spine loss in prefrontal cortex (PFC) pyramidal neurons and medium spiny neurons of the nucleus accumbens (NAcc). Cerebrolysin (Cbl), a neurotrophic peptide mixture, has been reported to ameliorate the synaptic and dendritic pathology in models of aging and neurodevelopmental disorder such as Rett syndrome. This study sought to determine whether Cbl was capable of reducing behavioral and neuronal alterations in nVHL rats. The behavioral analysis included locomotor activity induced by novel environment and amphetamine, social interaction, and sensoriomotor gating. The morphological evaluation included dendritic analysis by using the Golgi-Cox procedure and stereology to quantify the total cell number in PFC and NAcc. Behavioral data show a reduction in the hyperresponsiveness to novel environment- and amphetamine-induced locomotion, with an increase in the total time spent in social interactions and in prepulse inhibition in Cbl-treated nVHL rats. In addition, neuropathological analysis of the limbic regions also showed amelioration of dendritic retraction and spine loss in Cbl-treated nVHL rats. Cbl treatment also ameliorated dendritic pathology and neuronal loss in the PFC and NAcc in nVHL rats. This study demonstrates that Cbl promotes behavioral improvements and recovery of dendritic neuronal damage in postpubertal nVHL rats and suggests that Cbl may have neurotrophic effects in this neurodevelopmental model of schizophrenia. These findings support the possibility that Cbl has beneficial effects in the management of schizophrenia symptoms. PMID:21932359

  1. Ameliorative effects of melatonin administration and photoperiods on diurnal fluctuations in cloacal temperature of Marshall broiler chickens during the hot dry season

    NASA Astrophysics Data System (ADS)

    Sinkalu, Victor O.; Ayo, Joseph O.; Adelaiye, Alexander B.; Hambolu, Joseph O.

    2015-01-01

    Experiments were performed with the aim of determining the effect of melatonin administration on diurnal fluctuations in cloacal temperature (CT) of Marshall broiler chickens during the hot dry season. Birds in group I (12L:12D cycle) were raised under natural photoperiod of 12-h light and 12-h darkness, without melatonin supplementation, while those in group II (LL) were kept under 24-h continuous lighting, without melatonin administration. Broiler chickens in group III (LL + melatonin) were raised under 24-h continuous lighting, with melatonin supplementation at 0.5 mg/kg per os. The cloacal temperatures of 15 labeled broiler chickens from each group were measured at 6:00, 13:00, and 19:00 h, 7 days apart, from days 14-42. Temperature-humidity index was highest at day 14 of the study, with the value of 36.72 ± 0.82 °C but lowest at day 28 with the value of 30.91 ± 0.80 °C ( P < 0.0001). The overall mean hourly cloacal temperature value of 41.51 ± 0.03 °C obtained in the 12L:12D cycle birds was significantly higher ( P < 0.001) than the value of 41.16 ± 0.03 °C recorded in the melatonin-treated group but lower than that of 41.65 ± 0.03 °C obtained in the LL birds. Mortality due to hyperthermia commenced at day 28 in both 12L:12D cycle and LL broiler chickens but was delayed till day 42 in LL + MEL broiler chickens. In conclusion, melatonin administration alleviated the deleterious effects of heat stress on broiler chickens by maintaining their cloacal temperature at relatively low values.

  2. Oral administration of poly-γ-glutamate ameliorates atopic dermatitis in Nc/Nga mice by suppressing Th2-biased immune response and production of IL-17A.

    PubMed

    Lee, Tae-Young; Kim, Doo-Jin; Won, Ji-Na; Lee, Il-Han; Sung, Moon-Hee; Poo, Haryoung

    2014-03-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that is closely related to dysregulation of the T helper type 1 and 2 (Th1)/Th2 balance. A previous study showed that high molecular mass poly-γ-glutamate (γ-PGA) isolated from Bacillus subtilis sp. Chungkookjang induces the production of IL-12 from dendritic cells (DCs). Here, we investigated the effect of γ-PGA on AD-like skin disease using an Nc/Nga mouse model. In vitro, γ-PGA activated DCs and induced IL-12 production in mice. In vivo, oral administration of γ-PGA markedly reduced the AD symptoms, similar to the response seen in the dexamethasone (Dex)-treated group. Treatment with γ-PGA also decreased the serum levels of IgG1, the skin levels of Th2 cytokines, the extent of skin inflammation, and the accumulation of mast cells. Furthermore, γ-PGA was effective against established AD, significantly decreasing serum IgE and Th2 cytokines in the inflamed tissue. Interestingly, the production of IL-17A in splenocytes was also suppressed by γ-PGA, indicating that it inhibits both Th2 and Th17 immune responses. Collectively, these results suggest that oral administration of γ-PGA could be a therapeutic strategy for treating AD via the modulation of Th2-biased immune responses in an Nc/Nga mouse model. PMID:24025551

  3. Oral Administration of the Probiotic Lactobacillus casei Ameliorates Gut Morphology and Physiology in Malnourished-Giardia intestinalis-Infected BALB/c Mice

    PubMed Central

    Shukla, Geeta; Singh, Sumedha; Verma, Angela

    2013-01-01

    Malnutrition reduces the host immunity and enhances the host susceptibility to various diseases. The present study describes the effect of oral administration of probiotic Lactobacillus casei to malnourished-Giardia-infected BALB/c mice with respect to surface alterations and brush border membrane enzyme activity of the small intestine. It was observed that probiotic feeding either prior to or simultaneously with Giardia infection to malnourished mice led to significantly enhanced activity of disaccharidases compared with malnourished and Giardia-infected mice. Scanning electron microscopy also revealed less mucosal damage in the villi of small intestine of probiotic-fed malnourished-Giardia-infected mice compared with completely damaged, mummified, or blunted villi of malnourished-Giardia-infected mice. The findings indicate that probiotics can be used as the prophylactic candidate in abrogating the gut and intestinal dissacharidases anamolies in malnourished hosts suffering from the intestinal diseases. PMID:27335861

  4. Liver-Specific Deletion of Phosphatase and Tensin Homolog Deleted on Chromosome 10 Significantly Ameliorates Chronic EtOH-Induced Increases in Hepatocellular Damage.

    PubMed

    Shearn, Colin T; Orlicky, David J; McCullough, Rebecca L; Jiang, Hua; Maclean, Kenneth N; Mercer, Kelly E; Stiles, Bangyan L; Saba, Laura M; Ronis, Martin J; Petersen, Dennis R

    2016-01-01

    Alcoholic liver disease is a significant contributor to global liver failure. In murine models, chronic ethanol consumption dysregulates PTEN/Akt signaling. Hepatospecific deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTENLKO) mice possess constitutive activation of Akt(s) and increased de novo lipogenesis resulting in increased hepatocellular steatosis. This makes PTENLKO a viable model to examine the effects of ethanol in an environment of preexisting steatosis. The aim of this study was to determine the impact of chronic ethanol consumption and the absence of PTEN (PTENLKO) compared to Alb-Cre control mice (PTENf/f) on hepatocellular damage as evidenced by changes in lipid accumulation, protein carbonylation and alanine amino transferase (ALT). In the control PTENf/f animals, ethanol significantly increased ALT, liver triglycerides and steatosis. In contrast, chronic ethanol consumption in PTENLKO mice decreased hepatocellular damage when compared to PTENLKO pair-fed controls. Consumption of ethanol elevated protein carbonylation in PTENf/f animals but had no effect in PTENLKO animals. In PTENLKO mice, overall hepatic mRNA expression of genes that contribute to GSH homeostasis as well as reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations were significantly elevated compared to respective PTENf/f counterparts. These data indicate that during conditions of constitutive Akt activation and steatosis, increased GSH homeostasis assists in mitigation of ethanol-dependent induction of oxidative stress and hepatocellular damage. Furthermore, data herein suggest a divergence in EtOH-induced hepatocellular damage and increases in steatosis due to polyunsaturated fatty acids downstream of PTEN. PMID:27124661

  5. Liver-Specific Deletion of Phosphatase and Tensin Homolog Deleted on Chromosome 10 Significantly Ameliorates Chronic EtOH-Induced Increases in Hepatocellular Damage

    PubMed Central

    Orlicky, David J.; McCullough, Rebecca L.; Jiang, Hua; Maclean, Kenneth N.; Mercer, Kelly E.; Stiles, Bangyan L.; Saba, Laura M.; Ronis, Martin J.; Petersen, Dennis R.

    2016-01-01

    Alcoholic liver disease is a significant contributor to global liver failure. In murine models, chronic ethanol consumption dysregulates PTEN/Akt signaling. Hepatospecific deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTENLKO) mice possess constitutive activation of Akt(s) and increased de novo lipogenesis resulting in increased hepatocellular steatosis. This makes PTENLKO a viable model to examine the effects of ethanol in an environment of preexisting steatosis. The aim of this study was to determine the impact of chronic ethanol consumption and the absence of PTEN (PTENLKO) compared to Alb-Cre control mice (PTENf/f) on hepatocellular damage as evidenced by changes in lipid accumulation, protein carbonylation and alanine amino transferase (ALT). In the control PTENf/f animals, ethanol significantly increased ALT, liver triglycerides and steatosis. In contrast, chronic ethanol consumption in PTENLKO mice decreased hepatocellular damage when compared to PTENLKO pair-fed controls. Consumption of ethanol elevated protein carbonylation in PTENf/f animals but had no effect in PTENLKO animals. In PTENLKO mice, overall hepatic mRNA expression of genes that contribute to GSH homeostasis as well as reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations were significantly elevated compared to respective PTENf/f counterparts. These data indicate that during conditions of constitutive Akt activation and steatosis, increased GSH homeostasis assists in mitigation of ethanol-dependent induction of oxidative stress and hepatocellular damage. Furthermore, data herein suggest a divergence in EtOH-induced hepatocellular damage and increases in steatosis due to polyunsaturated fatty acids downstream of PTEN. PMID:27124661

  6. Deficits in coordinated motor behavior and in nigrostriatal dopaminergic system ameliorated and VMAT2 expression up-regulated in aged male rats by administration of testosterone propionate.

    PubMed

    Wang, Li; Kang, Yunxiao; Zhang, Guoliang; Zhang, Yingbo; Cui, Rui; Yan, Wensheng; Tan, Huibing; Li, Shuangcheng; Wu, Baiyila; Cui, Huixian; Shi, Geming

    2016-06-01

    The effects of testosterone propionate (TP) supplements on the coordinated motor behavior and nigrostriatal dopaminergic (NSDA) system were analyzed in aged male rats. The present study showed the coordinated motor behavioral deficits, the reduced activity of NSDA system and the decreased expression of vesicular monoamine transporter 2 (VMAT2) in 24month-old male rats. Long term TP treatment improved the motor coordination dysfunction with aging. Increased tyrosine hydroxylase and dopamine transporter, as well as dopamine and its metabolites were found in the NSDA system of TP-treated 24month-old male rats, indicative of the amelioratory effects of TP supplements on NSDA system of aged male rats. The enhancement of dopaminergic (DAergic) activity of NSDA system by TP supplements might underlie the amelioration of the coordinated motor dysfunction in aged male rats. TP supplements up-regulated VMAT2 expression in NSDA system of aged male rats. Up-regulation of VMAT2 expression in aged male rats following chronic TP treatment might be involved in the maintenance of DAergic function of NSDA system in aged male rats. PMID:26956479

  7. Haematolohical Profile of Subacute Oral Toxicity of Molybdenum and Ameliorative Efficacy of Copper Salt in Goats

    PubMed Central

    Kusum; Raina, R.; Verma, P. K.; Pankaj, N. K.; Kant, V.; Kumar, J.; Srivastava, A. K.

    2010-01-01

    Molybdenum toxicity produces a state of secondary hypocuprosis, resulting into alterations in normal hematological profile. In the present study, ammonium molybdate alone and with copper sulfate (II) pentahydrate (ameliorative agent) was administered orally for 30 consecutive days in healthy goats of group 1 and 2, respectively, to access the effect on the hematological profile on different predetermined days of dosing. Administration of ammonium molybdate alone produced significant decline in the mean values of hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), and mean corpuscular hemoglobin concentration (MCHC), with a significant increase in neutrophil level and mean corpuscular volume (MCV). However, values of erythrocyte sedimentation rate, mean corpuscular hemoglobin, and differential leukocyte count were not significantly altered. On comparing observations of ameliorative group with the group 1 goats, it is concluded that the ameliorative copper salt has beneficial effects in alleviating the alterations in the values of Hb, PCV, TLC, TEC, MCV, MCHC, and neutrophils. PMID:21170251

  8. 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

  9. 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

  10. 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

  11. Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

    PubMed Central

    Miura, Yuichiro; Payne, Matthew S.; Jobe, Alan H.; Kallapur, Suhas G.; Saito, Masatoshi; Stock, Sarah J.; Spiller, O. Brad; Ireland, Demelza J.; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A.; Newnham, John P.

    2014-01-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  12. Maternal intravenous administration of azithromycin results in significant fetal uptake in a sheep model of second trimester pregnancy.

    PubMed

    Kemp, Matthew W; Miura, Yuichiro; Payne, Matthew S; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Stock, Sarah J; Spiller, O Brad; Ireland, Demelza J; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A; Newnham, John P

    2014-11-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  13. Intranasal administration of glial-derived neurotrophic factor (GDNF) rapidly and significantly increases whole-brain GDNF level in rats.

    PubMed

    Bender, T S; Migliore, M M; Campbell, R B; John Gatley, S; Waszczak, B L

    2015-09-10

    Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) exerts significant neuroprotective effects on substantia nigra (SN) neurons in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD). In this study we used enzyme-linked immunosorbent assay (ELISA) to determine GDNF brain levels and distribution to target regions (i.e. striatum and SN) following intranasal administration of GDNF at different time points after administration. Brain levels increased significantly within 1h following a single 50-μg dose of GDNF in a liposomal formulation, returning to baseline by 24h. In a second study, different doses of GDNF (10-150 μg) in phosphate-buffered saline (PBS) were studied at the 1-h time point. Dose-dependent increases in brain GDNF levels were observed with apparent saturation of uptake at doses above 100 μg. Liposomes delivered 10-fold more GDNF to brain than PBS despite yielding similar neuroprotective efficacy in the 6-OHDA model, suggesting incomplete release of GDNF from liposomes in tissue. In a third study, autoradiography was performed on brain sections taken 1h after intranasal (125)I-labeled GDNF. Radioactivity was detected throughout the brain along the rostral-to-caudal axis, indicating that nasally administered GDNF can reach target areas. Collectively, these results demonstrate that intranasal administration of GDNF in liposomes or PBS achieves significant increases in GDNF in target brain areas, supporting use of intranasal administration as a non-invasive means of delivering GDNF to the brain to protect dopamine neurons and arrest disease progression in PD. PMID:26166725

  14. ADMINISTRATION OF ANTENATAL GLUCOCORTICOIDS AND POSTNATAL SURFACTANT AMELIORATES RESPIRATORY DISTRESS SYNDROME-ASSOCIATED NEONATAL LETHALITY IN ERK3−/− PUPS

    PubMed Central

    Guaman, Milenka Cuevas; Sbrana, Elena; Shope, Cynthia; Showalter, Lori; Hu, Min; Meloche, Sylvain; Aagaard, Kjersti

    2014-01-01

    BACKGROUND Respiratory distress syndrome (RDS) persists as a prevalent cause of infant morbidity and mortality. We have previously demonstrated that deletion of Erk3 results in pulmonary immaturity and neonatal lethality. Using RNA-Seq, we identified corticotrophin releasing hormone (CRH) and surfactant protein B (SFTPB) as potential molecular mediators of Erk3-dependent lung maturation. In this study, we characterized the impact of antenatal glucocorticoids and postnatal surfactant on neonatal survival of Erk3 null mice. METHODS In a double crossover design, we administered dexamethasone (dex) or saline to pregnant dams during the saccular stage of lung development, followed by postnatal surfactant or saline via inhalation intubation. Survival was recorded, detailed lung histological analysis and staining for CRH and SFTPB protein expression was performed. RESULTS Without treatment, Erk3 null pups die within 6 hours of birth with reduced aerated space, impaired thinning of the alveolar septa, and abundant PAS-positive glycogen stores; as described in human RDS. The administration of dex and surfactant improved RDS-associated lethality of Erk3−/− pups, and partially restored functional fetal lung maturation by accelerating the down-regulation of pulmonary CRH and partially rescuing production of SFTPB. CONCLUSION These findings emphasize that Erk3 is integral to terminal differentiation of type II cells, SFTPB production, and fetal pulmonary maturity. PMID:24732107

  15. Oral administration of geraniol ameliorates acute experimental murine colitis by inhibiting pro-inflammatory cytokines and NF-κB signaling.

    PubMed

    Medicherla, Kanakaraju; Sahu, Bidya Dhar; Kuncha, Madhusudana; Kumar, Jerald Mahesh; Sudhakar, Godi; Sistla, Ramakrishna

    2015-09-01

    Ulcerative colitis is associated with a considerable reduction in the quality of life of patients. The use of phyto-ingredients is becoming an increasingly attractive approach for the management of colitis. Geraniol is a monoterpene with anti-inflammatory and antioxidative properties. In this study, we investigated the therapeutic potential of geraniol as a complementary and alternative medicine against dextran sulphate sodium (DSS)-induced ulcerative colitis in mice. Disease activity indices (DAI) comprising body weight loss, presence of occult blood and stool consistency were assessed for evaluation of colitis symptoms. Intestinal damage was assessed by evaluating colon length and its histology. Pre-treatment with geraniol significantly reduced the DAI score, improved stool consistency (without occult blood) and increased the colon length. The amount of pro-inflammatory cytokines, specifically TNF-α, IL-1β and IL-6 and the activity of myeloperoxidase in colon tissue were significantly decreased in geraniol pre-treated mice. Western blot analyses revealed that geraniol interfered with NF-κB signaling by inhibiting NF-κB (p65)-DNA binding, and IκBα phosphorylation, degradation and subsequent increase in nuclear translocation. Moreover, the expressions of downstream target pro-inflammatory enzymes such as iNOS and COX-2 were significantly reduced by geraniol. Pre-treatment with geraniol also restored the DSS-induced decline in antioxidant parameters such as reduced glutathione and superoxide dismutase activity and attenuated the increase in lipid peroxidation marker, thiobarbituric acid reactive substances and nitrative stress marker, nitrites in colon tissue. Thus, our results suggest that geraniol is a potential therapeutic agent for inflammatory bowel disease. PMID:26190278

  16. 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

  17. 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

  18. Oral administration of fermented wild ginseng ameliorates DSS-induced acute colitis by inhibiting NF-κB signaling and protects intestinal epithelial barrier

    PubMed Central

    Seong, Myeong A; Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong Su; Choi, Seungho; Jang, Young Saeng; Lee, Taek Hwan; Jung, Kyung Hoon; Kang, Dong Kyu; Hurh, Byung Seok; Kim, Dae Eung; Kim, Sun Yeou; Oh, Seung Hyun

    2015-01-01

    Ginseng has been widely used for therapeutic and preventive purposes for thousands of years. However, orally administered ginseng has very low bioavailability and absorption in the intestine. Therefore, fermented ginseng was developed to enhance the beneficial effects of ginseng in the intestine. In this study, we investigated the molecular mechanisms underlying the anti-inflammatory activity of fermented wild ginseng (FWG). We found that FWG significantly alleviated the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis mouse model, and decreased expression level of pro-inflammatory cytokines in colonic tissue. Moreover, we observed that FWG suppressed the infiltration of macrophages in DSS-induced colitis. FWG also attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB into the nucleus. Our data indicate that FWG contains anti-inflammatory activity via NF-κB inactivation and could be useful for treating colitis. [BMB Reports 2015; 48(7): 419-425] PMID:25936779

  19. 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

  20. 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

  1. Annual committee reports on significant legislative, judicial and administrative developments in 1983: Public Lands and Land-Use Committee

    SciTech Connect

    Not Available

    1984-01-01

    The Supreme Court made three major land-use decisions during 1983, two dealing with federalism and the third with federal jiduciary obligation. The US Forest Service Small Tracts Act added flexibility to the disposal of small tracts. Court cases relating to national forests dealt with title disputes, oil and gas leasing, Indian religious practices, dual permitting under the Wilderness Act, and licensing hydro projects on Indian lands. The committee reports uneven administrative progress by the Forests Service in managing the forests. Legislation relating to Department of Interior Management Lands focuses on Outer Continental Shelf and federal coal leases and wilderness areas. The Supreme Court made several decisions involving the classification of sand and gravel as minerals, trespass, nonimpairment standards, herbicides, and other issues. 132 references.

  2. The intra-nasal administration of insulin induces significant hypoglycaemia and classical counterregulatory hormonal responses in normal man.

    PubMed

    Paquot, N; Scheen, A J; Franchimont, P; Lefebvre, P J

    1988-01-01

    The present study aimed at investigating the metabolic and hormonal consequences of intra-nasal administration of insulin in normal man. Lyophylisated regular porcine insulin (Insuline Ordinaire Organon) diluted with a non ionic detergent (Laureth-9 0,25%) was administered intra-nasally in 8 overnight fasted healthy volunteers using a calibrated aerosol delivery device (90 microliters = 9 U of insulin/spray) up to a total insulin dose close to 1 U/kg body weight. After intra-nasal insulin administration, plasma insulin levels rose from 5 +/- 1 to 38 +/- 10 mU/l (2p less than 0.01) at min 15, blood glucose concentrations decreased from 4.4 +/- 0.2 to 3.2 +/- 0.3 mmol/l (2p less than 0.01) at min 45, plasma C-peptide levels diminished from 327 +/- 31 to 174 +/- 28 mumol/l (2p less than 0.01) at min 60 and plasma free fatty acids concentrations fell from 336 +/- 109 to 130 +/- 31 mumol/l (2p less than 0.05) at min 30. The fall in blood glucose resulted in a prompt increase in plasma glucagon levels (from 78 +/- 28 to 150 +/- 24 ng/l at min 45; 2p less than 0.05) and in later rises in plasma growth hormone and cortisol concentrations. There was a close relationship between the individual maximal decreases in blood glucose levels and the individual maximal increases in plasma insulin (r = 0.81), glucagon (r = 0.88), cortisol (r = 0.87) and growth hormone (r = 0.76) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3292305

  3. Administrators' Perceptions of Factors Related to Student Retention at Colleges with a Significant Black Student Enrollment Affiliated with the Association for Biblical Higher Education

    ERIC Educational Resources Information Center

    Wilson, Wesley B.

    2013-01-01

    This study described and explored the factors perceived as relevant to student retention by administrators at colleges and universities with significant Black student populations. The sample was 31 institutions affiliated with the Association for Biblical Higher Education (ABHE) that had Black student enrollment of 20% or more. The study sought to…

  4. From 9/11 to Recession: Historically Significant Events in America and Their Impact on Research Administration

    ERIC Educational Resources Information Center

    Minnema, Linnea

    2011-01-01

    Federally sponsored research funding sources are not stagnant programs. Many things influence the nature of research, not all of them purely scientific. Historically significant events draw public attention to causes, and in the age of immediate information those events can have a powerful and lasting impact on research funding. September 11, 2001…

  5. 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

  6. 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

  7. Reoxygenation of Asphyxiated Newborn Piglets: Administration of 100% Oxygen Causes Significantly Higher Apoptosis in Cortical Neurons, as Compared to 21%

    PubMed Central

    Faa, G.; Fanos, V.; Fanni, D.; Gerosa, C.; Faa, A.; Fraschini, M.; Pais, M. E.; Di Felice, E.; Papalois, A.; Varsami, M.; Xanthos, T.; Iacovidou, N.

    2014-01-01

    Objective. Evaluation of neuronal changes in an animal experimental model of normocapnic hypoxia- reoxygenation. Materials and Methods. Fifty male piglets were the study subjects; normocapnic hypoxia was induced in 40 piglets and ten were sham-operated (controls). When bradycardia and/or severe hypotension occurred, reoxygenation was initiated. Animals were allocated in 4 groups according to the oxygen concentration, they were resuscitated with 18%, 21%, 40%, and 100% O2. Persisting asystole despite 10 minutes of cardiopulmonary resuscitation and return of spontaneous circulation were the endpoints of the experiment. Surviving animals were euthanized and brain cortex samples were collected, hematoxylin and eosin-stained, and examined for apoptotic bodies observing 10 consecutive high power fields. Results. Histological examination of the control group did not show any pathological change. On the contrary, apoptosis of neurons was found in 87.5% of treated animals. When specimens were examined according to the oxygen concentration used for resuscitation, we found marked intergroup variability; a higher percentage of apoptotic neurons was observed in piglets of group 4 (100% oxygen) compared to the others (P = 0.001). Conclusions. This preliminary data shows that normocapnic hypoxia and reoxygenation in Landrace/Large White piglets resulted in significant histological changes in the brain cortex. The degree of pathological changes in cortical neurons was significantly associated with the oxygen concentration used for reoxygenation, with a higher percentage of apoptotic neurons being observed in piglets reoxygenated with 100% compared to 18% O2 and to 21% O2. PMID:24783208

  8. 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

  9. 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

  10. Delayed Administration of Bone Marrow Mesenchymal Stem Cell Conditioned Medium Significantly Improves Outcome After Retinal Ischemia in Rats

    PubMed Central

    Dreixler, John C.; Poston, Jacqueline N.; Balyasnikova, Irina; Shaikh, Afzhal R.; Tupper, Kelsey Y.; Conway, Sineadh; Boddapati, Venkat; Marcet, Marcus M.; Lesniak, Maciej S.; Roth, Steven

    2014-01-01

    Purpose. Delayed treatment after ischemia is often unsatisfactory. We hypothesized that injection of bone marrow stem cell (BMSC) conditioned medium after ischemia could rescue ischemic retina, and in this study we characterized the functional and histological outcomes and mechanisms of this neuroprotection. Methods. Retinal ischemia was produced in adult Wistar rats by increasing intraocular pressure for 55 minutes. Conditioned medium (CM) from rat BMSCs or unconditioned medium (uCM) was injected into the vitreous 24 hours after the end of ischemia. Recovery was assessed 7 days after ischemia using electroretinography, at which time we euthanized the animals and then prepared 4-μm-thick paraffin-embedded retinal sections. TUNEL and Western blot were used to identify apoptotic cells and apoptosis-related gene expression 24 hours after injections; that is, 48 hours after ischemia. Protein content in CM versus uCM was studied using tandem mass spectrometry, and bioinformatics methods were used to model protein interactions. Results. Intravitreal injection of CM 24 hours after ischemia significantly improved retinal function and attenuated cell loss in the retinal ganglion cell layer. CM attenuated postischemic apoptosis and apoptosis-related gene expression. By spectral counting, 19 proteins that met stringent identification criteria were increased in the CM compared to uCM; the majority were extracellular matrix proteins that mapped into an interactional network together with other proteins involved in cell growth and adhesion. Conclusions. By restoring retinal function, attenuating apoptosis, and preventing retinal cell loss after ischemia, CM is a robust means of delayed postischemic intervention. We identified some potential candidate proteins for this effect. PMID:24699381

  11. The incidence and significance of acute kidney injury following emergent contrast administration in patients with STEMI and stroke.

    PubMed

    Marchick, Michael Robert; Allen, Brandon Russell; Weeks, Emily Cassin; Shuster, Jonathan Jacob; Elie, Marie-Carmelle

    2016-09-01

    The authors have investigated the incidence of acute kidney injury (AKI) and short-term mortality following an activated STEMI and stroke alert at a tertiary referral and academic center. A single center, retrospective chart review of STEMI and stroke activation patients from January 2010 to March 2012. Data was collected and reviewed from an institutional database following IRB-approval. Inclusion criteria were STEMI patients taken for cardiac catheterization, excluding patients receiving hemodialysis due to end-stage renal disease (ESRD). Primary outcome measures were the incidence of AKI using the RIFLE criteria and short-term mortality. 745 patients were included (488 stroke, 257 STEMI). The median age was 65, and 39 % were female. Overall inpatient mortality was 7.0 %. 5.4 % (40/745) of patients experienced some degree of AKI (8.6 % of STEMI, 3.7 % of stroke patients). Overall, 30 % of patients with AKI died during their hospitalization. AKI was associated with a 7.1-fold (95 % CI 3.4-15.1) increase in mortality in the entire cohort. Among STEMI patients, AKI was associated with a 66.6-fold (95 % CI 12.9-343.4) increase in mortality. These findings follow similar trends published among critically ill patients with AKI. The risk of death with concomitant AKI in this hospital population is significant and deserves future study. Early recognition and awareness in the emergency department is paramount to the patient's survival. Future studies should focus on modalities to improve early recognition and preventative therapies. PMID:26910240

  12. 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

  13. Ethanolic Extract of the Seed of Zizyphus jujuba var. spinosa Ameliorates Cognitive Impairment Induced by Cholinergic Blockade in Mice

    PubMed Central

    Lee, Hyung Eun; Lee, So Young; Kim, Ju Sun; Park, Se Jin; Kim, Jong Min; Lee, Young Woo; Jung, Jun Man; Kim, Dong Hyun; Shin, Bum Young; Jang, Dae Sik; Kang, Sam Sik; Ryu, Jong Hoon

    2013-01-01

    In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naïve mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer’s disease. PMID:24244815

  14. Difference in method of administration did not significantly impact item response: an IRT-based analysis from the Patient-Reported Outcomes Measurement Information System (PROMIS) initiative

    PubMed Central

    Rose, Matthias; Gandek, Barbara; Stone, Arthur A.; Junghaenel, Doerte U.; Ware, John E.

    2013-01-01

    Purpose To test the impact of method of administration (MOA) on the measurement characteristics of items developed in the Patient-Reported Outcomes Measurement Information System (PROMIS). Methods Two non-overlapping parallel 8-item forms from each of three PROMIS domains (physical function, fatigue, and depression) were completed by 923 adults (age 18–89) with chronic obstructive pulmonary disease, depression, or rheumatoid arthritis. In a randomized crossover design, subjects answered one form by interactive voice response (IVR) technology, paper questionnaire (PQ), personal digital assistant (PDA), or personal computer (PC) on the Internet, and a second form by PC, in the same administration. Structural invariance, equivalence of item responses, and measurement precision were evaluated using confirmatory factor analysis and item response theory methods. Results Multigroup confirmatory factor analysis supported equivalence of factor structure across MOA. Analyses by item response theory found no differences in item location parameters and strongly supported the equivalence of scores across MOA. Conclusions We found no statistically or clinically significant differences in score levels in IVR, PQ, or PDA administration as compared to PC. Availability of large item response theory-calibrated PROMIS item banks allowed for innovations in study design and analysis. PMID:23877585

  15. 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

  16. Orally Administrated Lactobacillus pentosus var. plantarum C29 Ameliorates Age-Dependent Colitis by Inhibiting the Nuclear Factor-Kappa B Signaling Pathway via the Regulation of Lipopolysaccharide Production by Gut Microbiota

    PubMed Central

    Jeong, Jin-Ju; Kim, Kyung-Ah; Jang, Se-Eun; Woo, Jae-Yeon; Han, Myung Joo; Kim, Dong-Hyun

    2015-01-01

    To evaluate the anti-inflammaging effect of lactic acid bacteria (LAB) on age-dependent inflammation, we first screened and selected a tumor necrosis factor (TNF)-α and reactive oxygen species (ROS)-inhibitory LAB, Lactobacillus pentosus var. plantarum C29, among the LABs isolated from fermented vegetables using LPS-stimulated mouse peritoneal macrophages. Oral administration of C29 (2 × 109 CFU/rat) for 8 weeks in aged Fischer 344 rats (age, 16 months) inhibited the expression of the inflammatory markers myeloperoxidase, inducible nitric oxide (NO) synthase, cyclooxygenase-2, pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-6 and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein 1 (AP1), and mitogen-activated protein kinases (MAPKs). Treatment with C29 induced the expression of tight junction proteins ZO-1, occludin, and claudin-1, and reduced intestinal microbial LPS and plasmatic LPS levels and ROS, as well as the Firmicutes to Bacteroidetes ratio, which is significantly higher in aged rats than in young rats. C29 treatment also reduced plasmatic reactive oxygen species, malondialdehyde, C-reactive protein, and TNF-α, and suppressed expression of senescence markers p16 and p53 in the colon of the aged rats, but increased SIRT 1 expression. Based on these findings, we concluded that C29 treatment may suppress aging-dependent colitis by inhibiting NF-κB, AP1, and MAPK activation via the inhibition of gut microbiota LPS production and the induction of tight junction protein expression. PMID:25689583

  17. Bacteriophage administration significantly reduces Shigella colonization and shedding by Shigella-challenged mice without deleterious side effects and distortions in the gut microbiota

    PubMed Central

    Mai, Volker; Ukhanova, Maria; Reinhard, Mary K; Li, Manrong; Sulakvelidze, Alexander

    2015-01-01

    We used a mouse model to establish safety and efficacy of a bacteriophage cocktail, ShigActive™, in reducing fecal Shigella counts after oral challenge with a susceptible strain. Groups of inbred C57BL/6J mice challenged with Shigella sonnei strain S43-NalAcR were treated with a phage cocktail (ShigActive™) composed of 5 lytic Shigella bacteriophages and ampicillin. The treatments were administered (i) 1 h after, (ii) 3 h after, (iii) 1 h before and after, and (iv) 1 h before bacterial challenge. The treatment regimens elicited a 10- to 100-fold reduction in the CFU's of the challenge strain in fecal and cecum specimens compared to untreated control mice, (P < 0.05). ShigActiveTM treatment was at least as effective as treatment with ampicillin but had a significantly less impact on the gut microbiota. Long-term safety studies did not identify any side effects or distortions in overall gut microbiota associated with bacteriophage administration. Shigella phages may be therapeutically effective in a “classical phage therapy” approach, at least during the early stages after Shigella ingestion. Oral prophylactic “phagebiotic” administration of lytic bacteriophages may help to maintain a healthy gut microbiota by killing specifically targeted bacterial pathogens in the GI tract, without deleterious side effects and without altering the normal gut microbiota. PMID:26909243

  18. Swertisin, a C-glucosylflavone, ameliorates scopolamine-induced memory impairment in mice with its adenosine A1 receptor antagonistic property.

    PubMed

    Lee, Hyung Eun; Jeon, Se Jin; Ryu, Byeol; Park, Se Jin; Ko, Sang Yoon; Lee, Younghwan; Kim, Eunji; Lee, Sunhee; Kim, Haneul; Jang, Dae Sik; Ryu, Jong Hoon

    2016-06-01

    Swertisin, a C-glucosylflavone isolated from Swertia japonica, has been known to have anti-inflammatory or antidiabetic activities. Until yet, however, its cognitive function is not investigated. In the present study, we endeavored to elucidate the effects of swertisin on cholinergic blockade-induced memory impairment. Swertisin (5 or 10mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairment in the several behavioral tasks. Also, single administration of swertisin (10mg/kg, p.o.) in normal naïve mice enhanced the latency time in the passive avoidance task. In addition, the ameliorating effect of swertisin on scopolamine-induced memory impairment was significantly antagonized by a sub-effective dose of N6-cyclopentyladenosine (CPA, 0.1mg/kg, i.p). The adenosine A1 receptor antagonistic property of swertisin was confirmed by receptor binding assay. Furthermore, the administration of swertisin significantly increased the phosphorylation levels of hippocampal or cortical protein kinase A (PKA, 5 or 10mg/kg) and CREB (10mg/kg), and co-administration of CPA (0.1mg/kg, i.p) blocked the increased phosphorylated levels of PKA and CREB in the both cortex and hippocampus. Taken together, these results indicate that the memory-ameliorating effects of swertisin may be, in part, mediated through the adenosinergic neurotransmitter system, and that swertisin may be useful for the treatment of cognitive dysfunction observed in several diseases such as Alzheimer's disease. PMID:26996316

  19. 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

  20. Adipose-derived stem cells ameliorate allergic airway inflammation by inducing regulatory T cells in a mouse model of asthma.

    PubMed

    Cho, Kyu-Sup; Park, Mi-Kyung; Kang, Shin-Ae; Park, Hee-Young; Hong, Sung-Lyong; Park, Hye-Kyung; Yu, Hak-Sun; Roh, Hwan-Jung

    2014-01-01

    Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-β, and PGE2 were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-β, and PGE2 and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production. PMID:25246732

  1. 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

  2. Ursodeoxycholic Acid Ameliorates Fructose-Induced Metabolic Syndrome in Rats

    PubMed Central

    2014-01-01

    The metabolic syndrome (MS) is characterized by insulin resistance, dyslipidemia and hypertension. It is associated with increased risk of cardiovascular diseases and type-2 diabetes. Consumption of fructose is linked to increased prevalence of MS. Ursodeoxycholic acid (UDCA) is a steroid bile acid with antioxidant, anti-inflammatory activities and has been shown to improve insulin resistance. The current study aims to investigate the effect of UDCA (150 mg/kg) on MS induced in rats by fructose administration (10%) in drinking water for 12 weeks. The effects of UDCA were compared to fenofibrate (100 mg/kg), an agonist of PPAR-α receptors. Treatment with UDCA or fenofibrate started from the 6th week after fructose administration once daily. Fructose administration resulted in significant increase in body weight, elevations of blood glucose, serum insulin, cholesterol, triglycerides, advanced glycation end products (AGEs), uric acid levels, insulin resistance index and blood pressure compared to control rats. Moreover, fructose increased oxidative stress in aortic tissues indicated by significant increases of malondialdehyde (MDA), expression of iNOS and reduction of reduced glutathione (GSH) content. These disturbances were associated with decreased eNOS expression, increased infiltration of leukocytes and loss of aortic vascular elasticity. Treatment with UDCA successfully ameliorated the deleterious effects of fructose. The protective effect of UDCA could be attributed to its ability to decrease uric acid level, improve insulin resistance and diminish oxidative stress in vascular tissues. These results might support possible clinical application of UDCA in MS patients especially those present with liver diseases, taking into account its tolerability and safety. However, further investigations on human subjects are needed before the clinical application of UDCA for this indication. PMID:25202970

  3. Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

    PubMed

    Wilding, Laura A; Bassis, Christine M; Walacavage, Kim; Hashway, Sara; Leroueil, Pascale R; Morishita, Masako; Maynard, Andrew D; Philbert, Martin A; Bergin, Ingrid L

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome. PMID:26525505

  4. Melatonin ameliorates metabolic risk factors, modulates apoptotic proteins, and protects the rat heart against diabetes-induced apoptosis.

    PubMed

    Amin, Ali H; El-Missiry, Mohamed A; Othman, Azza I

    2015-01-15

    The present study investigated the ability of melatonin in reducing metabolic risk factors and cardiac apoptosis induced by diabetes. Streptozotocin (60 mg/kg, i.p.) was injected into male rats, and after diabetic induction melatonin (10mg/kg i.g.) was administered orally for 21 days. Diabetic hearts showed increased number of apoptotic cells with downregulation of Bcl-2 and activation of p53 and CD95 as well as the caspases 9, 8 and 3. In addition, there was a significant decrease in insulin level, hyperglycemia, elevated HOMA-IR, glycosylated hemoglobin (HbA1c), total lipids, triglycerides, total cholesterol, low and very low-density lipoprotein and decreased high-density lipoprotein. These changes were coupled with a significant increase in the activities of creatin kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum of the diabetic rats indicating myocardium injury. Oral administration of melatonin for 3 weeks after diabetes induction ameliorated the levels of hyperglycemia, insulin, HbA1c, lipids profile and HOMA-IR. The oral melatonin treatment of diabetic rats significantly decreased the number of apoptotic cells in the heart compared to diabetic rats. It enhanced Bcl-2 expression and blocked the activation of CD95 as well as caspases 9, 8 and 3. These changes were accompanied with significant improvement of CK-MB and LDH in the serum indicating the ameliorative effect of melatonin on myocardium injury. Melatonin effectively ameliorated diabetic myocardium injury, apoptosis, reduced the metabolic risk factors and modulated important steps in both extrinsic and intrinsic pathways of apoptosis. Thus, melatonin may be a promising pharmacological agent for ameliorating potential cardiomyopathy associated with diabetes. PMID:25510232

  5. Berberine Ameliorates Allodynia Induced by Chronic Constriction Injury of the Sciatic Nerve in Rats.

    PubMed

    Kim, Hyun Jee

    2015-08-01

    The objective of this study was to investigate whether berberine could ameliorate allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After inducement of CCI, significant increases in the number of paw lifts from a cold plate test (cold allodynia) and decreased paw withdrawal threshold in the von Frey hair stimulation test (mechanical allodynia) were observed. However, these cold and mechanical allodynia were markedly alleviated by berberine administration in a dose-dependent manner. Sciatic nerve myeloperoxidase and malondialdehyde activities were also attenuated by berberine administration. Continuous injection for 7 days induced no development of tolerance. The antiallodynic effect of 20 mg/kg berberine was comparable to that of amitriptyline 10 mg/kg. This study demonstrated that berberine could mitigate allodynia induced by CCI, a neuropathic pain model, and it suggested that the anti-inflammatory and antioxidative properties of berberine contributed to the antiallodynic effect in the CCI model. PMID:25674823

  6. Ameliorative Effects of Curcumin on Artesunate-Induced Subchronic Toxicity in Testis of Swiss Albino Male Mice

    PubMed Central

    Rajput, Dhrupadsinh K.; Patel, Pragnesh B.; Highland, Hyacinth N.

    2015-01-01

    India is one of the endemic areas where control of malaria has become a formidable task. Artesunate is the current antimalarial drug used to treat malaria, especially chloroquine resistant. The objective of the present study was to investigate the dose-dependent effect of oral administration of artesunate on the oxidative parameters in testes of adult male Swiss albino mice and ameliorative efficacy of curcumin, a widely used antioxidant. An oral dose of 150 mg/kg body weight (bwt; low dose) and 300 mg/kg bwt (high dose) of artesunate was administered for a period of 45 days to male mice, and ameliorative efficacy of curcumin was also assessed. The results revealed that artesunate caused significant alteration in oxidative parameters in dose-dependent manner. Administration of artesunate brought about significant decrease in activities of superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase, whereas lipid peroxidation and glutathione-S-transferase activity were found to be significantly increased. The results obtained show that oxidative insult is incurred upon the intracellular antioxidant system of testis tissue by artesunate treatment. Further, administration of curcumin at the dose level of 80 mg/kg bwt along with both doses of artesunate attenuated adverse effects in male mice. PMID:26673878

  7. Rikkunshito Ameliorates Cancer Cachexia Partly through Elevation of Glucarate in Plasma

    PubMed Central

    Ohbuchi, Katsuya; Nishiumi, Shin; Fujitsuka, Naoki; Hattori, Tomohisa; Yamamoto, Masahiro; Inui, Akio; Azuma, Takeshi; Yoshida, Masaru

    2015-01-01

    Cancer cachexia, which is characterized by decreased food intake, weight loss and systemic inflammation, increases patient's morbidity and mortality. We previously showed that rikkunshito (RKT), a Japanese traditional herbal medicine (Kampo), ameliorated the symptoms of cancer cachexia through ghrelin signaling-dependent and independent pathways. To investigate other mechanisms of RKT action in cancer cachexia, we performed metabolome analysis of plasma in a rat model bearing the Yoshida AH-130 hepatoma. A total of 110 metabolites were detected in plasma and RKT treatment significantly altered levels of 23 of those metabolites in cachexia model rats. Among them, glucarate, which is known to have anticarcinogenic activity through detoxification of carcinogens via inhibition of β-glucuronidase, was increased in plasma following administration of RKT. In our AH-130 ascites-induced cachexia rat model, administration of glucarate delayed onset of weight loss, improved muscle atrophy, and reduced ascites content. Additionally, glucarate reduced levels of plasma interferon-γ (IFN-γ) in tumor-bearing rats and was also found to suppress LPS-induced IFN-γ expression in splenocytes in vitro. These results suggest that glucarate has anti-inflammatory activity via a direct effect on immune host cells and suggest that RKT may also ameliorate inflammation partly through the elevation of glucarate in plasma. PMID:26451159

  8. 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

  9. Mass Administration of Ivermectin for the Elimination of Onchocerciasis Significantly Reduced and Maintained Low the Prevalence of Strongyloides stercoralis in Esmeraldas, Ecuador

    PubMed Central

    Anselmi, Mariella; Buonfrate, Dora; Guevara Espinoza, Angel; Prandi, Rosanna; Marquez, Monica; Gobbo, Maria; Montresor, Antonio; Albonico, Marco; Racines Orbe, Marcia; Bisoffi, Zeno

    2015-01-01

    Objectives To evaluate the effect of ivermectin mass drug administration on strongyloidiasis and other soil transmitted helminthiases. Methods We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador) during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis. Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin) and 2013 (six years after the interruption of the intervention) were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic. Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis). Results In the areas where ivermectin was distributed the strongyloidiasis prevalence fell from 6.8% in 1990 to zero in 1996 and 1999. In 2013 prevalence in children was zero with stool examination and 1.3% with serology, in adult 0.7% and 2.7%. In areas not covered by ivermectin distribution the prevalence was 23.5% and 16.1% in 1996 and 1999, respectively. In 2013 the prevalence was 0.6% with fecal exam and 9.3% with serology in children and 2.3% and 17.9% in adults. Regarding other soil transmitted helminthiases: in areas where ivermectin was distributed the prevalence of T. trichiura was significantly reduced, while A. lumbricoides and hookworms were seemingly unaffected. Conclusions Periodic mass distribution of ivermectin had a significant impact on the prevalence of strongyloidiasis, less on trichuriasis and apparently no effect on ascariasis and hookworm infections. PMID:26540412

  10. Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway.

    PubMed

    Mun, Se Hwan; Kim, Hyuk Soon; Kim, Jie Wan; Ko, Na Young; Kim, Do Kyun; Lee, Beob Yi; Kim, Bokyung; Won, Hyung Sik; Shin, Hwa-Sup; Han, Jeung-Whan; Lee, Hoi Young; Kim, Young Mi; Choi, Wahn Soo

    2009-09-01

    We investigated whether oral administration of curcumin suppressed type II collagen-induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-alpha-stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cdelta (PKCdelta) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun signaling pathway. PMID:19763044

  11. Amelioration of doxorubicin‑induced cardiotoxicity by resveratrol.

    PubMed

    Al-Harthi, Sameer E; Alarabi, Ohoud M; Ramadan, Wafaa S; Alaama, Mohamed N; Al-Kreathy, Huda M; Damanhouri, Zoheir A; Khan, Lateef M; Osman, Abdel-Moneim M

    2014-09-01

    Doxorubicin (DOX), is a highly active anticancer agent, but its clinical use is limited by its severe cardiotoxic side‑effects associated with increased oxidative stress and apoptosis. Resveratrol (RSVL) is a naturally occurring polyphenolic compound (trans-3,5,4'-trihydroxystilbene) found primarily in root extracts of the oriental plant Polygonum cuspidatum and of numerous additional plant species. It has recently been shown that RSVL has a number of beneficial effects in different biological systems, which include anti-oxidant, antineoplastic, anticarcinogenic, cardioprotective and antiviral effects. In this study, we examined whether RSVL has protective effects against DOX‑induced free radical production and cardiotoxicity in male rats. The tested dose of DOX (20 mg/kg) caused a significant increase in the serum activities of the cardiac enzymes lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) and the level of malondialdehyde (MDA) in the heart tissue. However, there was a significant decrease in the glutathione level in the heart tissue. Simultaneous treatment of rats with RSVL [10 mg/kg, intraperitoneal (i.p.) injection] reduced the activity of LDH and CPK and significantly reduced MDA production in the heart. The total antioxidant capacity was increased following RSVL administration. Electron microscopy examination of the heart tissue showed that DOX treatment results in massive fragmentation and lysis of the myofibrils, and that mitochondria show either vacuolization or complete loss of the cristae. Simultaneous treatment with RSVL ameliorated the effect of DOX administration on cardiac tissue, with cardiomyocytes appearing normal compared to the control samples, and mitochondria retaining their normal structure. PMID:25059399

  12. Esculetin Ameliorates Carbon Tetrachloride-Mediated Hepatic Apoptosis in Rats

    PubMed Central

    Tien, Yun-Chen; Liao, Jung-Chun; Chiu, Chuan-Sung; Huang, Tai-Hung; Huang, Chih-Yang; Chang, Wen-Te; Peng, Wen-Huang

    2011-01-01

    Esculetin (ESC) is a coumarin that is present in several plants such as Fraxinus rhynchophylla and Artemisia capillaris. Our previous study found that FR ethanol extract (FREtOH) significantly ameliorated rats’ liver function. This study was intended to investigate the protective mechanism of ESC in hepatic apoptosis in rats induced by carbon tetrachloride. Rat hepatic apoptosis was induced by oral administration of CCl4. All rats were administered orally with CCl4 (20%, 0.5 mL/rat) twice a week for 8 weeks. Rats in the ESC groups were treated daily with ESC, and silymarin group were treated daily with silymarin. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) as well as the activities of the anti-oxidative enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase in the liver were measured. In addition, expression of liver apoptosis proteins and anti-apoptotic proteins were detected. ESC (100, 500 mg/kg) significantly reduced the elevated activities of serum ALT and AST caused by CCl4 and significantly increased the activities of catalase, GPx and SOD. Furthermore, ESC (100, 500 mg/kg) significantly decreased the levels of the proapoptotic proteins (t-Bid, Bak and Bad) and significantly increased the levels of the anti-apoptotic proteins (Bcl-2 and Bcl-xL). ESC inhibited the release of cytochrome c from mitochondria. In addition, the levels of activated caspase-9 and activated caspase-3 were significantly decreased in rats treated with ESC than those in rats treated with CCl4 alone. ESC significantly reduced CCl4-induced hepatic apoptosis in rats. PMID:21747724

  13. 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

  14. Subcutaneous administration of liraglutide ameliorates learning and memory impairment by modulating tau hyperphosphorylation via the glycogen synthase kinase-3β pathway in an amyloid β protein induced alzheimer disease mouse model.

    PubMed

    Qi, Liqin; Ke, Linfang; Liu, Xiaohong; Liao, Lianming; Ke, Sujie; Liu, Xiaoying; Wang, Yanping; Lin, Xiaowei; Zhou, Yu; Wu, Lijuan; Chen, Zhou; Liu, Libin

    2016-07-15

    Type 2 diabetes mellitus is a risk factor for Alzheimer's disease (AD). The glucagon-like peptide-1 analog liraglutide, a novel long-lasting incretin hormone, has been used to treat type 2 diabetes mellitus. In addition, liraglutide has been shown to be neurotrophic and neuroprotective. Here, we investigated the effects of liraglutide on amyloid β protein (Aβ)-induced AD in mice and explored its mechanism of action. The results showed that subcutaneous administration of liraglutide (25nmol/day), once daily for 8 weeks, prevented memory impairments in the Y Maze and Morris Water Maze following Aβ1-42 intracerebroventricular injection, and alleviated the ultra-structural changes of pyramidal neurons and chemical synapses in the hippocampal CA1 region. Furthermore, liraglutide reduced Aβ1-42-induced tau phosphorylation via the protein kinase B and glycogen synthase kinase-3β pathways. Thus liraglutide may alleviate cognitive impairment in AD by at least decreasing the phosphorylation of tau. PMID:27131827

  15. 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

  16. 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

  17. Nobiletin Ameliorates the Deficits in Hippocampal BDNF, TrkB, and Synapsin I Induced by Chronic Unpredictable Mild Stress

    PubMed Central

    Li, Jing; Zhou, Ying; Liu, Bin-Bin; Liu, Qing; Geng, Di; Weng, Lian-Jin; Yi, Li-Tao

    2013-01-01

    Background. Our previous study has demonstrated that nobiletin could reverse the behavioral alterations in stressed mice. However, the relation of its antidepressant-like action with neurotrophic molecular expression remains unknown. This study aimed to explore the antidepressant-like mechanism of nobiletin related to the neurotrophic system in rats exposed to chronic unpredictable mild stress (CUMS). Methods. Depressive-like anhedonia (assessed by sucrose preference) and serum corticosterone secretion were evaluated in the CUMS, followed by brain-derived neurotrophic factor (BDNF), its tropomyosin-related kinase receptor B (TrkB), and the downstream target synapsin I expressions in the hippocampus. Results. Anhedonia, which occurred within week 2, was rapidly ameliorated by nobiletin. While fluoxetine needed additional 2 weeks to improve the anhedonia. In addition, nobiletin administration for 5 weeks significantly ameliorated CUMS-induced increase in serum corticosterone levels. Furthermore, we also found that CUMS-induced deficits of hippocampal BDNF, TrkB, and synapsin I were ameliorated by nobiletin. Conclusions. Taken together, these findings suggest that nobiletin produces rapidly acting antidepressant-like responses in the CUMS and imply that BDNF-TrkB pathway may play an important role in the antidepressant-like effect of nobiletin. PMID:23573124

  18. Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazol-induced kindling and associated depression and memory deficit.

    PubMed

    Pahwa, Priyanka; Goel, Rajesh Kumar

    2016-04-01

    Asparagus racemosus (A. racemosus) roots are extensively used in traditional medicine for the management of epilepsy. The aim of the present study was to investigate the ameliorative effect of A. racemosus root extract (ARE) against pentylenetetrazol-induced kindling and associated depression and memory deficit. Kindling was successfully induced by repeated administration of a subconvulsant dose of PTZ (35 mg/kg; i.p.) at an interval of 48 ± 2 h in 43 days (21 injections). Pretreatment with valproate (300 mg/kg; i.p.), a major antiepileptic drug as well as ARE significantly suppressed the progression of kindling. Moreover, ARE also ameliorated the kindling-associated depression and memory deficit as indicated by decreased immobility time and increased step-down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complemented with analogous neurochemical changes. In conclusion, the results of the present study showed that ARE treatment has an ameliorative effect against PTZ-induced kindling and associated behavioral comorbidities. PMID:26970996

  19. Ovariectomy ameliorates dextromethorphan--induced memory impairment in young female rats.

    PubMed

    Jahng, Jeong Won; Cho, Hee Jeong; Kim, Jae Goo; Kim, Nam Youl; Lee, Seoul; Lee, Yil Seob

    2006-01-01

    We have previously found that dextromethorphan (DM), over-the-counter cough suppressant, impairs memory retention in water maze task, when it is repeatedly administrated to adolescent female rats at high doses. In this study we examined first if ovariectomy ameliorates the DM-induced memory impairment in female rats, and then whether or not the DM effect is revived by estrogen replacement in ovariectomized female rats. Female rat pups received bilateral ovariectomy or sham operation on postnatal day (PND) 21, and then intraperitoneal DM (40 mg/kg) daily during PND 28-37. Rats were subjected to the Morris water maze task from PND 38, approximately 24 h after the last DM injection. In probe trial, goal quadrant dwell time was significantly reduced by DM in the sham operated group, however, the reduction by DM did not occur in the ovariectomy group. When 17beta-estradiol was supplied to ovariectomized females during DM treatment, the goal quadrant dwell time was significantly decreased, compared to the vehicle control group. Furthermore, a major effect of estrogen replacement was found in the escape latency during the last 3 days of initial learning trials. These results suggest that ovariectomy may ameliorate the adverse effect of DM treatment on memory retention in young female rats, and that estrogen replacement may revive it, i.e. estrogen may take a major role in DM-induced memory impairment in female rats. PMID:16563229

  20. Blueberry anthocyanins ameliorate radiation-induced lung injury through the protein kinase RNA-activated pathway.

    PubMed

    Liu, Yunen; Tan, Dehong; Tong, Changci; Zhang, Yubiao; Xu, Ying; Liu, Xinwei; Gao, Yan; Hou, Mingxiao

    2015-12-01

    The purpose of this study was to explore the effect of blueberry anthocyanins (BA) on radiation-induced lung injury and investigate the mechanism of action. Seven days after BA(20 and 80 mg/kg/d)administration, 6 weeks old male Sprague-Dawley rats rats were irradiated by LEKTA precise linear accelerator at a single dose of 20 Gy only once. and the rats were continuously treated with BA for 4 weeks. Moreover, human pulmonary alveolar epithelial cells (HPAEpiC) were transfected with either control-siRNA or siRNA targeting protein kinase R (PKR). Cells were then irradiated and treated with 75 μg/mL BA for 72 h. The results showed that BA significantly ameliorated radiation-induced lung inflammation, lung collagen deposition, apoptosis and PKR expression and activation. In vitro, BA significantly protected cells from radiation-induced cell death through modulating expression of Bcl-2, Bax and Caspase-3. Suppression of PKR by siRNA resulted in ablation of BA protection on radiation-induced cell death and modulation of anti-apoptotic and pro-apoptotic proteins, as well as Caspase-3 expression. These findings suggest that BA is effective in ameliorating radiation-induced lung injury, likely through the PKR signaling pathway. PMID:26551926

  1. Ameliorative effects of Gualou Guizhi decoction on inflammation in focal cerebral ischemic-reperfusion injury

    PubMed Central

    ZHANG, YUQIN; ZHANG, SHENGNAN; LI, HUANG; HUANG, MEI; XU, WEI; CHU, KEDAN; CHEN, LIDIAN; CHEN, XIANWEN

    2015-01-01

    Gualou Guizhi decoction (GLGZD) is a well-established Traditional Chinese Medicinal formulation which has long been used to treat stroke in a clinical setting in China. The present study investigated the ameliorative effects of GLGZD on inflammation in focal cerebral ischemic-reperfusion injury. A rat model of middle cerebral artery occlusion (MCAO) was employed. Rats were administrated GLGZD (7.2 and 14.4 g/kg per day) or saline as control 2 h after reperfusion and daily over the following seven days. Neurological deficit score and screen test were evaluated at 1, 3, 5 and 7 days after MCAO. Brain infarct size and brain histological changes were observed via 2,3,5-triphenyltetrazolium chloride staining and regular hematoxylin & eosin staining. Furthermore, inflammation mediators and nuclear factor-κB (NF-κB) were investigated using ELISA and immunohistochemistry. GLGZD treatment significantly improved neurological function, ameliorated histological changes to the brain and decreased infarct size in focal cerebral ischemic-reperfusion injury. GLGZD was found to significantly reduce interleukin (IL)-1, tumor necrosis factor-α and NF-κB levels, while increasing levels of IL-10. In conclusion, the present study suggested that GLGZD has a neuroprotective effect on focal cerebral ischemic-reperfusion injury and this effect is likely to be associated with the anti-inflammatory function of GLGZD. PMID:25815894

  2. 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

  3. 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

  4. Intermedin ameliorates IgA nephropathy by inhibition of oxidative stress and inflammation.

    PubMed

    Wang, Yanhong; Tian, Jihua; Guo, Haixiu; Mi, Yang; Zhang, Ruijing; Li, Rongshan

    2016-05-01

    IgA nephropathy (IgAN) is the most frequent form of glomerulonephritis worldwide. The role of oxidative stress and inflammation in the pathogenesis of IgAN has been reported. Intermedin (IMD) is a newly discovered peptide that is closely related to adrenomedullin. We have recently reported that IMD can significantly reduce renal ischemia/reperfusion injury by diminishing oxidative stress and suppressing inflammation. The present study was designed to explore whether IMD ameliorates IgAN via oxidative stress- and inflammation-dependent mechanisms. Our results showed that IMD administration resulted in the prevention of albuminuria and ameliorated renal pathomorphological changes. These findings were associated with (1) decreased renal TGF-β1 and collagen IV expression, (2) an increased SOD level and reduced MDA level, (3) the inhibition of the renal activation of NF-κB p65 and (4) the downregulation of the expression of inflammatory factors (TNF-α, MCP-1 and MMP-9) in the kidney. These results indicate that IMD in the kidney protects against IgAN by reducing oxidative stress and suppressing inflammation. PMID:25916508

  5. Sesamin ameliorates oxidative liver injury induced by carbon tetrachloride in rat

    PubMed Central

    Lv, Dan; Zhu, Chang-Qing; Liu, Li

    2015-01-01

    Sesamin is naturally occurring lignan from sesame oil with putative antioxidant property. The present study was designed to investigate the protective role of sesamin against carbon tetrachloride induced oxidative liver injury. Male Wistar albino rats (180-200 g) were divided in to 5 groups (n=6). Hepatotoxicity was induced by the administration of CCl4 (0.1 ml/100 g bw., 50% v/v with olive oil) intraperitoneally. Sesamin was administered in two different dose (5 and 10 ml/kg bw) to evaluate the hepatoprotective activity. Sesamin significantly reduced the elevated serum liver marker enzymes (P<0.0001). Reduction of TBARS (P<0.01 and P<0.001) followed by enhancement of GSH., SOD and catalase (P<0.0001) in liver homogenate in sesamin treated groups shows the amelioration of oxidative stress induced by CCl4. Histopathological report also supported the hepatoprotection offered by sesamin. Sesamin effects in both the dose were in comparable to reference standard drug silymarin. From these above findings it has been concluded that sesamin ameliorate the oxidative liver injury in terms of reduction of lipid peroxidation and enhancement of liver antioxidant enzymes. PMID:26191289

  6. Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats.

    PubMed

    Kaur, Gurpreet; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar S

    2015-03-01

    The present study was designed to investigate the ameliorative potential of Ocimum sanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress) and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimum sanctum (100 and 200 mg/kg p.o.) and its saponin rich fraction (100 and 200 mg/kg p.o.) for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels. PMID:25673470

  7. CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

    PubMed Central

    Mogami, Sachiko; Sadakane, Chiharu; Nahata, Miwa; Mizuhara, Yasuharu; Yamada, Chihiro; Hattori, Tomohisa; Takeda, Hiroshi

    2016-01-01

    Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities. PMID:27273195

  8. CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia.

    PubMed

    Mogami, Sachiko; Sadakane, Chiharu; Nahata, Miwa; Mizuhara, Yasuharu; Yamada, Chihiro; Hattori, Tomohisa; Takeda, Hiroshi

    2016-01-01

    Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities. PMID:27273195

  9. All-trans retinoic acid ameliorates glycemic control in diabetic mice via modulating pancreatic islet production of vascular endothelial growth factor-A.

    PubMed

    Chien, Chiao-Yun; Yuan, Tze-An; Cho, Candy Hsin-Hua; Chang, Fang-Pei; Mao, Wan-Yu; Wu, Ruei-Ren; Lee, Hsuan-Shu; Shen, Chia-Ning

    2016-09-01

    Patients with type 1 diabetes mellitus are associated with impairment in vitamin A metabolism. This study evaluated whether treatment with retinoic acid, the biologically active metabolite of vitamin A, can ameliorate diabetes. All-trans retinoic acid (atRA) was used to treat streptozotocin (STZ)-induced diabetic mice which revealed atRA administration ameliorated blood glucose levels of diabetic mice. This hyperglycemic amelioration was accompanied by an increase in the amount of β cells co-expressed Pdx1 and insulin and by restoration of the vascular laminin expression. The atRA-induced production of vascular endothelial growth factor-A from the pancreatic islets was possibly the key factor that mediated the restoration of islet vascularity and recovery of β-cell mass. Furthermore, the combination of islet transplantation and atRA administration significantly rescued hyperglycemia in diabetic mice. These findings suggest that vitamin A derivatives can potentially be used as a supplementary treatment to improve diabetes management and glycemic control. PMID:27381866

  10. Orazipone, a locally acting immunomodulator, ameliorates intestinal radiation injury: A preclinical study in a novel rat model

    SciTech Connect

    Boerma, Marjan; Wang, Junru; Richter, Konrad K.; Hauer-Jensen, Martin . E-mail: mhjensen@life.uams.edu

    2006-10-01

    Purpose: Intestinal radiation injury (radiation enteropathy) is relevant to cancer treatment, as well as to radiation accidents and radiation terrorism scenarios. This study assessed the protective efficacy of orazipone, a locally-acting small molecule immunomodulator. Methods and Materials: Male rats were orchiectomized, a 4-cm segment of small bowel was sutured to the inside of the scrotum, a proximal anteperistaltic ileostomy was created for intraluminal drug administration, and intestinal continuity was re-established by end-to-side anastomosis. After three weeks postoperative recovery, the intestine in the 'scrotal hernia' was exposed locally to single-dose or fractionated X-radiation. Orazipone (30 mg/kg/day) or vehicle was administered daily through the ileostomy, either during and after irradiation, or only after irradiation. Structural, cellular, and molecular aspects of intestinal radiation toxicity were assessed two weeks after irradiation. Results: Orazipone significantly ameliorated histologic injury and transforming growth factor-{beta} immunoreactivity levels, both after single-dose and fractionated irradiation. Intestinal wall thickness was significantly reduced after single-dose and nonsignificantly after fractionated irradiation. Mucosal surface area and numbers of mast cells were partially restored by orazipone after single-dose irradiation. Conclusions: This work (1) demonstrates the utility of the ileostomy rat model for intraluminal administration of response modifiers in single-dose and fractionated radiation studies; (2) shows that mucosal immunomodulation during and/or after irradiation ameliorates intestinal toxicity; and (3) highlights important differences between single-dose and fractionated radiation regimens.

  11. Ameliorative potential of Tamarindus indica on high fat diet induced nonalcoholic fatty liver disease in rats.

    PubMed

    Sasidharan, Suja Rani; Joseph, Joshua Allan; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Madhavan, Chandrasekharan Nair Ariyattu; Agarwal, Amit

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms. PMID:24688399

  12. Ameliorative Potential of Tamarindus indica on High Fat Diet Induced Nonalcoholic Fatty Liver Disease in Rats

    PubMed Central

    Sasidharan, Suja Rani; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Ariyattu Madhavan, Chandrasekharan Nair; Agarwal, Amit

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms. PMID:24688399

  13. DOCOSAHEXAENOIC ACID PARTIALLY AMELIORATES DEFICITS IN SOCIAL BEHAVIOR AND ULTRASONIC VOCALIZATIONS CAUSED BY PRENATAL ETHANOL EXPOSURE

    PubMed Central

    Wellmann, Kristen A.; George, Finney; Brnouti, Fares; Mooney, Sandra M.

    2015-01-01

    Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long-Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10 g/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol’s damaging effects. PMID:25746516

  14. Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure.

    PubMed

    Wellmann, Kristen A; George, Finney; Brnouti, Fares; Mooney, Sandra M

    2015-06-01

    Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long-Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10g/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol's damaging effects. PMID:25746516

  15. 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

  16. The AT1 receptor antagonist, L-158,809, prevents or ameliorates fractionated whole-brain irradiation-induced cognitive impairment

    PubMed Central

    Robbins, Mike E.; Payne, Valerie; Tommasi, Ellen; Diz, Debra I; Hsu, Fang-Chi; Brown, William R.; Wheeler, Kenneth T.; Olson, John; Zhao, Weiling

    2009-01-01

    Purpose We hypothesized that administration of the angiotensin type 1 (AT1) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. Methods and Materials Groups of 80 young adult male Fischer 344 × Brown Norway (F344×BN) rats, 12–14 weeks old, received either: i] fractionated WBI; 40 Gy of γ rays in 4 weeks, 2 fractions/week, ii] sham-irradiation; iii] WBI plus L-158,809 (20 mg/L drinking water) starting 3 days prior, during and for 14, 28, or 54 weeks post-irradiation; and iv] sham-irradiation plus L-158,809 for 14, 28, or 54 weeks post-irradiation. An additional group of rats (n = 20) received L-158,809 prior to, during, and for 5 weeks post-irradiation, after which they received normal drinking water up to 28 weeks post-irradiation Results Administration of L-158,809 prior to, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks post-irradiation. Moreover, giving L-158,809 prior to, during, and for only 5 weeks post-irradiation ameliorated the significant cognitive impairment observed 26 weeks post-irradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks post-irradiation, respectively. Conclusions Administering L-158,809 prior to, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks post-irradiation. These findings offer the promise of improving the quality of life for brain tumor patients. PMID:19084353

  17. The AT{sub 1} Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation-Induced Cognitive Impairment

    SciTech Connect

    Robbins, Mike E. Payne, Valerie B.S.; Tommasi, Ellen B.S.; Diz, Debra I.; Hsu, Fang-Chi; Brown, William R.; Wheeler, Kenneth T.; Olson, John; Zhao Weiling

    2009-02-01

    Purpose: We hypothesized that administration of the angiotensin type 1 (AT1) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. Materials and Methods: Groups of 80 young adult male Fischer 344 x Brown Norway (F344xBN) rats, 12-14 weeks old, received either: (1) fractionated WBI; 40 Gy of {gamma} rays in 4 weeks, 2 fractions/week, (2) sham-irradiation; (3) WBI plus L-158,809 (20 mg/L drinking water) starting 3 days prior, during, and for 14, 28, or 54 weeks postirradiation; and (4) sham-irradiation plus L-158,809 for 14, 28, or 54 weeks postirradiation. An additional group of rats (n = 20) received L-158,809 before, during, and for 5 weeks postirradiation, after which they received normal drinking water up to 28 weeks postirradiation. Results: Administration of L-158,809 before, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks postirradiation. Moreover, giving L-158,809 before, during, and for only 5 weeks postirradiation ameliorated the significant cognitive impairment observed 26 weeks postirradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks postirradiation, respectively. Conclusions: Administering L-158,809 before, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks postirradiation. These findings offer the promise of improving the quality of life for brain tumor patients.

  18. Significant School Law Cases Pending Before the U.S. Supreme Court. What Do They Portend for the Governance and Administration of the Public Schools?

    ERIC Educational Resources Information Center

    Shannon, Thomas A.

    Civil rights is the central theme of the cases affecting public school governance that the U.S. Supreme Court has agreed to hear this term. This paper discusses those cases in detail. It also notes that the cases the court refuses to hear have as significant an impact on school district governance as those cases it actually hears. School law cases…

  19. Evaluating the ameliorative efficacy of Spirulina platensis on spermatogenesis and steroidogenesis in cadmium-intoxicated rats.

    PubMed

    Farag, Mayada R; Abd El-Aziz, R M; Ali, H A; Ahmed, Sahar A

    2016-02-01

    The present study was conducted to evaluate the ameliorative efficacy of Spirulina platensis (SP) on reproductive dysfunctions induced by cadmium chloride (CdCl2) in male rats. Rats (n = 40) were divided into five groups (eight rats/each). Group 1: served as control without any treatment. Group 2: Rats were administered SP (150 mg/kg body weight (BW)) in drinking water for 10 days. Group 3: Rats were subcutaneously injected with CdCl2 (2 mg/kg BW) daily for 10 days. Group 4: Rats were co-treated with both CdCl2 (2 mg/kg BW) and SP (150 mg/kg BW) daily for 10 days (SP prophylactic group). Group 5: Rats received CdCl2 for 10 days followed by administration of SP alone in drinking water daily for another 30 days with the same mentioned routes and doses (SP treatment group). From our findings, the administration of SP alone or co-administration with Cd significantly attenuated the harmful effects of Cd, suggesting its beneficial role in improving spermatogenesis and steroidogenesis after Cd exposure. PMID:26423278

  20. Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model

    PubMed Central

    Jiang, Chun-Bin; Cheng, Mei-Lien; Liu, Chia-Yuan; Chang, Szu-Wen; Chiang Chiau, Jen-Shiu; Lee, Hung-Chang

    2015-01-01

    Background and Aims Intestinal mucositis is a frequently encountered side effect in oncology patients undergoing chemotherapy. No well-established or up to date therapeutic strategies are available. To study a novel way to alleviate mucositis, we investigate the effects and safety of probiotic supplementation in ameliorating 5-FU-induced intestinal mucositis in a mouse model. Methods Seventy-two mice were injected saline or 5-Fluorouracil (5-FU) intraperitoneally daily. Mice were either orally administrated daily saline, probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35) or Lactobacillus acidophilus and Bifidobacterium bifidum (LaBi). Diarrhea score, pro-inflammatory cytokines serum levels, intestinal villus height and crypt depth and total RNA from tissue were assessed. Samples of blood, liver and spleen tissues were assessed for translocation. Results Marked diarrhea developed in the 5-FU groups but was attenuated after oral Lcr35 and LaBi administrations. Diarrhea scores decreased significantly from 2.64 to 1.45 and 0.80, respectively (P<0.001). Those mice in 5-FU groups had significantly higher proinflammatory cytokine levels (TNF-α: 234.80 vs. 29.10, P<0.001, IL-6: 25.13 vs. 7.43, P<0.001, IFN-γ: 22.07 vs. 17.06, P = 0.137). A repairing of damage in jejunal villi was observed following probiotics administration. We also found TNF-α, IL-1β and IL-6 mRNA expressions were up-regulated in intestinal mucositis tissues following 5-FU treatment (TNF-α: 4.35 vs. 1.18, IL-1β: 2.29 vs. 1.07, IL-6: 1.49 vs. 1.02) and that probiotics treatment suppressed this up-regulation (P<0.05). No bacterial translocation was found in this study. Conclusions In conclusion, our results show that oral administration of probiotics Lcr35 and LaBi can ameliorate chemotherapy-induced intestinal mucositis in a mouse model. This suggests probiotics may serve as an alternative therapeutic strategy for the prevention or management of chemotherapy-induced mucositis in

  1. Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis.

    PubMed

    Abramovitch, Shirley; Sharvit, Efrat; Weisman, Yosef; Bentov, Amir; Brazowski, Eli; Cohen, Gili; Volovelsky, Oded; Reif, Shimon

    2015-01-15

    1,25(OH)2D3, the active form of vitamin D, has an antiproliferative and antifibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo. The antifibrotic effect of 1,25(OH)2D3 was investigated in a thioacetamide (TAA) model (as a preventive treatment and as a remedial treatment) and in a bile duct ligation model. In the preventive model, rats received simultaneously intraperitoneum injection of TAA and/or 1,25(OH)2D3 for 10 wk. In the remedial model, rats were treated with TAA for 10 wk and then received 1,25(OH)2D3 or saline for 8 wk. Fibrotic score was determined by Masson staining. Collagen I, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP1), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) expression were measured by Western blot analysis and real-time PCR. Hypercalemia was detected by chemistry measurements. Preventive treatment of 1,25(OH)2D3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of the TAA + 1,25(OH)2D3 group compared with the TAA group. 1,25(OH)2D3 significantly inhibited expression of PDGF and TGF-β by ∼50% and suppressed the expression of collagen Iα1, TIMP1, and α-SMA by approximately three-, two-, and threefold, respectively. In contrast, 1,25(OH)2D3 was inefficient in amelioration of established liver fibrosis. Administration of 1,25(OH)2D3 to bile duct ligation rats led to a high mortality rate probably caused by hypercalcemia. We conclude that 1,25(OH)2D3 may be considered as a potential preventive treatment in an in vivo model but failed to ameliorate established cirrhosis. PMID:25214398

  2. 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

  3. 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

  4. 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

  5. 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

  6. Simvastatin treatment ameliorates injury of rat testes induced by cadmium toxicity.

    PubMed

    Fouad, Amr A; Albuali, Waleed H; Jresat, Iyad

    2013-06-01

    Cadmium-induced testicular toxicity is mediated through oxidative stress and inflammation which eventually lead to cell death. Simvastatin, the antihyperlipidemic agent, exhibits additional antioxidant and anti-inflammatory activities. The aim of the present work was to investigate the protective effect of simvastatin against cadmium-induced testicular toxicity in rats. The rats received a single intraperitoneal (i.p.) injection of cadmium chloride (2 mg/kg). Simvastatin treatment (5 mg/kg/day, i.p.) was applied for three consecutive days, starting 1 day before cadmium administration. Cadmium significantly decreased serum testosterone, and testicular reduced glutathione and catalase activity, and significantly increased testicular malondialdehyde, nitric oxide, and cadmium ion levels. Simvastatin significantly ameliorated the biochemical changes induced by cadmium. Cadmium-induced testicular tissue injury observed by histopathological examination was attenuated by simvastatin. In addition, simvastatin significantly decreased the expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, nuclear factor-κB, and caspase-3, and increased heme oxygenase-1 expression in testicular tissue of rats exposed to cadmium toxicity. It was concluded that simvastatin, through its antioxidant and anti-inflammatory activities, provided a significant protective effect against cadmium-induced testicular toxicity in rats. However, starting treatment with simvastatin before cadmium exposure, as done in the present work, is not clinically applicable. Therefore, other investigations are needed to assess the protective effect of simvastatin treatment following induction of cadmium testicular toxicity. PMID:23625729

  7. Effect of Soil Ameliorators on Ectomycorrhizal Fungal Communities that Colonize Seedlings of Pinus densiflora in Abandoned Coal Mine Spoils

    PubMed Central

    Lee, Eun-Hwa; Eo, Ju-Kyeong; Lee, Chang-Seok

    2012-01-01

    In this study, the effect of soil ameliorators on ectomycorrhizal (ECM) fungal communities in coal mine spoils was investigated. Organic fertilizers and slaked lime were applied as soil ameliorators in 3 abandoned coal mine spoils. One year after the initial treatment, roots of Pinus densiflora seedlings were collected and the number of ECM species, colonization rate, and species diversity were assessed. The results showed that the soil ameliorators significantly increased ECM colonization on the roots of P. densiflora. The results suggest that soil ameliorators can have a positive effect on ECM fungi in terms of growth of host plants and show the potential use of soil ameliorator treatment for revegetation with ECM-colonized pine seedlings in the coal mine spoils. PMID:23115509

  8. 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

  9. Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses

    PubMed Central

    Lean, Qi Ying; Eri, Rajaraman D.; Randall-Demllo, Sarron; Sohal, Sukhwinder Singh; Stewart, Niall; Peterson, Gregory M.; Gueven, Nuri; Patel, Rahul P.

    2015-01-01

    Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS). Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8), colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis. PMID:26218284

  10. Aqueous extract of Monodora myristica ameliorates cadmium-induced hepatotoxicity in male rats.

    PubMed

    Oyinloye, Babatunji Emmanuel; Adenowo, Abiola Fatimah; Osunsanmi, Foluso Oluwagbemiga; Ogunyinka, Bolajoko Idiat; Nwozo, Sarah Onyenibe; Kappo, Abidemi Paul

    2016-01-01

    In recent years, indigenous medicinal plants exhibiting diverse biological activities have been explored in the amelioration of hepatotoxicity. This study investigates the protective effect of Monodora myristica (MM) on cadmium-induced liver damage in experimental animals. Male Wistar albino rats were maintained on 200 mg/L cadmium: Cd (Cd as CdCl2) in the animals' main drinking water to induce hepatotoxicity. Added to this, the animals received aqueous extracts of MM at a dose of 200 or 400 and 20 mg/kg bw of Livolin forte (LF) for 21 days. At the end of the experiment, levels of serum enzyme biomarkers (alanine transaminase, alkaline phosphatase and aspartate transaminase) as well as total cholesterol (TC), triacylglyceride (TG) and malondialdehyde were significantly raised in the cadmium treated groups. Conversely, cadmium treatment elicited noticeable decrease in hepatic enzymatic and non-enzymatic antioxidants (reduced glutathione: GSH, catalase: CAT, superoxide dismutase: SOD). Co-treatment with MM at varying doses as well as LF considerably decreased the elevated levels of the serum biomarkers as well as TC, TG and malondialdehyde in the cadmium-treated groups in a dose dependant manner. Additionally, MM exhibited reversal potential on cadmium-toxicity at the tested doses as its administration was accompanied by a pronounced increase in GSH, SOD, and CAT levels. Histopathological results were parallel to these findings. These results demonstrates that aqueous extracts of MM is effective in the amelioration of hepatic damages arising from cadmium-induced toxicity, indicating that the antioxidant bio-constituents of MM play an important role in the prevention of liver toxicity possibly by inhibiting bioaccumulation of free radicals in animal models. PMID:27330907

  11. Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes

    SciTech Connect

    Lai, H.C.; Yeh, Y.C.; Wang, L.C.; Ting, C.T.; Lee, W.L.; Lee, H.W.; Wang, K.Y.; Wu, A.; Su, C.S.; Liu, T.J.

    2011-12-15

    Background: Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells. Methods: Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1 {mu}M), propofol (1 {mu}M), or propofol plus doxorubicin (given 1 h post propofol). After 24 h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted. Results: Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-{delta} was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment. Conclusions: Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application. -- Highlights: Black-Right-Pointing-Pointer We evaluate how propofol prevents doxorubicin-induced toxicity in cardiomyocytes. Black-Right-Pointing-Pointer Propofol reduces doxorubicin-imposed nitrative and oxidative stress. Black-Right-Pointing-Pointer Propofol suppresses mitochondrion-, p53- and PKC-related apoptotic signaling. Black-Right-Pointing-Pointer Propofol ameliorates apoptosis and

  12. Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats.

    PubMed

    Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang

    2009-11-01

    Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required. PMID:19524415

  13. Herbal formulation, DIA-2 and Rosiglitazone ameliorates hyperglycemia and hepatic steatosis in type 2 diabetic rats.

    PubMed

    Kesavanarayanan, K S; Priya, R J; Selvakkumar, C; Kavimani, S; Prathiba, D

    2015-08-01

    DIA-2 is a herbal mixture containing standardized extract of Allium sativum and Lagerstroemia speciosa. Recently we have reported the anti-diabetic effect of DIA-2 in high fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic (T2D) rats. The purpose of this study was to investigate and compare the effects of DIA-2 with Rosiglitazone (RG) on plasma biomarkers of hepatocellular injury, liver carbohydrate metabolizing enzymes, glycogen content, oxidant/antioxidant status and histopathological changes in T2D rats. ALT and ALP levels were significantly decreased after DIA-2 and RG treatment compared to T2D rats. Total protein and albumin remained unaltered in all the groups. Significant decrease in AST levels were observed after DIA-2 (125 mg/kg) and RG treatment. Hepatic hexokinase activity was significantly increased after RG and DIA-2 treatment and fructose-1, 6-bisphosphatase activity were inversely correlated with hexokinase activity. Hepatic gucose-6-phosphatase activity was significantly (p < 0.05) reduced after DIA-2 (62.5 mg/kg) and RG treatment. Lipid peroxides levels was significantly decreased in the liver of DIA-2 (62.5; p < 0.01 & 125 mg/kg; p < 0.05) treated animals. Hepatic glycogen content (p < 0.05) and antioxidant enzymes [SOD (p < 0.01; 62.5 mg/kg); GPx and GSH (125 mg/kg; p < 0.01)] were significantly increased after DIA-2 treatment. RG treatment on hepatic glycogen, GPx (p < 0.01) and SOD, GSH (p < 0.05) levels were significant when compared to T2D rats. These biochemical parameters were also correlated with histopathological evaluation. The above findings revealed that administration of DIA-2 could ameliorate the biochemical and histopathological changes in liver of T2D rats indicating the protective role of DIA-2 against HFD/STZ induced diabetes. In addition, DIA-2 and RG treatment resulted in amelioration of hepatic steatosis in T2D rats. PMID:26367735

  14. 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

  15. Radiation-Induced Testicular Injury and Its Amelioration by Tinospora cordifolia (An Indian Medicinal Plant) Extract

    PubMed Central

    Sharma, Priyanka; Parmar, Jyoti; Sharma, Priyanka; Verma, Preeti; Goyal, P. K.

    2011-01-01

    The primary objective of this investigation is to determine the deleterious effects of sub lethal gamma radiation on testes and their possible inhibition by Tinospora cordifolia extract (TCE). For this purpose, one group of male Swiss albino mice was exposed to 7.5 Gy gamma radiation to serve as the irradiated control, while the other group received TCE (75 mg/kg b. wt./day) orally for 5 consecutive days half an hr before irradiation to serve as experimental. Exposure of animals to 7.5 Gy gamma radiation resulted into significant decrease in body weight, tissue weight, testes- body weight ratio and tubular diameter up to 15 days of irradiation. Cent percent mortality was recorded by day 17th in irradiated control, whereas all animals survived in experimental group. TCE pretreatment rendered significant increase in body weight, tissue weight, testes- body weight ratio and tubular diameter at various intervals as compared to irradiated group. Radiation induced histological lesions in testicular architecture were observed more severe in irradiated control then the experimental. TCE administration before irradiation significantly ameliorated radiation induced elevation in lipid peroxidation and decline in glutathione concentration in testes. These observations indicate the radio- protective potential of Tinospora cordifolia root extract in testicular constituents against gamma irradiation in mice. PMID:21350610

  16. The ameliorative effect of propolis against methoxychlor induced ovarian toxicity in rat.

    PubMed

    El-Sharkawy, Eman E; Kames, Amany O G; Sayed, S M; Nisr, Neveen A E L; Wahba, Nahed M; Elsherif, Walaa M; Nafady, Allam M; Abdel-Hafeez, M M; Aamer, A A

    2014-12-01

    A study was designed to evaluate ameliorative effect of propolis against methoxychlor (MXC) induced ovarian toxicity in rat. The organochlorine pesticide (MXC) is a known endocrine disruptor with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether chronic exposure to MXC could cause ovarian dysfunction, two groups of Sprague-Dawley adult female rats were exposed to MXC alone in a dose of 200mg/kg, twice/weekly, orally or MXC dose as previous plus propolis in a dose of 200mg/l/day, in drinking water for 10 months. Another two groups of rat were given corn oil (control) or propolis. Multiple reproductive parameters, ovarian weight, serum hormone levels, ovarian oxidative status and ovarian morphology were examined. In MXC-exposed group, there is a significant decrease in body and ovarian weight vs. control. MXC decreases serum estradiol and progesterone levels. A significant increase in the levels of lipid peroxidation was obtained while a significant decrease of the total antioxidant was recorded. Ovarian histopathology showed primary, secondary and vesicular follicles displaying an atretic morphology. Increase in the ovarian surface epithelium height accompanied with vacuolated, pyknotic oocytes were obtained. The previous toxic effects were neutralized by the administration of propolis in MXC+propolis group. The present results suggest that propolis may be effective in decreasing of MXC-induced ovarian toxicity in rat. PMID:25034310

  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. 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

  3. 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

  4. Immunomodulation of airway epithelium cell activation by mesenchymal stromal cells ameliorates house dust mite-induced airway inflammation in mice.

    PubMed

    Duong, Khang M; Arikkatt, Jaisy; Ullah, M Ashik; Lynch, Jason P; Zhang, Vivian; Atkinson, Kerry; Sly, Peter D; Phipps, Simon

    2015-11-01

    Allergic asthma is underpinned by T helper 2 (Th2) inflammation. Redundancy in Th2 cytokine function and production by innate and adaptive immune cells suggests that strategies aimed at immunomodulation may prove more beneficial. Hence, we sought to determine whether administration of mesenchymal stromal cells (MSCs) to house dust mite (HDM) (Dermatophagoides pteronyssinus)-sensitized mice would suppress the development of Th2 inflammation and airway hyperresponsiveness (AHR) after HDM challenge. We report that the intravenous administration of allogeneic donor MSCs 1 hour before allergen challenge significantly attenuated the features of allergic asthma, including tissue eosinophilia, Th2 cytokine (IL-5 and IL-13) levels in bronchoalveolar lavage fluid, and AHR. The number of infiltrating type 2 innate lymphoid cells was not affected by MSC transfer, suggesting that MSCs may modulate the adaptive arm of Th2 immunity. The effect of MSC administration was long lasting; all features of allergic airway disease were significantly suppressed in response to a second round of HDM challenge 4 weeks after MSC administration. Further, we observed that MSCs decreased the release of epithelial cell-derived alarmins IL-1α and high mobility group box-1 in an IL-1 receptor antagonist-dependent manner. This significantly decreased the expression of the pro-Th2 cytokine IL-25 and reduced the number of activated and antigen-acquiring CD11c(+)CD11b(+) dendritic cells in the lung and mediastinal lymph nodes. Our findings suggest that MSC administration can ameliorate allergic airway inflammation by blunting the amplification of epithelial-derived inflammatory cytokines induced by HDM exposure and may offer long-term protection against Th2-mediated allergic airway inflammation and AHR. PMID:25789608

  5. Qingchang Wenzhong Decoction Ameliorates Dextran Sulphate Sodium-Induced Ulcerative Colitis in Rats by Downregulating the IP10/CXCR3 Axis-Mediated Inflammatory Response

    PubMed Central

    Mao, Tang-you; Shi, Rui; Zhao, Wei-han; Guo, Yi; Gao, Kang-li; Chen, Chen; Xie, Tian-hong; Li, Jun-xiang

    2016-01-01

    Qingchang Wenzhong Decoction (QCWZD) is an effective traditional Chinese medicine prescription. Our previous studies have shown that QCWZD has significant efficacy in patients with mild-to-moderate ulcerative colitis (UC) and in colonic mucosa repair in UC rat models. However, the exact underlying mechanism remains unknown. Thus, this study was conducted to determine QCWZD's efficacy and mechanism in dextran sulphate sodium- (DSS-) induced UC rat models, which were established by 7-day administration of 4.5% DSS solution. QCWZD was administered daily for 7 days, after which the rats were euthanized. Disease activity index (DAI), histological score (HS), and myeloperoxidase (MPO) level were determined to evaluate UC severity. Serum interferon gamma-induced protein 10 (IP10) levels were determined using ELISA kits. Western blotting and real-time polymerase chain reaction were, respectively, used to determine colonic protein and gene expression of IP10, chemokine (cys-x-cys motif) receptor (CXCR)3, and nuclear factor- (NF-) κB p65. Intragastric QCWZD administration ameliorated DSS-induced UC, as evidenced by decreased DAI, HS, and MPO levels. Furthermore, QCWZD decreased the protein and gene expression of IP10, CXCR3, and NF-κB p65. Overall, these results suggest that QCWZD ameliorates DSS-induced UC in rats by downregulating the IP10/CXCR3 axis-mediated inflammatory response and may be a novel UC therapy. PMID:27413386

  6. Thioredoxin Ameliorates Cutaneous Inflammation by Regulating the Epithelial Production and Release of Pro-Inflammatory Cytokines

    PubMed Central

    Tian, Hai; Matsuo, Yoshiyuki; Fukunaga, Atsushi; Ono, Ryusuke; Nishigori, Chikako; Yodoi, Junji

    2013-01-01

    Human thioredoxin-1 (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-. It has been demonstrated that systemic administration and transgenic overexpression of TRX ameliorate inflammation in various animal models, but its anti-inflammatory mechanism is not well characterized. We investigated the anti-inflammatory effects of topically applied recombinant human TRX (rhTRX) in a murine irritant contact dermatitis (ICD) induced by croton oil. Topically applied rhTRX was distributed only in the skin tissues under both non-inflammatory and inflammatory conditions, and significantly suppressed the inflammatory response by inhibiting the production of cytokines and chemokines, such as TNF-α, Il-1β, IL-6, CXCL-1, and MCP-1. In an in vitro study, rhTRX also significantly inhibited the formation of cytokines and chemokines produced by keratinocytes after exposure to croton oil and phorbol 12-myristate 13-acetate. These results indicate that TRX prevents skin inflammation via the inhibition of local formation of inflammatory cytokines and chemokines. As a promising new approach, local application of TRX may be useful for the treatment of various skin and mucosal inflammatory disorders. PMID:24058364

  7. 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

  8. Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice.

    PubMed

    Fukushima, Arata; Kinugawa, Shintaro; Takada, Shingo; Matsumoto, Junichi; Furihata, Takaaki; Mizushima, Wataru; Tsuda, Masaya; Yokota, Takashi; Matsushima, Shouji; Okita, Koichi; Tsutsui, Hiroyuki

    2016-05-15

    Insulin resistance can occur as a consequence of heart failure (HF). Activation of the renin-angiotensin system (RAS) may play a crucial role in this phenomenon. We thus investigated the effect of a direct renin inhibitor, aliskiren, on insulin resistance in HF after myocardial infarction (MI). MI and sham operation were performed in male C57BL/6J mice. The mice were divided into 4 groups and treated with sham-operation (Sham, n=10), sham-operation and aliskiren (Sham+Aliskiren; 10mg/kg/day, n=10), MI (n=11), or MI and aliskiren (MI+Aliskiren, n=11). After 4 weeks, MI mice showed left ventricular dilation and dysfunction, which were not affected by aliskiren. The percent decrease of blood glucose after insulin load was significantly smaller in MI than in Sham (14±5% vs. 36±2%), and was ameliorated in MI+Aliskiren (34±5%) mice. Insulin-stimulated serine-phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle of MI compared to Sham by 57% and 69%, and both changes were ameliorated in the MI+Aliskiren group (91% and 94%). Aliskiren administration in MI mice significantly inhibited plasma renin activity and angiotensin II (Ang II) levels. Moreover, (pro)renin receptor expression and local Ang II production were upregulated in skeletal muscle from MI and were attenuated in MI+Aliskiren mice, in tandem with a decrease in superoxide production and NAD(P)H oxidase activities. In conclusion, aliskiren ameliorated insulin resistance in HF by improving insulin signaling in the skeletal muscle, at least partly by inhibiting systemic and (pro)renin receptor-mediated local RAS activation, and subsequent NAD(P)H oxidase-induced oxidative stress. PMID:26988296

  9. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

    SciTech Connect

    Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana; Borkar, Roshan M.; Kumar, Jerald Mahesh; Kuncha, Madhusudana; Srinivas, R.; Shyam Sunder, R.; Sistla, Ramakrishna

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

  10. Metformin and resveratrol ameliorate muscle insulin resistance through preventing lipolysis and inflammation in hypoxic adipose tissue.

    PubMed

    Zhao, Wenjun; Li, Aiyun; Feng, Xin; Hou, Ting; Liu, Kang; Liu, Baolin; Zhang, Ning

    2016-09-01

    This study aims to investigate the effects of metformin and resveratrol on muscle insulin resistance with emphasis on the regulation of lipolysis in hypoxic adipose tissue. ICR mice were fed with high fat diet (HFD) for 10days with administration of metformin, resveratrol, or intraperitoneal injection of digoxin. Adipose hypoxia, inflammation and cAMP/PKA-dependent lipolysis were investigated. Moreover, lipid deposition and insulin resistance were examined in the muscle. Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1α expression and inflammation in the adipose tissue of HFD-fed mice. Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B. Metformin and resveratrol reduced FFAs influx and DAG accumulation, and thus improved insulin signaling in the muscle by inhibiting PKCθ translocation. This study presents a new view of regulating lipid metabolism to ameliorate insulin resistance and provides the clinical guiding significance for obesity and type 2 diabetes with metformin and resveratrol treatment. PMID:27343375

  11. Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs.

    PubMed

    Mazzola, S; Forni, M; Albertini, M; Bacci, M L; Zannoni, A; Gentilini, F; Lavitrano, M; Bach, F H; Otterbein, L E; Clement, M G

    2005-12-01

    Endotoxic shock, one of the most prominent causes of mortality in intensive care units, is characterized by pulmonary hypertension, systemic hypotension, heart failure, widespread endothelial activation/injury, and clotting culminating in disseminated intravascular coagulation and multi-organ system failure. In the last few years, studies in rodents have shown that administration of low concentrations of carbon monoxide (CO) exerts potent therapeutic effects in a variety of diseases/disorders. In this study, we have administered CO (one our pretreatment at 250 ppm) in a clinically relevant, well-characterized model of LPS-induced acute lung injury in pigs. Pretreatment only with inhaled CO significantly ameliorated several of the acute pathological changes induced by endotoxic shock. In terms of lung physiology, CO pretreatment corrected the LPS-induced changes in resistance and compliance and improved the derangement in pulmonary gas exchange. In terms of coagulation and inflammation, CO reduced the development of disseminated intravascular coagulation and completely suppressed serum levels of the proinflammatory IL-1beta in response to LPS, while augmenting the anti-inflammatory cytokine IL-10. Moreover, the effects of CO blunted the deterioration of kidney and liver function, suggesting a beneficial effect in terms of end organ damage associated with endotoxic shock. Lastly, CO pretreatment prevents LPS-induced ICAM expression on lung endothelium and inhibits leukocyte marginalization on lung parenchyma. PMID:16223783

  12. The Ameliorating Effect of Myrrh on Scopolamine-Induced Memory Impairments in Mice

    PubMed Central

    Baral, Samrat; Cho, Du-Hyong; Pariyar, Ramesh; Yoon, Chi-Su; Chang, Bo-yoon; Kim, Dae-Sung; Cho, Hyoung-Kwon; Kim, Sung Yeon; Oh, Hyuncheol; Kim, Youn-Chul; Kim, Jaehyo; Seo, Jungwon

    2015-01-01

    Myrrh has been used since ancient times for the treatment of various diseases such as inflammatory diseases, gynecological diseases, and hemiplegia. In the present study, we investigated the effects of aqueous extracts of myrrh resin (AEM) on scopolamine-induced memory impairments in mice. AEM was estimated with (2E,5E)-6-hydroxy-2,6-dimethylhepta-2,4-dienal as a representative constituent by HPLC. The oral administration of AEM for 7 days significantly reversed scopolamine-induced reduction of spontaneous alternation in the Y-maze test. In the passive avoidance task, AEM also restored the decreased latency time of the retention trial by scopolamine treatment. In addition, Western blot analysis and Immunohistochemistry revealed that AEM reversed scopolamine-decreased phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Our study demonstrates for the first time that AEM ameliorates the scopolamine-induced memory impairments in mice and increases the phosphorylation of Akt and ERK in the hippocampus of mice brain. These results suggest that AEM has the therapeutic potential in memory impairments. PMID:26635888

  13. Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation

    PubMed Central

    Cao, Ke; Xu, Jie; Pu, Wenjun; Dong, Zhizhong; Sun, Lei; Zang, Weijin; Gao, Feng; Zhang, Yong; Feng, Zhihui; Liu, Jiankang

    2015-01-01

    Obesity is associated with an increasing prevalence of cardiovascular diseases and metabolic syndrome. It is of paramount importance to reduce obesity-associated cardiac dysfunction and impaired energy metabolism. In this study, the activation of the AMP-activated protein kinase (AMPK) pathway by punicalagin (PU), a major ellagitannin in pomegranate was investigated in the heart of a rat obesity model. In male SD rats, eight-week administration of 150 mg/kg pomegranate extract (PE) containing 40% punicalagin sufficiently prevented high-fat diet (HFD)-induced obesity associated accumulation of cardiac triglyceride and cholesterol as well as myocardial damage. Concomitantly, the AMPK pathway was activated, which may account for prevention of mitochondrial loss via upregulating mitochondrial biogenesis and amelioration of oxidative stress via enhancing phase II enzymes in the hearts of HFD rats. Together with the normalized expression of uncoupling proteins and mitochondrial dynamic regulators, PE significantly prevented HFD-induced cardiac ATP loss. Through in vitro cultures, we showed that punicalagin was the predominant component that activated AMPK by quickly decreasing the cellular ATP/ADP ratio specifically in cardiomyocytes. Our findings demonstrated that punicalagin, the major active component in PE, could modulate mitochondria and phase II enzymes through AMPK pathway to prevent HFD-induced cardiac metabolic disorders. PMID:26369619

  14. Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD.

    PubMed

    Mishima, Eikan; Fukuda, Shinji; Shima, Hisato; Hirayama, Akiyoshi; Akiyama, Yasutoshi; Takeuchi, Yoichi; Fukuda, Noriko N; Suzuki, Takehiro; Suzuki, Chitose; Yuri, Akinori; Kikuchi, Koichi; Tomioka, Yoshihisa; Ito, Sadayoshi; Soga, Tomoyoshi; Abe, Takaaki

    2015-08-01

    The accumulation of uremic toxins is involved in the progression of CKD. Various uremic toxins are derived from gut microbiota, and an imbalance of gut microbiota or dysbiosis is related to renal failure. However, the pathophysiologic mechanisms underlying the relationship between the gut microbiota and renal failure are still obscure. Using an adenine-induced renal failure mouse model, we evaluated the effects of the ClC-2 chloride channel activator lubiprostone (commonly used for the treatment of constipation) on CKD. Oral administration of lubiprostone (500 µg/kg per day) changed the fecal and intestinal properties in mice with renal failure. Additionally, lubiprostone treatment reduced the elevated BUN and protected against tubulointerstitial damage, renal fibrosis, and inflammation. Gut microbiome analysis of 16S rRNA genes in the renal failure mice showed that lubiprostone treatment altered their microbial composition, especially the recovery of the levels of the Lactobacillaceae family and Prevotella genus, which were significantly reduced in the renal failure mice. Furthermore, capillary electrophoresis-mass spectrometry-based metabolome analysis showed that lubiprostone treatment decreased the plasma level of uremic toxins, such as indoxyl sulfate and hippurate, which are derived from gut microbiota, and a more recently discovered uremic toxin, trans-aconitate. These results suggest that lubiprostone ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota and intestinal environment. PMID:25525179

  15. Kojibiose ameliorates arachidic acid-induced metabolic alterations in hyperglycaemic rats.

    PubMed

    Moisés Laparra, José; Díez-Municio, Marina; Javier Moreno, F; Herrero, Miguel

    2015-11-14

    Herein we hypothesise the positive effects of kojibiose (KJ), a prebiotic disaccharide, selected for reducing hepatic expression of inflammatory markers in vivo that could modulate the severity of saturated arachidic acid (ARa)-induced liver dysfunction in hyperglycaemic rats. Animals were fed daily (20 d) with ARa (0·3 mg) together or not with KJ (22 mg approximately 0·5 %, w/w diet). Glucose, total TAG and cholesterol contents and the phospholipid profile were determined in serum samples. Liver sections were collected for the expression (mRNA) of enzymes and innate biomarkers, and intrahepatic macrophage and T-cell populations were analysed by flow cytometry. ARa administration increased the proportion of liver to body weight that was associated with an increased (by 11 %) intrahepatic macrophage population. These effects were ameliorated when feeding with KJ, which also normalised the plasmatic levels of TAG and N-acyl-phosphatidylethenolamine in response to tissue damage. These results indicate that daily supplementation of KJ significantly improves the severity of ARa-induced hepatic alterations. PMID:26344377

  16. Treatment with SI000413, a new herbal formula, ameliorates murine collagen-induced arthritis.

    PubMed

    Park, Jee-Hun; Lee, Jeong-Min; Kim, Se-Na; Lee, Seung-Ha; Jun, Sung-Hoon; You, Jae-Hoon; Ahn, Kyoo-Seok; Kang, Hee

    2008-07-01

    We tested the effects of SI000413, a new formula, consisting of Pyrolae herba and Trachelospermi caulis, on type II collagen-induced arthritis (CIA). CIA was induced in DBA/1J mice by immunization with bovine type II collagen (CII) on days 1 and 21. SI000413 was orally administered 3 times per week throughout the experiment and indomethacin was served as a positive control. Clinical scores, the count of arthritic legs, levels of interleukin 6 (IL-6) and anti-CII antibody, and lymphocyte subsets in blood were examined. SI000413 suppressed CIA development in a dose dependent manner and reduced the incidence of arthritic legs in mice. Histological analysis showed administration of SI000413 reduced inflammatory signs and cartilage destruction. Serum levels of IL-6 and anti-CII antibody were significantly decreased in SI000413-treated mice and the percentages of CD4 T cell, CD8 T cell and B cell in blood were restored to normal levels. In conclusion, we demonstrate that SI000413 ameliorates CIA both clinically and histologically and inhibits the production of anti-CII antibody and pro-inflammatory cytokine in the CIA mouse. These findings suggest that SI000413 is a potential new therapeutic herbal formula for the treatment of RA. PMID:18591771

  17. Oridonin ameliorates neuropathological changes and behavioural deficits in a mouse model of cerebral amyloidosis.

    PubMed

    Zhang, Zhi-Yuan; Daniels, Rolf; Schluesener, Hermann J

    2013-12-01

    Alzheimer's disease (AD) is the most common form of neurodegeneration and the major cause of dementia. This multifactorial disorder is clinically defined by progressive behavioural and cognitive deficits, and neuropathologically characterized by β-amyloid aggregation, hyperphosphorylated tau and neuroinflammation. Oridonin, a diterpenoid isolated from Chinese herb Rabdosia rubescens, has multiple biological properties, especially anti-inflammatory and neuroregulatory activities. Potential therapeutic effects of Oridonin were investigated in an animal model of cerebral amyloidosis for AD, transgenic APP/PS1 mice. Oridonin was suspended in carboxymethylcellulose or loaded with a nanostructured emulsion, and was orally administrated or injected. Before, during and following the experimental treatments, behavioural tests were performed with these transgenic mice and their naive littermates. Following relatively short-term treatments of 10 days, brain tissue of mice were removed for immunohistochemical assays. The results indicate that both oral treatment and injection of Oridonin significantly attenuated β-amyloid deposition, plaque-associated APP expression and microglial activation in brain of transgenic mice. Furthermore, injection of Oridonin-nanoemulsion ameliorated deficits in nesting, an important affiliative behaviour, and in social interaction. Additional in vitro studies indicated that Oridonin effectively attenuated inflammatory reaction of macrophage and microglial cell lines. Our results suggest that Oridonin might be considered a promising therapeutic option for human AD or other neurodegenerative diseases. PMID:24034629

  18. Sodium butyrate ameliorates histone hypoacetylation and neurodegenerative phenotypes in a mouse model for DRPLA.

    PubMed

    Ying, Mingyao; Xu, Rener; Wu, Xiaohui; Zhu, Huaxing; Zhuang, Yuan; Han, Min; Xu, Tian

    2006-05-01

    Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive neurodegenerative disease caused by polyglutamine expansion within the Atrophin-1 protein. To study the mechanism of this disease and to test potential therapeutic methods, we established Atro-118Q transgenic mice, which express in neurons a mutant human Atrophin-1 protein that contains an expanded stretch of 118 glutamines. Consistent with the results from previous studies on transgenic mice that expressed mutant Atrophin-1 with 65 glutamines, Atro-118Q mice exhibited several neurodegenerative phenotypes that are commonly seen in DRPLA patients, including ataxia, tremors, and other motor defects. Overexpression of wild-type human Atrophin-1 could not rescue the motor and survival defects in Atro-118Q mice, indicating that the mutant protein with polyglutamine expansion does not simply function in a dominant negative manner. Biochemical analysis of Atro-118Q mice revealed hypoacetylation of histone H3 in brain tissues and thus suggested that global gene repression is an underlying mechanism for neurodegeneration in this mouse model. We further show that intraperitoneal administration of sodium butyrate, a histone deacetylase inhibitor, ameliorated the histone acetylation defects, significantly improved motor performance, and extended the average life span of Atro-118Q mice. These results support the hypothesis that transcription deregulation plays an important role in the pathogenesis of polyglutamine expansion diseases and suggest that reversion of transcription repression with small molecules such as sodium butyrate is a feasible approach to treating DRPLA symptoms. PMID:16407196

  19. Amelioration of ferric nitrilotriacetate-induced hepatotoxicity in Wistar rats by diallylsulfide.

    PubMed

    Ansar, S; Iqbal, M

    2016-03-01

    Garlic contains diallylsulfide (DAS) and other structurally related compounds that are widely believed to be active agents in preventing cancer. This study shows the effect of DAS (a phenolic antioxidant used in foods, cosmetics, and pharmaceutical products) on ferric nitrilotriacetate (Fe-NTA)-induced hepatotoxicity in rats. Male albino rats of Wistar strain weighing 125-150 g were given a single dose of Fe-NTA (9 mg kg(-1) body weight, intraperitoneally) after 1 week of treatment with 100 and 200 mg kg(-1) DAS in corn oil respectively administered through the gavage. Fe-NTA administration led to 2.5-fold increase in the values of both alanine transaminase and aspartate aminotransferase, respectively, and 3.2-fold increase in the activity of lactate dehydrogenase, microsomal lipid peroxidation to approximately 2.0-fold compared to saline-treated control. The activities of glutathione (GSH) and other antioxidant enzymes decreased to a range of 2.2-2.5-fold. These changes were reversed significantly (p < 0.001) in animals receiving a pretreatment of DAS. DAS protected against hepatic lipid peroxidation, hydrogen peroxide generation, preserved GSH levels, and GSH metabolizing enzymes to 60-80% as compared to Fe-NTA alone-treated group. Present data suggest that DAS can ameliorate the toxic effects of Fe-NTA and suppress oxidant-induced tissue injury and hepatotoxicity in rats. PMID:25904316

  20. Exogenous Lipocalin 2 Ameliorates Acute Rejection in a Mouse Model of Renal Transplantation

    PubMed Central

    Ashraf, M. I.; Schwelberger, H. G.; Brendel, K. A.; Feurle, J.; Andrassy, J.; Kotsch, K.; Regele, H.; Pratschke, J.; Maier, H. T.

    2016-01-01

    Abstract Lipocalin 2 (Lcn2) is rapidly produced by damaged nephron epithelia and is one of the most promising new markers of renal injury, delayed graft function and acute allograft rejection (AR); however, the functional importance of Lcn2 in renal transplantation is largely unknown. To understand the role of Lcn2 in renal AR, kidneys from Balb/c mice were transplanted into C57Bl/6 mice and vice versa and analyzed for morphological and physiological outcomes of AR at posttransplantation days 3, 5, and 7. The allografts showed a steady increase in intensity of interstitial infiltration, tubulitis and periarterial aggregation of lymphocytes associated with a substantial elevation in serum levels of creatinine, urea and Lcn2. Perioperative administration of recombinant Lcn2:siderophore:Fe complex (rLcn2) to recipients resulted in functional and morphological amelioration of the allograft at day 7 almost as efficiently as daily immunosuppression with cyclosporine A (CsA). No significant differences were observed in various donor–recipient combinations (C57Bl/6 wild‐type and Lcn2−/−, Balb/c donors and recipients). Histochemical analyses of the allografts showed reduced cell death in recipients treated with rLcn2 or CsA. These results demonstrate that Lcn2 plays an important role in reducing the extent of kidney AR and indicate the therapeutic potential of Lcn2 in transplantation. PMID:26595644

  1. 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

  2. Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-{kappa}B pathway

    SciTech Connect

    Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui; Han, Bing; Pan, Chunming; Zhao, Shuangxia; Song, Huaidong; Ma, Qinyun

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Stevioside ameliorates high-fat diet-induced insulin resistance. Black-Right-Pointing-Pointer Stevioside alleviates the adipose tissue inflammation. Black-Right-Pointing-Pointer Stevioside reduces macrophages infiltration into the adipose tissue. Black-Right-Pointing-Pointer Stevioside suppresses the activation of NF-{kappa}B in the adipose tissue. -- Abstract: Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration of SVS for 1 month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-{alpha}, IL6, IL10, IL1{beta}, KC, MIP-1{alpha}, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-{kappa}B) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-{kappa}B pathway.

  3. Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways.

    PubMed

    Peng, Shuang; Hang, Nan; Liu, Wen; Guo, Wenjie; Jiang, Chunhong; Yang, Xiaoling; Xu, Qiang; Sun, Yang

    2016-05-01

    Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders. PMID:27175331

  4. Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways

    PubMed Central

    Peng, Shuang; Hang, Nan; Liu, Wen; Guo, Wenjie; Jiang, Chunhong; Yang, Xiaoling; Xu, Qiang; Sun, Yang

    2016-01-01

    Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders. PMID:27175331

  5. Oral ingestion of aloe vera phytosterols alters hepatic gene expression profiles and ameliorates obesity-associated metabolic disorders in zucker diabetic fatty rats.

    PubMed

    Misawa, Eriko; Tanaka, Miyuki; Nomaguchi, Kouji; Nabeshima, Kazumi; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

    2012-03-21

    We investigated the effects of the oral administration of lophenol (Lo) and cycloartanol (Cy), two kinds of antidiabetic phytosterol isolated from Aloe vera , on glucose and lipid metabolism in Zucker diabetic fatty (ZDF) rats. We demonstrated that the administrations of Lo and Cy suppressed random and fasting glucose levels and reduced visceral fat weights significantly. It was also observed that treatments with Lo and Cy decreased serum and hepatic lipid concentrations (triglyceride, nonesterified fatty acid, and total cholesterol). Additionally, Lo and Cy treatments resulted in a tendency for reduction in serum monocyte chemotactic protein-1 (MCP-1) level and an elevation in serum adiponectin level. Furthermore, the expression levels of hepatic genes encoding gluconeogenic enzymes (G6 Pase, PEPCK), lipogenic enzymes (ACC, FAS), and SREBP-1 were decreased significantly by the administrations of aloe sterols. In contrast, Lo and Cy administration increased mRNA levels of glycolysis enzyme (GK) in the liver. It was also observed that the hepatic β-oxidation enzymes (ACO, CPT1) and PPARα expressions tended to increase in the livers of the Lo- and Cy-treated rats compared with those in ZDF-control rats. We therefore conclude that orally ingested aloe sterols altered the expressions of genes related to glucose and lipid metabolism, and ameliorated obesity-associated metabolic disorders in ZDF rats. These findings suggest that aloe sterols could be beneficial in preventing and improving metabolic disorders with obesity and diabetes in rats. PMID:22352711

  6. Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. spinosa Ameliorates Aβ1–42 Oligomer-Induced Memory Impairment in Mice

    PubMed Central

    Ko, Sang Yoon; Lee, Hyung Eun; Park, Se Jin; Jeon, Se Jin; Kim, Boseong; Gao, Qingtao; Jang, Dae Sik; Ryu, Jong Hoon

    2015-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder associated with progressive memory loss and neuronal cell death. Although numerous previous studies have been focused on disease progression or reverse pathological symptoms, therapeutic strategies for AD are limited. Alternatively, the identification of traditional herbal medicines or their active compounds has received much attention. The aims of the present study were to characterize the ameliorating effects of spinosin, a C-glucosylflavone isolated from Zizyphus jujuba var. spinosa, on memory impairment or the pathological changes induced through amyloid-β1–42 oligomer (AβO) in mice. Memory impairment was induced by intracerebroventricular injection of AβO (50 μM) and spinosin (5, 10, and 20 mg/kg) was administered for 7 days. In the behavioral tasks, the subchronic administration of spinosin (20 mg/kg, p.o.) significantly ameliorated AβO-induced cognitive impairment in the passive avoidance task or the Y-maze task. To identify the effects of spinosin on the pathological changes induced through AβO, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after AβO injection. In addition, spinosin rescued the AβO-induced decrease in choline acetyltransferase expression levels. These results suggest that spinosin ameliorated memory impairment induced through AβO, and these effects were regulated, in part, through neuroprotective activity via the anti-inflammatory effects of spinosin. Therefore, spinosin might be a useful agent against the amyloid b protein-induced cognitive dysfunction observed in AD patients. PMID:25767684

  7. Betahistine ameliorates olanzapine-induced weight gain through modulation of histaminergic, NPY and AMPK pathways.

    PubMed

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2014-10-01

    Olanzapine is widely used to treat schizophrenia and other disorders, but causes adverse obesity and other metabolic side-effects. Both animal and clinical studies have shown that co-treatment with betahistine (a histaminergic H1 receptor agonist and H3 receptor antagonist) is effective for ameliorating olanzapine-induced weight gain/obesity. To reveal the mechanisms underlying these effects, this study investigated the effects of co-treatment of olanzapine and betahistine (O+B) on expressions of histaminergic H1 receptor (H1R), AMP-activated protein kinase (AMPK), neuropeptide Y (NPY), and proopiomelanocortin (POMC) in the hypothalamus associated with reducing olanzapine-induced weight gain. Olanzapine significantly upregulated the mRNA and protein expressions of H1R, while O+B co-treatment significantly downregulated the H1R levels, compared to the olanzapine-only treatment group. The NPY mRNA expression was significantly enhanced by olanzapine, but it was significantly reversed by O+B co-treatment. The hypothalamic H1R expression was positively correlated with total food intake, and NPY expression. Olanzapine also increased AMPKα activation measured by the AMPKα phosphorylation (pAMPKα)/AMPKα ratio compared with controls, whereas O+B co-treatment decreased the pAMPKα/AMPKα ratio, compared with olanzapine only treatment. The pAMPKα/AMPKα ratio was positively correlated with total food intake and H1R expression. Although olanzapine administration decreased the POMC mRNA level, this level was not affected by O+B co-treatment. Therefore, these results suggested that co-treatment with betahistine may reverse olanzapine-induced body weight gain via the H1R-NPY and H1R-pAMPKα pathways. PMID:24992721

  8. Grape Seed Proanthocyanidin Extract Ameliorates Diabetic Bladder Dysfunction via the Activation of the Nrf2 Pathway

    PubMed Central

    Chen, Shouzhen; Zhu, Yaofeng; Liu, Zhifeng; Gao, Zhaoyun; Li, Baoying; Zhang, Dongqing; Zhang, Zhaocun; Jiang, Xuewen; Liu, Zhengfang; Meng, Lingquan; Yang, Yue; Shi, Benkang

    2015-01-01

    Diabetes Mellitus (DM)-induced bladder dysfunction is predominantly due to the long-term oxidative stress caused by hyperglycemia. Grape seed proanthocyanidin extract (GSPE) has been reported to possess a broad spectrum of pharmacological and therapeutic properties against oxidative stress. However, its protective effects against diabetic bladder dysfunction have not been clarified. This study focuses on the effects of GSPE on bladder dysfunction in diabetic rats induced by streptozotocin. After 8 weeks of GSPE administration, the bladder function of the diabetic rats was improved significantly, as indicated by both urodynamics analysis and histopathological manifestation. Moreover, the disordered activities of antioxidant enzymes (SOD and GSH-Px) and abnormal oxidative stress levels were partly reversed by treatment with GSPE. Furthermore, the level of apoptosis in the bladder caused by DM was decreased following the administration of GSPE according to the Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) assay. Additionally, GSPE affected the expression of apoptosis-related proteins such as Bax, Bcl-2 and cleaved caspase-3. Furthermore, GSPE showed neuroprotective effects on the bladder of diabetic rats, as shown by the increased expression of nerve growth factor (NGF) and decreased expression of the precursor of nerve growth factor (proNGF). GSPE also activated nuclear erythroid2-related factor2 (Nrf2), which is a key antioxidative transcription factor, with the concomitant elevation of downstream hemeoxygenase-1 (HO-1). These findings suggested that GSPE could ameliorate diabetic bladder dysfunction and decrease the apoptosis of the bladder in diabetic rats, a finding that may be associated with its antioxidant activity and ability to activate the Nrf2 defense pathway. PMID:25974036

  9. Dual ameliorative effects of Ningdong granule on dopamine in rat models of Tourette's syndrome

    PubMed Central

    Zhang, Feng; Li, Anyuan

    2015-01-01

    Dopamine (DA) is a key neuromodulator in the brain that supports motor and cognitive functions. Here, we use apomorphine (Apo) and 3,3'-iminodipropionitrile (IDPN) to develop two rat models of Tourette's syndrome (TS), a common neuropsychiatric disorder characterized by stereotyped repetitive involuntary tics. The models enabled the assessment of unique ameliorative effects of Ningdong granule (NDG), a traditional Chinese medicine (TCM) preparation dedicated to the treatment of TS, on the striatal DA content of rats. By using high-performance liquid chromatography (HPLC), we found that long-term administration of NDG could, at least partially, restore the striatal dopamine alterations, either by increasing them after IDPN treatment or by decreasing them after Apo treatment. Taken together, our data indicated that NDG could ameliorate the abnormal striatal DA content dually, and the unique therapeutic property may be meaningful for the treatment of TS. PMID:25592875

  10. Oridonin ameliorates lupus-like symptoms of MRL(lpr/lpr) mice by inhibition of B-cell activating factor (BAFF).

    PubMed

    Zhou, Lin; Sun, Lijuan; Wu, Hongkun; Zhang, Lingzhen; Chen, Mingcang; Liu, Jianwen; Zhong, Renqian

    2013-09-01

    Oridonin, a pharmacologically safe agent extracted from Isodon Serra, has been shown to possess potent anti-inflammatory properties. However, it is not clear whether Oridonin affects B-cell activating factor (BAFF) expression, thereby exerting beneficial effects in the treatment of BAFF-associated autoimmune diseases such as systemic lupus erythematosus (SLE). Thus, the current study aimed to find the function of Oridonin in regulation of BAFF and amelioration of SLE. In vitro, we explored the effect of Oridonin on BAFF expression and production in mouse macrophages. Moreover, using a spontaneous murine SLE model, we investigated the role of Oridonin delivery in the treatment of lupus-like disease in MRL(lpr/lpr) mice, by measuring the changes in lupus symptoms, renal damage, BAFF expression, and B cell subsets. Our results showed that Oridonin significantly inhibited BAFF expression in mouse macrophages by suppressing the transcriptional activation of its promoter. And in vivo administration of Oridonin efficiently ameliorated the serological and clinical manifestations of SLE in MRL(lpr/lpr) mice, as shown by increased survival benefit, reduced proteinuria levels, diminished production of specific auto-antibodies, and attenuated renal damage, in association with down-regulation of BAFF and a lower rate of B-cell maturation and differentiation. Thus, it suggests that Oridonin will serve as a novel natural therapeutic strategy for SLE by inhibition of BAFF. PMID:23712004

  11. Sulforaphane ameliorates neurobehavioral deficits and protects the brain from amyloid β deposits and peroxidation in mice with Alzheimer-like lesions.

    PubMed

    Zhang, Rui; Miao, Qian-Wei; Zhu, Chun-Xiao; Zhao, Yue; Liu, Li; Yang, Jun; An, Li

    2015-03-01

    Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly individuals and its effective therapies are still unavailable. This study was designed to investigate the neuroprotection of sulforaphane (SFN) in AD-lesion mice induced by combined administration of d-galactose and aluminium. Results showed that SFN ameliorated spatial cognitive impairment and locomotor activity decrease in Morris water maze and open field test, respectively. And attenuated numbers of amyloid β (Aβ) plaques in both hippocampus and cerebral cortex of AD-lesion mice were detected by immunohistochemistry. According to spectrophotometry and quantitative reverse-transcriptase polymerase chain reaction results, a significant increase in carbonyl group level and obvious decreases in both activity and messenger RNA expression of glutathione peroxidase were found in brain of AD-lesion mice compared with control, but not in SFN-treated AD-lesion mice. In conclusion, SFN ameliorates neurobehavioral deficits and protects the brain from Aβ deposits and peroxidation in mice with Alzheimer-like lesions, suggesting SFN is likely a potential phytochemical to be used in AD therapeutics. PMID:25024455

  12. Propionate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation and Oxidative Stress

    PubMed Central

    Tong, Ling-chang; Wang, Yue; Wang, Zhi-bin; Liu, Wei-ye; Sun, Sheng; Li, Ling; Su, Ding-feng; Zhang, Li-chao

    2016-01-01

    Propionate is a short chain fatty acid that is abundant as butyrate in the gut and blood. However, propionate has not been studied as extensively as butyrate in the treatment of colitis. The present study was to investigate the effects of sodium propionate on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium (DSS)-induced colitis mice. Animals in DSS group received drinking water from 1 to 6 days and DSS [3% (w/v) dissolved in double distilled water] instead of drinking water from 7 to 14 days. Animals in DSS+propionate (DSS+Prop) group were given 1% sodium propionate for 14 consecutive days and supplemented with 3% DSS solution on day 7–14. Intestinal barrier function, proinflammatory factors, oxidative stress, and signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon were determined. It was found that sodium propionate ameliorated body weight loss, colon-length shortening and colonic damage in colitis mice. Sodium propionate significantly inhibited the increase of FITC-dextran in serum and the decrease of zonula occludens-1 (ZO-1), occludin, and E-cadherin expression in the colonic tissue. It also inhibited the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA and phosphorylation of STAT3 in colitis mice markedly, reduced the myeloperoxidase (MPO) level, and increased the superoxide dismutase and catalase level in colon and serum compared with DSS group. Sodium propionate inhibited macrophages with CD68 marker infiltration into the colonic mucosa of colitis mice. These results suggest that oral administration of sodium propionate could ameliorate DSS-induced colitis mainly by improving intestinal barrier function and reducing inflammation and oxidative stress via the STAT3 signaling pathway. PMID:27574508

  13. Evaluation of enzyme dose and dose-frequency in ameliorating substrate accumulation in MPS IIIA Huntaway dog brain.

    PubMed

    King, Barbara; Marshall, Neil; Beard, Helen; Hassiotis, Sofia; Trim, Paul J; Snel, Marten F; Rozaklis, Tina; Jolly, Robert D; Hopwood, John J; Hemsley, Kim M

    2015-03-01

    Intracerebrospinal fluid (CSF) infusion of replacement enzyme is under evaluation for amelioration of disease-related symptoms and biomarker changes in patients with the lysosomal storage disorder mucopolysaccharidosis type IIIA (MPS IIIA; www.clinicaltrials.gov ; NCT#01155778; #01299727). Determining the optimal dose/dose-frequency is important, given the invasive method for chronically supplying recombinant protein to the brain, the main site of symptom generation. To examine these variables, we utilised MPS IIIA Huntaway dogs, providing recombinant human sulphamidase (rhSGSH) to young pre-symptomatic dogs from an age when MPS IIIA dog brain exhibits significant accumulation of primary (heparan sulphate) and secondary (glycolipid) substrates. Enzyme was infused into CSF via the cisterna magna at one of two doses (3 mg or 15 mg/infusion), with the higher dose supplied at two different intervals; fortnightly or monthly. Euthanasia was carried out 24 h after the final injection. Dose- and frequency-dependent reductions in heparan sulphate were observed in CSF and deeper layers of cerebral cortex. When we examined the amount of immunostaining of the general endo/lysosomal marker, LIMP-2, or quantified activated microglia, the higher fortnightly dose resulted in superior outcomes in affected dogs. Secondary lesions such as accumulation of GM3 ganglioside and development of GAD-reactive axonal spheroids were treated to a similar degree by both rhSGSH doses and dose frequencies. Our findings indicate that the lower fortnightly dose is sub-optimal for ameliorating existing and preventing further development of disease-related pathology in young MPS IIIA dog brain; however, increasing the dose fivefold but halving the frequency of administration enabled near normalisation of disease-related biomarkers. PMID:25421091

  14. Gestational naltrexone ameliorates fetal ethanol exposures enhancing effect on the postnatal behavioral and neural response to ethanol

    PubMed Central

    Youngentob, Steven L; Kent, Paul F; Youngentob, Lisa M

    2012-01-01

    The association between gestational exposure to ethanol and adolescent ethanol abuse is well established. Recent animal studies support the role of fetal ethanol experience-induced chemosensory plasticity as contributing to this observation. Previously, we established that fetal ethanol exposure, delivered through a dam’s diet throughout gestation, tuned the neural response of the peripheral olfactory system of early postnatal rats to the odor of ethanol. This occurred in conjunction with a loss of responsiveness to other odorants. The instinctive behavioral response to the odor of ethanol was also enhanced. Importantly, there was a significant contributory link between the altered response to the odor of ethanol and increased ethanol avidity when assessed in the same animals. Here, we tested whether the neural and behavioral olfactory plasticity, and their relationship to enhanced ethanol intake, is a result of the mere exposure to ethanol or whether it requires the animal to associate ethanol’s reinforcing properties with its odor attributes. In this later respect, the opioid system is important in the mediation (or modulation) of the reinforcing aspects of ethanol. To block endogenous opiates during prenatal life, pregnant rats received daily intraperitoneal administration of the opiate antagonist naltrexone from gestational day 6–21 jointly with ethanol delivered via diet. Relative to control progeny, we found that gestational exposure to naltrexone ameliorated the enhanced postnatal behavioral response to the odor of ethanol and postnatal drug avidity. Our findings support the proposition that in utero ethanol-induced olfactory plasticity (and its relationship to postnatal intake) requires, at least in part, the associative pairing between ethanol’s odor quality and its reinforcing aspects. We also found suggestive evidence that fetal naltrexone ameliorated the untoward effects of gestational ethanol exposure on the neural response to non

  15. Propionate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation and Oxidative Stress.

    PubMed

    Tong, Ling-Chang; Wang, Yue; Wang, Zhi-Bin; Liu, Wei-Ye; Sun, Sheng; Li, Ling; Su, Ding-Feng; Zhang, Li-Chao

    2016-01-01

    Propionate is a short chain fatty acid that is abundant as butyrate in the gut and blood. However, propionate has not been studied as extensively as butyrate in the treatment of colitis. The present study was to investigate the effects of sodium propionate on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium (DSS)-induced colitis mice. Animals in DSS group received drinking water from 1 to 6 days and DSS [3% (w/v) dissolved in double distilled water] instead of drinking water from 7 to 14 days. Animals in DSS+propionate (DSS+Prop) group were given 1% sodium propionate for 14 consecutive days and supplemented with 3% DSS solution on day 7-14. Intestinal barrier function, proinflammatory factors, oxidative stress, and signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon were determined. It was found that sodium propionate ameliorated body weight loss, colon-length shortening and colonic damage in colitis mice. Sodium propionate significantly inhibited the increase of FITC-dextran in serum and the decrease of zonula occludens-1 (ZO-1), occludin, and E-cadherin expression in the colonic tissue. It also inhibited the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA and phosphorylation of STAT3 in colitis mice markedly, reduced the myeloperoxidase (MPO) level, and increased the superoxide dismutase and catalase level in colon and serum compared with DSS group. Sodium propionate inhibited macrophages with CD68 marker infiltration into the colonic mucosa of colitis mice. These results suggest that oral administration of sodium propionate could ameliorate DSS-induced colitis mainly by improving intestinal barrier function and reducing inflammation and oxidative stress via the STAT3 signaling pathway. PMID:27574508

  16. Embelin Reduces Systemic Inflammation and Ameliorates Organ Injuries in Septic Rats Through Downregulating STAT3 and NF-κB Pathways.

    PubMed

    Zhou, Xian-Long; Huang, Lei; Cao, Jun

    2015-08-01

    Current evidence shows that the majority of the damage induced during sepsis is pursuant to induction and overproduction of endogenous cytokines. Embelin has been reported to suppress cytokine expressions in inflammatory disorders. The present study was designed to investigate the effects of embelin on cecal and ligation and puncture (CLP)-induced rat sepsis. Single-dose administration of embelin 1 h after surgery significantly improved survival of rats with CLP-induced sepsis. In addition, embelin treatment reduced the serum levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 and decreased organ inflammation and injuries. Moreover, embelin suppressed the activation of p65 subunit of nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription 3 (STAT3). Collectively, these results indicated that embelin ameliorates sepsis in rats through suppressing STAT3 and NF-κB pathways. PMID:25682469

  17. Significant Treasures.

    ERIC Educational Resources Information Center

    Andrews, Ian A.

    1999-01-01

    Provides a crossword puzzle with an answer key corresponding to the book entitled "Significant Treasures/Tresors Parlants" that is filled with color and black-and-white prints of paintings and artifacts from 131 museums and art galleries as a sampling of the 2,200 such Canadian institutions. (CMK)

  18. 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.

  19. [In situ immobilization of Pb and Cd in orchard soil using soil ameliorants].

    PubMed

    Tang, Min; Zhang, Jin-Zhong; Zhang, Dan; Chen, Shun; Zhang, Xun; Liu, Wan-Ping; Yu, Jian

    2012-10-01

    In situ immobilization of Pb and Cd in soil of two gardens in Golden Orchard of Chongqing was studied using soil ameliorants, which included eight treatments: control, quicklime, superphosphate, organic manure, quicklime + superphosphate, quicklime + organic manure, superphosphate + organic manure, and quicklime + superphosphate + organic manure. The results showed that all ameliorant treatments could decrease soil acidity in both the loquat garden and peach garden except the superphosphate treatment. Compared with the control, the soil pH in the two gardens increased by 0. 93 and 0. 79 with quicklime treatment for 120 d, respectively. Ameliorant treatments could decrease the bioavailability of Pb and Cd in the soil, and thus reduce the contents of Pb and Cd in the fruits. The available Pb contents in the soil of loquat garden and peach garden significantly decreased after the 150 d treatment with quicklime and superphosphate, by 3.46% and 3.56%, respectively, and the Pb contents in loquat and peach decreased by 18.3% and 14.44%, respectively. The available Cd content in the soil of loquat garden decreased by 10. 95% after the 150 d treatment with quicklime. The available Cd content in the soil of peach garden decreased by 7.09% after the 150 d treatment with quicklime, superphosphate and organic manure. Ameliorant treatments could further decrease the Cd content in loquat, and the Cd contents in loquat and peach decreased by 30.91% and 24.62% with quicklime treatment, respectively. PMID:23233990

  20. Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle.

    PubMed

    Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

    2015-01-01

    The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid content in skeletal muscle was measured. Genes and proteins of the AMPK signaling pathway were analyzed by real time RT-PCR and Western blot. Adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) and other genes involved in mitochondrial function and fat oxidation were analyzed by real time RT-PCR. Histological staining was also performed. JLD or pioglitazone administration ameliorated fasting plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), ALT, AST and non-esterified fatty acid (NEFA) (P < 0.05). Treatment with JLD or pioglitazone significantly reverted muscle lipid content (P < 0.05). JLD (1.5 g/kg) significantly increased plasma adiponectin concentration by 60.17% and increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in skeletal muscle (P < 0.05). JLD administration increased levels of ADIPOR1 and ADIPOR2 by 1.48 and 1.29 respectively. Levels of genes involved in mitochondrial function and fat oxidation were increased. This study provides the molecular mechanism by which JLD ameliorates HFD-induced insulin resistance in rats. PMID:26064395

  1. Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle

    PubMed Central

    Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

    2015-01-01

    The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid content in skeletal muscle was measured. Genes and proteins of the AMPK signaling pathway were analyzed by real time RT-PCR and Western blot. Adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) and other genes involved in mitochondrial function and fat oxidation were analyzed by real time RT-PCR. Histological staining was also performed. JLD or pioglitazone administration ameliorated fasting plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), ALT, AST and non-esterified fatty acid (NEFA) (P < 0.05). Treatment with JLD or pioglitazone significantly reverted muscle lipid content (P < 0.05). JLD (1.5 g/kg) significantly increased plasma adiponectin concentration by 60.17% and increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in skeletal muscle (P < 0.05). JLD administration increased levels of ADIPOR1 and ADIPOR2 by 1.48 and 1.29 respectively. Levels of genes involved in mitochondrial function and fat oxidation were increased. This study provides the molecular mechanism by which JLD ameliorates HFD-induced insulin resistance in rats. PMID:26064395

  2. 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...

  3. Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice.

    PubMed

    Arumugam, Paritha I; Mullins, Eric S; Shanmukhappa, Shiva Kumar; Monia, Brett P; Loberg, Anastacia; Shaw, Maureen A; Rizvi, Tilat; Wansapura, Janaka; Degen, Jay L; Malik, Punam

    2015-10-01

    Sickle cell disease (SCD) results in vascular occlusions, chronic hemolytic anemia, and cumulative organ damage. A conspicuous feature of SCD is chronic inflammation and coagulation system activation. Thrombin (factor IIa [FIIa]) is both a central protease in hemostasis and a key modifier of inflammatory processes. To explore the hypothesis that reduced prothrombin (factor II [FII]) levels in SCD will limit vaso-occlusion, vasculopathy, and inflammation, we used 2 strategies to suppress FII in SCD mice. Weekly administration of FII antisense oligonucleotide "gapmer" to Berkeley SCD mice to selectively reduce circulating FII levels to ∼10% of normal for 15 weeks significantly diminished early mortality. More comprehensive, long-term comparative studies were done using mice with genetic diminution of circulating FII. Here, cohorts of FII(lox/-) mice (constitutively carrying ∼10% normal FII) and FII(WT) mice were tracked in parallel for a year following the imposition of SCD via hematopoietic stem cell transplantation. This genetically imposed suppression of FII levels resulted in an impressive reduction in inflammation (reduction in leukocytosis, thrombocytosis, and circulating interleukin-6 levels), reduced endothelial cell dysfunction (reduced endothelial activation and circulating soluble vascular cell adhesion molecule), and a significant improvement in SCD-associated end-organ damage (nephropathy, pulmonary hypertension, pulmonary inflammation, liver function, inflammatory infiltration, and microinfarctions). Notably, all of these benefits were achieved with a relatively modest 1.25-fold increase in prothrombin times, and in the absence of hemorrhagic complications. Taken together, these data establish that prothrombin is a powerful modifier of SCD-induced end-organ damage, and present a novel therapeutic target to ameliorate SCD pathologies. PMID:26286849

  4. Cysteamine treatment ameliorates alterations in GAD67 expression and spatial memory in heterozygous reeler mice

    PubMed Central

    Kutiyanawalla, Ammar; Promsote, Wanwisa; Terry, Alvin; Pillai, Anilkumar

    2011-01-01

    Brain derived neurotrophic factor (BDNF) signaling through its receptor, TrkB is known to regulate GABAergic function and glutamic acid decarboxylase (GAD) 67 expression in neurons. Alterations in BDNF signaling have been implicated in the pathophysiology of schizophrenia and as a result, they are a potential therapeutic target. Interestingly, heterozygous reeler mice (HRM) have decreased GAD67 expression in the frontal cortex and hippocampus and they exhibit many behavioral and neurochemical abnormalities similar to schizophrenia. In the present study, we evaluated the potential of cysteamine, a neuroprotective compound to improve the deficits in GAD67 expression and cognitive function in HRM. We found that cysteamine administration (150 mg/kg/day, through drinking water) for 30 days significantly ameliorated the decreases in GAD67, mature BDNF and full-length TrkB protein levels found in frontal cortex and hippocampus of HRM. A significant attenuation of the increased levels of truncated BDNF in frontal cortex and hippocampus, as well as truncated TrkB in frontal cortex of HRM was also observed following cysteamine treatment. In behavioral studies, HRM were impaired in a Y-maze spatial recognition memory task, but not in a spontaneous alternation task or a sensorimotor, prepulse inhibition (PPI) procedure. Cysteamine improved Y-maze spatial recognition in HRM to the level of wide-type controls and it improved PPI in both wild-type and HRM. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in GAD67 expression suggesting that TrkB signaling plays an important role in GAD67 regulation by cysteamine. PMID:21777509

  5. Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat.

    PubMed

    Prakash, Prem; Singh, Vishal; Jain, Manish; Rana, Minakshi; Khanna, Vivek; Barthwal, Manoj Kumar; Dikshit, Madhu

    2014-03-15

    High dietary fructose causes insulin resistance syndrome (IRS), primarily due to simultaneous induction of genes involved in glucose, lipid and mitochondrial oxidative metabolism. The present study evaluates effect of a hepatoprotective agent, silymarin (SYM) on fructose-induced metabolic abnormalities in the rat and also assessed the associated thrombotic complications. Wistar rats were kept on high fructose (HFr) diet throughout the 12-week study duration (9 weeks of HFr feeding and subsequently 3 weeks of HFr plus SYM oral administration [once daily]). SYM treatment significantly reduced the HFr diet-induced increase expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α/β, peroxisome proliferator-activated receptor (PPAR)-α, forkhead box protein O1 (FOXO1), sterol regulatory element binding protein (SREBP)-1c, liver X receptor (LXR)-β, fatty acid synthase (FAS) and PPARγ genes in rat liver. SYM also reduced HFr diet mediated increase in plasma triglycerides (TG), non-esterified fatty acids (NEFA), uric acid, malondialdehyde (MDA), total nitrite and pro-inflammatory cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-gamma [IFN-γ] and tumor necrosis factor [TNF]) levels. Moreover, SYM ameliorated HFr diet induced reduction in glucose utilization and endothelial dysfunction. Additionally, SYM significantly reduced platelet activation (adhesion and aggregation), prolonged ferric chloride-induced blood vessel occlusion time and protected against exacerbated myocardial ischemia reperfusion (MI-RP) injury. SYM treatment prevented HFr induced mRNA expression of hepatic PGC-1α/β and also its target transcription factors which was accompanied with recovery in insulin sensitivity and reduced propensity towards thrombotic complications and aggravated MI-RP injury. PMID:24486395

  6. Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice

    PubMed Central

    Arumugam, Paritha I.; Mullins, Eric S.; Shanmukhappa, Shiva Kumar; Monia, Brett P.; Loberg, Anastacia; Shaw, Maureen A.; Rizvi, Tilat; Wansapura, Janaka; Degen, Jay L.

    2015-01-01

    Sickle cell disease (SCD) results in vascular occlusions, chronic hemolytic anemia, and cumulative organ damage. A conspicuous feature of SCD is chronic inflammation and coagulation system activation. Thrombin (factor IIa [FIIa]) is both a central protease in hemostasis and a key modifier of inflammatory processes. To explore the hypothesis that reduced prothrombin (factor II [FII]) levels in SCD will limit vaso-occlusion, vasculopathy, and inflammation, we used 2 strategies to suppress FII in SCD mice. Weekly administration of FII antisense oligonucleotide “gapmer” to Berkeley SCD mice to selectively reduce circulating FII levels to ∼10% of normal for 15 weeks significantly diminished early mortality. More comprehensive, long-term comparative studies were done using mice with genetic diminution of circulating FII. Here, cohorts of FIIlox/− mice (constitutively carrying ∼10% normal FII) and FIIWT mice were tracked in parallel for a year following the imposition of SCD via hematopoietic stem cell transplantation. This genetically imposed suppression of FII levels resulted in an impressive reduction in inflammation (reduction in leukocytosis, thrombocytosis, and circulating interleukin-6 levels), reduced endothelial cell dysfunction (reduced endothelial activation and circulating soluble vascular cell adhesion molecule), and a significant improvement in SCD-associated end-organ damage (nephropathy, pulmonary hypertension, pulmonary inflammation, liver function, inflammatory infiltration, and microinfarctions). Notably, all of these benefits were achieved with a relatively modest 1.25-fold increase in prothrombin times, and in the absence of hemorrhagic complications. Taken together, these data establish that prothrombin is a powerful modifier of SCD-induced end-organ damage, and present a novel therapeutic target to ameliorate SCD pathologies. PMID:26286849

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. The amelioration effect of tranexamic acid in wrinkles induced by skin dryness.

    PubMed

    Hiramoto, Keiichi; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

    2016-05-01

    Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medical amino acid widely used as an anti-inflammatory and a whitening agent. This study examined the effect of tranexamic acid administration in wrinkle formation following skin dryness. We administered tranexamic acid (750mg/kg/day) orally for 20 consecutive days to Naruto Research Institute Otsuka Atrichia (NOA) mice, which naturally develop skin dryness. In these NOA mice, deterioration of transepidermal water loss (TEWL), generation of wrinkles, decrease of collagen type I, and increases in mast cell proliferation and tryptase and matrix metalloproteinase (MMP-1) release were observed. However, these symptoms were improved by tranexamic acid treatment. Moreover, the increase in the β-endorphin level in the blood and the expression of μ-opioid receptor on the surface of fibroblasts increased by tranexamic acid treatment. In addition, when the fibroblasts induced by tranexamic acid treatment were removed, the amelioration effect by tranexamic acid treatment was halved. On the other hand, tranexamic acid treated NOA mice and mast cell removal in tranexamic acid treated NOA mice did not result in changes in the wrinkle amelioration effect. Additionally, the amelioration effect of mast cell deficient NOA mice was half that of tranexamic acid treated NOA mice. These results indicate that tranexamic acid decreased the proliferation of mast cells and increases the proliferation of fibroblasts, subsequently improving wrinkles caused by skin dryness. PMID:27133035

  13. Ameliorants to immobilize Cd in rice paddy soils contaminated by abandoned metal mines in Korea.

    PubMed

    Ok, Yong Sik; Kim, Sung-Chul; Kim, Dong-Kuk; Skousen, Jeffrey G; Lee, Jin-Soo; Cheong, Young-Wook; Kim, Su-Jung; Yang, Jae E

    2011-01-01

    The cadmium (Cd) content of rice grain grown in metal-contaminated paddy soils near abandoned metal mines in South Korea was found to exceed safety guidelines (0.2 mg Cd kg⁻¹) set by the Korea Food and Drug Administration (KFDA). However, current remediation technologies for heavy metal-contaminated soils have limited application with respect to rice paddy soils. Laboratory and greenhouse experiments were conducted to assess the effects of amending contaminated rice paddy soils with zerovalent iron (ZVI), lime, humus, compost, and combinations of these compounds to immobilize Cd and inhibit Cd translocation to rice grain. Sequential extraction analysis revealed that treatment with the ameliorants induced a 50-90% decrease in the bioavailable Cd fractions when compared to the untreated control soil. When compared to the control, Cd uptake by rice was decreased in response to treatment with ZVI + humus (69%), lime (65%), ZVI + compost (61%), compost (46%), ZVI (42%), and humus (14%). In addition, ameliorants did not influence rice yield when compared to that of the control. Overall, the results of this study indicated that remediation technologies using ameliorants effectively reduce Cd bioavailability and uptake in contaminated rice paddy soils. PMID:21052787

  14. Melatonin ameliorates bisphenol A-induced biochemical toxicity in testicular mitochondria of mouse.

    PubMed

    Anjum, Sameya; Rahman, Shakilur; Kaur, Manpreet; Ahmad, Firoz; Rashid, Hina; Ansari, Rizwan Ahmad; Raisuddin, Sheikh

    2011-11-01

    Bisphenol A (BPA) is a monomer of polycarbonate plastic used to manufacture plastic baby bottles and lining of food cans. It has endocrine-disrupting potential and exerts both toxic and estrogenic effects on mammalian cells. We studied BPA-induced perturbation of mitochondrial marker enzymes in testes of Swiss albino mice and its amelioration by melatonin. Mice exposed to standardized dose of BPA (10 mg/kg body weight) orally for 14 days showed decrease in activities of marker mitochondrial enzymes such as succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, monoamine oxidase and NADH dehydrogenase. Besides, it also affected activities of antioxidant enzymes such as superoxide dismutase, glutathione reductase and glutathione peroxidase. BPA also caused lipid peroxidation (LPO) and decrease in reduced glutathione (GSH) content of mitochondria. Concomitant melatonin administration (10 mg/kg body weight; intraperitoneally for 14 days) lowered mitochondrial lipid peroxidation. It also restored the activity of mitochondrial marker enzymes and ameliorated decreased enzymatic and non-enzymatic antioxidants of mitochondria. These results demonstrate that melatonin has a potential role in ameliorating BPA-induced mitochondrial toxicity and the protection is due to its antioxidant property or by the direct free radical scavenging activity. PMID:21840368

  15. 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.

  16. Linagliptin Ameliorates Methylglyoxal-Induced Peritoneal Fibrosis in Mice

    PubMed Central

    Nagai, Takuo; Doi, Shigehiro; Nakashima, Ayumu; Irifuku, Taisuke; Sasaki, Kensuke; Ueno, Toshinori; Masaki, Takao

    2016-01-01

    Recent studies have reported increases of methylglyoxal (MGO) in peritoneal dialysis patients, and that MGO-mediated inflammation plays an important role in the development of peritoneal fibrosis through production of transforming growth factor-β1 (TGF-β1). Linagliptin, a dipeptidyl peptidase-4 inhibitor, exerts anti-inflammatory effects independent of blood glucose levels. In this study, we examined whether linagliptin suppresses MGO-induced peritoneal fibrosis in mice. Male C57/BL6 mice were divided into three groups: control, MGO injection plus saline, and MGO injection plus linagliptin (n = 6 per group). Peritoneal fibrosis was induced by daily intraperitoneal injection of saline containing 40 mmol/L MGO for 21 days. Saline was administered intraperitoneally to the control group. Linagliptin (10 mg/kg) or saline were administrated by once-daily oral gavage from 3 weeks before starting MGO injections. Immunohistochemical staining revealed that linagliptin suppressed expression of α-smooth muscle actin and fibroblast-specific protein-1, deposition of type I and III collagen, and macrophage (F4/80) infiltration. Peritoneal equilibration testing showed improved peritoneal functions in mice treated with linagliptin. Peritoneal injection of MGO increased plasma levels of glucagon-like peptide-1 (GLP-1) in mice, and a further increase was observed in linagliptin-treated mice. Although MGO increased plasma glucose levels, linagliptin did not decrease plasma glucose levels. Moreover, linagliptin reduced the TGF-β1 concentration in the peritoneal fluid of MGO-treated mice. GLP-1 receptor (GLP-1R) was expressed in monocytes/macrophages and linagliptin suppressed GLP-1R expression in MGO-injected mice. These results suggest that oral administration of linagliptin ameliorates MGO-induced peritoneal fibrosis. PMID:27513960

  17. 2-Deoxy-d-Glucose Ameliorates PKD Progression.

    PubMed

    Chiaravalli, Marco; Rowe, Isaline; Mannella, Valeria; Quilici, Giacomo; Canu, Tamara; Bianchi, Veronica; Gurgone, Antonia; Antunes, Sofia; D'Adamo, Patrizia; Esposito, Antonio; Musco, Giovanna; Boletta, Alessandra

    2016-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of ESRD for which there exists no approved therapy in the United States. Defective glucose metabolism has been identified as a feature of ADPKD, and inhibition of glycolysis using glucose analogs ameliorates aggressive PKD in preclinical models. Here, we investigated the effects of chronic treatment with low doses of the glucose analog 2-deoxy-d-glucose (2DG) on ADPKD progression in orthologous and slowly progressive murine models created by inducible inactivation of the Pkd1 gene postnatally. As previously reported, early inactivation (postnatal days 11 and 12) of Pkd1 resulted in PKD developing within weeks, whereas late inactivation (postnatal days 25-28) resulted in PKD developing in months. Irrespective of the timing of Pkd1 gene inactivation, cystic kidneys showed enhanced uptake of (13)C-glucose and conversion to (13)C-lactate. Administration of 2DG restored normal renal levels of the phosphorylated forms of AMP-activated protein kinase and its target acetyl-CoA carboxylase. Furthermore, 2DG greatly retarded disease progression in both model systems, reducing the increase in total kidney volume and cystic index and markedly reducing CD45-positive cell infiltration. Notably, chronic administration of low doses (100 mg/kg 5 days per week) of 2DG did not result in any obvious sign of toxicity as assessed by analysis of brain and heart histology as well as behavioral tests. Our data provide proof of principle support for the use of 2DG as a therapeutic strategy in ADPKD. PMID:26534924

  18. Whole Body Vibration Improves Insulin Resistance in db/db Mice: Amelioration of Lipid Accumulation and Oxidative Stress.

    PubMed

    Liu, Ying; Zhai, Mingming; Guo, Fan; Shi, Tengrui; Liu, Jiangzheng; Wang, Xin; Zhang, Xiaodi; Jing, Da; Hai, Chunxu

    2016-07-01

    Insulin resistance (IR) is the hallmark of type 2 diabetes mellitus (T2DM), which is one of the most important chronic noncommunicable diseases. Effective and feasible strategies to treat IR are still urgently needed. Previous research studies reported that whole body vibration (WBV) was beneficial for IR in clinical; however, its underlying mechanisms remains unknown. In the present study, db/db mice were treated with WBV administration 60 min/day for 12 weeks and the impaired insulin sensitivity was improved. Besides, liver steatosis was also ameliorated. Further explorations revealed that WBV could reduce the expression of SREBP1c and increase the expression of GSH-Px and consequently suppress oxidative stress. In conclusion, WBV attenuates oxidative stress to ameliorate liver steatosis and thus improves insulin resistance in db/db mice. Therefore, WBV administration is a promising treatment for individuals who suffered from central obesity and IR. PMID:26945578

  19. Menatetrenone ameliorates reduction in bone mineral density and bone strength in sciatic neurectomized rats.

    PubMed

    Iwasaki-Ishizuka, Yoshiko; Yamato, Hideyuki; Murayama, Hisashi; Abe, Masako; Takahashi, Kei; Kurokawa, Kiyoshi; Fukagawa, Masafumi; Ezawa, Ikuko

    2003-08-01

    Vitamin K2 (menaquinone) acts on the bone metabolism. Menatetrenon (MK-4) is a vitamin K2 homologue that has been used as a therapeutic agent for osteoporosis in Japan. Rat models of immobilization induced by sciatic neurectomy are characterized by transiently increased bone resorption and sustained reduction in bone formation. Using such a rat model, we investigated the efficacy of MK-4 on bone loss. Male Sprague-Dawley rats were subjected to unilateral sciatic neurectomy and administered MK-4 for 28 d beginning day 21 after operation. The effect of MK-4 on the immobilized bone was assessed by measuring the bone mineral density of the femur, breaking force of the femoral diaphysis, and bone histomorphometry in tibial diaphysis. The BMD on both the femoral distal metaphysis and diaphysis was reduced by sciatic neurectomy. The administration of MK-4 ameliorated this reduction in a dose-dependent manner. The administration of 30 mg/kg MK-4 ameliorated the reduction in bone strength. An improvement in bone formation was observed following the administration of MK-4. These results suggest that MK-4 has a therapeutic potential for immobilization-induced osteopenia. PMID:14598912

  20. Evaluation of ameliorative potential of supranutritional selenium on enrofloxacin-induced testicular toxicity.

    PubMed

    Rungsung, Soya; Khan, Adil Mehraj; Sood, Naresh Kumar; Rampal, Satyavan; Singh Saini, Simrat Pal

    2016-05-25

    The study was designed to assess the ameliorative potential of selenium (Se) on enrofloxacin-induced testicular toxicity in rats. There was a significant decrease in body weight and non-significant decrease in mean testicular weight of enrofloxacin treated rats. In enrofloxacin treated rats, total sperm count and viability decreased where as sperm abnormalities increased. Testicular histopathology revealed dose dependent dysregulation of spermatogenesis and presence of necrotic debris in seminiferous tubules which was marginally improved with Se. Enrofloxacin also produced a dose dependent decrease in testosterone level. The activity of testicular antioxidant enzymes decreased where as lipid peroxidation increased in a dose-dependent manner. Se supplementation partially restored oxidative stress and sperm damage and did not affect the plasma concentrations of enrofloxacin or ciprofloxacain. The results indicate that enrofloxacin produces a dose-dependent testicular toxicity in rats that is moderately ameliorated with supranutritional Se. PMID:27083143

  1. Anti‑inflammatory effects of Panax notoginseng saponins ameliorate acute lung injury induced by oleic acid and lipopolysaccharide in rats.

    PubMed

    Chen, Yu-Qing; Rong, Ling; Qiao, Jian-Ou

    2014-09-01

    This study investigated the effect of Panax notoginseng saponins (PNS) on acute lung injury (ALI) induced by oleic acid (OA) and lipopolysaccharide (LPS). A total of 28 Wistar rats were divided into four groups: sham; sham + PNS; OA‑LPS‑induced ALI and ALI + PNS. Lung tissue histology, lung wet‑to‑dry (W/D) weight ratio, extravascular lung water (EVLW) and epithelial sodium channel α (αENaC) mRNA and protein expression were examined. In addition, levels of inflammatory cytokines, including tumor necrosis factor α (TNF‑α), interleukin (IL)‑6 and IL‑10, as well as total leukocyte and neutrophil counts, were analyzed in rat bronchoalveolar lavage fluid (BALF) and serum. ALI + PNS rats were observed to exhibit significantly lower pulmonary parenchymal damage and EVLW compared with ALI rats. Furthermore, total leukocyte and neutrophil counts, and levels of inflammatory cytokines were significantly decreased following PNS administration in ALI rats. In addition, the decrease in αENaC mRNA and protein expression observed in the lung tissue of ALI rats was partially restored following PNS treatment. PNS treatment was demonstrated to ameliorate OA‑LPS‑induced ALI, potentially through restoration of αENaC mRNA and protein expression and through PNS‑induced anti‑inflammatory effects. PMID:24938646

  2. 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

  3. Ameliorative Effects of Acacia Honey against Sodium Arsenite-Induced Oxidative Stress in Some Viscera of Male Wistar Albino Rats

    PubMed Central

    Aliyu, Muhammad; Ibrahim, Sani; Inuwa, Hajiya M.; Sallau, Abdullahi B.; Abbas, Olagunju; Aimola, Idowu A.; Habila, Nathan; Uche, Ndidi S.

    2013-01-01

    Cancer is a leading cause of death worldwide and its development is frequently associated with oxidative stress-induced by carcinogens such as arsenicals. Most foods are basically health-promoting or disease-preventing and a typical example of such type is honey. This study was undertaken to investigate the ameliorative effects of Acacia honey on sodium arsenite-induced oxidative stress in the heart, lung and kidney tissues of male Wistar rats. Male Wistar albino rats divided into four groups of five rats each were administered distilled water, Acacia honey (20%), sodium arsenite (5 mg/kg body weight), Acacia honey, and sodium arsenite daily for one week. They were sacrificed anesthetically using 60 mg/kg sodium pentothal. The tissues were used for the assessment of glutathione peroxidase, catalase, and superoxide dismutase activities, protein content and lipid peroxidation. Sodium arsenite significantly (P < 0.05) suppressed the glutathione peroxidase, catalase, superoxide dismutase activities with simultaneous induction of lipid peroxidation. Administration of Acacia honey significantly increased (P < 0.05) glutathione peroxidase, catalase, and superoxide dismutase activities with concomitant suppression of lipid peroxidation as evident by the decrease in malondialdehyde level. From the results obtained, Acacia honey mitigates sodium arsenite induced-oxidative stress in male Wistar albino rats, which suggest that it may attenuate oxidative stress implicated in chemical carcinogenesis. PMID:24368942

  4. The Significance of National Association for the Education of Young Children Accreditation in Elevating Quality of Early Childhood Education: Administrators', Teachers', and Parents' Beliefs about Accreditation and Its Process

    ERIC Educational Resources Information Center

    Vardanyan, Kristine

    2013-01-01

    The following is a doctoral dissertation that studied administrators', teachers', and parents' perceptions and attitudes related to an early childhood center/preschool accreditation experience. A qualitative case study of one preschool center focused on the influence that the decision to pursue accreditation and implement the National Association…

  5. Chronic melatonin administration mitigates behavioral dysfunction induced by γ-irradiation.

    PubMed

    Haridas, Seenu; Kumar, Mayank; Manda, Kailash

    2012-11-01

    Melatonin, a 'hormone of darkness,' has been reported to play a role in a wide variety of physiological responses including reproduction, circadian homeostasis, sleep, retinal neuromodulation, and vasomotor responses. Our recent studies reported a prophylactic effect of exogenous melatonin against radiation-induced neurocognitive changes. However, there is no reported evidence for a mitigating effect of chronic melatonin administration against radiation-induced behavioral alterations. In the present study, C57BL/6 mice were given either whole day chronic melatonin administration (CMA) or chronic night-time melatonin administration (CNMA) by a low dose of melatonin in drinking water for a period of 2 weeks and 1 month following exposure to 6 Gy of γ-radiation. Various behavioral endpoints, such as locomotor activities, gross behavioral traits, basal anxiety level, and depressive tendencies were scored at different time points. Radiation exposure significantly impaired gross behavioral traits as observed in the open field exploratory paradigms and forced swim test. Both the CMA and CNMA significantly ameliorated the radiation-induced changes in exploratory tendencies, risk-taking behavior and gross behavior traits, such as rearing and grooming. Melatonin administration afforded anxiolytic function against radiation in terms of center exploration tendencies. The radiation-induced augmentation of immobility time in the forced swim test, indices of depression-like behavior was also inhibited by chronic melatonin administration. The results demonstrated the mitigating effect of chronic melatonin administration on radiation-induced affective disorders in mice. PMID:23026539

  6. EPA-enriched phospholipids ameliorate cancer-associated cachexia mainly via inhibiting lipolysis.

    PubMed

    Du, Lei; Yang, Yu-Hong; Wang, Yu-Ming; Xue, Chang-Hu; Kurihara, Hideyuki; Takahashi, Koretaro

    2015-12-01

    Excessive loss of fat mass is considered as a key feature of body weight loss in cancer-associated cachexia (CAC). It affects the efficacy and tolerability of cancer therapy and reduces the quality and length of cancer patients' lives. The aim of the present study was to evaluate the effects of EPA-enriched phospholipids (EPA-PL) derived from starfish Asterias amurensis on cachectic weight loss in mice bearing S180 ascitic tumor, and TNF-α-stimulated lipolysis in 3T3-L1 adipocytes and to elucidate the possible mechanisms involved. Our findings revealed that oral administration of EPA-PL at 100 mg per kg body weight (BW) per day for 14 days prevented body weight loss in CAC mice by preserving the white adipose tissue (WAT) mass. We found that serum levels of nonesterified fatty acid (NEFA) and pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin (IL)-6 increased in CAC mice but decreased significantly after oral treatment of EPA-PL. In addition, EPA-PL treatment also suppressed the overexpression of several key lipolytic factors and raised the mRNA levels of some adipogenic factors in the WAT of CAC mice. Moreover, treatment of EPA-PL (200 and 400 μM) markedly inhibited TNF-α-stimulated lipolysis in adipocytes. Furthermore, the antilipolytic effects of EPA-PL were stimulated by the extracellular signal-regulated kinase 1/2 (ERK 1/2) inhibitor PD 98059 and blocked via the AMP-activated protein kinase (AMPK) inhibitor compound C and the phosphoinositide-3-kinase (PI3K) inhibitor LY 294002. Taken together, these data suggest that the dietary EPA-PL ameliorates CAC mainly via inhibiting lipolysis and at least in part for recovering the function of adipogenesis. PMID:26373883

  7. Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse

    PubMed Central

    Kumari, Mrinalini; Singh, Poonam

    2015-01-01

    Objective: The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. Materials and Methods: Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. Results: Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. Conclusion: The fruit extract of TT ameliorates the MTZ-induced alterations in the testis. PMID:26069369

  8. Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.

    PubMed

    Wyrwoll, Caitlin S; Noble, June; Thomson, Adrian; Tesic, Dijana; Miller, Mark R; Rog-Zielinska, Eva A; Moran, Carmel M; Seckl, Jonathan R; Chapman, Karen E; Holmes, Megan C

    2016-05-31

    Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction. PMID:27185937

  9. Hydrogen-rich saline ameliorates the severity of L-arginine-induced acute pancreatitis in rats

    SciTech Connect

    Chen, Han; Sun, Yan Ping; Li, Yang; Liu, Wen Wu; Xiang, Hong Gang; Fan, Lie Ying; Sun, Qiang; Xu, Xin Yun; Cai, Jian Mei; Ruan, Can Ping; Su, Ning; Yan, Rong Lin; Sun, Xue Jun; Wang, Qiang

    2010-03-05

    Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the L-arginine (L-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of L-Arg, each at concentrations of 250 mg/100 g body weight, with an interval of 1 h. Hydrogen-rich saline (>0.6 mM, 6 ml/kg) or saline (6 ml/kg) was administered, respectively, via tail vein 15 min after each L-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-{kappa}B) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of L-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-{kappa}B activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-{kappa}B activation and to promote acinar cell proliferation.

  10. A novel NF-κB inhibitor, DHMEQ, ameliorates pristane-induced lupus in mice.

    PubMed

    Qu, Huiqing; Bian, Weihua; Xu, Yanyan

    2014-07-01

    Nuclear factor (NF)-κB is strongly associated with the development of immune regulation and inflammation. The aim of the present study was to identify whether a NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), ameliorates systemic lupus erythematosus (SLE) in a pristane-induced mouse model. SLE was induced in 8-week-old female BALB/c mice by the injection of 0.5 ml pristane. The therapeutic effect of 12 mg/kg DHMEQ on the pristane-induced BALB/c mouse model of lupus was investigated to elucidate the effects on SLE. The intraperitoneal administration of DHMEQ three times per week was initiated when the mice were 16 weeks-old (8 weeks following the pristane injection) and the treatment was continued for 16 weeks. Serum IgG autoantibodies against nucleosomes, dsDNA and histones were detected at weeks 8, 16 and 32. In addition, the expression levels of interleukin (IL)-1β, 6 and 17, as well as tumor necrosis factor (TNF)-α, were analyzed at week 32. Renal lesions were also observed. DHMEQ was shown to antagonize the increasing levels of anti-nucleosome, anti-dsDNA and anti-histone autoantibodies, as well as the increasing levels of IL-1β, 6 and 17 and TNF-α. In addition, DHMEQ reduced the number of renal lesions caused by pristane, as reflected by milder proteinuria and reduced renal pathology. The renal expression levels of phosphorylated-p38 mitogen-activated protein kinase (MAPK), phosphorylated-c-Jun N-terminal kinase (JNK) and NF-κB p65 were significantly downregulated. Therefore, the results of the present study indicate that DHMEQ has a beneficial effect on pristane-induced lupus through regulating cytokine levels and the MAPK/JNK/NF-κB signaling pathway. PMID:24944605

  11. A novel NF-κB inhibitor, DHMEQ, ameliorates pristane-induced lupus in mice

    PubMed Central

    QU, HUIQING; BIAN, WEIHUA; XU, YANYAN

    2014-01-01

    Nuclear factor (NF)-κB is strongly associated with the development of immune regulation and inflammation. The aim of the present study was to identify whether a NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), ameliorates systemic lupus erythematosus (SLE) in a pristane-induced mouse model. SLE was induced in 8-week-old female BALB/c mice by the injection of 0.5 ml pristane. The therapeutic effect of 12 mg/kg DHMEQ on the pristane-induced BALB/c mouse model of lupus was investigated to elucidate the effects on SLE. The intraperitoneal administration of DHMEQ three times per week was initiated when the mice were 16 weeks-old (8 weeks following the pristane injection) and the treatment was continued for 16 weeks. Serum IgG autoantibodies against nucleosomes, dsDNA and histones were detected at weeks 8, 16 and 32. In addition, the expression levels of interleukin (IL)-1β, 6 and 17, as well as tumor necrosis factor (TNF)-α, were analyzed at week 32. Renal lesions were also observed. DHMEQ was shown to antagonize the increasing levels of anti-nucleosome, anti-dsDNA and anti-histone autoantibodies, as well as the increasing levels of IL-1β, 6 and 17 and TNF-α. In addition, DHMEQ reduced the number of renal lesions caused by pristane, as reflected by milder proteinuria and reduced renal pathology. The renal expression levels of phosphorylated-p38 mitogen-activated protein kinase (MAPK), phosphorylated-c-Jun N-terminal kinase (JNK) and NF-κB p65 were significantly downregulated. Therefore, the results of the present study indicate that DHMEQ has a beneficial effect on pristane-induced lupus through regulating cytokine levels and the MAPK/JNK/NF-κB signaling pathway. PMID:24944605

  12. Molecular and Histopathological Study on the Ameliorative Effects of Curcumin Against Lead Acetate-Induced Hepatotoxicity and Nephrototoxicity in Wistar Rats.

    PubMed

    Soliman, Mohamed M; Baiomy, Ahmed A; Yassin, Magdy H

    2015-09-01

    Lead (Pb(2+)) toxicity is the most common form of heavy metal intoxication in humans and animals. Therefore, the current study was conducted to evaluate the potential ameliorative effects of curcumin on lead acetate (LA)-induced deleterious effects in the liver and kidney. Forty male Wistar rats were divided into four equal groups; first group was used as a control and given both corn oil orally and vehicle of lead acetate intraperitoneally (i.p). Groups from 2-4 were treated with lead acetate (LA; 50 mg/kg BW i.p), curcumin (200 mg/kg BW orally), and curcumin plus lead acetate, respectively. Curcumin was administered 3 weeks before LA injection for 7 days. Pb(2+)-intoxicated rats have higher Pb(2+) levels compared to other treated groups. Results revealed that lead acetate significantly increased the serum levels of hepatic transaminases (GPT and GOT), urea and creatinine, while albumin was significantly decreased. In parallel, serum IgG, IgM, and IgA were significantly decreased in LA-injected rats. LA groups showed decrease in messenger RNA (mRNA) expression of catalase, SOD, GST, GPx, and alpha-1 acid glycoprotein (AGP), while the gene expression of desmin, vimentin, transforming growth factor-β1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), and alpha-2 macroglobulin (α-2M) was increased. Prior and coadministration of curcumin with LA for 7 days significantly improved the ameliorated changes in liver and kidney, immunoglobulins, and mRNA expression. Moreover, curcumin ameliorated LA-induced congestion of hepatic and renal blood vessels and decreased fibrous tissue proliferation and necrosis of hepatocytes. In the kidney, LA-induced degeneration in tubular epithelium and intraluminal hyaline casts and prior curcumin administration restored normal renal structure with mild congestion of renal blood vessels. The results clarify the potential of curcumin to counteract the immunosuppressive alteration in gene expression as well as hepatic and renal

  13. Role of beta-carotene in ameliorating the cadmium-induced oxidative stress in rat brain and testis.

    PubMed

    El-Missiry, M A; Shalaby, F

    2000-01-01

    The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with beta-carotene was investigated. Adult male rats were intragastrically administered 2 mg CdCl2/kg body weight three times a week intragastrically for 3 and 6 weeks. Brain and testicular thiobarbituric acid reactive substances (TBARS) was elevated after 3 and 6 weeks of Cd administration, indicating increased lipid peroxidation (LPO) and oxidative stress. Cellular damage was indicated by inhibition of adenosine triphosphatase (ATPase) activity and increased lactate dehydrogenase (LDH) activity in brain and testicular tissues. Chronic Cd administration resulted in a decline in glutathione (GSH) content and a decrease of superoxide dismutase (SOD) and glutathione S-transferase (GST) activity in both organs. Administration of beta-carotene (250 IU/kg i.g.) concurrent with Cd ameliorated Cd-induced LPO. The brain and testicular antioxidants, SOD, GST, and GSH, decreased by Cd alone, were restored by beta-carotene cotreatment. Concurrent treatment with beta-carotene also ameliorated the decrease in ATPase activity and the increase in LDH activity in brain and testis of Cd-treated rats, indicating a prophylactic action of beta-carotene on Cd toxicity. Therefore, the results indicate that the nutritional antioxidant beta-carotene ameliorated oxidative stress and the loss of cellular antioxidants and suggest that beta-carotene may control Cd-induced brain and testicular toxicity. PMID:10969995

  14. Aqueous Extract of Allium sativum (Linn.) Bulbs Ameliorated Pituitary-Testicular Injury and Dysfunction in Wistar Rats with Pb-Induced Reproductive Disturbances

    PubMed Central

    Ayoka, Abiodun O.; Ademoye, Aderonke K.; Imafidon, Christian E.; Ojo, Esther O.; Oladele, Ayowole A.

    2016-01-01

    AIM: To determine the effects of aqueous extract of Allium sativum bulbs (AEASAB) on pituitary-testicular injury and dysfunction in Wistar rats with lead-induced reproductive disturbances. MATERIALS AND METHODS: Male Wistar rats were divided into 7 groups such that the control group received propylene glycol at 0.2 ml/100 g intraperitoneally for 10 consecutive days, the toxic group received lead (Pb) alone at 15 mg/kg/day via intraperitoneal route for 10 days while the treatment groups were pretreated with lead as the toxic group after which they received graded doses of the extract at 50, 100 and 200 mg/kg/day via oral route for 28 days. RESULTS: Pb administration induced significant deleterious alterations in the antioxidant status of the brain and testis, sperm characterization (counts, motility and viability) as well as reproductive hormones (FSH, LH and testosterone) of exposed rats (p < 0.05). These were significantly reversed in the AEASAB-treated groups (p < 0.05). Also, there was marked improvement in the Pb-induced vascular congestion and cellular loss in the pituitary while the observed Pb-induced severe testicular vacuolation was significantly reversed in the representative photomicrographs, following administration of the extract. CONCLUSION: AEASAB treatment ameliorated the pituitary-testicular injury and dysfunction in Wistar rats with Pb-Induced reproductive disturbances. PMID:27335588

  15. Intravenous Mycobacterium Bovis Bacillus Calmette-Guérin Ameliorates Nonalcoholic Fatty Liver Disease in Obese, Diabetic ob/ob Mice

    PubMed Central

    Inafuku, Masashi; Matsuzaki, Goro; Oku, Hirosuke

    2015-01-01

    Inflammation and immune response profoundly influence metabolic syndrome and fatty acid metabolism. To analyze influence of systemic inflammatory response to metabolic syndrome, we inoculated an attenuated vaccine strain of Mycobacterium bovis Bacillus Calmette–Guérin (BCG) into leptin-deficient ob/ob mice. BCG administration significantly decreased epididymal white adipose tissue weight, serum insulin levels, and a homeostasis model assessment of insulin resistance. Serum high molecular weight (HMW) adiponectin level and HMW/total adiponectin ratio of the BCG treated mice were significantly higher than those of control mice. Hepatic triglyceride accumulation and macrovesicular steatosis were markedly alleviated, and the enzymatic activities and mRNA levels of lipogenic-related genes in liver were significantly decreased in the BCG injected mice. We also exposed human hepatocellular carcinoma HepG2 cells to high levels of palmitate, which enhanced endoplasmic reticulum stress-related gene expression and impaired insulin-stimulated Akt phosphorylation (Ser473). BCG treatment ameliorated both of these detrimental events. The present study therefore suggested that BCG administration suppressed development of nonalcoholic fatty liver disease, at least partly, by alleviating fatty acid-induced insulin resistance in the liver. PMID:26039731

  16. Administrative Synergy

    ERIC Educational Resources Information Center

    Hewitt, Kimberly Kappler; Weckstein, Daniel K.

    2012-01-01

    One of the biggest obstacles to overcome in creating and sustaining an administrative professional learning community (PLC) is time. Administrators are constantly deluged by the tyranny of the urgent. It is a Herculean task to carve out time for PLCs, but it is imperative to do so. In this article, the authors describe how an administrative PLC…

  17. Neurobiological and pharmacological validity of curcumin in ameliorating memory performance of senescence-accelerated mice.

    PubMed

    Sun, Chen Y; Qi, Shuang S; Zhou, Peng; Cui, Huai R; Chen, Shi X; Dai, Kai Y; Tang, Mao L

    2013-04-01

    The senescence-accelerated mouse prone 8 (SAMP8 mice) is known as a neurodegenerative model and may show age-related deficits of cognition. Curcumin, a major active component of spic turmeric, could increase the capacity of learning and memory in the aged rat. However, it is not known whether curcumin could improve cognitive deficits in SAMP8 mice. The present study was undertaken to evaluate the effect of curcumin on the learning and memory of SAMP8 mice and its possible mechanisms. Subjects were randomly divided into four groups: SAMR1 mice, SAMP8 mice and two SAMP8 mice groups treated, intragastrically, with curcumin at the dose of 20 and 50mg/kg per day, respectively. After 25days, spatial memory, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, p-calcium/calmodulin-dependent kinase II (p-CaMKII) and p-N-methyl-d-aspartate receptor subunit 1 (p-NMDAR1) expression in the hippocampus of mice were examined by using the Morris water maze, biochemical analysis, immunohistochemistry and Western blot. Compared with SAMR1 mice, SAMP8 mice had longer escape latency, higher MDA content, lower SOD activity in the hippocampus, and lower intensity of p-CaMKII in the stratum lucidum of hippocampal CA3 and p-NMDAR1 expression in the hippocampal membrane fraction. Both 20 and 50mg/kg curcumin administration significantly shortened the escape latencies and decreased the hippocampal MDA content in the SAMP8 mice. 50mg/kg curcumin administration significantly ameliorated the hippocampal SOD activity, and increased the intensity of p-CaMKII in the stratum lucidum of hippocampal CA3 and p-NMDAR1 expression in the hippocampal membrane fraction of the SAMP8 mice. The present study demonstrated that curcumin treatment could attenuate cognitive deficits of SAMP8 mice in a dose-dependent manner by decreasing the oxidative stress and improving the expression of p-CaMKII and p-NMDAR1 in the hippocampus. Thus treatment with curcumin may have a potential therapeutic agent

  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. Synergistic effect of Pseudomonas putida and Bacillus amyloliquefaciens ameliorates drought stress in chickpea (Cicer arietinum L.)

    PubMed Central

    Kumar, Manoj; Mishra, Sankalp; Dixit, Vijaykant; Kumar, Manoj; Agarwal, Lalit; Chauhan, Puneet Singh; Nautiyal, Chandra Shekhar

    2016-01-01

    Two plant growth promoting rhizobacteria (PGPR) Pseudomonas putida NBRIRA and Bacillus amyloliquefaciens NBRISN13 with ability to tolerate abiotic stress along with multiple PGP traits like ACC deaminase activity, minerals solubilisation, hormones production, biofilm formation, siderophore activity were evaluated for their synergistic effect to ameliorate drought stress in chickpea. Earlier we have reported both the strains individually for their PGP attributes and stress amelioration in host plants. The present study explains in detail the possibilities and benefits of utilizing these 2 PGPR in consortium for improving the chickpea growth under control and drought stressed condition. In vitro results clearly demonstrate that both the PGPR strains are compatible to each other and their synergistic growth enhances the PGP attributes. Greenhouse experiments were conducted to evaluate the effect of inoculation of both strains individually and consortia in drought tolerant and sensitive cultivars (BG362 and P1003). The growth parameters were observed significantly higher in consortium as compared to individual PGPR. Colonization of both PGPR in chickpea rhizosphere has been visualized by using gfp labeling. Apart from growth parameters, defense enzymes, soil enzymes and microbial diversity were significantly modulated in individually PGPR and in consortia inoculated plants. Negative effects of drought stress has been ameliorated and apparently seen by higher biomass and reversal of stress indicators in chickpea cultivars treated with PGPR individually or in consortia. Findings from the present study demonstrate that synergistic application has better potential to improve plant growth promotion under drought stress conditions. PMID:26362119

  20. Synergistic effect of Pseudomonas putida and Bacillus amyloliquefaciens ameliorates drought stress in chickpea (Cicer arietinum L.).

    PubMed

    Kumar, Manoj; Mishra, Sankalp; Dixit, Vijaykant; Kumar, Manoj; Agarwal, Lalit; Chauhan, Puneet Singh; Nautiyal, Chandra Shekhar

    2016-01-01

    Two plant growth promoting rhizobacteria (PGPR) Pseudomonas putida NBRIRA and Bacillus amyloliquefaciens NBRISN13 with ability to tolerate abiotic stress along with multiple PGP traits like ACC deaminase activity, minerals solubilisation, hormones production, biofilm formation, siderophore activity were evaluated for their synergistic effect to ameliorate drought stress in chickpea. Earlier we have reported both the strains individually for their PGP attributes and stress amelioration in host plants. The present study explains in detail the possibilities and benefits of utilizing these 2 PGPR in consortium for improving the chickpea growth under control and drought stressed condition. In vitro results clearly demonstrate that both the PGPR strains are compatible to each other and their synergistic growth enhances the PGP attributes. Greenhouse experiments were conducted to evaluate the effect of inoculation of both strains individually and consortia in drought tolerant and sensitive cultivars (BG362 and P1003). The growth parameters were observed significantly higher in consortium as compared to individual PGPR. Colonization of both PGPR in chickpea rhizosphere has been visualized by using gfp labeling. Apart from growth parameters, defense enzymes, soil enzymes and microbial diversity were significantly modulated in individually PGPR and in consortia inoculated plants. Negative effects of drought stress has been ameliorated and apparently seen by higher biomass and reversal of stress indicators in chickpea cultivars treated with PGPR individually or in consortia. Findings from the present study demonstrate that synergistic application has better potential to improve plant growth promotion under drought stress conditions. PMID:26362119

  1. Ginger and alpha lipoic acid ameliorate age-related ultrastructural changes in rat liver.

    PubMed

    Mahmoud, Y I; Hegazy, H G

    2016-01-01

    Because of the important role that oxidative stress is thought to play in the aging process, antioxidants could be candidates for preventing its related pathologies. We investigated the ameliorative effects of two antioxidant supplements, ginger and alpha lipoic acid (ALA), on hepatic ultrastructural alterations in old rats. Livers of young (4 months) and old (24 months) Wistar rats were studied using transmission electron microscopy. Livers of old rats showed sinusoidal collapse and congestion, endothelial thickening and defenestration, and inconsistent perisinusoidal extracellular matrix deposition. Aged hepatocytes were characterized by hypertrophy, cytoplasmic vacuolization and a significant increase in the volume densities of the nuclei, mitochondria and dense bodies. Lipofuscin accumulation and decreased microvilli in bile canaliculi and space of Disse also were observed. The adverse alterations were ameliorated significantly by both ginger and ALA supplementation; ALA was more effective than ginger. Ginger and ALA appear to be promising anti-aging agents based on their amelioration of ultrastructural alterations in livers of old rats. PMID:26528730

  2. Possible ameliorative effect of breastfeeding and the uptake of human colostrum against coeliac disease in autistic rats

    PubMed Central

    Selim, Manar E; Al-Ayadhi, Laila Y

    2013-01-01

    AIM: To examine the possible ameliorative effect of breastfeeding and the uptake of human colostrum against coeliac disease in autistic rats. METHODS: Female rats were fed a standard diet and received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception. In study 1, neonatal rats were randomly subjected to blood tests to investigate autism. In study 2, the 1st group was fed by the mother after an injection of interferon-γ (IFN-γ) and administration of gliadin. The pups in the 2nd group were prevented from accessing maternal milk, injected IFN-γ, administered gliadin, and hand-fed human colostrum. The normal littermates fed by the table mothers were injected with physiological saline and served as normal controls in this study. RESULTS: The protein concentration was higher in group 2 than in group 1 in the duodenum (161.6 ± 9 and 135.4 ± 7 mg/g of tissue, respectively, P < 0.01). A significant increase (P < 0.001) in body weight was detected in human colostrum-treated pups on post natal day (PND) 7 and 21 vs suckling pups in group 1. A delay in eye opening was noticed in the treated rats in group 1 on PND 13 compared with the control group and group 2. Administration of a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception resulted in significantly reduced calcium and vitamin D levels in study 1 compared with the control groups (P < 0.001). However, human colostrum uptake inhibited increases in the level of transglutaminase antibody in autistic pups with coeliac disease. CONCLUSION: The effects of early-life nutrition and human colostrum on the functional maturation of the duodenal villi in autistic rats with coeliac disease that might limit or prevent the coeliac risk with autism. PMID:23745030

  3. Celastrol Ameliorates Ulcerative Colitis-Related Colorectal Cancer in Mice via Suppressing Inflammatory Responses and Epithelial-Mesenchymal Transition

    PubMed Central

    Lin, Lianjie; Sun, Yan; Wang, Dongxu; Zheng, Shihang; Zhang, Jing; Zheng, Changqing

    2016-01-01

    Celastrol, also named as tripterine, is a pharmacologically active ingredient extracted from the root of traditional Chinese herb Tripterygium wilfordii Hook F with potent anti-inflammatory and anti-tumor activities. In the present study, we investigated the effects of celastrol on ulcerative colitis-related colorectal cancer (UC-CRC) as well as CRC in vivo and in vitro and explored its underlying mechanisms. UC-CRC model was induced in C57BL/6 mice by administration of azoxymethane (AOM) and dextran sodium sulfate (DSS). Colonic tumor xenograft models were developed in BALB/c-nu mice by subcutaneous injection with HCT116 and HT-29 cells. Intragastric administration of celastrol (2 mg/kg/d) for 14 weeks significantly increased the survival ratio and reduced the multiplicity of colonic neoplasms compared with AOM/DSS model mice. Mechanically, celastrol treatment significantly prevented AOM/DSS-induced up-regulation of expression levels of oncologic markers including mutated p53 and phospho-p53, β-catenin and proliferating cell nuclear antigen (PCNA). In addition, treatment with celastrol inhibited inflammatory responses, as indicated by the decrease of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, down-regulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and inactivation of nuclear factor κB (NF-κB). Moreover, celastrol obviously suppressed epithelial-mesenchymal transition (EMT) through up-regulating E-cadherin and down-regulating N-cadherin, Vimentin and Snail. Additionally, we also demonstrated that celastrol inhibited human CRC cell proliferation and attenuated colonic xenograft tumor growth via reversing EMT. Taken together, celastrol could effectively ameliorate UC-CRC by suppressing inflammatory responses and EMT, suggesting a potential drug candidate for UC-CRC therapy. PMID:26793111

  4. 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

  5. Myricetin protects against diet-induced obesity and ameliorates oxidative stress in C57BL/6 mice*

    PubMed Central

    Su, Hong-ming; Feng, Li-na; Zheng, Xiao-dong; Chen, Wei

    2016-01-01

    Background: Myricetin is a naturally occurring antioxidant commonly found in various plants. However, little information is available with respect to its direct anti-obesity effects. Objective: This study was undertaken to investigate the effect of myricetin on high-fat diet (HFD)-induced obesity in C57BL/6 mice. Results: Administration of myricetin dramatically reduced the body weight of diet-induced obese mice compared with solely HFD-induced mice. Several parameters related to obesity including serum glucose, triglyceride, and cholesterol were significantly decreased in myricetin-treated mice. Moreover, obesity-associated oxidative stress (glutathione peroxidase (GPX) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA)) and inflammation (tumor necrosis factor-α (TNF-α)) were ameliorated in myricetin-treated mice. Further investigation revealed that the protective effect of myricetin against HFD-induced obesity in mice appeared to be partially mediated through the down-regulation of mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and lipogenic transcription factor sterol regulatory element-binding protein 1c (SREBP-1c). Conclusions: Consumption of myricetin may help to prevent obesity and obesity-related metabolic complications. PMID:27256677

  6. Bacopaside I ameliorates cognitive impairment in APP/PS1 mice via immune-mediated clearance of β-amyloid

    PubMed Central

    Li, Yuanyuan; Yuan, Xing; Shen, Yunheng; Zhao, Jing; Yue, Rongcai; Liu, Fang; He, Weiwei; Wang, Rui; Shan, Lei; Zhang, Weidong

    2016-01-01

    Standardized extracts of Bacopa monniera (BME) have been shown to exert a neuroprotective effect against mental diseases, such as depression, anxiety and Alzheimer's disease (AD), in chronic administration studies. However, its mechanism of action has remained unclear. In this study, we evaluated the therapeutic effect of Bacopaside I (BS-I), a major triterpenoid saponin of BME, on the cognitive impairment and neuropathology in APP/PS1 transgenic mice and explored the possible mechanism from a biological systems perspective. We found that BS-I treatment significantly ameliorated learning deficits, improved long-term spatial memory, and reduced plaque load in APP/PS1 mice. We constructed BS-I's therapeutic effect network by mapping the nodes onto the protein-protein interaction (PPI) network constructed according to their functional categories based on genomic and proteomic data. Because many of the top enrichment categories related to the processes of the immune system and phagocytosis were detected, we proposed that BS-I promotes amyloid clearance via the induction of a suitable degree of innate immune stimulation and phagocytosis. Our research may help to clarify the neuroprotective effect of BME and indicated that natural saponins target the immune system, which may offer new research avenues to discover novel treatments for AD. PMID:26946062

  7. Tetrandrine stimulates the apoptosis of hepatic stellate cells and ameliorates development of fibrosis in a thioacetamide rat model

    PubMed Central

    Yin, Ming-Fu; Lian, Li-Hua; Piao, Dong-Ming; Nan, Ji-Xing

    2007-01-01

    AIM: To investigate the therapeutic effect of tetrandrine on liver fibrosis induced by thioacetamide in rats in vivo and in vitro. METHODS: In vitro study: we investigated the effect of tetrandrine on the apoptosis of rat hepatic stellate cells transformed by simian virus 40 (T-HSC/Cl-6), which retains the features of activated cells. In vivo study: hepatic fibrosis was induced in rats by thioacetamide. Tetrandrine was given orally to rats at doses of 5, 10 or 20 mg/kg for 4 wk compared with intraperitoneal injection of interferon-г. RESULTS: In vitro study: 5, 10 or 25 μg/mL of tetrandrine-induced activation of caspase-3 in t-HSC/Cl-6 cells occurred dose-dependently. In vivo study: tetrandrine treatment as well as interferon-г significantly ameliorated the development of fibrosis as determined by lowered serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil) and the levels of liver hydroxyproline (Hyp), hyaluronic acid (HA), laminin (LN) and also improved histological findings. The effects of tetrandrine at the concentration of 20 mg/kg were better than the other concentration groups. CONCLUSION: Tetrandrine promotes the apoptosis of activated HSCs in vitro. Tetrandrine administration can prevent liver fibrosis and liver damage induced by thioacetamide in rats in vivo, indicating that it might exert a direct effect on rat HSCs. PMID:17451202

  8. The Efficiency of Barley (Hordeum vulgare) Bran in Ameliorating Blood and Treating Fatty Heart and Liver of Male Rats

    PubMed Central

    Abulnaja, Khalid O.; El Rabey, Haddad A.

    2015-01-01

    The current study focused on testing the hypolipidemic activity of two doses of barley bran on hypercholesterolemic male rats. Twenty-four male albino rats weighing 180–200 gm were divided into four groups. The first group (G1) was the negative control, the second group (G2) was the positive control group fed 2% cholesterol in the diet, and rats of the third and the fourth groups were fed 2% cholesterol and were cosupplemented with 5% and 10% barley bran, respectively, for 8 weeks. The hypercholesterolemic rats of (G2) showed an increase in lipid profile, liver enzymes, lactate dehydrogenase, creatine kinase-MB, and lipid peroxide and a decrease in antioxidant enzymes, whereas kidney function, fasting blood sugar, glycated hemoglobin total protein, and total bilirubin were not significantly affected compared with the negative control group in G1. Moreover, histology of heart, liver, and kidney of G2 rats showed histopathological changes compared with the negative control. Administration of the two doses of barley bran in G3 and G4 to the hypercholesterolemic rats ameliorated the level of lipids, liver enzymes, lactate dehydrogenase, and creatine kinase-MB. In addition, the histology of heart, liver, and kidney tissues nearly restored the normal state as in G1. PMID:25866539

  9. YiQiFuMai Powder Injection Ameliorates Cerebral Ischemia by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis

    PubMed Central

    Hu, Yang

    2016-01-01

    YiQiFuMai (YQFM) powder injection as a modern preparation derived from Sheng Mai San, a traditional Chinese medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. However, its neuroprotective effect and underlying mechanism in cerebral ischemia remain to be explored. The present study was designed to investigate the neuroprotective effect of YQFM on endoplasmic reticulum (ER) stress-mediated neuronal apoptosis in the permanent middle cerebral artery occlusion- (MCAO-) injured mice and the oxygen-glucose deprivation- (OGD-) induced pheochromocytoma (PC12) cells. The results showed that single administration of YQFM (1.342 g/kg, i.p.) could reduce the brain infarction and improve the neurological deficits and the cerebral blood flow (CBF) after MCAO for 24 h in mice. Moreover, incubation with YQFM (100, 200, and 400 μg/mL) could increase the cell viability, decrease the caspase-3 activity, and inhibit the cell apoptosis in OGD-induced PC12 cells for 12 h. In addition, YQFM treatment could significantly modulate cleaved caspase-3 and Bcl-2 expressions and inhibit the expressions of ER stress-related marker proteins and signaling pathways in vivo and in vitro. In conclusion, our findings provide the first evidence that YQFM ameliorates cerebral ischemic injury linked with modulating ER stress-related signaling pathways, which provided some new insights for its prevention and treatment of cerebral ischemia diseases. PMID:27087890

  10. Amelioration of intracellular stress and reduction of neural tube defects in embryos of diabetic mice by phytochemical quercetin

    PubMed Central

    Cao, Lixue; Tan, Chengyu; Meng, Fantong; Liu, Peiyan; Reece, E. Albert; Zhao, Zhiyong

    2016-01-01

    Diabetes mellitus in early pregnancy causes birth defects, including neural tube defects (NTDs). Hyperglycemia increases production of nitric oxide (NO) through NO synthase 2 (Nos2) and reactive oxygen species (ROS), generating nitrosative and oxidative stress conditions in the embryo. The present study aimed to target nitrosative stress using a naturally occurring Nos2 inhibitor, quercetin, to prevent NTDs in the embryos of diabetic mice. Daily administration of quercetin to diabetic pregnant mice during the hyperglycemia-susceptible period of organogenesis significantly reduced NTDs and cell apoptosis in the embryos, compared with those of vehicle-treated diabetic pregnant mice. Using HPLC-coupled ESI-MS/MS, quercetin metabolites, including methylated and sulfonylated derivatives, were detected in the conceptuses. The methylated metabolite, 3-O-methylquercetin, was shown to reduce ROS level in embryonic stem cells cultured in high glucose. Quercetin treatment decreased the levels of Nos2 expression, protein nitrosylation, and protein nitration, alleviating nitrosative stress. Quercetin increased the expression of superoxide dismutase 1 and 2, and reduced the levels of oxidative stress markers. Expression of genes of redox regulating enzymes and DNA damage repair factors was upregulated. Our study demonstrates that quercetin ameliorates intracellular stresses, regulates gene expression, and reduces embryonic malformations in diabetic pregnancy. PMID:26887929

  11. A new phenylpyrazoleanilide, y-320, inhibits interleukin 17 production and ameliorates collagen-induced arthritis in mice and cynomolgus monkeys.

    PubMed

    Ushio, Hiroyuki; Ishibuchi, Seigo; Oshita, Koichi; Seki, Noriyasu; Kataoka, Hirotoshi; Sugahara, Kunio; Adachi, Kunitomo; Chiba, Kenji

    2013-01-01

    Interleukin (IL)-15 and IL-17 are thought to play an important role in the pathogenesis of rheumatoid arthritis (RA) because both pro-inflammatory cytokines are found in synovial fluid of RA patients. In this study, we examined the pharmacological profiles of Y-320, a new phenylpyrazoleanilide immunomodulator. Y-320 inhibited IL-17 production by CD4 T cells stimulated with IL-15 with IC50 values of 20 to 60 nM. Oral administration of Y-320 (0.3 to 3 mg/kg) significantly inhibited the development and progression of arthritis and joint destruction with reduction of IL-17 mRNA expression in arthritic joints of type II collagen-induced arthritis (CIA) in DBA/1J mice. Y-320 in combination with anti-murine tumor necrosis factor-α monoclonal antibody showed a synergistic effect on mouse CIA. Moreover, therapeutic treatment with Y-320 (0.3 and 1 mg/kg orally) ameliorated CIA in cynomolgus monkeys. Our results suggest that Y-320, an orally active inhibitor for IL-17 production, provides a useful therapy for RA. PMID:24366113

  12. Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy.

    PubMed

    Kurahashi, Toshihiro; Lee, Jaeyong; Nabeshima, Atsunori; Homma, Takujiro; Kang, Eun Sil; Saito, Yuka; Yamada, Sohsuke; Nakayama, Toshiyuki; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi

    2016-08-15

    Aldehyde reductase (AKR1A) plays a role in the biosynthesis of ascorbic acid (AsA), and AKR1A-deficient mice produce about 10-15% of the AsA that is produced by wild-type mice. We found that acetaminophen (AAP) hepatotoxicity was aggravated in AKR1A-deficient mice. The pre-administration of AsA in the drinking water markedly ameliorated the AAP hepatotoxicity in the AKR1A-deficient mice. Treatment of the mice with AAP decreased both glutathione and AsA levels in the liver in the early phase after AAP administration, and an AsA deficiency delayed the recovery of the glutathione content in the healing phase. While in cysteine supply systems; a neutral amino acid transporter ASCT1, a cystine transporter xCT, enzymes for the transsulfuration pathway, and autophagy markers, were all elevated in the liver as the result of the AAP treatment, the AsA deficiency suppressed their induction. Thus, AsA appeared to exert a protective effect against AAP hepatotoxicity by ameliorating the supply of cysteine that is available for glutathione synthesis as a whole. Because some drugs produce reactive oxygen species, resulting in the consumption of glutathione during the metabolic process, the intake of sufficient amounts of AsA would be beneficial for protecting against the hepatic damage caused by such drugs. PMID:27288086

  13. Pyrroloquinoline quinone ameliorates l-thyroxine-induced hyperthyroidism and associated problems in rats.

    PubMed

    Kumar, Narendra; Kar, Anand; Panda, Sunanda

    2014-08-01

    Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant. In this study, we have evaluated its hitherto unknown role in l-thyroxin (L-T4 )-induced hyperthyroidism considering laboratory rat as a model. Alterations in the serum concentration of thyroxin (T4 ) and triiodothyronine (T3 ); lipid peroxidation (LPO) of liver, kidney, heart, muscles and brain; in the endogenous antioxidants such as superoxide dismutase, catalase and glutathione and in serum total cholesterol, high-density lipoprotien, triglycerides, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and urea were evaluated. Administration of l-T4 (500-µg kg(-1) body weight) enhanced not only the serum T3 and T4 levels but also the tissue LPO, serum SGOT, SGPT and urea with a parallel decrease in the levels of antioxidants and serum lipids. However, on simultaneous administration of PQQ (5 mg kg(-1) for 6 days), all these adverse effects were ameliorated, indicating the potential of PQQ in the amelioration of hyperthyroidism and associated problems. Possibly, the curative effects were mediated through inhibition of oxidative stress. We suggest that PQQ may be considered for therapeutic use for hyperthyroidism after dose standardization. PMID:25048014

  14. Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats

    PubMed Central

    Kumar, Venkatashivam Shiva; Rajmane, Anuchandra Ramchandra; Adil, Mohammad; Kandhare, Amit Dattatraya; Ghosh, Pinaki; Bodhankar, Subhash Laxman

    2014-01-01

    The aim of this study was to evaluate the effect of naringin on experimentally induced inflammatory bowel disease in rats. Naringin (20, 40 and 80 mg/kg) was given orally for 7 days to Wistar rats before induction of colitis by intrarectal instillation of 2 mL of 4% (v/v) acetic acid solution. The degree of colonic mucosal damage was analyzed by examining mucosal damage, ulcer area, ulcer index and stool consistency. Intrarectal administration of 4% acetic acid resulted in significant modulation of serum alkaline phosphatase, lactate dehydrogenase, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) content along with colonic nitric oxide (NO), xanthine oxidase (XO) level and protein carbonyl content in the colonic tissue as well as in blood. Naringin (40 and 80 mg/kg) exerted a dose dependent (P < 0.05) ameliorative effect, as it significantly increased hematological parameter as well as colonic SOD and GSH. There was a significant (P < 0.05) and dose dependant inhibition of macroscopical score, ulcer area along with colonic MDA, MPO activity by the 7 days of pretreatment of naringin (40 and 80 mg/kg). Biochemical studies revealed a significant (P < 0.05) dose dependant inhibition in serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels by pretreatment of naringin. Increased levels of colonic NO, XO, protein carbonyl content and DNA damage were also significantly decreased by naringin pretreatment. The findings of the present investigation propose that naringin has an anti-inflammatory, anti-oxidant and anti-apoptotic potential effect at colorectal sites as it modulates the production and expression of oxidative mediators such as MDA, MPO, NO and XO, thus reducing DNA damage. PMID:24683411

  15. D-004 ameliorates phenylephrine-induced urodynamic changes and increased prostate and bladder oxidative stress in rats

    PubMed Central

    Oyarzábal, Ambar; Pérez, Yohani; Mas, Rosa; Ravelo, Yazmin; Jiménez, Sonia

    2015-01-01

    Background Lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) mainly depend on alpha1-adrenoreceptors (α1-ADR) stimulation, but a link with oxidative stress (OS) is also involved. D-004, a lipid extract of Roystonea regia fruits, antagonizes ADR-induced responses and produces antioxidant effects. The objective of this study was to investigate whether D-004 produce antioxidant effects in rats with phenylephrine (PHE)-induced urodynamic changes. Methods Rats were randomized into eight groups (ten rats/group): a negative vehicle control and seven groups injected with PHE: a positive control, three treated with D-004 (200, 400 and 800 mg/kg) and three others with tamsulosin (0.4 mg/kg), grape seed extract (GSE) (250 mg/kg) and vitamin E (VE) (250 mg/kg), respectively. Results Effects on urinary total volume (UTV), volume voided per micturition (VM), malondialdehyde (MDA) and carbonyl groups (CG) concentrations in prostate and bladder homogenates were study outcomes. While VM and UTV lowered significantly in the positive control as compared to the negative control group, the opposite occurred with prostate and bladder MDA and CG values. D-004 (200-800 mg/kg) increased significantly both VM and UTV, lowered significantly MDA in prostate and bladder homogenates, and reduced GC levels only in the prostate. Tamsulosin increased significantly VM and UTV, but unchanged oxidative variables. GSE and VE unchanged the UTV, whereas VE, not GSE, modestly but significantly attenuated the PHE-induced decrease of VM. Conclusions Single oral administration of D-004 (200-800 mg/kg) was the only treatment that ameliorated the urodynamic changes and reduced increased oxidative variables in the prostate of rats with PHE-induced prostate hyperplasia. PMID:26816837

  16. Critical role of renal dipeptidyl peptidase-4 in ameliorating kidney injury induced by saxagliptin in Dahl salt-sensitive hypertensive rats.

    PubMed

    Sakai, Mariko; Uchii, Masako; Myojo, Kensuke; Kitayama, Tetsuya; Kunori, Shunji

    2015-08-15

    Saxagliptin, a potent dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently used to treat type 2 diabetes mellitus, and it has been reported to exhibit a slower rate of dissociation from DPP-4 compared with another DPP-4 inhibitor, sitagliptin. In this study, we compared the effects of saxagliptin and sitagliptin on hypertension-related renal injury and the plasma and renal DPP-4 activity levels in Dahl salt-sensitive hypertensive (Dahl-S) rats. The high-salt diet (8% NaCl) significantly increased the blood pressure and quantity of urinary albumin excretion and induced renal glomerular injury in the Dahl-S rats. Treatment with saxagliptin (14mg/kg/day via drinking water) for 4 weeks significantly suppressed the increase in urinary albumin excretion and tended to ameliorate glomerular injury without altering the blood glucose levels and systolic blood pressure. On the other hand, the administration of sitagliptin (140mg/kg/day via drinking water) did not affect urinary albumin excretion and glomerular injury in the Dahl-S rats. Meanwhile, the high-salt diet increased the renal DPP-4 activity but did not affect the plasma DPP-4 activity in the Dahl-S rats. Both saxagliptin and sitagliptin suppressed the plasma DPP-4 activity by 95% or more. Although the renal DPP-4 activity was also inhibited by both drugs, the inhibitory effect of saxagliptin was more potent than that of sitagliptin. These results indicate that saxagliptin has a potent renoprotective effect in the Dahl-S rats, independent of its glucose-lowering actions. The inhibition of the renal DPP-4 activity induced by saxagliptin may contribute to ameliorating renal injury in hypertension-related renal injury. PMID:25936515

  17. Potential of 3,4-dihydroxy-phenyl lactic acid for ameliorating ischemia-reperfusion-induced microvascular disturbance in rat mesentery.

    PubMed

    Han, Jing-Yan; Horie, Yoshinori; Fan, Jing-Yu; Sun, Kai; Guo, Jun; Miura, Soichiro; Hibi, Toshifumi

    2009-01-01

    This study intended to examine the effect of 3,4-dihydroxy-phenyl lactic acid (DLA), a major ingredient of Salvia miltiorrhiza, on ischemia-reperfusion (I/R)-induced rat mesenteric microcirculatory injury. DLA (5 mg.kg(-1).h(-1)), superoxide dismutase (SOD, 12,000 U.kg(-1).h(-1)), or catalase (CAT, 20 mg/kg) was continuously infused either starting from 10 min before the ischemia or 10 min after the initiation of reperfusion. The venule diameter, number of adherent leukocytes, FITC-albumin leakage, dihydrorhodamine 123 fluorescence, and mast cell degranulation were determined using an intravital microscope. The production of hydrogen peroxide (H(2)O(2)) and the expression of adhesion molecules CD11b/CD18 in neutrophils were evaluated by in vitro experiments. The results showed that pretreatment with DLA significantly reduced peroxide production in and leukocyte adhesion to venular wall, albumin leakage, and mast cell degranulation induced by I/R. The DLA posttreatment exerted an ameliorating effect on I/R-induced disorders as well, characterized by inhibiting further increase in peroxide production in venular wall and albumin leakage and diminishing the number of leukocytes that had adhered to the venular wall. In vitro experiments revealed that treatment with DLA significantly attenuated TNF-alpha plus fMLP-evoked production of H(2)O(2) and the H(2)O(2)-elicited expression of CD11b/CD18 on neutrophils. SOD and CAT manifested similarly but with the exception that either SOD or CAT were unable to retrieve the adherent leukocytes if administrated after initiation of reperfusion and to depress the H(2)O(2)-induced expression of CD11b/CD18 on neutrophils. It is concluded that DLA protects from and ameliorates the I/R-induced microcirculatory disturbance by interfering with both peroxide production and adhesion molecule expression. PMID:19008340

  18. Sialyllactose ameliorates myopathic phenotypes in symptomatic GNE myopathy model mice.

    PubMed

    Yonekawa, Takahiro; Malicdan, May Christine V; Cho, Anna; Hayashi, Yukiko K; Nonaka, Ikuya; Mine, Toshiki; Yamamoto, Takeshi; Nishino, Ichizo; Noguchi, Satoru

    2014-10-01

    Patients with GNE myopathy, a progressive and debilitating disease caused by a genetic defect in sialic acid biosynthesis, rely on supportive care and eventually become wheelchair-bound. To elucidate whether GNE myopathy is treatable at a progressive stage of the disease, we examined the efficacy of sialic acid supplementation on symptomatic old GNE myopathy mice that have ongoing, active muscle degeneration. We examined the therapeutic effect of a less metabolized sialic acid compound (6'-sialyllactose) or free sialic acid (N-acetylneuraminic acid) by oral, continuous administration to 50-week-old GNE myopathy mice for 30 weeks. To evaluate effects on their motor performance in living mice, spontaneous locomotion activity on a running wheel was measured chronologically at 50, 65, 72 and 80 weeks of age. The size, force production, and pathology of isolated gastrocnemius muscle were analysed at the end point. Sialic acid level in skeletal muscle was also measured. Spontaneous locomotion activity was recovered in 6'-sialyllactose-treated mice, while NeuAc-treated mice slowed the disease progression. Treatment with 6'-sialyllactose led to marked restoration of hyposialylation in muscle and consequently to robust improvement in the muscle size, contractile parameters, and pathology as compared to NeuAc. This is due to the fact that 6'-sialyllactose is longer working as it is further metabolized to free sialic acid after initial absorption. 6'-sialyllactose ameliorated muscle atrophy and degeneration in symptomatic GNE myopathy mice. Our results provide evidence that GNE myopathy can be treated even at a progressive stage and 6'-sialyllactose has more remarkable advantage than free sialic acid, providing a conceptual proof for clinical use in patients. PMID:25062695

  19. Early-onset motor impairment and increased accumulation of phosphorylated α-synuclein in the motor cortex of normal aging mice are ameliorated by coenzyme Q.

    PubMed

    Takahashi, Kazuhide; Ohsawa, Ikuroh; Shirasawa, Takuji; Takahashi, Mayumi

    2016-08-01

    Brain mitochondrial function declines with age; however, the accompanying behavioral and histological alterations that are characteristic of Parkinson's disease (PD) are poorly understood. We found that the mitochondrial oxygen consumption rate (OCR) and coenzyme Q (CoQ) content were reduced in aged (15-month-old) male mice compared to those in young (6-month-old) male mice. Concomitantly, motor functions, including the rate of movement and exploratory and voluntary motor activities, were significantly reduced in the aged mice compared to the young mice. In the motor cortex of the aged mouse brain, the accumulation of α-synuclein (α-syn) phosphorylated at serine129 (Ser129) significantly increased, and the level of vesicular glutamate transporter 1 (VGluT1) decreased compared with that in the young mouse brain. The administration of exogenous water-soluble CoQ10 to aged mice via drinking water restored the mitochondrial OCR, motor function, and phosphorylated α-syn and VGluT1 levels in the motor cortex. These results suggest that early-onset motor impairment and the increased accumulation of Ser129-phosphorylated α-syn in the motor cortex are ameliorated by the exogenous administration of CoQ10. PMID:27143639

  20. Modernizing Administration.

    ERIC Educational Resources Information Center

    Lombardi, Vincent L.; Hildebrand, Verna

    1981-01-01

    Suggests assignment of research duties and rotation of teaching and management roles for college administrators, to increase their effectiveness and diminish the negative effects of declining enrollments. (JD)

  1. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses.

    PubMed

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-09-01

    Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle microvascular recruitment. We demonstrated that a high-fat diet induces vascular adiponectin and insulin resistance but globular adiponectin administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK- and nitric oxide-dependent mechanism. This suggests that globular adiponectin might have a therapeutic potential for improving insulin resistance and preventing cardiovascular complications in patients with diabetes via modulation of microvascular insulin responses. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague-Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by

  2. Continued Administration of Ciliary Neurotrophic Factor Protects Mice from Inflammatory Pathology in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Kuhlmann, Tanja; Remington, Leah; Cognet, Isabelle; Bourbonniere, Lyne; Zehntner, Simone; Guilhot, Florence; Herman, Alexandra; Guay-Giroux, Angélique; Antel, Jack P.; Owens, Trevor; Gauchat, Jean-François

    2006-01-01

    Multiple sclerosis is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. We show that daily administration (days 8 to 24) of murine ciliary neurotrophic factor (CNTF), a neurotrophic factor that has been described as a survival and differentiation factor for neurons and oligodendrocytes, significantly ameliorates the clinical course of a mouse model of multiple sclerosis. In the acute phase of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein peptide 35-55, treatment with CNTF did not change the peripheral immune response but did reduce the number of perivascular infiltrates and T cells and the level of diffuse microglial activation in spinal cord. Blood brain barrier permeability was significantly reduced in CNTF-treated animals. Beneficial effects of CNTF did not persist after it was withdrawn. After cessation of CNTF treatment, inflammation and symptoms returned to control levels. However, slight but significantly higher numbers of oligodendrocytes, NG2-positive cells, axons, and neurons were observed in mice that had been treated with high concentrations of CNTF. Our results show that CNTF inhibits inflammation in the spinal cord, resulting in amelioration of the clinical course of experimental autoimmune encephalomyelitis during time of treatment. PMID:16877358

  3. 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

  4. 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

  5. Ameliorative effects of Anoectochilus formosanus extract on osteopenia in ovariectomized rats.

    PubMed

    Shih, C C; Wu, Y W; Lin, W C

    2001-10-01

    The purpose of this study was to determine ameliorative effects of crude aqueous extract of Anoectochilus formosanus (AFE) on osteopenia in ovariectomized (OVX) rats. First, all of the rats were divided into sham and OVX groups. The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were divided into four groups treated with water, 17beta-estradiol (30 microg/kg, daily s.c. injection) or AFE (0.5, 2 g/kg, daily, orally) for 12 weeks. In OVX rats, the increases of body weight and serum total cholesterol were significantly decreased by AFE or 17beta-estradiol treatment. In OVX rats, atrophy of uterus and vagina was preserved by treatment with 17beta-estradiol, but not by AFE. The decreased weight of pituitary was increased by treatment with both 17beta-estradiol and AFE. There were decreases in bone density and calcium content including the right femur and the fourth lumbar vertebra, when compared with the sham control rats. Treatment with either 17beta-estradiol or AFE ameliorated these changes induced by OVX. In addition, ovariectomy increased serum alkaline phosphatase levels. The increases were suppressed by the treatment with 17beta-estradiol and AFE. Our results demonstrated that AEF could ameliorate ovariectomy-induced osteopenia. PMID:11535369

  6. Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by aqueous leaf extract of Cnidoscolus aconitifolius in rats.

    PubMed

    Saba, A B; Oyagbemi, A A; Azeez, O I

    2010-01-01

    This study was conducted to explore possible protective effect ofCnidoscolus aconitifolius (CA) leaf extract on carbon tetrachloride (CCl4)-induced hepatotoxicity and haemotoxicity in experimental animal models. Thirty six rats of six per group were used in this study. Group I received 10ml/kg normal saline as control. Group II-VI rats were administered with 1.25ml/kg body weight (bwt) of carbon tetrachloride intraperitonealy. Animals in groups III, IV, V and VI were however pre-treated with aqueous extract of Cnidoscolus aconitifolius at 100, 250, 500 and 750mg/kg body weight (bwt) respectively. Administration of CCL4 in untreated rats led to microcytic hypochromic anaemia, thrombocytopenia, increased erythrocyte fragility and stress induced leucocytosis accompanied with significant increase in neutrophils and decrease in lymphocyte counts. CCl4 also led to significant increase in serum transaminases (ALT and AST) and phosphatase (ALP) respectively compared with control animals. Also, CCL4 produced significant increase in serum blood urea nitrogen (BUN) and creatinine compared with normal rats. Pre-treatment with Cnidoscolus aconitifolius leaf extract brought about significant restoration of the haematological parameters to values that were comparable to those of the control with concomitant decrease in the activities of the marker of hepatic damage enzymes (ALT, AST and ALP), in a dose-dependent manner. Similarly, serum levels of blood urea nitrogen (BUN) and creatinine were also brought to near normal by the CA in a dose-dependent manner. From this study, we conclude that pre-exposure to Cnidoscolus aconitifolius leaf extract considerably reduced the effect of CCl4 on the blood parameters and ameliorated hepatic damage by the haloalkane. PMID:22314953

  7. Administrative Support.

    ERIC Educational Resources Information Center

    Doran, Dorothy; And Others

    This guide is intended to assist business education teachers in administrative support courses. The materials presented are based on the Arizona validated occupational competencies and tasks for the occupations of receptionist, secretary, and administrative assistant. Word processing skills have been infused into each of the three sections. The…

  8. Administrative Ecology

    ERIC Educational Resources Information Center

    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  9. N-acetylcysteine pretreatment ameliorates mercuric chloride-induced oxidative renal damage in rats.

    PubMed

    Ekor, M; Adesanoye, O A; Farombi, E O

    2010-12-01

    The effectiveness of the antioxidant thiol, N-acetylcysteine (NAC), in enhancing methylmercury (CH3HgCl) excretion and its utility as a possible antidote in CH3HgCl poisoning has been reported. NAC, however, has been reported to be ineffective in accelerating excretion of divalent toxic metals, including inorganic mercury, Hg2+. In this study, we evaluated the possible protective effect of short-term pretreatment with NAC against mercuric chloride (HgCl2) toxicity in rat model. This is aimed at determining its chemopreventive or prophylactic benefit in situations of high risk exposure (occupational/industrial) to mercury. Rats were divided into three treatment groups. Group I received saline (10 ml/kg) and served as control. Group II received HgCl2 (5mg/kg) and group III received NAC (10mg/kg) plus (5mg/kg). All administration was via intraperitoneal (i.p.) injection. Saline and NAC were administered for 5days and HgCl2 was administered to rats in groups II and III on the 5th day. Animals were sacrificed 24 hours after HgCl2 injection and samples obtained for biochemical evaluation. Results revealed that single i.p. injection of HgCl2 induced significant renal oxidative damage resulting in significant decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), depletion of reduced glutathione (GSH) and increase in malondialdehyde (MDA) levels in these rats. The activities of glucose-6-phosphatase (G6Pase) and 5'-nucleotidase (5'-NTD) (markers of microsomal damage) also decreased in these HgCl2 treated rats. The oxidative damage induced by HgCl2 led to significant alterations in renal histology and caused functional impairment (indicated by elevated blood urea nitrogen (BUN) and serum creatinine) in these rats. NAC was effective in attenuating the oxidative damage, functional impairments and histopathological changes that characterized HgCl2 intoxication in this study. Renal antioxidant defense system was re-enforced by

  10. Matrine ameliorates spontaneously developed colitis in interleukin-10-deficient mice.

    PubMed

    Wu, Cong; Xu, Zheng; Gai, Renhua; Huang, Kehe

    2016-07-01

    Interleukin-10 (IL-10)-deficient mice spontaneously develop T cell-mediated colitis. Previous reports have shown that Matrine may reduce the symptoms of acute colitis induced by trinitrobenzene sulfonic acid (TNBS). However, whether Matrine impacts chronic colitis remains unknown. In this study, we investigated whether Matrine could limit the symptoms of spontaneously developed colitis and its potential molecular mechanisms. IL-10 deficient mice were given Matrine or a PBS control by oral gavage daily for 4weeks and were euthanized at week 2 or week 4. We measured body weight, colon length and weight, and histological scores. We also evaluated the spontaneous secretion of IL-12/23p40, IFN-γ and IL-17 in colon explant cultures as well as IFN-γ and IL-17 secretion in unseparated mesenteric lymph node (MLN) cells, and assessed IFN-γ, IL-17, IL-1β and IL-6 mRNA expression in colon tissue. In addition, we analyzed the proportions of CD4-positive and CD8-positive cells in unseparated MLN cells. Our results show that Matrine-treated mice exhibited better body weight recovery than controls and that histological scores and spontaneously secreted IL-12/23p40, IFN-γ and IL-17 in colon tissue were significantly decreased in treated mice compared with controls. The proportion of CD4-positive cells of MLNs in treated mice was significantly smaller than that in controls at week 4. Both cytokine production and mRNA expression of IFN-γ and IL-17 were significantly reduced in treated mice compared with controls. Taken together, our results indicate that Matrine may ameliorate spontaneously developed chronic colitis and could be considered as a therapeutic alternative for chronic colitis. PMID:27179305

  11. Febuxostat ameliorates doxorubicin-induced cardiotoxicity in rats.

    PubMed

    Krishnamurthy, Bhaskar; Rani, Neha; Bharti, Saurabh; Golechha, Mahaveer; Bhatia, Jagriti; Nag, Tapas Chandra; Ray, Ruma; Arava, Sudheer; Arya, Dharamvir Singh

    2015-07-25

    The clinical use of doxorubicin is associated with dose limiting cardiotoxicity. This is a manifestation of free radical production triggered by doxorubicin. Therefore, we evaluated the efficacy of febuxostat, a xanthine oxidase inhibitor and antioxidant, in blocking cardiotoxicity associated with doxorubicin in rats. Male albino Wistar rats were divided into four groups: control (normal saline 2.5mL/kg/dayi.p. on alternate days, a total of 6 doses); Doxorubicin (2.5mg/kg/dayi.p. on alternate days, a total of 6 doses), Doxorubicin+Febuxostat (10mg/kg/day oral) and Doxorubicin+Carvedilol (30mg/kg/day oral) for 14days. Febuxostat significantly ameliorated the doxorubicin-induced deranged cardiac functions as there was significant improvement in arterial pressures, left ventricular end diastolic pressure and inotropic and lusitropic states of the myocardium. These changes were well substantiated with biochemical findings, wherein febuxostat prevented the depletion of non-protein sulfhydryls level, with increased manganese superoxide dismutase level and reduced cardiac injury markers (creatine kinase-MB and B-type natriuretic peptide levels) and thiobarbituric acid reactive substances level. Febuxostat also exhibited significant anti-inflammatory (decreased expression of NF-κBp65, IKK-β and TNF-α) and anti-apoptotic effect (increased Bcl-2 expression and decreased Bax and caspase-3 expression and TUNEL positivity). Hematoxylin and Eosin, Masson Trichome, Picro Sirius Red and ultrastructural studies further corroborated with hemodynamic and biochemical findings showing that febuxostat mitigated doxorubicin-induced increases in inflammatory cells, edema, collagen deposition, interstitial fibrosis, perivascular fibrosis and mitochondrial damage and better preservation of myocardial architecture. In addition, all these changes were comparable to those produced by carvedilol. Thus, our results suggest that the antioxidant and anti-apoptotic effect of febuxostat

  12. Mussel beds — amensalism or amelioration for intertidal fauna?

    NASA Astrophysics Data System (ADS)

    Dittmann, Sabine

    1990-09-01

    The faunal assemblages of a mussel bed ( Mytilus edulis L.) and ambient sandflat were compared to study how a bioherm of suspension feeding organisms affects benthic communities in a tidal flat. During a survey of mussel beds in the Wadden Sea at the island of Sylt (North Sea), a total of 52 macrofaunal species and 44 meiobenthic plathelminth species were detected. They occupied different microhabitats in the mussel bed. 56% of the macrofauna species were dwelling in the sediment beneath the mussels and 42% were epibenthic or epiphytic. The latter were restricted in their occurrence to the mussel bed. Along a transect from the sandflat to the mussel bed the mean species densities of macrofauna did not differ significantly, while abundances were significantly lower in the mussel bed than in the sandflat. The composition of the assemblages shifted from a dominance of Polychaeta in the sandflat to Oligochaeta in the mussel bed. Surface filter-feeding polychaetes of the sandflat ( Tharyx marioni) were displaced by deposit feeding polychaetes under the mussel cover ( Capitella capitata, Heteromastus filiformis). The total meiobenthic density was lower and single taxa (Ostracoda, Plathelminthes, Nematoda) were significantly less abundant in the mud of the mussel bed. The plathelminth assemblage was dominated by grazing species ( Archaphanostoma agile), and differed in community structure from a sandflat aseemblage. An amensalistic relationship was found between the suspension-feeding mussels and suspension-feeding infauna, while deposit-feeders were enhanced. The presence of epibenthic microhabitats results in a variety of trophic groups co-occurring in a mussel bed. This is hypothesized as trophic group amelioration and described as an attribute of heterotrophic reefs.

  13. Escherichia coli Strain Nissle 1917 Ameliorates Experimental Colitis via Toll-Like Receptor 2- and Toll-Like Receptor 4-Dependent Pathways

    PubMed Central

    Grabig, A.; Paclik, D.; Guzy, C.; Dankof, A.; Baumgart, D. C.; Erckenbrecht, J.; Raupach, B.; Sonnenborn, U.; Eckert, J.; Schumann, R. R.; Wiedenmann, B.; Dignass, A. U.; Sturm, A.

    2006-01-01

    Toll-like receptors (TLRs) are key components of the innate immune system that trigger antimicrobial host defense responses. The aim of the present study was to analyze the effects of probiotic Escherichia coli Nissle strain 1917 in experimental colitis induced in TLR-2 and TLR-4 knockout mice. Colitis was induced in wild-type (wt), TLR-2 knockout, and TLR-4 knockout mice via administration of 5% dextran sodium sulfate (DSS). Mice were treated with either 0.9% NaCl or 107 E. coli Nissle 1917 twice daily, followed by the determination of disease activity, mucosal damage, and cytokine secretion. wt and TLR-2 knockout mice exposed to DSS developed acute colitis, whereas TLR-4 knockout mice developed significantly less inflammation. In wt mice, but not TLR-2 or TLR-4 knockout mice, E. coli Nissle 1917 ameliorated colitis and decreased proinflammatory cytokine secretion. In TLR-2 knockout mice a selective reduction of gamma interferon secretion was observed after E. coli Nissle 1917 treatment. In TLR-4 knockout mice, cytokine secretion was almost undetectable and not modulated by E. coli Nissle 1917, indicating that TLR-4 knockout mice do not develop colitis similar to the wt mice. Coculture of E. coli Nissle 1917 and human T cells increased TLR-2 and TLR-4 protein expression in T cells and increased NF-κB activity via TLR-2 and TLR-4. In conclusion, our data provide evidence that E. coli Nissle 1917 ameliorates experimental induced colitis in mice via TLR-2- and TLR-4-dependent pathways. PMID:16790781

  14. Cucurbitacin E ameliorates hepatic fibrosis in vivo and in vitro through activation of AMPK and blocking mTOR-dependent signaling pathway.

    PubMed

    Wu, Yan-Ling; Zhang, Yu-Jing; Yao, You-Li; Li, Zhi-Man; Han, Xin; Lian, Li-Hua; Zhao, Yu-Qing; Nan, Ji-Xing

    2016-09-01

    The study evaluated the potential protective effect and underlying mechanism of Cucurbitacin E (CuE) in both thioacetamide-induced hepatic fibrosis and activated HSCs. CuE inhibited the proliferation of activated HSC/T-6 cells in a concentration- and time-dependent manner; triggered the activation of caspase-3, cleaved PARP, altered ratio of bcl-2-to-bax, and affected cytochrome C protein in a time- and concentration-dependent manner. CuE arrested activated HSCs at the G2/M phase. Furthermore, CuE reduced levels of p-Erk/MAPK and also inhibited the protein and mRNA expressions of α-SMA, TIMP-1 and collagen I in activated HSC-T6 cells. CuE inhibited PI3K and Akt phosphorylation, and reduced the levels of p-mTOR and p-P70S6K and increased the expression of p-AMPK, which is similar with AICAR and metformin. C57BL/6 mice were intraperitoneally injected with thioacetamide (TAA) for five continuous weeks (100 or 200mg/kg, three times per week) along with daily administration of CuE (5 or 10mg/kg/d) and curcumin (Cur, 20mg/kg). CuE treatments significantly reduced serum ALT/AST levels, α-SMA, TIMP-1, and collagen I protein expressions. HE, Masson trichrome, Sirius red and immunohistochemical staining also suggested that CuE could ameliorate hepatic fibrosis. Our findings suggest that CuE induces apoptosis of activated HSC and ameliorates TAA-induced hepatic fibrosis through activation of AMPK and blocking mTOR-dependent signaling pathway. PMID:27363783

  15. Possible role of fibroblast growth factor 21 on atherosclerosis via amelioration of endoplasmic reticulum stress-mediated apoptosis in apoE(-/-) mice.

    PubMed

    Wu, Xi; Qi, Yong-Fen; Chang, Jin-Rui; Lu, Wei-Wei; Zhang, Jin-Sheng; Wang, Shao-Ping; Cheng, Shu-Juan; Zhang, Ming; Fan, Qian; Lv, Yuan; Zhu, Hui; Xin, Man-Kun; Lv, Yun; Liu, Jing-Hua

    2015-09-01

    Fibroblast growth factor 21 (FGF-21) is an endocrine factor that can be secreted into circulation by the liver. FGF-21 takes part in metabolic actions and is thought to be a promising candidate for the treatment of diabetes. However, the role of FGF-21 in atherosclerosis is unknown. In this study, apoE(-/-) mice were fed an atherogenic diet for 4 weeks with and without subcutaneous injections of FGF-21. ApoE(-/-) mice fed an atherogenic diet showed hyperlipidemia, a large plaque area in aortas and increased vessel wall thickness. Plasma FGF-21 content and protein level of FGF receptor 1 (FGFR1) in aortas was greater in apoE(-/-) than C57BL/6J mice. Exogenous FGF-21 treatment significantly ameliorated dyslipidemia in apoE(-/-) mice. FGF-21-treated apoE(-/-) mice showed reduced number of aortic plaques and plaque area as well as reduced number of TUNEL-positive cells. Protein levels of the endoplasmic reticulum stress markers glucose-regulated protein 94, caspase-12 and C/EBP homologous protein were reduced by 34.5, 31.4 and 26.5 %, respectively, in apoE(-/-) mice. Endogenous expression of FGF-21 and its receptor FGFR1 were upregulated in apoE(-/-) mice, and exogenous administration of FGF-21 ameliorated the atherogenic-induced dyslipidemia and vascular atherosclerotic lesions. FGF-21 protecting against atherosclerosis might be in part by its inhibitory effects on endoplasmic reticulum stress-mediated apoptosis. PMID:25092223

  16. The Thyroid Hormone Analog DITPA Ameliorates Metabolic Parameters of Male Mice With Mct8 Deficiency.

    PubMed

    Ferrara, Alfonso Massimiliano; Liao, Xiao-Hui; Ye, Honggang; Weiss, Roy E; Dumitrescu, Alexandra M; Refetoff, Samuel

    2015-11-01

    Mutations in the gene encoding the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), cause mental retardation in humans associated with a specific thyroid hormone phenotype manifesting high serum T3 and low T4 and rT3 levels. Moreover, these patients have failure to thrive, and physiological changes compatible with thyrotoxicosis. Recent studies in Mct8-deficient (Mct8KO) mice revealed that the high serum T3 causes increased energy expenditure. The TH analog, diiodothyropropionic acid (DITPA), enters cells independently of Mct8 transport and shows thyromimetic action but with a lower metabolic activity than TH. In this study DITPA was given daily ip to adult Mct8KO mice to determine its effect on thyroid tests in serum and metabolism (total energy expenditure, respiratory exchange rate, and food and water intake). In addition, we measured the expression of TH-responsive genes in the brain, liver, and muscles to assess the thyromimetic effects of DITPA. Administration of 0.3 mg DITPA per 100 g body weight to Mct8KO mice brought serum T3 levels and the metabolic parameters studied to levels observed in untreated Wt animals. Analysis of TH target genes revealed amelioration of the thyrotoxic state in liver, somewhat in the soleus, but there was no amelioration of the brain hypothyroidism. In conclusion, at the dose used, DITPA mainly ameliorated the hypermetabolism of Mct8KO mice. This thyroid hormone analog is suitable for the treatment of the hypermetabolism in patients with MCT8 deficiency, as suggested in limited preliminary human trials. PMID:26322373

  17. Cholinesterase inhibitors ameliorate behavioral deficits induced by MK-801 in mice.

    PubMed

    Csernansky, John G; Martin, Maureen; Shah, Renu; Bertchume, Amy; Colvin, Jenny; Dong, Hongxin

    2005-12-01

    Enhancing cholinergic function has been suggested as a possible strategy for ameliorating the cognitive deficits of schizophrenia. The purpose of this study was to examine the effects of acetylcholinesterase (AChE) inhibitors in mice treated with the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, which has been suggested as an animal model of the cognitive deficits of schizophrenia. Three separate experiments were conducted to test the effects of physostigmine, donepezil, or galantamine on deficits in learning and memory induced by MK-801. In each experiment, MK-801 (0.05 or 0.10 mg/kg) or saline was administered i.p. 20 min prior to behavioral testing over a total of 12 days. At 30 min prior to administration of MK-801 or saline, one of three doses of the AChE inhibitor (ie physostigmine-0.03, 0.10, or 0.30 mg/kg; donepezil-0.10, 0.30, or 1.00 mg/kg; or galantamine-0.25, 0.50, or 1.00 mg/kg) or saline was administered s.c. Behavioral testing was performed in all experimental animals using the following sequence: (1) spatial reversal learning, (2) locomotion, (3) fear conditioning, and (4) shock sensitivity. Both doses of MK-801 produced impairments in spatial reversal learning and in contextual and cued memory, as well as hyperlocomotion. Physostigmine and donepezil, but not galantamine, ameliorated MK-801-induced deficits in spatial reversal learning and in contextual and cued memory in a dose-dependent manner. Also, physostigmine, but not donepezil or galantamine, reversed MK-801-induced hyperlocomotion. Galantamine, but not physostigmine or donepezil, altered shock sensitivity. These results suggest that AChE inhibitors may differ in their capacity to ameliorate learning and memory deficits produced by MK-801 in mice, which may have relevance for the cognitive effects of cholinomimetic drugs in patients with schizophrenia. PMID:15956997

  18. Ameliorating Effects of Iron and Zinc on Vigna mungo L. Treated with Tannery Effluent

    PubMed Central

    Srivastava, Shefali; Mishra, Kumkum; Tandon, Pramod Kumar

    2014-01-01

    Different dilutions, that is, 25, 50, 75, and 100%, of tannery effluent (TE) were chosen for the present study to assess the phytotoxic effects on Vigna mungo L. For amelioration purposes, different levels and combinations of iron and zinc were supplied to the plants along with 50% TE that is chosen on the basis of prior test under Petri dish culture. Cytotoxic and biochemical analysis and plant tolerance index (PTI) of plant were observed. Mitotic index deceased with increase in effluent concentration whereas abnormality % was increased. The pigments (chlorophyll a, total, and carotenoids) were decreased with increasing treatment levels of TE at both growth stages. However, carotenoid content increased significantly at all dilution levels of TE after first growth stage. Chlorophyll b was increased significantly after 35 days of growth but decreased after 70 days. The protein contents were also significantly decreased with increase in all TE treatments and increased significantly in zinc recovery treatments. Activities of catalase and peroxidase enzymes were significantly affected and increased significantly with effluent treatments. PTI showed an enhanced tolerance capacity of plant with treatment of iron and zinc. A negative correlation was found (r = −0.97) between plant height and different dilutions of effluent whereas it was positively correlated (r = 0.95) with iron and zinc treatments. The study represents the ameliorative effect of iron and zinc for phytotoxic damage in V. mungo caused by tannery effluent. PMID:25505908

  19. Escherichia coli strain Nissle 1917 ameliorates experimental colitis by modulating intestinal permeability, the inflammatory response and clinical signs in a faecal transplantation model.

    PubMed

    Souza, Éricka L; Elian, Samir D; Paula, Laís M; Garcia, Cristiana C; Vieira, Angélica T; Teixeira, Mauro M; Arantes, Rosa M; Nicoli, Jacques R; Martins, Flaviano S

    2016-03-01

    Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the gut that include ulcerative colitis and Crohn's disease. Probiotics are live micro-organisms that may be used as adjuvant therapy for patients with IBD. The aim of this study was to evaluate the effect of prophylactic ingestion of Escherichia coli strain Nissle 1917 (EcN) in a murine model of colitis. For induction of colitis, mice were given a 3.5 % dextran sodium sulfate (DSS) solution for 7 days in drinking water. EcN administration to mice subjected to DSS-induced colitis resulted in significant reduction in clinical and histopathological signs of disease and preservation of intestinal permeability. We observed reduced inflammation, as assessed by reduced levels of neutrophils, eosinophils, chemokines and cytokines. We observed an increase in the number of regulatory T-cells in Peyer's patches. Germ-free mice received faecal content from control or EcN-treated mice and were then subjected to DSS-induced colitis. We observed protection from colitis in animals that were colonized with faecal content from EcN-treated mice. These results suggest that preventative oral administration of EcN or faecal microbiota transplantation with EcN-containing microbiota ameliorates DSS-induced colitis by modifying inflammatory responsiveness to DSS. PMID:26758971

  20. 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

  1. Ontology representation and analysis of vaccine formulation and administration and their effects on vaccine immune responses

    PubMed Central

    2012-01-01

    Background A vaccine is a processed material that if administered, is able to stimulate an adaptive immune response to prevent or ameliorate a disease. A vaccination process may protect the host against subsequent exposure to an infectious agent and result in reduced disease or total prevention of the disease. Vaccine formulation and administration methods may affect vaccine safety and efficacy significantly. Results In this report, the detailed classification and definitions of vaccine components and vaccine administration processes are represented using OWL within the framework of the Vaccine Ontology (VO). Different use cases demonstrate how different vaccine formulations and routes of vaccine administration affect the protection efficacy, general immune responses, and adverse events following vaccination. For example, vaccinations of mice with Brucella abortus vaccine strain RB51 using intraperitoneal or intranasal administration resulted in different protection levels. As shown in the vaccine adverse event data provided by US FDA, live attenuated and nonliving vaccines are usually administered in different routes and have different local and systematic adverse effect manifestations. Conclusions Vaccine formulation and administration route can independently or collaboratively affect host response outcomes (positive protective immunity or adverse events) after vaccination. Ontological representation of different vaccine and vaccination factors in these two areas allows better understanding and analysis of the causal effects between different factors and immune responses. PMID:23256535

  2. Hyperbaric oxygen treatment ameliorates lung injury in paraquat intoxicated rats.

    PubMed

    Akcılar, Raziye; Akcılar, Aydın; Şimşek, Hasan; Koçak, Fatma Emel; Koçak, Cengiz; Yümün, Gündüz; Bayat, Zeynep

    2015-01-01

    Paraquat (PQ) is an agrochemical agent commonly used worldwide, which can cause acute lung injury (ALI) and death. Hyperbaric oxygen treatment (HBOT) is a therapeutic method, but the mechanisms of the protective effect of HBOT on ALI remain elusive. The purpose of this study was to evaluate the effect of HBOT on acute lung injury induced by PQ in rats. Wistar Albino rats (n=21) were separated into three groups of seven animals each: control (C), PQ, and PQ + HBOT groups. 20 mg/kg PQ was administered intraperitoneally in PQ and PQ + HBOT groups to induce experimental lung injury. Three days after PQ treatment, PQ + HBOT group was administered 100% O2 at 2.0 ATA for 1 hour per day, for five consecutive days. At the end of the study, lung tissue was obtained for determining total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and histopathological determination. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-β1 mRNA levels were assessed by quantitative reverse transcription-polymerase chain reaction. In addition, the inducible nitric oxide synthase (iNOS) level in the plasma was determined. Plasma iNOS, OSI, tissue TNF-α, TGF-β1 and bFGF mRNA levels, and histological injury scores in PQ + HBOT group were significantly lower than PQ group. TAS level in PQ + HBOT group was significantly higher than PQ group. The findings suggest that HBOT could effectively ameliorate PQ-induced lung injury in rats. PMID:26722498

  3. Hyperbaric oxygen treatment ameliorates lung injury in paraquat intoxicated rats

    PubMed Central

    Akcılar, Raziye; Akcılar, Aydın; Şimşek, Hasan; Koçak, Fatma Emel; Koçak, Cengiz; Yümün, Gündüz; Bayat, Zeynep

    2015-01-01

    Paraquat (PQ) is an agrochemical agent commonly used worldwide, which can cause acute lung injury (ALI) and death. Hyperbaric oxygen treatment (HBOT) is a therapeutic method, but the mechanisms of the protective effect of HBOT on ALI remain elusive. The purpose of this study was to evaluate the effect of HBOT on acute lung injury induced by PQ in rats. Wistar Albino rats (n=21) were separated into three groups of seven animals each: control (C), PQ, and PQ + HBOT groups. 20 mg/kg PQ was administered intraperitoneally in PQ and PQ + HBOT groups to induce experimental lung injury. Three days after PQ treatment, PQ + HBOT group was administered 100% O2 at 2.0 ATA for 1 hour per day, for five consecutive days. At the end of the study, lung tissue was obtained for determining total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and histopathological determination. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-β1 mRNA levels were assessed by quantitative reverse transcription-polymerase chain reaction. In addition, the inducible nitric oxide synthase (iNOS) level in the plasma was determined. Plasma iNOS, OSI, tissue TNF-α, TGF-β1 and bFGF mRNA levels, and histological injury scores in PQ + HBOT group were significantly lower than PQ group. TAS level in PQ + HBOT group was significantly higher than PQ group. The findings suggest that HBOT could effectively ameliorate PQ-induced lung injury in rats. PMID:26722498

  4. NAD+ Biosynthesis Ameliorates a Zebrafish Model of Muscular Dystrophy

    PubMed Central

    Goody, Michelle F.; Kelly, Meghan W.; Reynolds, Christine J.; Khalil, Andre; Crawford, Bryan D.; Henry, Clarissa A.

    2012-01-01

    Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex– or integrin alpha7–deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction with integrin

  5. NAD+ biosynthesis ameliorates a zebrafish model of muscular dystrophy.

    PubMed

    Goody, Michelle F; Kelly, Meghan W; Reynolds, Christine J; Khalil, Andre; Crawford, Bryan D; Henry, Clarissa A

    2012-01-01

    Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex- or integrin alpha7-deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction with integrin alpha

  6. Dexmedetomidine ameliorates nocifensive behavior in humanized sickle cell mice.

    PubMed

    Calhoun, Gabriela; Wang, Li; Almeida, Luis E F; Kenyon, Nicholas; Afsar, Nina; Nouraie, Mehdi; Finkel, Julia C; Quezado, Zenaide M N

    2015-05-01

    Patients with sickle cell disease (SCD) can have recurrent episodes of vaso-occlusive crises, which are associated with severe pain. While opioids are the mainstay of analgesic therapy, in some patients, increasing opioid use results in continued and increasing pain. Many believe that this phenomenon results from opioid-induced tolerance or hyperalgesia or that SCD pain involves non-opioid-responsive mechanisms. Dexmedetomidine, a specific α2-adrenoreceptor agonist, which has sedative and analgesic properties, reduces opioid requirements, and can facilitate opioid withdrawal in clinical settings. We hypothesized that dexmedetomidine would ameliorate the nociception phenotype of SCD mice. Townes and BERK SCD mice, strains known to have altered nociception phenotypes, were used in a crossover preclinical trial that measured nocifensive behavior before and after treatment with dexmedetomidine or vehicle. In a linear dose-effect relationship, over 60-min, dexmedetomidine, compared with vehicle, significantly increased hot plate latency in Townes and BERK mice (P≤0.006). In sickle, but not control mice, dexmedetomidine improved grip force, an indicator of muscle pain (P=0.002). As expected, dexmedetomidine had a sedative effect in sickle and control mice as it decreased wakefulness scores compared with vehicle (all P<0.001). Interestingly, the effects of dexmedetomidine on hot plate latency and wakefulness scores were different in sickle and control mice, i.e., dexmedetomidine-related increases in hotplate latency and decreases in wakefulness scores were significantly smaller in Townes sickle compared to control mice. In conclusion, these findings of beneficial effects of dexmedetomidine on the nociception phenotype in SCD mice might support the conduct of studies of dexmedetomidine in SCD patients. PMID:25724786

  7. 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

  8. Apricot Kernel Oil Ameliorates Cyclophosphamide-Associated Immunosuppression in Rats.

    PubMed

    Tian, Honglei; Yan, Haiyan; Tan, Siwei; Zhan, Ping; Mao, Xiaoying; Wang, Peng; Wang, Zhouping

    2016-08-01

    The effects of dietary apricot kernel oil (AKO), which contains high levels of oleic and linoleic acids and lower levels of α-tocopherol, were evaluated in a rat model of cyclophosphamide-induced immunosuppression. Rats had intraperitoneal injection with cyclophosphamide to induce immunosuppression and were then infused with AKO or normal saline (NS) for 4 weeks. Enzyme-linked immunosorbent assays were used to detect antimicrobial factors in lymphocytes and anti-inflammatory factors in hepatocytes. Hematoxylin & eosin staining was conducted prior to histopathological analysis of the spleen, liver, and thymus. Significant differences were observed between the immune functions of the healthy control group, the normal saline group, and the AKO group. Compared to the normal saline-treated group, lymphocytes isolated from rats administered AKO showed significant improvement in immunoglobulin (Ig)A, IgM, IgG, interleukin (IL)-2, IL-12, and tumor necrosis factor-α (TNF-α) levels (p < 0.01). Liver tissue levels of malondialdehyde and activities of superoxide dismutase and glutathione peroxidase indicated reduced oxidative stress in rats treated with AKO (p < 0.01). Dietary AKO positively affected rat growth and inhibited cyclophosphamide-associated organ degeneration. These results suggested that AKO may enhance the immune system in vivo. These effects may reflect the activities of intermediate oleic and linoleic acid metabolites, which play a vital role in the immune system, and the α-tocopherol in AKO may further enhance this phenomenon. Thus, the use of AKO as a nutritional supplement can be proposed to ameliorate chemotherapy-associated immunosuppression. PMID:27262314

  9. Melanocortin antagonism ameliorates muscle wasting and inflammation in chronic kidney disease

    PubMed Central

    Cheung, Wai W.

    2012-01-01

    Aberrant melanocortin signaling has been implicated in the pathogenesis of wasting in chronic kidney disease (CKD). Previously, we demonstrated that agouti-related peptide (AgRP), a melenocortin-4 receptor antagonist, reduced CKD-associated cachexia in CKD mice. Our previous studies with AgRP utilized dual energy X-ray (DXA) densitometry to assess the body composition in mice (Cheung W, Kuo HJ, Markison S, Chen C, Foster AC, Marks DL, Mak RH. J Am Soc Nephrol 18: 2517–2524, 2007; Cheung W, Yu PX, Little BM, Cone RD, Marks DL, Mak RH. J Clin Invest 115: 1659–1665, 2005). DXA is unable to differentiate water content in mice, and fluid retention in CKD may lead to an overestimate of lean mass. In this study, we employed quantitative magnetic resonance technique to evaluate body composition change following central administration of AgRP in a CKD mouse model. AgRP treatment improved energy expenditure, total body mass, fat mass, and lean body mass in CKD mouse. We also investigated the effect of CKD-associated cachexia on the signaling pathways leading to wasting in skeletal muscle, as well as whether these changes can be ameliorated by central administration of AgRP. AgRP treatment caused an overall decrease in proinflammatory cytokines, which may be one important mechanism of its effects. Muscle wasting in CKD may be due to the activation of proteolytic pathways as well as inhibition of myogenesis and muscle regeneration processes. Our results suggest that these aberrant pathological pathways leading to muscle wasting in CKD mice were ameliorated by central administration of AgRP. PMID:22914778

  10. 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

    , MCP-1, and MIP-1α and plasma cTnI were increased (P < 0.05). Histologically, all rats in control group showed significant (P < 0.05) cardiac injury. Furthermore, all rats in control group showed significant (P < 0.05) apoptosis. Simvastatin significantly counteracted the increase in myocardium level of TNF-α, IL-1B, IL-6, MCP-1 and MIP-1α, plasma cTnI, and apoptosis (P < 0.05). Histological analysis revealed that Simvastatin markedly reduced (P < 0.05) the severity of heart injury in the rats that underwent LAD ligation procedure. Conclusions. The results of the present study reveal that Simvastatin may ameliorate myocardial I/R injury in rats via interfering with inflammatory reactions and apoptosis which were induced by I/R injury. PMID:24455299

  11. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats.

    PubMed

    Nagib, Marwa M; Tadros, Mariane G; ElSayed, Moushira I; Khalifa, Amani E

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5days. OLM-M (1, 3 and 10mg/kg) was administered orally during 21days prior to the induction of colitis, and for 5days after. Sulfasalazine (500mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. PMID:23665423

  12. Sesamin Ameliorates High-Fat Diet–Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress

    PubMed Central

    Zhang, Ruijuan; Yu, Yan; Deng, Jianjun; Zhang, Chao; Zhang, Jinghua; Cheng, Yue; Luo, Xiaoqin; Han, Bei; Yang, Haixia

    2016-01-01

    The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia. PMID:27171111

  13. Sesamin Ameliorates High-Fat Diet-Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress.

    PubMed

    Zhang, Ruijuan; Yu, Yan; Deng, Jianjun; Zhang, Chao; Zhang, Jinghua; Cheng, Yue; Luo, Xiaoqin; Han, Bei; Yang, Haixia

    2016-01-01

    The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia. PMID:27171111

  14. Evaluation of the Effectiveness of Piper cubeba Extract in the Amelioration of CCl4-Induced Liver Injuries and Oxidative Damage in the Rodent Model

    PubMed Central

    AlSaid, Mansour; Mothana, Ramzi; Raish, Mohammad; Al-Sohaibani, Mohammed; Al-Yahya, Mohammed; Ahmad, Ajaz; Al-Dosari, Mohammed; Rafatullah, Syed

    2015-01-01

    Background. Liver diseases still represent a major health burden worldwide. Moreover, medicinal plants have gained popularity in the treatment of several diseases including liver. Thus, the present study was to evaluate the effectiveness of Piper cubeba fruits in the amelioration of CCl4-induced liver injuries and oxidative damage in the rodent model. Methods. Hepatoprotective activity was assessed using various biochemical parameters like SGOT, SGPT, γ-GGT, ALP, total bilirubin, LDH, and total protein. Meanwhile, in vivo antioxidant activities as LPO, NP-SH, and CAT were measured in rat liver as well as mRNA expression of cytokines such as TNFα, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. The extent of liver damage was also analyzed through histopathological observations. Results. Treatment with PCEE significantly and dose dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, PCEE significantly reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes NP-SH and CAT towards normal levels. The administration of PCEE significantly downregulated the CCl4-induced proinflammatory cytokines TNFα and IL-6 mRNA expression in dose dependent manner, while it upregulated the IL-10 and induced hepatoprotective effect by downregulating mRNA expression of iNOS and HO-1 gene. PMID:25654097

  15. Effects of prolonged consumption of water with elevated nitrate levels on certain metabolic parameters of dairy cattle and use of clinoptilolite for their amelioration.

    PubMed

    Katsoulos, P D; Karatzia, M A; Polizopoulou, Z; Florou-Paneri, P; Karatzias, H

    2015-06-01

    Elevated levels of nitrates in feed and water can pose a significant risk for dairy cattle, due to their cumulative action. The effect of prolonged consumption of water naturally contaminated with nitrates on some metabolic parameters in dairy cows was investigated at the present study. Concurrently, whether in-feed inclusion of clinoptilolite, a natural zeolite with high selectivity for ammonia cations, could ameliorate nitrate consumption consequences was examined. Two experiments were run simultaneously in two farms each. In both, farms were assigned into two groups according to nitrate levels in borehole water (NG > 40 ppm; CG < 40 ppm). Furthermore, in experiment 2, the incorporation of clinoptilolite in the ration was taken into account (NC-clinoptilolite feeding; CNC-controls). In experiment 1, blood urea nitrogen (BUN) and beta-hydroxybutyrate (BHBA) concentrations appeared to be affected by nitrate consumption and were significantly higher in NG animals. In experiment 2, BUN concentration was significantly lower in the NC group. The prolonged consumption of water with increased nitrate levels seemed, to some degree, to impair protein metabolism and glucose utilization, while the dietary administration of clinoptilolite could alleviate the nitrates' effects. PMID:25874417

  16. Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways.

    PubMed

    Zhou, Jun; Xu, Gang; Ma, Shuai; Li, Fen; Yuan, Miao; Xu, Huibi; Huang, Kaixun

    2015-11-27

    Catalpol, a bioactive component from the root of Rehmannia glutinosa, has been shown to possess hypoglycemic effects in type 2 diabetic animal models, however, the underlying mechanisms remain poorly understood. Here we investigated the effect of catalpol on high-fat diet (HFD)-induced insulin resistance and adipose tissue inflammation in mice. Oral administration of catalpol at 100 mg/kg for 4 weeks had no effect on body weight of HFD-induced obese mice, but it significantly improved fasting glucose and insulin levels, glucose tolerance and insulin tolerance. Moreover, macrophage infiltration into adipose tissue was markedly reduced by catalpol. Intriguingly, catalpol also significantly reduced mRNA expressions of M1 pro-inflammatory cytokines, but increased M2 anti-inflammatory gene expressions in adipose tissue. Concurrently, catalpol significantly suppressed the c-Jun NH2-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways in adipose tissue. Collectively, these results suggest that catalpol may ameliorate HFD-induced insulin resistance in mice by attenuating adipose tissue inflammation and suppressing the JNK and NF-κB pathways, and thus provide important new insights into the underlying mechanisms of the antidiabetic effect of catalpol. PMID:26474703

  17. Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes.

    PubMed

    Lee, Hee Jae; Hong, Young-Shick; Jun, Woojin; Yang, Soo Jin

    2015-11-01

    Low-grade chronic inflammation (metaflammation) is a major contributing factor for the onset and development of metabolic diseases, such as type 2 diabetes, obesity, and cardiovascular disease. Nicotinamide riboside (NR), which is present in milk and beer, is a functional vitamin B3 having advantageous effects on metabolic regulation. However, the anti-inflammatory capacity of NR is unknown. This study evaluated whether NR modulates hepatic nucleotide binding and oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Male, 8-week-old KK/HlJ mice were allocated to the control or NR group. NR (100 mg/kg/day) or vehicle (phosphate-buffered saline) was administrated by an osmotic pump for 7 days. Glucose control, lipid profiles, NLRP3 inflammasome, and inflammation markers were analyzed, and structural and histological analyses were conducted. NR treatment did not affect body weight gain, food intake, and liver function. Glucose control based on the oral glucose tolerance test and levels of serum insulin and adiponectin was improved by NR treatment. Among tested lipid profiles, NR lowered the total cholesterol concentration in the liver. Histological and structural analysis by hematoxylin and eosin staining and transmission electron microscopy, respectively, showed that NR rescued the disrupted cellular integrity of the mitochondria and nucleus in the livers of obese and diabetic KK mice. In addition, NR treatment significantly improved hepatic proinflammatory markers, including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1. These ameliorations were accompanied by significant shifts of NLRP3 inflammasome components (NLRP3, ASC, and caspase1). These results demonstrate that NR attenuates hepatic metaflammation by modulating the NLRP3 inflammasome. PMID:25974041

  18. Antioxidant and anti-inflammatory potential of pomegranate rind extract to ameliorate cisplatin-induced acute kidney injury.

    PubMed

    Karwasra, Ritu; Kalra, Prerna; Gupta, Yogendra Kumar; Saini, Deepika; Kumar, Ajay; Singh, Surender

    2016-07-13

    Cisplatin is a chemotherapeutic agent, but the therapeutic utility is limited due to its dose dependent nephrotoxicity. The aim of the present study was to evaluate the nephroprotective effect of pomegranate in cisplatin-induced acute kidney injury. Wistar rats were allocated into six groups as follows: the normal control, cisplatin-induced, pomegranate rind extract treatment (50, 100 and 200 mg kg(-1)) and pomegranate rind extract per se group. All the experimental test drugs/vehicle were administered orally for a period of ten days. Intraperitoneal injection of cisplatin (8 mg kg(-1)) was administered on day 7 to all the groups except the normal control and pomegranate per se group. On day 10, cisplatin resulted in significant nephrotoxicity in Wistar rats with a drastic elevation of serum creatinine and BUN, a decline in the concentrations of GSH, MDA and superoxide dismutase (SOD), and an elevation in the TNF-α level in renal tissues. Pathological changes in renal tissues were examined by histopathology and dysfunction in mitochondria and proximal tubule cells was detected by transmission electron microscopy. The rate of apoptosis and the expression of caspase-3, Il-1β and IL-6 in rat renal tissues were detected by immunohistochemistry. The administration of pomegranate at a dose of 200 mg per kg body weight significantly (p < 0.001) ameliorates increased serum creatinine and BUN. In parallel to this, pomegranate also exhibits anti-apoptotic activity through the reduction of active caspase-3 expression in kidneys. Additionally, in-silico studies also confirmed a renoprotective effect of pomegranate. The above findings suggest that pomegranate can be used as a dietary supplement in the treatment of cisplatin-induced kidney injury by reducing apoptosis, oxidative stress and inflammation. PMID:27273121

  19. Amelioration of acidic soil using various renewable waste resources.

    PubMed

    Moon, Deok Hyun; Chang, Yoon-Young; Ok, Yong Sik; Cheong, Kyung Hoon; Koutsospyros, Agamemnon; Park, Jeong-Hun

    2014-01-01

    In this study, improvement of acidic soil with respect to soil pH and exchangeable cations was attempted for sample with an initial pH of approximately 5. Acidic soil was amended with various waste resources in the range of 1 to 5 wt.% including waste oyster shells (WOS), calcined oyster shells (COS), Class C fly ash (FA), and cement kiln dust (CKD) to improve soil pH and exchangeable cations. Upon treatment, the soil pH was monitored for periods up to 3 months. The exchangeable cations were measured after 1 month of curing. After a curing period of 1 month, a maize growth experiment was conducted with selected-treated samples to evaluate the effectiveness of treatment. The treatment results indicate that in order to increase the soil pH to a value of 7, 1 wt.% of WOS, 3 wt.% of FA, and 1 wt.% of CKD are required. In the case of COS, 1 wt.% was more than enough to increase the soil pH value to 7 because of COS's strong alkalinity. Moreover, the soil pH increases after a curing period of 7 days and remains virtually unchanged thereafter up to 1 month of curing. Upon treatment, the summation of cations (Ca, Mg, K, and Na) significantly increased. The growth of maize is superior in the treated samples rather than the untreated one, indicating that the amelioration of acidic soil is beneficial to plant growth, since soil pH was improved and nutrients were replenished. PMID:24078235

  20. Black Cohosh Ameliorates Metabolic Disorders in Female Ovariectomized Rats.

    PubMed

    Sun, Yu; Yu, Qiuxiao; Shen, Qiyang; Bai, Wenpei; Kang, Jihong

    2016-06-01

    Estrogen deficiency is associated with metabolic derangements in menopausal women. Black cohosh has been widely used as an alternative therapy in the treatment of menopausal syndrome. However, its role in metabolism needs to be defined. The aim of the present study was to investigate the long-term effect of black cohosh on glucose and lipid metabolism in a rat model of post-menopause. Adult female Sprague-Dawley rats were sham operated (SHAM), ovariectomized (OVX), OVX with the treatment of estradiol valerate (OVX + E), or OVX with the treatment of isopropanolic black cohosh extract (OVX + iCR). Body weight, body composition, and blood glucose levels of the animals were monitored. The rats were then sacrificed after 3 months of the treatments. At the end of the experiment, OVX + iCR and OVX + E rats exhibited a significant decrease in body weight gain, body and abdominal fat mass, serum triglycerides levels, hepatic fat accumulation, and adipocyte hypertrophy compared with OVX rats. In addition, insulin resistance and glucose intolerance were improved in OVX + iCR but not in OVX + E rats. No hepatotoxicity was detected in OVX + iCR animals. Furthermore, western blot analysis suggested the increased lipolysis in adipose tissue of OVX + iCR and OVX + E rats. Data from in vitro experiments using cultured primary rat adipocytes also showed that black cohosh could affect lipolysis of adipocytes. In conclusion, the long-term treatment of black cohosh at a proper dosage ameliorated metabolic derangements in OVX rats. Thus, this drug is promising for the treatment of metabolic disorders in menopausal and post-menopausal women. PMID:26414761

  1. Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

    PubMed Central

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

    2012-01-01

    Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR. PMID:22315654

  2. Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress.

    PubMed

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

    2012-01-01

    Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR. PMID:22315654

  3. Administrative IT

    ERIC Educational Resources Information Center

    Grayson, Katherine, Ed.

    2006-01-01

    When it comes to Administrative IT solutions and processes, best practices range across the spectrum. Enterprise resource planning (ERP), student information systems (SIS), and tech support are prominent and continuing areas of focus. But widespread change can also be accomplished via the implementation of campuswide document imaging and sharing,…

  4. Engineering Administration.

    ERIC Educational Resources Information Center

    Naval Personnel Program Support Activity, Washington, DC.

    This book is intended to acquaint naval engineering officers with their duties in the engineering department. Standard shipboard organizations are analyzed in connection with personnel assignments, division operations, and watch systems. Detailed descriptions are included for the administration of directives, ship's bills, damage control, training…

  5. ADMINISTRATIVE CLIMATE.

    ERIC Educational Resources Information Center

    BRUCE, ROBERT L.; CARTER, G.L., JR.

    IN THE COOPERATIVE EXTENSION SERVICE, STYLES OF LEADERSHIP PROFOUNDLY AFFECT THE QUALITY OF THE SERVICE RENDERED. ACCORDINGLY, MAJOR INFLUENCES ON ADMINISTRATIVE CLIMATE AND EMPLOYEE PRODUCTIVITY ARE EXAMINED IN ESSAYS ON (1) SOURCES OF JOB SATISFACTION AND DISSATISFACTION, (2) MOTIVATIONAL THEORIES BASED ON JOB-RELATED SATISFACTIONS AND NEEDS,…

  6. Database Administrator

    ERIC Educational Resources Information Center

    Moore, Pam

    2010-01-01

    The Internet and electronic commerce (e-commerce) generate lots of data. Data must be stored, organized, and managed. Database administrators, or DBAs, work with database software to find ways to do this. They identify user needs, set up computer databases, and test systems. They ensure that systems perform as they should and add people to the…

  7. 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…

  8. 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

  9. Apelin administration ameliorates high fat diet-induced cardiac hypertrophy and contractile dysfunction.

    PubMed

    Ceylan-Isik, Asli F; Kandadi, Machender R; Xu, Xihui; Hua, Yinan; Chicco, Adam J; Ren, Jun; Nair, Sreejayan

    2013-10-01

    Apelin has been recognized as an adipokine that plays an important role in regulating energy metabolism and is credited with antiobesity and antidiabetic properties. This study was designed to examine the effect of exogenous apelin on obesity-associated cardiac dysfunction. Oral glucose tolerance test, echocardiography, cardiomyocyte contractile and intracellular Ca(2+) properties were assessed in adult C57BL/6J mice fed - low or a - high-fat diet for 24weeks followed by apelin treatment (100nmol/kg, i.p. for 2weeks). High-fat diet resulted in increased left ventricular diastolic and systolic diameters, and wall thickness, compromised fractional shortening, impaired cardiomyocyte mechanics (peak-shortening, maximal velocity of shortening/relengthening, and duration of shortening and relengthening) and compromised intracellular Ca(2+) handling, all of which were reconciled by apelin. Apelin treatment also reversed high fat diet-induced changes in intracellular Ca(2+) regulatory proteins, ER stress, and autophagy. In addition, microRNAs (miR) -133a, miR-208 and miR-1 which were elevated following high-fat feeding were attenuated by apelin treatment. In cultured cardiomyocytes apelin reconciled palmitic acid-induced cardiomyocyte contractile anomalies. Collectively, these data depict a pivotal role of apelin in obesity-associated cardiac contractile dysfunction, suggesting a therapeutic potential of apelin in the management of cardiac dysfunction associated with obesity. PMID:23859766

  10. Tamarindus indica L. and Moringa oleifera M. extract administration ameliorates fluoride toxicity in rabbits.

    PubMed

    Ranjan, R; Swarup, D; Patra, R C; Chandra, Vikas

    2009-11-01

    Aqueous extracts of T. indica fruit pulp (100 mg/kg body weight) and M. oleifera seeds (50 mg/kg body wight) orally once daily for 90 days lowered plasma fluoride concentrations in rabbits receiving fluorinated drinking water (200 mg NaF/ Liter water). Cortical indices and metaphysial width in animals receiving extracts also revealed beneficial effects of plant extracts. Changes in plasma biochemistry suggested less hepatic and renal damages in animals receiving plant extracts along with fluorinated water in comparison to that receiving fluorinated water alone. Preliminary results revealed these plant extracts have some potential to mitigate fluoride toxicity. PMID:20099463

  11. Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma.

    PubMed

    Firinci, Fatih; Karaman, Meral; Baran, Yusuf; Bagriyanik, Alper; Ayyildiz, Zeynep Arikan; Kiray, Muge; Kozanoglu, Ilknur; Yilmaz, Osman; Uzuner, Nevin; Karaman, Ozkan

    2011-08-01

    Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n=6), Group 2 (ovalbumin induced asthma only, n=10), Group 3 (ovalbumin induced asthma + MSCs, n=10), and Group 4 (MSCs only, n=10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma. PMID:21439399

  12. Simvastatin Ameliorates Radiation Enteropathy Development After Localized, Fractionated Irradiation by a Protein C-Independent Mechanism

    SciTech Connect

    Wang Junru; Boerma, Marjan; Fu Qiang; Kulkarni, Ashwini; Fink, Louis M.; Hauer-Jensen, Martin . E-mail: mhjensen@life.uams.edu

    2007-08-01

    Purpose: Microvascular injury plays a key role in normal tissue radiation responses. Statins, in addition to their lipid-lowering effects, have vasculoprotective properties that may counteract some effects of radiation on normal tissues. We examined whether administration of simvastatin ameliorates intestinal radiation injury, and whether the effect depends on protein C activation. Methods and Materials: Rats received localized, fractionated small bowel irradiation. The animals were fed either regular chow or chow containing simvastatin from 2 weeks before irradiation until termination of the experiment. Groups of rats were euthanized at 2 weeks and 26 weeks for assessment of early and delayed radiation injury by quantitative histology, morphometry, and quantitative immunohistochemistry. Dependency on protein C activation was examined in thrombomodulin (TM) mutant mice with deficient ability to activate protein C. Results: Simvastatin administration was associated with lower radiation injury scores (p < 0.0001), improved mucosal preservation (p = 0.0009), and reduced thickening of the intestinal wall and subserosa (p = 0.008 and p = 0.004), neutrophil infiltration (p = 0.04), and accumulation of collagen I (p = 0.0003). The effect of simvastatin was consistently more pronounced for delayed than for early injury. Surprisingly, simvastatin reduced intestinal radiation injury in TM mutant mice, indicating that the enteroprotective effect of simvastatin after localized irradiation is unrelated to protein C activation. Conclusions: Simvastatin ameliorates the intestinal radiation response. The radioprotective effect of simvastatin after localized small bowel irradiation does not appear to be related to protein C activation. Statins should undergo clinical testing as a strategy to minimize side effects of radiation on the intestine and other normal tissues.

  13. Naringin and Sertraline Ameliorate Doxorubicin-Induced Behavioral Deficits Through Modulation of Serotonin Level and Mitochondrial Complexes Protection Pathway in Rat Hippocampus.

    PubMed

    Kwatra, Mohit; Jangra, Ashok; Mishra, Murli; Sharma, Yogita; Ahmed, Sahabuddin; Ghosh, Pinaki; Kumar, Vikas; Vohora, Divya; Khanam, Razia

    2016-09-01

    The present study was designed to investigate the neuroprotective effect of naringin (NR) alone as well as its combination with sertraline (SRT) against doxorubicin (DOX)-induced neurobehavioral and neurochemical anomalies. DOX (15 mg/kg; i.p.) administration caused behavioral alterations, oxidative stress, neuroinflammation, mitochondrial dysfunction and monoamines alteration in male Wistar rats. NR (50 and 100 mg/kg; i.p.) and SRT (5 mg/kg; i.p.) treatment significantly attenuated DOX-induced anxiety and depressive-like behavior as evident from elevated plus maze (EPM) and modified forced swimming test (mFST), respectively. NR treatment significantly attenuated DOX-induced raised plasma corticosterone (CORT), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the hippocampus (HC). Furthermore, we found that combination of NR and SRT regimen ameliorated DOX-induced behavioral anomalies through modulation of the 5-HT level and mitochondrial complexes protection pathway along with alleviation of oxidative stress in the HC region. Therefore, NR treatment alone or in combination with SRT could be beneficial against DOX-induced neurotoxicity. PMID:27209303

  14. Baclofen, a GABABR Agonist, Ameliorates Immune-Complex Mediated Acute Lung Injury by Modulating Pro-Inflammatory Mediators

    PubMed Central

    Jin, Shunying; Merchant, Michael L.; Ritzenthaler, Jeffrey D.; McLeish, Kenneth R.; Lederer, Eleanor D.; Torres-Gonzalez, Edilson; Fraig, Mostafa; Barati, Michelle T.; Lentsch, Alex B.; Roman, Jesse; Klein, Jon B.; Rane, Madhavi J.

    2015-01-01

    Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting a

  15. A Change of Administration: A Significant Organizational Life Event.

    ERIC Educational Resources Information Center

    Stine, Deborah E.

    The case study presented in this paper illustrates how the succession process for principals is similar to that described by Gabarro in his study of corporate succession. Leader succession involves five major stages: (1) taking hold; (2) immersion; (3) reshaping; (4) consolidation; and (5) refinement. Success most frequently occurs in conjunction…

  16. Tempol, a Superoxide Dismutase Mimetic Agent, Ameliorates Cisplatin-Induced Nephrotoxicity through Alleviation of Mitochondrial Dysfunction in Mice

    PubMed Central

    Ahmed, Lamiaa A.; Shehata, Nagwa I.; Abdelkader, Noha F.; Khattab, Mahmoud M.

    2014-01-01

    Background Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice. Methods and Findings Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg) with or without oral administration of tempol (100 mg/kg/day). Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP) content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I–IV activities and mitochondrial nitric oxide synthase (mNOS) protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma. Conclusion This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction

  17. Soluble MOG35-55/I-Ab Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells

    PubMed Central

    Gong, Yeli; Wang, Zhigang; Liang, Zhihui; Duan, Hongxia; Ouyang, Lichen; Yu, Qian; Xu, Zhe; Shen, Guanxin; Weng, Xiufang; Wu, Xiongwen

    2012-01-01

    The MOG35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice is a useful animal model to explore therapeutic approaches to T cell-mediated autoimmune diseases because the dominant T-cell epitope(s) have been defined. It is rational that antigen-specific immunosuppression can be induced by using MHC-peptide complexes as specific TCR ligand(s) that interact with autoreactive T cells in the absence of co-stimulation. In this study, a soluble divalent MOG35-55/I-Ab fusion protein (MOG35-55/I-Ab dimer) was constructed to specifically target the autoreactive CD4+ T cells in the EAE mouse. Intraperitoneal administration of the MOG35-55/I-Ab dimer significantly delayed and ameliorated EAE symptoms by reducing EAE-related inflammation in the mouse CNS and reducing encephalitogenic Th1 and Th17 cells in the peripheral lymphoid organs. We observed that dimer intervention at a concentration of 1.2 nM suppressed MOG35-55 peptide-specific 2D2 transgenic T cells (2D2 T cells) proliferation by over 90% after in vitro activation with MOG35-55 peptide. The mechanisms involved in this antigen-specific dimer-mediated suppression were found to be downregulated TCR-CD3 expression as well as upregulated expression of membrane-bound TGF-β (mTGF-β) and IL-10 suppressive cytokines by the autoreactive CD4+ T cells. Collectively, our data demonstrates that soluble divalent MHC class II molecules can abrogate pathogenic T cells in EAE. Furthermore, our data suggests that this strategy may provide an efficient and clinically useful option to treat autoimmune diseases. PMID:23077616

  18. Ginger Essential Oil Ameliorates Hepatic Injury and Lipid Accumulation in High Fat Diet-Induced Nonalcoholic Fatty Liver Disease.

    PubMed

    Lai, Yi-Syuan; Lee, Wan-Ching; Lin, Yu-En; Ho, Chi-Tang; Lu, Kuan-Hung; Lin, Shih-Hang; Panyod, Suraphan; Chu, Yung-Lin; Sheen, Lee-Yan

    2016-03-16

    The objective of this study was to investigate the hepatoprotective efficacy and mechanism of action of ginger essential oil (GEO) against the development of nonalcoholic fatty liver disease (NAFLD). Mice were maintained on either a control diet or high-fat diet (HFD) supplemented with GEO (12.5, 62.5, and 125 mg/kg) or citral (2.5 and 25 mg/kg) for 12 weeks. We demonstrated that GEO and its major component (citral) lowered HFD-induced obesity in a dose-dependent manner, accompanied by anti-hyperlipidemic effects by reducing serum free fatty acid, triglyceride, and total cholesterol levels. Moreover, liver histological results showed that administration of 62.5 and 125 mg/kg GEO and 25 mg/kg citral significantly reduced hepatic lipid accumulation. Further assessment by Western blotting and investigation of the lipid metabolism revealed that hepatic protein expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and cytochrome P450 2E1 (CYP2E1) were down-regulated by GEO and citral, indicating that GEO and citral suppressed HFD-stimulated lipid biosynthesis and oxidative stress. Furthermore, GEO and citral effectively enhanced the antioxidant capacities and reduced inflammatory response in mouse liver, which exerted protective effects against steatohepatitis. Collectively, GEO and citral exhibited potent hepatoprotective effects against NAFLD induced by HFD in obese mice. Thus, GEO might be an effective dietary supplement to ameliorate NAFLD-related metabolic diseases, and citral could play a vital role in its management. PMID:26900108

  19. Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice.

    PubMed

    Sheng, Xiaoyan; Wang, Min; Lu, Meng; Xi, Beili; Sheng, Hongguang; Zang, Ying Qin

    2011-05-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and inflammatory disorders. In this study, we tested the effect of rhein, a lipophilic anthraquinone derived from a traditional Chinese herbal medicine Rheum palmatum L., on NAFLD-associated hepatic steatosis, insulin resistance, and the T helper (Th)1/Th2 cytokine imbalance in high-fat diet-induced obese (DIO) mice. We found that oral administration of rhein for 40 days significantly increased energy expenditure, reduced body weight, particularly body fat content, improved insulin resistance, and lowered circulating cholesterol levels in DIO mice without affecting food intake. Rhein treatment also reduced liver triglyceride levels, reversed hepatic steatosis, and normalized alanine aminotransferase (ALT) levels in these mice. Gene analysis and Western blot showed that rhein markedly suppressed the expression of the lipogenic enzyme sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes in the liver. Luciferase reporter assay revealed that rhein suppressed the transcriptional activity of SREBP-1c through its upstream regulator, liver X receptor (LXR). This suggests that rhein exerts its effects by targeting LXR, which is also supported by its inability to reduce body weight in LXR knockout mice. Moreover, multiplex ELISA displayed a downregulated Th1 response after rhein treatment. Rhein shifted the Th1/Th2 responses by inhibiting T-box expressed in T-cells (T-bet) expression and enhancing GATA-binding protein-3 (GATA-3) expression through increased signal transducer and activator of transcription 6 (STAT6) phosphorylation. These data indicate that rhein ameliorated NAFLD and associated disorders through LXR-mediated negative energy balance, metabolic regulatory pathways, and immunomodulatory activities involved in hepatic steatosis. The combined effects of rhein to target hepatic metabolic and immune pathways may be beneficial for complex metabolic

  20. Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro by activating autophagy

    PubMed Central

    Liu, Hong; Gu, Liu-bao; Tu, Yue; Hu, Hao; Huang, Yan-ru; Sun, Wei

    2016-01-01

    Aim: A previous report shows that emodin extracted from the Chinese herbs rhubarb and giant knotweed rhizome can ameliorate the anticancer drug cisplatin-induced injury of HEK293 cells. In this study, we investigated whether and how emodin could protect renal tubular epithelial cells against cisplatin-induced nephrotoxicity in vitro. Methods: The viability and apoptosis of normal rat renal tubular epithelial cells (NRK-52E) were detected using formazan assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy maker LC3 I/II, and AMPK/mTOR signaling pathway-related proteins were measured with Western blot analysis. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy. Results: Cisplatin (10-50 μmol/L) dose-dependently induced cell damage and apoptosis in NRK-52E cells, whereas emodin (10 and 100 μmol/L) significantly ameliorated cisplatin-induced cell damage, apoptosis and caspase-3 cleavage. Emodin dose-dependently increased LC3-II levels and induced RFP-LC3-containing punctate structures in NRK-52E cells. Furthermore, the protective effects of emodin were abolished by bafilomycin A1 (10 nmol/L), and mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 μmol/L) not only abolished emodin-induced autophagy activation, but also emodin-induced anti-apoptotic effects. Conclusion: Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro through modulating the AMPK/mTOR signaling pathways and activating autophagy. Emodin may have therapeutic potential for the prevention of cisplatin-induced nephrotoxicity. PMID:26775661

  1. Amelioration of scopolamine-induced amnesia by phosphatidylserine and curcumin in the day-old chick.

    PubMed

    Barber, Teresa A; Edris, Edward M; Levinsky, Paul J; Williams, Justin M; Brouwer, Ari R; Gessay, Shawn A

    2016-09-01

    In the one-trial taste-avoidance task in day-old chicks, acetylcholine receptor activation has been shown to be important for memory formation. Injection of scopolamine produces amnesia, which appears to be very similar in type to that of Alzheimer's disease, which is correlated with low levels of acetylcholine in the brain. Traditional pharmacological treatments of Alzheimer's disease, such as cholinesterase inhibitors and glutamate receptor blockers, improve memory and delay the onset of impairments in memory compared with placebo controls. These agents also ameliorate scopolamine-induced amnesia in the day-old chick trained on the one-trial taste-avoidance task. The present experiments examined the ability of two less traditional treatments for Alzheimer's disease, phosphatidylserine and curcumin, to ameliorate scopolamine-induced amnesia in day-old chicks. The results showed that 37.9 mmol/l phosphatidylserine and 2.7 mmol/l curcumin significantly improved retention in chicks administered scopolamine, whereas lower doses were not effective. Scopolamine did not produce state-dependent learning, indicating that this paradigm in day-old chicks might be a useful one to study the effects of possible Alzheimer's treatments. In addition, chicks administered curcumin or phosphatidylserine showed little avoidance of a bead associated with water reward, indicating that these drugs did not produce response inhibition. The current results extend the findings that some nontraditional memory enhancers can ameliorate memory impairment and support the hypothesis that these treatments might be of benefit in the treatment of Alzheimer's disease. PMID:27388114

  2. Polymerase I pathway inhibitor ameliorates experimental autoimmune encephalomyelitis.

    PubMed

    Achiron, Anat; Mashiach, Roi; Zilkha-Falb, Rina; Meijler, Michael M; Gurevich, Michael

    2013-10-15

    Applying high throughput gene expression microarrays we identified that the suppression of polymerase 1 (POL1) pathway is associated with benign course of multiple sclerosis (MS). This finding supports the rationale for direct targeting of the POL1 transcription machinery as an innovative strategy to suppress MS. To evaluate the effects of a specific polymerase I inhibitor (POL1-I) on experimental autoimmune encephalomyelitis (EAE), we immunized female C57BL/6J mice (8 weeks) with MOG35-55/CFA. A new POL1-I was administered at a daily dose of 12.5mg/kg body weight by oral gavage either from the day of immunization until disease onset (EAE score 1.0, immunization model), at disease onset (EAE score=1.0) for the following 14 days (treatment model), or by alternate daily dose of 25.0mg/kg body weight, by oral gavage from the day of immunization for the following 25 days (combined model). POL1-I remarkably suppressed EAE in the immunization model; while in the Vehicle group the onset of EAE occurred on day 10.0±0.4 with maximal clinical score of 3.2±0.2, in the POL1-I treated mice onset was significantly delayed and occurred on day 16.9±1.1 (p=0.001), and maximal disease score 2.0±0.1 was reduced (p=0.004). In the treatment model POL1-I treatment significantly reduced disease activity; maximal score was 2.0±0.5 while in the Vehicle group it reached a mean maximal score of 3.9±0.1, (p=0.0008). In the combined model, POL1-I treatment completely inhibited disease activity. The effect of POL1-I treatment was modulated through decreased expression of POL1 pathway key-related genes LRPPRC, pre-RNA, POLR1D and RRN3 together with activation of P53 dependent apoptosis of CD4+ splenocytes. Our findings demonstrate that POL1 pathway inhibition delayed and suppressed the development of EAE and ameliorated the disease in mice with persistent clinical signs. PMID:23998422

  3. Basic Fibroblast Growth Factor Ameliorates Endothelial Dysfunction in Radiation-Induced Bladder Injury

    PubMed Central

    Zhang, Shiwei; Qiu, Xuefeng; Zhang, Yanting; Fu, Kai; Zhao, Xiaozhi; Wu, Jinhui; Hu, Yiqiao; Zhu, Weiming; Guo, Hongqian

    2015-01-01

    This study was designed to explore the effect of basic fibroblast growth factor (bFGF) on radiation-induced endothelial dysfunction and histological changes in the urinary bladder. bFGF was administrated to human umbilical vein cells (HUVEC) or urinary bladder immediately after radiation. Reduced expression of thrombomodulin (TM) was indicated in the HUVEC and urinary bladder after treatment with radiation. Decreased apoptosis was observed in HUVEC treated with bFGF. Administration of bFGF increased the expression of TM in HUVEC medium, as well as in the urinary bladder at the early and delayed phases of radiation-induced bladder injury (RIBI). At the early phase, injection of bFGF increased the thickness of urothelium and reduced inflammation within the urinary bladder. At the delayed phase, bFGF was effective in reducing fibrosis within the urinary bladder. Our results indicate that endothelial dysfunction is a prominent feature of RIBI. Administration of bFGF can ameliorate radiation-induced endothelial dysfunction in urinary bladder and preserve bladder histology at early and delayed phases of RIBI. PMID:26351640

  4. 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

  5. Antidepressant fluvoxamine reduces cerebral infarct volume and ameliorates sensorimotor dysfunction in experimental stroke.

    PubMed

    Sato, Shinsuke; Kawamata, Takakazu; Kobayashi, Tomonori; Okada, Yoshikazu

    2014-07-01

    The sigma-1 receptor has been reported to be associated with diverse biological activities including cellular differentiation, neuroplasticity, neuroprotection, and cognitive functioning of the brain. Fluvoxamine, one of the currently known antidepressants, is a sigma-1 receptor agonist; its effectiveness in treating acute cerebral ischemia has not been reported. We studied the in-vivo effects of this compound using an animal model of focal cerebral ischemia. Forty male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion and assigned to five treatment groups (n=8 each). Postischemic neurological deficits and infarct volume were determined 24 h after stroke-inducing surgery. Significant reductions in infarct volume (total and cortical) were found in group 2 (fluvoxamine 20 mg/kg given 6 h before and immediately after ischemic onset) and group 3 (fluvoxamine given immediately after ischemic onset and 2 h later) compared with controls. Fluvoxamine induced significant amelioration of sensorimotor dysfunction, as indicated by the scores of forelimb and hindlimb placing tests. Moreover, NE-100, a selective sigma-1 receptor antagonist, completely blocked the neuroprotective effect of fluvoxamine. The present findings suggest that the sigma-1 receptor agonist fluvoxamine reduces infarct volume and ameliorates neurological impairment even on postischemic treatment. From the clinical viewpoint, fluvoxamine may be a promising new therapeutic approach for cerebral infarction. PMID:24709917

  6. Protective effect of potato peel powder in ameliorating oxidative stress in streptozotocin diabetic rats.

    PubMed

    Singh, Nandita; Kamath, Vasudeva; Rajini, P S

    2005-06-01

    The potential of dietary potato peel (PP) powder in ameliorating oxidative stress (OS) and hyperglycemia was investigated in streptozotocin (STZ)-induced diabetic rats. In a 4-week feeding trial, incorporation of potato peel powder (5 and 10%) in the diet of diabetic rats was found to significantly reduce the plasma glucose level and also reduce drastically the polyuria of STZ diabetic rats. The total food intake was significantly reduced in the diabetic rats fed 10% PP powder compared to the control diabetic rats. However, the body weight gain over 28 days was nearly four times greater in PP powder supplemented diabetic rats (both at 5 and 10%) compared to the control diabetic rats. PP powder in the diet also decreased the elevated activities of serum transaminases (ALT and AST) and nearly normalized the hepatic MDA and GSH levels as well as the activities of specific antioxidant enzymes in liver of diabetic rats. The result of these studies clearly establishes the modulatory propensity of PP against diabetes induced alterations. Considering that potato peels are discarded as waste and not effectively utilized, these results suggest the possibility that PP waste could be effectively used as an ingredient in health and functional food to ameliorate certain disease states such as diabetes. PMID:16021831

  7. Amelioration of oxidative stress by Tabernamontana divaricata on alloxan-induced diabetic rats

    PubMed Central

    Kanthlal, S. K.; Kumar, B. Anil; Joseph, Jipnomon; Aravind, R.; Frank, P. Royal

    2014-01-01

    Objective: The purpose of this study was to evaluate the anti-diabetic activity of ethanol extract of Tabernamontana divaricata (L.) and its ameliorative effect on oxidative stress in alloxan-induced diabetic rats. Materials and Methods: Diabetes was induced by single intraperitoneal injection of alloxan monohydrate (140 mg/kg body weight). Methanol extract of T. divaricata was administered at the doses of 100 and 200 mg/kg body weight in diabetic induced rats including glibenclamide (3 mg/kg) as a reference drug. In the continuous 21 days treatment, fasting blood glucose level was determined on 0, 7, 14 and 21 days. On day 21, serum lipid profiles and glycosylated hemoglobin, liver antioxidant enzymes levels were estimated. Results: Experimental findings showed a significant anti-diabetic potential of the extract in terms of reduction in blood glucose levels and a correct effect on the altered biochemical parameters. Observed data were found statistically significant in correction of antioxidant enzyme level accompanied with diabetes, particularly at the dose of 200 mg/kg body weight. Conclusion: Based on the results, it can be concluded that the T. divaricata is found to be effective in type 2 diabetes in rats and to have an ameliorative effect on the associated oxidative stress. PMID:25593402

  8. Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury

    PubMed Central

    Nakano, Tomoko; Kotani, Tomomi; Mano, Yukio; Tsuda, Hiroyuki; Imai, Kenji; Ushida, Takafumi; Li, Hua; Miki, Rika; Sumigama, Seiji; Sato, Yoshiaki; Iwase, Akira; Hirakawa, Akihiro; Asai, Masato; Toyokuni, Shinya; Kikkawa, Fumitaka

    2015-01-01

    Fetal brain injury is often related to prenatal inflammation; however, there is a lack of effective therapy. Recently, molecular hydrogen (H2), a specific antioxidant to hydroxyl radical and peroxynitrite, has been reported to have anti-inflammatory properties. The aim of this study was to investigate whether maternal H2 administration could protect the fetal brain against inflammation. Pregnant C3H/HeN mice received an intraperitoneal injection of lipopolysaccharide (LPS) on gestational day 15.5 and were provided with H2 water for 24 h prior to LPS injection. Pup brain samples were collected on gestational day 16.5, and the levels of apoptosis and oxidative damage were evaluated using immunohistochemistry. Interleukin-6 (IL-6) levels were examined using real-time PCR. The levels of apoptosis and oxidative damage, as well as the levels of IL-6 mRNA, increased significantly when the mother was injected with LPS than that in the control group. However, these levels were significantly reduced when H2 was administered prior to the LPS-injection. Our results suggest that LPS-induced apoptosis, oxidative damage and inflammation in the fetal brain were ameliorated by maternal H2 administration. Antenatal H2 administration might protect the premature brain against maternal inflammation. PMID:26566302

  9. Amelioration of Diabetes by Protein S.

    PubMed

    Yasuma, Taro; Yano, Yutaka; D'Alessandro-Gabazza, Corina N; Toda, Masaaki; Gil-Bernabe, Paloma; Kobayashi, Tetsu; Nishihama, Kota; Hinneh, Josephine A; Mifuji-Moroka, Rumi; Roeen, Ziaurahman; Morser, John; Cann, Isaac; Motoh, Iwasa; Takei, Yoshiyuki; Gabazza, Esteban C

    2016-07-01

    Protein S is an anticoagulant factor that also regulates inflammation and cell apoptosis. The effect of protein S on diabetes and its complications is unknown. This study compared the development of diabetes between wild-type and transgenic mice overexpressing human protein S and the development of diabetic glomerulosclerosis between mice treated with and without human protein S and between wild-type and protein S transgenic mice. Mice overexpressing protein S showed significant improvements in blood glucose level, glucose tolerance, insulin sensitivity, and insulin secretion compared with wild-type counterparts. Exogenous protein S improved insulin sensitivity in adipocytes, skeletal muscle, and liver cell lines in db/db mice compared with controls. Significant inhibition of apoptosis with increased expression of BIRC3 and Bcl-2 and enhanced activation of Akt/PKB was induced by protein S in islet β-cells compared with controls. Diabetic wild-type mice treated with protein S and diabetic protein S transgenic mice developed significantly less severe diabetic glomerulosclerosis than controls. Patients with type 2 diabetes had significantly lower circulating free protein S than healthy control subjects. This study shows that protein S attenuates diabetes by inhibiting apoptosis of β-cells and the development of diabetic nephropathy. PMID:27207541

  10. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology

    PubMed Central

    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S.; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  11. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology.

    PubMed

    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  12. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

    SciTech Connect

    Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung; Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang; Kim, Won

    2014-08-08

    Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

  13. Atorvastatin Ameliorates Radiation-Induced Cardiac Fibrosis in Rats.

    PubMed

    Zhang, KunYi; He, XuYu; Zhou, Yingling; Gao, Lijuan; Qi, Zhengyu; Chen, Jiyan; Gao, Xiuren

    2015-12-01

    Radiation-induced heart injury is one of the major side effects of radiotherapy for thoracic malignancies. Previous studies have shown that radiotherapy induced myocardial fibrosis and intensified myocardial remodeling. In this study, we investigated whether atorvastatin could inhibit radiation-induced heart fibrosis in Sprague-Dawley rats, which were randomly divided into six groups: control; radiation only; and four treatment groups receiving atorvastatin plus radiation (E1, E2, E3 and E4). All rats, except the control group, received local heart irradiation in 7 daily fractions of 3 Gy for a total of 21 Gy. Rats in groups E1 (10 mg/kg/day) and E2 (20 mg/kg/day) received atorvastatin and radiation treatment until week 12 after exposure. Rats in groups E3 (10 mg/kg/day) and E4 (20 mg/kg/day) received atorvastatin treatment from 3 months before irradiation to week 12 after irradiation. The expressions of TGF-β1, Smad2, Smad3, fibronectin, ROCK I and p-Akt in heart tissues were evaluated using real-time PCR or Western blot analyses. Atorvastatin significantly reduced the expression of TGF-β1, Smad3/P-Smad3, ROCK I and p-Akt in rats of the E1-E4 groups and in a dose-dependent manner. Fibronectin exhibited a similar pattern of expression changes. In addition, echocardiography showed that atorvastatin treatment can inhibit the increase of left ventricular end-diastolic dimension, left ventricular end-systolic diameter and left ventricular posterior wall thickness, and prevent the decrease of ejection fraction and fraction shortening in E1-E4 groups compared with the radiation only group. This study demonstrated that radiation exposure increased the expression of fibronectin in cardiac fibroblasts and induced cardiac fibrosis through activation of the TGF-β1/Smad3, RhoA/ROCK, and PI3K/AKT signaling pathways. Statins ameliorated radiation-induced cardiac fibrosis in Sprague-Dawley rats. Our results suggest that atorvastatin is effective for the treatment of radiation

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

    PubMed Central

    Lee, Chen-Chen; Wang, Ching-Chiung; Huang, Huei-Mei; Lin, Chu-Lun; Leu, Sy-Jye; Lee, Yueh-Lun

    2015-01-01

    This study investigated the immunomodulatory effects of ferulic acid (FA) on antigen-presenting dendritic cells (DCs) in vitro and its antiallergic effects against ovalbumin- (OVA-) induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation induced a high level of interleukin- (IL-) 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF-) α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4), MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE) and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13), and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN-) γ production in bronchoalveolar lavage fluid (BALF) and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model. PMID:26495021

  20. Japanese Huperzia serrata extract and the constituent, huperzine A, ameliorate the scopolamine-induced cognitive impairment in mice.

    PubMed

    Ohba, Takuya; Yoshino, Yuta; Ishisaka, Mitsue; Abe, Naohito; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Oyama, Masayoshi; Tabira, Takeshi; Hara, Hideaki

    2015-01-01

    Huperzia serrata has been used as a Chinese folk medicine for many years. It contains huperzine A, which has a protective effect against memory deficits in animal models; however, it is unclear if H. serrata extract exerts any effects in Alzheimer's disease (AD) models. We used H. serrata collected in Japan and determined its huperzine A content using HPLC. We determined its inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. H. serrata extract (30 mg/kg/day) and donepezil (10 mg/kg/day) were orally administrated for 7 days. After repeated administration, we performed the Y-maze and passive avoidance tests. H. serrata extract contained 0.5% huperzine A; H. serrata extract inhibited AChE, but not BuChE. H. serrata extract ameliorated cognitive function in mice. These results indicate that Japanese H. serrata extract ameliorates cognitive function deficits by inhibiting AChE. Therefore, H. serrata extract may be valuable for the prevention or treatment of dementia in AD. PMID:26059088

  1. Raising the "civilized minimum" of pain amelioration for prisoners to avoid cruel and unusual punishment.

    PubMed

    McGrath, James

    2002-01-01

    This Article addresses the problems with our nation's cultural and legal prohibitions against certain pain management treatments. The practice of pain management has not kept pace with the many medical advances that have made it possible for physicians to ameliorate most pain. The Author notes that some patients are denied access to certain forms of treatments due to the mistaken belief that addiction may ensue. Additionally, some individuals are under-treated for their pain to a greater degree than are others. This is especially the case for our nation's prisoners. The Author contends that prisoners are frequently denied effective pain amelioration. He notes, however, that there has been improvement in medical treatment in general for prisoners due to court challenges based on the Eighth Amendment's prohibition against cruel and unusual punishment. Yet, due to the protection of qualified immunity given to jailers and prison health care providers, prisoners cannot bring a claim for negligence or medical malpractice, they must allege a violation of their constitutional rights, a significantly higher legal standard. Prisoners must meet a subjective test showing that there was a deliberate indifference to their medical needs that violates the protection of the Eighth Amendment. The Author concludes that because medical advances have made it possible to alleviate most pain suffering, withholding pain treatment or providing a less effective treatment is tantamount to inflicting pain and should be viewed as a violation of the Eighth Amendment. PMID:15212044

  2. Raising the "civilized minimum" of pain amelioration for prisoners to avoid cruel and unusual punishment.

    PubMed

    McGrath, James

    2002-01-01

    This Article addresses the problems with our nation's cultural and legal prohibitions against certain pain management treatments. The practice of pain management has not kept pace with the many medical advances that have made it possible for physicians to ameliorate most pain. The Author notes that some patients are denied access to certain forms of treatments due to the mistaken belief that addiction may ensue. Additionally, some individuals are under-treated for their pain to a greater degree than are others. This is especially the case for our nation's prisoners. The Author contends that prisoners are frequently denied effective pain amelioration. He notes, however, that there has been improvement in medical treatment in general for prisoners due to court challenges based on the Eighth Amendment's prohibition against cruel and unusual punishment. Yet, due to the protection of qualified immunity given to jailers and prison health care providers, prisoners cannot bring a claim for negligence or medical malpractice, they must allege a violation of their constitutional rights, a significantly higher legal standard. Prisoners must meet a subjective test showing that there was a deliberate indifference to their medical needs that violates the protection of the Eighth Amendment. The Author concludes that because medical advances have made it possible to alleviate most pain suffering, withholding pain treatment or providing a less effective treatment is tantamount to inflicting pain and should be viewed as a violation of the Eighth Amendment. PMID:15212041

  3. Amelioration of Stroke-Induced Neurological Deficiency by Lyophilized Powder of Catapol and Puerarin

    PubMed Central

    Liu, Yang; Xue, Qiang; Li, Xu; Zhang, Jifen; Fu, Zhifeng; Feng, Binbin; Chen, Yi; Xu, Xiaoyu

    2014-01-01

    Catalpol and puerarin are active ingredients isolated from Rehmannia glutinosa Libosch and Radix Puerariae, respectively. They are popular in research for their poly-pharmacological effects. This research focused on effect of anti-stroke by lyophilized powder of catalpol and puerarin (C-P) and potential mechanisms. At the beginning of research, C-P was identified and analyzed by HPLC. Neurological function was evaluated by Longa score, neurological complex function score and beam balance score after permanent middle cerebral artery occlusion (PMCAO) in mice. Infarct volume and water content were evaluated after treatment of C-P. Anti-oxidative stress, anti-apoptosis, angiogenesis and neurogenesis were investigated by ELISA, WB and immunohistochemical stain respectively. With treatment of C-P, neurological deficiency of PMCAO mice was ameliorated. Morphologically, infarct volume and water content in ischemic hemisphere were significantly reduced by C-P. In vivo and in vitro, oxidative stress injury was extenuated by C-P. Meanwhile, Caspase-3 was down-regulated and Bxl-2 was up-regulated by C-P in vivo. In addition, C-P enhanced angiogenesis around the infarct of cortex and neurogenesis in the Hippocampal Dentate Gyrus (DG). Hence, C-P ameliorated stroke-induced neurological deficiency through its multiple neuroprotections. What's more, this article provides us a novel formula of active ingredients for stroke. PMID:24719562

  4. CXCR7 suppression modulates microglial chemotaxis to ameliorate experimentally-induced autoimmune encephalomyelitis.

    PubMed

    Bao, Jianhong; Zhu, Jinying; Luo, Sheng; Cheng, Ying; Zhou, Saijun

    2016-01-01

    Multiple sclerosis (MS) is the prototypical inflammatory demyelinating disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE), widely used as an animal model of MS, classically manifests as an ascending paralysis that is characterized by extensive infiltration of the CNS by inflammatory cells. Although several studies uncover the significant role of microglia in the development of EAE, the cellular mechanisms of microglia that govern EAE pathogenesis remain unknown. In the current study, we report that CXCR7 expression is dynamic regulated in activated microglia during CNS autoimmunity and positively correlates with the clinical severity of EAE. In addition, microglial chemotaxis is mediated by CXCR7 during CNS autoimmunity, signaling through extracellular signal-regulated kinase (ERK)1/2 activation, whereas p38 mitogen-activated protein kinase (MAPK) and (c-Jun N-terminal kinase) JNK are not involved. Most importantly, CXCR7 neutralizing treatment ameliorates the clinical severity of EAE along with ERK1/2 phosphorylation reduction. Collectively, our data demonstrate that CXCR7 suppression modulates microglial chemotaxis to ameliorate EAE. PMID:26607112

  5. Oxymatrine Prevents NF-κB Nuclear Translocation And Ameliorates Acute Intestinal Inflammation

    PubMed Central

    Guzman, Javier Rivera; Koo, Ja Seol; Goldsmith, Jason R.; Mühlbauer, Marcus; Narula, Acharan; Jobin, Christian

    2013-01-01

    Oxymatrine is a traditional Chinese herbal product that exhibits anti-inflammatory effects in models of heart, brain and liver injury. We investigated the impact of oxymatrine in an acute model of intestinal injury and inflammation. Oxymatrine significantly decreased LPS-induced NF-κB-driven luciferase activity, correlating with diminished induction of Cxcl2, Tnfα and Il6 mRNA expression in rat IEC-6 and murine BMDC. Although oxymatrine decreased LPS-induced p65 nuclear translocation and binding to the Cxcl2 gene promoter, this effect was independent of IκBα degradation/phosphorylation. DSS-induced weight loss and histological damage were ameliorated in oxymatrine-treated C57BL/6-WT-mice. While this effect correlated with reduced colonic Il6 and Il1β mRNA accumulation, global NF-κB activity as measured in NF-κBEGFP mice was unaffected. Our data demonstrate that oxymatrine reduces LPS-induced NF-κB nuclear translocation and activity independently of IκBα status, prevents intestinal inflammation through blockade of inflammatory signaling and ameliorates overall intestinal inflammation in vivo. PMID:23568217

  6. Ameliorative effect of grapefruit juice on amiodarone-induced cytogenetic and testicular damage in albino rats

    PubMed Central

    Sakr, Saber Abdelruhman; Zoil, Mohamed El-said; El-shafey, Samraa Samy

    2013-01-01

    Objective To evaluate the ameliorative role of grapefruit juice on the cytogenetic and testicular damage induced by the antiarrythmic drug amiodarone in albino rats. Methods Animals were divided into four groups. Group I was considered as control. Group II was given grapefruit juice at a dose level of 27 mL/kg body weight. Group III was orally administered amiodarone (18 mg/kg body weight) daily for 5 weeks. Animals were sacrificed after 5 weeks of treatment. Bone marrow was collected from the femurs for analysis of chromosomal aberrations and mitotic indices. Testes were removed and stained with H&E for histological examination. Sperms were collected from epidedymis for detection of sperm head abnormalities. Comet assay was used to detect DNA damage. Results Amiodarone treatment caused a significant increase in the percentage of chromosomal aberrations, decreased the mitotic index and increased DNA damage. The testis showed many histopathological alterations, inhibition of spermatogenesis and morphometric changes. The number of sperm head abnormalities was increased. Treating animals with amiodarone and grapefruit juice caused a reduction in chromosomal aberrations, mitotic index, DNA damage and testicular alterations caused by amiodarone. Conclusions The results of this study indicated that grapefruit juice ameliorates the cytotoxicty and testicular alterations induced by amiodarone in albino rats and this is may be due to the potent antioxidant effects of its components. PMID:23836512

  7. Treatment with Anti-EGF Ab Ameliorates Experimental Autoimmune Encephalomyelitis via Induction of Neurogenesis and Oligodendrogenesis

    PubMed Central

    Amir-Levy, Yifat; Mausner-Fainberg, Karin; Karni, Arnon

    2014-01-01

    Background. The neural stem cells (NSCs) migrate to the damaged sites in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). However, the differentiation into neurons or oligodendrocytes is blocked. Epidermal growth factor (EGF) stimulates NSC proliferation and mobilization to demyelinated lesions but also induces astrogenesis and glial scar. Objective. To examine the clinical and histopathological effects of EGF neutralization on EAE. Methods. EAE-induced SJL mice were intravenously treated with either anti-EGF neutralizing antibody (Ab) or isotype control or PBS. On day 9 after immunization, 3 mice of each group were daily treated for 9 days with BrdU and then sacrificed for immunohistochemical analysis. Results. Treatment with anti-EGF Ab significantly ameliorated EAE symptoms during the second relapse. Anti-EGF Ab induced a shift from BrdU+GFAP+ NSCs to BrdU+DCX+ neuroblasts in the subventricular zone (SVZ), increased BrdU+NeuN+ neurons in the granular cell layer of the dentate gyrus, and increased BrdU+O4+ oligodendrocytes in the SVZ. There was no change in the inflammatory infiltrates in response to anti-EGF Ab. Conclusions. Therapy with anti-EGF Ab ameliorates EAE via induction of neurogenesis and oligodendrogenesis. No immunosuppressive effect was found. Further investigation is needed to support these notions of beneficial effect of anti-EGF Ab in MS. PMID:25610650

  8. Treatment with Anti-EGF Ab Ameliorates Experimental Autoimmune Encephalomyelitis via Induction of Neurogenesis and Oligodendrogenesis.

    PubMed

    Amir-Levy, Yifat; Mausner-Fainberg, Karin; Karni, Arnon

    2014-01-01

    Background. The neural stem cells (NSCs) migrate to the damaged sites in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). However, the differentiation into neurons or oligodendrocytes is blocked. Epidermal growth factor (EGF) stimulates NSC proliferation and mobilization to demyelinated lesions but also induces astrogenesis and glial scar. Objective. To examine the clinical and histopathological effects of EGF neutralization on EAE. Methods. EAE-induced SJL mice were intravenously treated with either anti-EGF neutralizing antibody (Ab) or isotype control or PBS. On day 9 after immunization, 3 mice of each group were daily treated for 9 days with BrdU and then sacrificed for immunohistochemical analysis. Results. Treatment with anti-EGF Ab significantly ameliorated EAE symptoms during the second relapse. Anti-EGF Ab induced a shift from BrdU(+)GFAP(+) NSCs to BrdU(+)DCX(+) neuroblasts in the subventricular zone (SVZ), increased BrdU(+)NeuN(+) neurons in the granular cell layer of the dentate gyrus, and increased BrdU(+)O4(+) oligodendrocytes in the SVZ. There was no change in the inflammatory infiltrates in response to anti-EGF Ab. Conclusions. Therapy with anti-EGF Ab ameliorates EAE via induction of neurogenesis and oligodendrogenesis. No immunosuppressive effect was found. Further investigation is needed to support these notions of beneficial effect of anti-EGF Ab in MS. PMID:25610650

  9. Toxic effects of sub-chronic exposure of male albino rats to emamectin benzoate and possible ameliorative role of Foeniculum vulgare essential oil.

    PubMed

    El-Sheikh, El-Sayed A; Galal, Azza A A

    2015-05-01

    Emamectin benzoate (EB) is an avermectin insecticide used extensively in pest control on vegetable and field crops. Few studies have been done for evaluating adverse effects of EB. In the current study, we evaluated the toxic effects of EB on male rats and the possible ameliorative role of fennel essential oil (FEO). Thirty two male rats were randomly divided into 4 equal groups. All groups were treated orally with distilled water (control group), 0.5mlFEOkg(-1) BW (FEO group), 2.5mgEBkg(-1) BW (EB group), and 0.5mlFEOkg(-1) BW+2.5mgEBkg(-1) BW (FEO+EB group) for 28 days. The obtained results showed that EB treatment resulted in a significant decrease in body weight, body weight gain, RBC count, Hb concentration, % PCV, MCV and MCHC. Moreover, EB significantly decreased total leukocyte, lymphocyte, monocyte and platelet count but significantly increased granulocyte count. EB markedly decreased total protein, albumin, globulin, IgG and IgM concentrations with a significant increase in TNF-α secretion. EB had a negative impact on the liver as it significantly increased ALT, ALP, and MDA, while decreasing SOD activity. Regarding to the histopathological examination, EB treatment induced coagulative necrosis and blood vessels congestion of the liver in treated rats. Furthermore, it resulted in depletion and necrosis of the white pulp of the spleen in treated rats. The co-administration of FEO with EB, however, improved the majority of parameters studied, suggesting that FEO is an important substance in decreasing toxic effects of EB. PMID:25935540

  10. Toxic effects of methamidophos on paraoxonase 1 activity and on rat kidney and liver and ameliorating effects of alpha-tocopherol.

    PubMed

    Araoud, Manel; Neffeti, Fadoua; Douki, Wahiba; Khaled, Lamia; Najjar, Mohamed Fadhel; Kenani, Abderraouf; Houas, Zohra

    2016-07-01

    The role of alpha-tocopherol on nephrotoxicity and hepatotoxicity induced by methamidophos (MT) was investigated in wistar rats. Animals were given via gavage, for four weeks, a low dose of MT (MT1), a high dose of MT (MT2), vitamin E (200 mg/kg of bw) or both MT2 plus vitamin E (Vit E) and control group was given distillate water. MT treatment resulted in a significant decrease in the body weight of MT2-treated group. Moreover, MT-treated groups had significantly lower butyrylcholinesterase (p < 0.01) and paraoxonase 1 (PON1) activities compared with the control group (p < 0.05). However, MT2-treated group had significantly higher alkaline phosphatase activity compared with untreated rats (p < 0.05). Both MT-treated groups had significantly higher urea (p < 0.01) and uric acid levels (p < 0.05) compared with the control group. However, significant low uric acid level (p < 0.05) was noted in MT2 plus vit E-treated rats compared with MT2-treated group. Histopathological changes in organ tissues were observed in both MT-treated groups and MT2 plus vit E-treated rats. However, the damage was reduced in MT2 plus vit E-treated rats. Therefore, this study deduces that alpha-tocopherol administration may ameliorate the adverse effects of subacute exposure to MT on rat liver and kidney and this antioxidant can protect PON1 from oxidative stress induced by this organophosphorus pesticide. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 842-854, 2016. PMID:25535039

  11. Inhibition of Protease-activated Receptor 1 Ameliorates Intestinal Radiation Mucositis in a Preclinical Rat Model

    SciTech Connect

    Wang, Junru; Kulkarni, Ashwini; Chintala, Madhu; Fink, Louis M.; Hauer-Jensen, Martin

    2013-01-01

    Purpose: To determine, using a specific small-molecule inhibitor of protease-activated receptor 1 (PAR1) signaling, whether the beneficial effect of thrombin inhibition on radiation enteropathy development is due to inhibition of blood clotting or to cellular (PAR1-mediated) thrombin effects. Methods and Materials: Rats underwent fractionated X-irradiation (5 Gy Multiplication-Sign 9) of a 4-cm small-bowel segment. Early radiation toxicity was evaluated in rats receiving PAR1 inhibitor (SCH602539, 0, 10, or 15 mg/kg/d) from 1 day before to 2 weeks after the end of irradiation. The effect of PAR1 inhibition on development of chronic intestinal radiation fibrosis was evaluated in animals receiving SCH602539 (0, 15, or 30 mg/kg/d) until 2 weeks after irradiation, or continuously until termination of the experiment 26 weeks after irradiation. Results: Blockade of PAR1 ameliorated early intestinal toxicity, with reduced overall intestinal radiation injury (P=.002), number of myeloperoxidase-positive (P=.03) and proliferating cell nuclear antigen-positive (P=.04) cells, and collagen III accumulation (P=.005). In contrast, there was no difference in delayed radiation enteropathy in either the 2- or 26-week administration groups. Conclusion: Pharmacological blockade of PAR1 seems to reduce early radiation mucositis but does not affect the level of delayed intestinal radiation fibrosis. Early radiation enteropathy is related to activation of cellular thrombin receptors, whereas platelet activation or fibrin formation may play a greater role in the development of delayed toxicity. Because of the favorable side-effect profile, PAR1 blockade should be further explored as a method to ameliorate acute intestinal radiation toxicity in patients undergoing radiotherapy for cancer and to protect first responders and rescue personnel in radiologic/nuclear emergencies.

  12. Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications.

    PubMed

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2016-04-01

    Second generation antipsychotic drugs (SGAs) cause substantial body weight gain/obesity and other metabolic side-effects such as dyslipidaemia. Their antagonistic affinity to the histaminergic H1 receptor (H1R) has been identified as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H3 receptor antagonist) have been investigated for ameliorating SGA-induced weight gain/obesity in both animal models and clinical trials. It has been demonstrated that co-treatment with betahistine is effective in reducing weight gain, associated with olanzapine in drug-naïve patients with schizophrenia, as well as in the animal models of both drug-naïve rats and rats with chronic, repeated exposure to olanzapine. Betahistine co-treatment can reduce food intake and increase the effect of thermogenesis in brown adipose tissue by modulating hypothalamic H1R-NPY-AMPKα (NPY: neuropeptide Y; AMPKα: AMP-activated protein kinase α) pathways, and ameliorate olanzapine-induced dyslipidaemia through modulation of AMPKα-SREBP-1-PPARα-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPARα: Peroxisome proliferator-activated receptor-α) in the liver. Although reduced locomotor activity was observed from antipsychotic treatment in rats, betahistine did not affect locomotor activity. Importantly, betahistine co-treatment did not influence the effects of antipsychotics on serotonergic receptors in the key brain regions for antipsychotic therapeutic efficacy. However, betahistine co-treatment reverses the upregulated dopamine D2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D2 supersensitivity often observed in chronic antipsychotic treatment. Therefore, these results provide solid evidence supporting further clinical trials in treating antipsychotics-induced weight gain using betahistine in patients with schizophrenia and other mental

  13. Genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction.

    PubMed

    Guan, Lili; Feng, Haiyan; Gong, Dezheng; Zhao, Xu; Cai, Li; Wu, Qiong; Yuan, Bo; Yang, Mei; Zhao, Jie; Zou, Yuan

    2013-12-01

    Insulin resistance (IR) increases with age and plays a key role in the pathogenesis of type 2 diabetes mellitus. Oxidative stress and mitochondrial dysfunction are supposed to be major factors leading to age-related IR. Genipin, an extract from Gardenia jasminoides Ellis fruit, has been reported to stimulate insulin secretion in pancreatic islet cells by regulating mitochondrial function. In this study, we first investigated the effects of genipin on insulin sensitivity and the potential mitochondrial mechanisms in the liver of aging rats. The rats were randomly assigned to receive intraperitoneal injections of either 25mg/kg genipin or vehicle once daily for 12days. The aging rats showed hyperinsulinemia and hyperlipidemia, and insulin resistance as examined by the decreased glucose decay constant rate during insulin tolerance test (kITT). The hepatic tissues showed steatosis and reduced glycogen content. Hepatic malondialdehyde level and mitochondrial reactive oxygen species (ROS) were higher, and levels of mitochondrial membrane potential (MMP) and ATP were lower as compared with the normal control rats. Administration of genipin ameliorated systemic and hepatic insulin resistance, alleviated hyperinsulinemia, hyperglyceridemia and hepatic steatosis, relieved hepatic oxidative stress and mitochondrial dysfunction in aging rats. Furthermore, genipin not only improved insulin sensitivity by promoting insulin-stimulated glucose consumption and glycogen synthesis, inhibited cellular ROS overproduction and alleviated the reduction of levels of MMP and ATP, but also reversed oxidative stress-associated JNK hyperactivation and reduced Akt phosphorylation in palmitate-treated L02 hepatocytes. In conclusion, genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction. PMID:24041487

  14. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

    SciTech Connect

    Nagib, Marwa M.; Tadros, Mariane G.; ELSayed, Moushira I.; Khalifa, Amani E.

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

  15. Camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats.

    PubMed

    Meena, Sunita; Rajput, Yudhishthir S; Pandey, Amit K; Sharma, Rajan; Singh, Raghvendar

    2016-08-01

    This study was designed to assess anti-diabetic potential of goat, camel, cow and buffalo milk in streptozotocin (STZ) induced type 1 diabetic albino wistar rats. A total of 48 rats were taken for the study where one group was kept as non-diabetic control group (8 rats) while others (40 rats) were made diabetic by STZ (50 mg/kg of body weight) injection. Among diabetic rats, a control group (8 rats) was kept and referred as diabetic control whereas other four groups (8 rats each) of diabetic rats were fed on 50 ml of goat or camel or cow or buffalo milk for 4 weeks. All the rats (non-diabetic and diabetic) were maintained on standard diet for four weeks. STZ administration resulted in enhancement of glucose, total cholesterol, triglyceride, low density lipoprotein, HbA1c and reduction in high density lipoprotein in plasma and lowering of antioxidative enzymes (catalase, glutathione peroxidase and superoxide dismutase) activities in pancreas, kidney, liver and RBCs, coupled with enhanced levels of TBARS and protein carbonyls in pancreas, kidney, liver and plasma. OGTT carried out at the end of 4 week milk feeding indicated that all milks helped in early maintenance of glucose level. All milks reduced atherogenic index. In camel milk fed diabetic group, insulin concentration enhanced to level noted for non-diabetic control while goat, cow and buffalo milk failed to restore insulin level. HbA1c level was also restored only in camel milk fed diabetic group. The level of antioxidative enzymes (catalase, GPx and SOD) in pancreas enhanced in all milk fed groups. Camel milk and to a reasonable extent goat milk reduced formation of TBARS and PCs in tissues and blood. It can be concluded that camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats. Further, only camel milk completely ameliorated oxidative damage in pancreas and normalised insulin level. PMID:27600979

  16. Harpagoside ameliorates the amyloid-β-induced cognitive impairment in rats via up-regulating BDNF expression and MAPK/PI3K pathways.

    PubMed

    Li, J; Ding, X; Zhang, R; Jiang, W; Sun, X; Xia, Z; Wang, X; Wu, E; Zhang, Y; Hu, Y

    2015-09-10

    So far, no effective disease-modifying therapies for Alzheimer's disease (AD) aiming at protecting or reversing neurodegeneration of the disease have been established yet. The present work aims to elucidate the effect of Harpagoside (abbreviated HAR), an iridoid glycosides purified from the Chinese medicinal herb Scrophularia ningpoensis, on neurodegeneration induced by β-amyloid peptide (Aβ) and the underlying molecular mechanism. Here we show that HAR exerts neuroprotective effects against Aβ neurotoxicity. Rats injected aggregated Aβ₁₋₄₀ into the bilateral hippocampus displayed impaired spatial learning and memory ability in a Y-maze test and novel object recognition test, while HAR treatment ameliorated Aβ₁₋₄₀-induced behavioral deficits. Moreover, administration of HAR increased the expression levels of brain-derived neurotrophic factor (BDNF) and activated the extracellular-regulated protein kinase (ERK) and the phosphatidylinositol 3-kinase (PI3-kinase) pathways both in the cerebral cortex and hippocampus of the Aβ₁₋₄₀-insulted rat model. Furthermore, in cultured primary cortical neurons, Aβ₁₋₄₂ induced significant decrease of choline acetyltransferase (ChAT)-positive neuron number and neurite outgrowth length, both of which were dose dependently increased by HAR. In addition, HAR pretreatment also significantly attenuated the decrease of cell viability in Aβ₁₋₄₂-injured primary cortical neurons. Finally, when K252a, an inhibitor of Trk tyrosine kinases, and a BDNF neutralizing antibody were added to the culture medium 2 h prior to HAR addition, the protective effect of HAR on Aβ₁₋₄₂-induced neurodegeneration in the primary cortical neuron was almost inhibited. Taken together, HAR exerting neuroprotection effect and ameliorating learning and memory deficit appears to be associated, at least in part, with up-regulation of BDNF content as well as activating its downstream signaling pathways, e.g., MAPK

  17. Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice

    PubMed Central

    Jung, Yeon Suk; Park, Jung Hwa; Kim, Hyunha; Kim, So Young; Hwang, Ji Young; Hong, Ki Whan; Bae, Sun Sik; Choi, Byung Tae; Lee, Sae-Won; Shin, Hwa Kyoung

    2016-01-01

    Aim: Increasing evidence suggests that probucol, a lipid-lowering agent with anti-oxidant activities, may be useful for the treatment of ischemic stroke with hyperlipidemia via reduction in cholesterol and neuroinflammation. In this study we examined whether probucol could protect against brain ischemic injury via anti-neuroinflammatory action in normal and hyperlipidemic mice. Methods: Primary mouse microglia and murine BV2 microglia were exposed to lipopolysaccharide (LPS) for 3 h, and the release NO, PGE2, IL-1β and IL-6, as well as the changes in NF-κB, MAPK and AP-1 signaling pathways were assessed. ApoE KO mice were fed a high-fat diet containing 0.004%, 0.02%, 0.1% (wt/wt) probucol for 10 weeks, whereas normal C57BL/6J mice received probucol (3, 10, 30 mg·kg-1·d-1, po) for 4 d. Then all the mice were subjected to focal cerebral ischemia through middle cerebral artery occlusion (MCAO). The neurological deficits were scored 24 h after the surgery, and then brains were removed for measuring the cerebral infarct size and the production of pro-inflammatory mediators. Results: In LPS-treated BV2 cells and primary microglial cells, pretreatment with probucol (1, 5, 10 μmol/L) dose-dependently inhibited the release of NO, PGE2, IL-1β and IL-6, which occurred at the transcription levels. Furthermore, the inhibitory actions of probucol were associated with the downregulation of the NF-κB, MAPK and AP-1 signaling pathways. In the normal mice with MCAO, pre-administration of probucol dose-dependently decreased the infarct volume and improved neurological function. These effects were accompanied by the decreased production of pro-inflammatory mediators (iNOS, COX-2, IL-1, IL-6). In ApoE KO mice fed a high-fat diet, pre-administration of 0.1% probucol significantly reduced the infarct volume, improved the neurological deficits following MCAO, and decreased the total- and LDL-cholesterol levels. Conclusion: Probucol inhibits LPS-induced microglia activation and

  18. Pycnogenol ameliorates depression-like behavior in repeated corticosterone-induced depression mice model.

    PubMed

    Mei, Lin; Mochizuki, Miyako; Hasegawa, Noboru

    2014-01-01

    Oxidative stress is considered to be a mechanism of major depression. Pycnogenol (PYC) is a natural plant extract from the bark of Pinus pinaster Aiton and has potent antioxidant activities. We studied the ameliorative effect of PYC on depression-like behavior in chronic corticosterone- (CORT-) treated mice for 20 days. After the end of the CORT treatment period, PYC (0.2 mg/mL) was orally administered in normal drinking water. Depression-like behavior was investigated by the forced swimming test. Immobility time was significantly longer by CORT exposure. When the CORT-treated mice were supplemented with PYC, immobility time was significantly shortened. Our results indicate that orally administered PYC may serve to reduce CORT-induced stress by radical scavenging activity. PMID:24901001

  19. Ameliorating effect of luteolin on memory impairment in an Alzheimer's disease model

    PubMed Central

    WANG, HUIMIN; WANG, HUILING; CHENG, HUIXIN; CHE, ZHENYONG

    2016-01-01

    Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorder. It is characterized by the formation of amyloid plaques and neurofibrillary tangles in the brain, the degeneration of cholinergic neurons and neuronal cell death. The present study aimed to investigate the effect of luteolin, a flavonoid compound, on memory impairment in a streptozotocin (STZ)-induced Alzheimer's rat model. Morris water maze and probe tests were performed to examine the effect of luteolin treatment on cognition and memory. The effect of luteolin on CA1 pyramidal layer thickness was also examined. The results demonstrated that luteolin significantly ameliorated the spatial learning and memory impairment induced by STZ treatment. STZ significantly reduced the thickness of CA1 pyramidal layer and treatment of luteolin completely abolished the inhibitory effect of STZ. Our results suggest that luteolin has a potentially protective effect on learning defects and hippocampal structures in AD. PMID:27035793

  20. Rutaecarpine ameliorates hyperlipidemia and hyperglycemia in fat-fed, streptozotocin-treated rats via regulating the IRS-1/PI3K/Akt and AMPK/ACC2 signaling pathways

    PubMed Central

    Nie, Xu-qiang; Chen, Huai-hong; Zhang, Jian-yong; Zhang, Yu-jing; Yang, Jian-wen; Pan, Hui-jun; Song, Wen-xia; Murad, Ferid; He, Yu-qi; Bian, Ka

    2016-01-01

    Aim: We have shown that rutaecarpine extracted from the dried fruit of Chinese herb Evodia rutaecarpa (Juss) Benth (Wu Zhu Yu) promotes glucose consumption and anti-inflammatory cytokine expression in insulin-resistant primary skeletal muscle cells. In this study we investigated whether rutaecarpine ameliorated the obesity profiles, lipid abnormality, glucose metabolism and insulin resistance in rat model of hyperlipidemia and hyperglycemia. Methods: Rats fed on a high-fat diet for 8 weeks, followed by injection of streptozotocin (30 mg/kg, ip) to induce hyperlipidemia and hyperglycemia. One week after streptozotocin injection, the fat-fed, streptozotocin-treated rats were orally treated with rutaecarpine (25 mg·kg−1·d−1) or a positive control drug metformin (250 mg·kg−1·d−1) for 7 weeks. The body weight, visceral fat, blood lipid profiles and glucose levels, insulin sensitivity were measured. Serum levels of inflammatory cytokines were analyzed. IRS-1 and Akt/PKB phosphorylation, PI3K and NF-κB protein levels in liver tissues were assessed; pathological changes of livers and pancreases were examined. Glucose uptake and AMPK/ACC2 phosphorylation were studied in cultured rat skeletal muscle cells in vitro. Results: Administration of rutaecarpine or metformin significantly decreased obesity, visceral fat accumulation, water consumption, and serum TC, TG and LDL-cholesterol levels in fat-fed, streptozotocin-treated rats. The two drugs also attenuated hyperglycemia and enhanced insulin sensitivity. Moreover, the two drugs significantly decreased NF-κB protein levels in liver tissues and plasma TNF-α, IL-6, CRP and MCP-1 levels, and ameliorated the pathological changes in livers and pancreases. In addition, the two drugs increased PI3K p85 subunit levels and Akt/PKB phosphorylation, but decreased IRS-1 phosphorylation in liver tissues. Treatment of cultured skeletal muscle cells with rutaecarpine (20–180 μmol/L) or metformin (20 μmol/L) promoted the

  1. Okara ameliorates glucose tolerance in GK rats

    PubMed Central

    Hosokawa, Masaya; Katsukawa, Michiko; Tanaka, Hiroshi; Fukuda, Hitomi; Okuno, Sonomi; Tsuda, Kinsuke; Iritani, Nobuko

    2016-01-01

    Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARγ, adiponectin, and GLUT4, which up-regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes. PMID:27257347

  2. Okara ameliorates glucose tolerance in GK rats.

    PubMed

    Hosokawa, Masaya; Katsukawa, Michiko; Tanaka, Hiroshi; Fukuda, Hitomi; Okuno, Sonomi; Tsuda, Kinsuke; Iritani, Nobuko

    2016-05-01

    Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARγ, adiponectin, and GLUT4, which up-regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes. PMID:27257347

  3. In situ film forming fibroin gel intended for cutaneous administration.

    PubMed

    Gennari, Chiara G M; Selmin, Francesca; Ortenzi, Marco A; Franzé, Silvia; Musazzi, Umberto M; Casiraghi, Antonella; Minghetti, Paola; Cilurzo, Francesco

    2016-09-10

    The possible use of regenerated silk fibroin gels as in situ film forming formulations for cutaneous administration of drugs was studied. Ethanol was selected as volatile and skin tolerant solvent to favor the sol-gel transition of silk fibroin solutions. Glycerin was chosen to ameliorate the gel texture profile. Eighteen placebo formulations were prepared to individuate the optimal component ratios as a function of the texture analysis, spreadability and drying time. The in vitro biopharmaceutical performance was investigated by in vitro permeation test through human epidermis on formulations loading caffeine as a model drug. The data evidenced that the optimal technological performances were achieved using gels containing 70% ethanol and silk fibroin/glycerin ratio from 0.18 to 0.36. The caffeine flux (J) through the skin was significantly improved due to an increase of the drug thermodynamic activity (hydro-alcoholic solution: J∼0.8μg/cm(2)/h; in situ formed film: J∼1.4-1.7μg/cm(2)/h). In conclusion, silk fibroin can be advantageously proposed as a novel film forming material to develop dosage forms to be topically applied. PMID:27418564

  4. Cobrotoxin from Naja naja atra Venom Ameliorates Adriamycin Nephropathy in Rats

    PubMed Central

    Wang, Shu-Zhi; Xu, Yin-li; Zhu, Qi; Kou, Jian-qun; Qin, Zheng-Hong

    2015-01-01

    Chronic kidney disease (CKD) becomes a global health problem with high morbidity and mortality. Adriamycin- (ADR-) induced rodent chronic nephropathy is a classic experimental model of human minimal lesion nephrotic syndrome. The present study investigated the effect of cobrotoxin (CTX) on ADR-induced nephropathy. Rats were given 6 mg/kg ADR once through the tail vein to replicate ADR nephropathy model. CTX was administered to rats daily by placing a fast dissolving CTX membrane strip under the tongue starting from 5 days prior to ADR administration until the end of experiment. The results showed that CTX ameliorated the symptoms of ADR nephropathy syndrome with reduced body weight loss, proteinuria, hypoalbuminemia, dyslipidemia, serum electrolyte imbalance, oxidative stress, renal function abnormities, and kidney pathological lesions. Anti-inflammatory cytokine IL-10 expression was elevated after CTX administration in ADR nephropathy model. CTX inhibited the phosphorylation of IκB-α and NF-κB p65 nuclear translocation. Meanwhile, CTX upregulated the protein level of podocyte-specific nephrin and downregulated the level of fibrosis-related TGF-β. These findings suggest that CTX may be a potential drug for chronic kidney diseases. PMID:26640497

  5. Amelioration of dextran sodium sulfate-induced colitis in mice by Rhodobacter sphaeroides extract.

    PubMed

    Liu, Wen-Sheng; Chen, Man-Chin; Chiu, Kuo-Hsun; Wen, Zhi-Hong; Lee, Che-Hsin

    2012-01-01

    Bacteria can produce some compounds in response to their environment. These compounds are widely used in cosmetic and pharmaceutical applications. Some probiotics have immunomodulatory activities and modulate the symptoms of several diseases. Autoimmune diseases represent a complex group of conditions that are thought to be mediated through the development of autoreactive immunoresponses. Inflammatory bowel disease (IBD) is common autoimmune disease that affects many individuals worldwide. Previously, we found that the extracts of Rhodobacter sphaeroides (Lycogen) inhibited nitric oxide production and inducible nitric-oxide synthase expression in activated macrophages. In this study, the effect of Lycogen, a potent anti-inflammatory agent, was evaluated in mice with dextran sodium sulfate (DSS)-induced colitis. Oral administration of Lycogen reduced the expressions of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in female BABL/c mice. In addition, the increased number of bacterial flora in the colon induced by DSS was amelirated by Lycogen. The histological score of intestinal inflammation in 5% DSS-treated mice after oral administration of Lycogen was lower than that of control mice. Meanwhile, Lycogen dramatically prolonged the survival of mice with severe colitis. These findings identified that Lycogen is an anti-inflammatory agent with the capacity to ameliorate DSS-induced colitis. PMID:23159923

  6. Protocatechuic acid ameliorates neurocognitive functions impairment induced by chronic intermittent hypoxia

    PubMed Central

    Yin, Xue; Zhang, Xiuli; Lv, Changjun; Li, Chunli; Yu, Yan; Wang, Xiaozhi; Han, Fang

    2015-01-01

    Chronic intermittent hypoxia (CIH) is a serious consequence of obstructive sleep apnoea (OSA) and has deleterious effects on central neurons and neurocognitive functions. This study examined if protocatechuic acid (PCA) could improve learning and memory functions of rats exposed to CIH conditions and explore potential mechanisms. Neurocognitive functions were evaluated in male SD rats by step-through passive avoidance test and Morris water maze assay following exposure to CIH or room air conditions. Ultrastructure changes were investigated with transmission electron microscopy, and neuron apoptosis was confirmed by TUNEL assays. Ultrastructure changes were investigated with transmission electron microscope and neuron apoptosis was confirmed by TUNEL assays. The effects of PCA on oxidative stress, apoptosis, and brain IL-1β levels were investigated. Expression of Bcl-2, Bax, Cleaved Caspase-3, c-fos, SYN, BDNF and pro-BDNF were also studied along with JNK, P38 and ERK phosphorylation to elucidate the molecular mechanisms of PCA action. PCA was seen to enhance learning and memory ability, and alleviate oxidative stress, apoptosis and glial proliferation following CIH exposure in rats. In addition, PCA administration also decreased the level of IL-1β in brain and increased the expression of BDNF and SYN. We conclude that PCA administration will ameliorate CIH-induced cognitive dysfunctions. PMID:26419512

  7. Amelioration of the cardiovascular effects of cocaine in rhesus monkeys by a long-acting mutant form of cocaine esterase.

    PubMed

    Collins, Gregory T; Carey, Kathy A; Narasimhan, Diwahar; Nichols, Joseph; Berlin, Aaron A; Lukacs, Nicholas W; Sunahara, Roger K; Woods, James H; Ko, Mei-Chuan

    2011-04-01

    A long-acting mutant form of a naturally occurring bacterial cocaine esterase (T172R/G173Q CocE; double mutant CocE (DM CocE)) has previously been shown to antagonize the reinforcing, convulsant, and lethal effects of cocaine in rodents. However, the effectiveness and therapeutic characteristics of DM CocE in nonhuman primates, in a more clinically relevant context, are unknown. The current studies were aimed at (1) characterizing the cardiovascular effects of cocaine in freely moving rhesus monkeys, (2) evaluating the capacity of DM CocE to ameliorate these cocaine-induced cardiovascular effects when administered 10 min after cocaine, and (3) assessing the immunological responses of monkeys to DM CocE following repeated administration. Intravenous administration of cocaine produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR) that persisted throughout the 2-h observation period following a dose of 3.2 mg/kg cocaine. Cocaine failed to produce reliable changes in electrocardiograph (ECG) parameters, body temperature, and locomotor activity. DM CocE produced a rapid and dose-dependent amelioration of the cardiovascular effects, with saline-like MAP measures restored within 5-10 min, and saline-like HR measures restored within 20-40 min of DM CocE administration. Although administration of DM CocE produced increases in anti-CocE antibodies, they did not appear to have a neutralizing effect on the capacity of DM CocE to reverse the cardiovascular effects of cocaine. In conclusion, these findings in monkeys provide strong evidence to suggest that highly efficient cocaine esterases, such as DM CocE, can provide a potential therapeutic option for treatment of acute cocaine intoxication in humans. PMID:21289605

  8. Osteoclastogenesis inhibitory factor/osteoprotegerin ameliorates the decrease in both bone mineral density and bone strength in immobilized rats.

    PubMed

    Mochizuki, Shin-ichi; Fujise, Nobuaki; Higashio, Kanji; Tsuda, Eisuke

    2002-01-01

    Rat models of immobilization-induced osteopenia are characterized by uncoupling of bone metabolism, i.e., increased bone resorption and decreased bone formation in trabecular bone. Using such a rat model, the efficacy of osteoclastogenesis inhibitory factor (OCIF)/osteoprotegerin, a novel secreted protein that inhibits osteoclastogenesis, in reducing bone loss was investigated. Male Fischer rats were neurectomized and injected intramuscularly with either OCIF (0.2, 1.0, or 5.0 mg/kg body weight) or vehicle once daily for 7 days. On the eighth day after sciatic neurectomy, significant bone loss was observed in the vehicle-injected rats. OCIF ameliorated the decrease in bone mineral density (BMD) of both the proximal and distal femur in a dose-dependent manner. OCIF also ameliorated the decrease in bone strength of the femoral neck at the highest dose. A high correlation (r = 0.805) was detected between the BMD of the distal femur and the bone strength of the femoral neck. When OCIF was administered intermittently to the immobilized rats twice weekly (on days 1 and 4) after immobilization, it also ameliorated the decrease in BMD of the distal femur. These results suggest that OCIF has therapeutic potential for the treatment of immobilization-induced osteopenia. PMID:11810411

  9. Recombinant murine fibroblast growth factor 21 ameliorates obesity-related inflammation in monosodium glutamate-induced obesity rats.

    PubMed

    Wang, Wen-Fei; Li, Si-Ming; Ren, Gui-Ping; Zheng, Wei; Lu, Yu-Jia; Yu, Yin-Hang; Xu, Wen-Juan; Li, Tian-He; Zhou, Li-Hong; Liu, Yan; Li, De-Shan

    2015-05-01

    The aim of this study is to investigate the role of FGF21 in obesity-related inflammation in livers of monosodium glutamate (MSG)-induced obesity rats. The MSG rats were injected with recombinant murine fibroblast growth factor 21(FGF21) or equal volumes of vehicle. Metabolic parameters including body weight, Lee's index, food intake, visceral fat and liver weight, intraperitoneal glucose tolerance, glucose, and lipid levels were dynamically measured at specific time points. Liver function and routine blood test were also analyzed. Further, systemic inflammatory cytokines such as glucose transporter 1 (GLUT-1), leptin, TNF-α, and IL-6 mRNAs were determined by real-time PCR. FGF21 independently decreased body weight and whole-body fat mass without reducing food intake in the MSG rats. FGF21 reduced blood glucose level, Lee's index, visceral fat, and liver weight, and improved glucose tolerance, lipid metabolic spectrum, and hepatic steatosis in the MSG-obesity rats. Liver function parameters including AST, ALT, ALP, TP, T.Bili, and D.Bili levels significantly reduced in the FGF21-treated obesity rats compared to the controls. Further, FGF21 ameliorated the total and differential white blood cell (WBC) count, serum C-reactive protein (CRP), IL-6, and TNF-α levels in adipose tissues of the obesity rats, suggesting inflammation amelioration in the in the obesity rats by FGF21. FGF21 improves multiple metabolic disorders and ameliorates obesity-related inflammation in the MSG-induced obesity rats. PMID:25306889

  10. A coimmunization vaccine of Aβ42 ameliorates cognitive deficits without brain inflammation in an Alzheimer’s disease model

    PubMed Central

    2014-01-01

    Introduction Vaccination against amyloid-β protein (Aβ42) induces high levels of antibody, making it a promising strategy for treating Alzheimer’s disease (AD). One drawback in the past was that clinical trial approval was withheld because of speculation that the Aβ42 vaccine induces CD4+ T cell infiltrations into the central nervous system. To reduce T-cell activation while concomitantly maintaining high anti-Aβ42 titers is a great challenge in immunology. Methods We aimed to demonstrate that coimmunization with Aβ42 protein and expression plasmid can be beneficial in a mouse AD model and can prevent inflammation. We immunized the AD mice with the coimmunization vaccine and assessed behavior change and Aβ42 deposition. Furthermore, to determine the safety of the coimmunization vaccine, we used an induced Aβ42-EAE model to mimic the meningoencephalitis that happened in the AN-1792 vaccine clinical phase II trial and tested whether the coimmunization vaccine could ameliorate T-cell-mediated brain inflammation. Results The coimmunization vaccination reduced Aβ plaques and significantly ameliorated cognitive deficit while inhibiting T-cell-mediated brain inflammation and infiltration. These studies demonstrate that the coimmunization strategy that we describe in this article can ameliorate AD pathology without notable adverse effects in mice. Conclusions A coimmunization strategy leading to the development of a safe immunotherapeutic/preventive protocol against AD in humans is warranted. PMID:24987466

  11. Interleukin-15 Administration Improves Diaphragm Muscle Pathology and Function in Dystrophic mdx Mice

    PubMed Central

    Harcourt, Leah J.; Holmes, Anna Greer; Gregorevic, Paul; Schertzer, Jonathan D.; Stupka, Nicole; Plant, David R.; Lynch, Gordon S.

    2005-01-01

    Interleukin (IL)-15, a cytokine expressed in skeletal muscle, has been shown to have muscle anabolic effects in vitro and to slow muscle wasting in rats with cancer cachexia. Whether IL-15 has therapeutic potential for diseases such as Duchenne muscular dystrophy (DMD) is unknown. We examined whether IL-15 administration could ameliorate the dystrophic pathology in the diaphragm muscle of the mdx mouse, an animal model for DMD. Four weeks of IL-15 treatment improved diaphragm strength, a highly significant finding because respiratory function is a mortality predictor in DMD. Enhanced diaphragm function was associated with increased muscle fiber cross-sectional area and decreased collagen infiltration. IL-15 administration was not associated with changes in T-cell populations or alterations in specific components of the ubiquitin proteasome pathway. To determine the effects of IL-15 on myofiber regeneration, muscles of IL-15-treated and untreated wild-type mice were injured myotoxically, and their functional recovery was assessed. IL-15 had a mild anabolic effect, increasing fiber cross-sectional area after 2 and 6 days but not after 10 days. Our findings demonstrate that IL-15 administration improves the pathophysiology of dystrophic muscle and highlight a possible therapeutic role for IL-15 in the treatment of neuromuscular disorders especially in which muscle wasting is indicated. PMID:15793293

  12. Routes of Administration and Dose Optimization of Soluble Antigen Arrays in Mice with Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Thati, Shara; Kuehl, Christopher; Hartwell, Brittany; Sestak, Joshua; Siahaan, Teruna; Forrest, Laird; Berkland, Cory

    2014-01-01

    Soluble Antigen Arrays (SAgAs) were developed for treating mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. SAgAs are composed of hyaluronan with grafted EAE antigen and LABL peptide (a ligand of ICAM-1). SAgA dose was tested by varying injection volume, SAgA concentration, and administration schedule. Routes of administration were explored to determine the efficacy of SAgAs when injected intramuscularly, subcutaneously, intraperitoneally, intravenously, or instilled into lungs. Injections proximal to the central nervous system (CNS) were compared to distal injection sites. Intravenous dosing was included to determine if SAgA efficiency results from systemic exposure. Pulmonary instillation was included since reports suggest T cells are licensed in the lungs before moving onto the CNS1,2. Decreasing the volume of injection or SAgA dose reduced treatment efficacy. Treating mice with a single injection on day 4, 7, or 10 also reduced efficacy compared to injecting on all three days. Surprisingly, changing the injection site did not lead to a significant difference in efficacy. Intravenous administration showed efficacy similar to other routes, suggesting SAgAs act systemically. When SAgAs were delivered via pulmonary instillation, however, EAE mice failed to develop any symptoms, suggesting a unique lung mechanism to ameliorate EAE in mice. PMID:25447242

  13. Synergy between anti-CD4 and anti-tumor necrosis factor in the amelioration of established collagen-induced arthritis.

    PubMed Central

    Williams, R O; Mason, L J; Feldmann, M; Maini, R N

    1994-01-01

    Anti-CD4 treatment is reported to prevent collagen-induced arthritis if administered before the onset of clinical disease but has relatively little effect on established arthritis. In contrast, we have recently shown that anti-tumor necrosis factor alpha/beta (TNF) treatment reduces the severity of established arthritis. We now study the effect of combined administration of anti-CD4 monoclonal antibody (YTS 191.1.2/YTA 3.1.2) and anti-TNF monoclonal antibody (TN3-19.12) in established arthritis. Anti-CD4 treatment caused some reduction in paw-swelling but did not significantly prevent joint erosion. A suboptimal dose of anti-TNF alone had no significant effect on arthritis. In contrast, anti-CD4 plus suboptimal anti-TNF significantly reduced paw-swelling, limb involvement, and joint erosion. As previously reported, an optimal dose of anti-TNF alone inhibited paw-swelling, limb involvement, and joint erosion. However, optimal anti-TNF combined with anti-CD4 caused significantly greater reductions in paw-swelling and joint erosion than those achieved by optimal anti-TNF alone. Coadministration of anti-CD4 was also effective in preventing an antibody response to the hamster anti-TNF antibody, which may have implications for long-term therapy in human disease. Thus anti-CD4 acts synergistically with anti-TNF in ameliorating established collagen-induced arthritis and this combined therapeutic approach may provide effective long-term control of rheumatoid arthritis. Images PMID:7908442

  14. Active Lactobacillus rhamnosus LA68 or Lactobacillus plantarum WCFS1 administration positively influences liver fatty acid composition in mice on a HFD regime.

    PubMed

    Ivanovic, Nevena; Minic, Rajna; Djuricic, Ivana; Radojevic Skodric, Sanja; Zivkovic, Irena; Sobajic, Sladjana; Djordjevic, Brizita

    2016-06-15

    Western life style, and high calorie diet in particular is causing major health problems such as insulin resistance, hepatic steatosis and heart disease in the modern age. High fat diet (HFD) induces similar changes in mice, such as increased body weight, hypercholesterolemia and accumulation of triglycerides in the liver. These changes can be ameliorated by the administration of some Lactobacillus species. The focus of this study was to analyze the fatty acid content of liver, heart and brain tissues of mice fed HFD and administered with either Lactobacillus plantarum WCFS1 or Lactobacillus rhamnosus LA68, and to analyze the fatty acid content of these organs after a two months washout period. The fatty acid composition of mouse liver tissue changed significantly due to probiotic administration during a 12 weeks HFD regime and active Lactobacillus administration had a slightly reversing effect toward the standard mouse diet group, but after the washout period these changes disappeared. The fatty acid composition of the heart and brain tissues was significantly changed in the HFD regime but probiotic administration had no significant influence on the fatty acid profile of these two organs. Upon the 8 weeks washout period the only remaining beneficial effect was the significantly lower mouse weight in the supplemented groups compared to the HFD group. PMID:27231730

  15. A novel protocol allowing oral delivery of a protein complement inhibitor that subsequently targets to inflamed colon mucosa and ameliorates murine colitis

    PubMed Central

    Elvington, M; Blichmann, P; Qiao, F; Scheiber, M; Wadsworth, C; Luzinov, I; Lucero, J; Vertegel, A; Tomlinson, S

    2014-01-01

    While there is evidence of a pathogenic role for complement in inflammatory bowel disease, there is also evidence for a protective role that relates to host defence and protection from endotoxaemia. There is thus concern regarding the use of systemic complement inhibition as a therapeutic strategy. Local delivery of a complement inhibitor to the colon by oral administration would ameliorate such concerns, but while formulations exist for oral delivery of low molecular weight drugs to the colon, they have not been used successfully for oral delivery of proteins. We describe a novel pellet formulation consisting of cross-linked dextran coated with an acrylic co-polymer that protects the complement inhibitor CR2-Crry from destruction in the gastrointestinal tract. CR2-Crry containing pellets administered by gavage, were characterized using a therapeutic protocol in a mouse model of dextran sulphate sodium (DSS)-induced colitis. Oral treatment of established colitis over a 5-day period significantly reduced mucosal inflammation and injury, with similar therapeutic benefit whether or not the proton pump inhibitor, omeprazole, was co-administered. Reduction in injury was associated with the targeting of CR2-Crry to the mucosal surface and reduced local complement activation. Treatment had no effect on systemic complement activity. This novel method for oral delivery of a targeted protein complement inhibitor will reduce systemic effects, thereby decreasing the risk of opportunistic infection, as well as lowering the required dose and treatment cost and improving patient compliance. Furthermore, the novel delivery system described here may provide similar benefits for administration of other protein-based drugs, such as anti-tumour necrosis factor-α antibodies. PMID:24730624

  16. Keratinocyte growth factor (KGF) gene therapy mediated by an attenuated form of Salmonella typhimurium ameliorates radiation induced pulmonary injury in rats.

    PubMed

    Liu, Chun-Jie; Ha, Xiao-Qin; Jiang, Jun-Jun; Lv, Tong-De; Wu, Chutse

    2011-01-01

    The aim of this study is to investigate the effect of KGF (Keratinocyte growth factor) gene therapy mediated by the attenuated Salmonella typhimurium Ty21a on radiation-induced pulmonary injury in rats model. Sprague-Dawley rats were divided into three groups: TPK group (treated with TPK strain, attenuated Salmonella typhimurium Ty21a-recombined human KGF gene); TP group (treated with TP strain, attenuated Salmonella typhimurium Ty21a-recombined blank plasmid); and Saline group (treated with saline). After intraperitoneal administration for 48 h, the thoraxes of the rats were exposed to X-ray (20 Gy), and the rats were administered again two weeks after radiation. On the 3rd, 5th, 7th, 14th and 28th day after radiation, the rats were sacrificed and lung tissues were harvested. Histological analysis was performed, MDA contents and SOD activity were detected, mRNA levels of KGF, TGF-β, SP-A and SP-C were measured by Real-time RT-PCR, and their concentrations in the BALF were quantified with ELISA. Administration of TPK strain improved the pathological changes of the lung on the 28th day. In the TPK group, KGF effectively expressed since the 3rd day, MDA contents decreased and SOD activity increased significantly, on the 7th day and 14th day respectively. SP-A and SP-C expression elevated, whereas TGF-β expression was inhibited in the TPK group. These results suggest that this novel gene therapy of KGF could ameliorate radiation-induced pulmonary injury in rats, and may be a promising therapy for the treatment of radiative pulmonary injury. PMID:21436609

  17. Intra-articular nuclear factor-κB blockade ameliorates collagen-induced arthritis in mice by eliciting regulatory T cells and macrophages.

    PubMed

    Min, S-Y; Yan, M; Du, Y; Wu, T; Khobahy, E; Kwon, S-R; Taneja, V; Bashmakov, A; Nukala, S; Ye, Y; Orme, J; Sajitharan, D; Kim, H-Y; Mohan, C

    2013-05-01

    Nuclear factor (NF)-κB is a transcription factor implicated in the pathogenesis of autoimmune disorders such as rheumatoid arthritis (RA). Here we have examined the effect of intra-articular administration of the IKK inhibitor, NEMO-binding domain peptide (NBD), on the severity of collagen-induced arthritis (CIA). NBD peptides were injected intra-articularly into the knee joints of DBA/1J mice after the onset of disease. Collagen-injected mice given a scrambled peptide served as controls. Arthritis severity was determined by visual examination of paws. Intra-articular NBD injection reduced the arthritis score and ameliorated morphological signs of bone destruction compared to the controls. Serum levels of type-II collagen-specific immunoglobulin (Ig)G2a antibodies were lower in NBD-treated mice versus the control mice, whereas the levels of type-II collagen-specific IgG1 antibodies were increased by NBD treatment. NBD treatment diminished the proinflammatory cytokines interleukin (IL)-17 and interferon (IFN)-γ in serum, but increased the regulatory cytokine IL-10. NBD-treated CIA mice exhibited significantly higher percentages and numbers of forkhead box protein 3 (FoxP3(+)) CD4(+) CD25(+) regulatory T cells than controls. Immunofluorescence analysis of NBD-treated mice revealed that FoxP3 and Ym1, a marker of alternatively activated macrophages, were juxtaposed to each other within draining inguinal lymph nodes. Intra-articular administration of NBD peptide is effective as an experimental therapy in a murine model of RA. Nevertheless, the intra-articular treatment modality is still associated with systemic effects on the immune system. PMID:23574318

  18. Manual therapy ameliorates delayed-onset muscle soreness and alters muscle metabolites in rats

    PubMed Central

    Urakawa, Susumu; Takamoto, Kouichi; Nakamura, Tomoya; Sakai, Shigekazu; Matsuda, Teru; Taguchi, Toru; Mizumura, Kazue; Ono, Taketoshi; Nishijo, Hisao

    2015-01-01

    Delayed-onset muscle soreness (DOMS) can be induced by lengthening contraction (LC); it can be characterized by tenderness and movement-related pain in the exercised muscle. Manual therapy (MT), including compression of exercised muscles, is widely used as physical rehabilitation to reduce pain and promote functional recovery. Although MT is beneficial for reducing musculoskeletal pain (i.e. DOMS), the physiological mechanisms of MT remain unclear. In the present study, we first developed an animal model of MT in DOMS; LC was applied to the rat gastrocnemius muscle under anesthesia, which induced mechanical hyperalgesia 2–4 days after LC. MT (manual compression) ameliorated mechanical hyperalgesia. Then, we used capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) to investigate early effects of MT on the metabolite profiles of the muscle experiencing DOMS. The rats were divided into the following three groups; (1) normal controls, (2) rats with LC application (LC group), and (3) rats undergoing MT after LC (LC + MT group). According to the CE-TOFMS analysis, a total of 171 metabolites were detected among the three groups, and 19 of these metabolites were significant among the groups. Furthermore, the concentrations of eight metabolites, including branched-chain amino acids, carnitine, and malic acid, were significantly different between the LC + MT and LC groups. The results suggest that MT significantly altered metabolite profiles in DOMS. According to our findings and previous data regarding metabolites in mitochondrial metabolism, the ameliorative effects of MT might be mediated partly through alterations in metabolites associated with mitochondrial respiration. PMID:25713324

  19. The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis

    PubMed Central

    Romano, B; Borrelli, F; Fasolino, I; Capasso, R; Piscitelli, F; Cascio, MG; Pertwee, RG; Coppola, D; Vassallo, L; Orlando, P; Di Marzo, V; Izzo, AA

    2013-01-01

    Background and Purpose The non-psychotropic cannabinoid cannabichromene is known to activate the transient receptor potential ankyrin-type1 (TRPA1) and to inhibit endocannabinoid inactivation, both of which are involved in inflammatory processes. We examined here the effects of this phytocannabinoid on peritoneal macrophages and its efficacy in an experimental model of colitis. Experimental Approach Murine peritoneal macrophages were activated in vitro by LPS. Nitrite levels were measured using a fluorescent assay; inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2) and cannabinoid (CB1 and CB2) receptors were analysed by RT-PCR (and/or Western blot analysis); colitis was induced by dinitrobenzene sulphonic acid (DNBS). Endocannabinoid (anandamide and 2-arachidonoylglycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry. Colonic inflammation was assessed by evaluating the myeloperoxidase activity as well as by histology and immunohistochemistry. Key Results LPS caused a significant production of nitrites, associated to up-regulation of anandamide, iNOS, COX-2, CB1 receptors and down-regulation of CB2 receptors mRNA expression. Cannabichromene significantly reduced LPS-stimulated nitrite levels, and its effect was mimicked by cannabinoid receptor and TRPA1 agonists (carvacrol and cinnamaldehyde) and enhanced by CB1 receptor antagonists. LPS-induced anandamide, iNOS, COX-2 and cannabinoid receptor changes were not significantly modified by cannabichromene, which, however, increased oleoylethanolamide levels. In vivo, cannabichromene ameliorated DNBS-induced colonic inflammation, as revealed by histology, immunohistochemistry and myeloperoxidase activity. Conclusion and Implications Cannabichromene exerts anti-inflammatory actions in activated macrophages – with tonic CB1 cannabinoid signalling being negatively coupled to this effect – and ameliorates experimental murine colitis. PMID:23373571

  20. CHOLINE AMELIORATES DEFICITS IN BALANCE CAUSED BY ACUTE NEONATAL ETHANOL EXPOSURE

    PubMed Central

    Bearer, Cynthia F.; Wellmann, Kristen A.; Tang, Ningfeng; He, Min; Mooney, Sandra M.

    2015-01-01

    Fetal alcohol spectrum disorder (FASD) is estimated to occur in 1% of all live births. The developing cerebellum is vulnerable to the toxic effects of alcohol. People with FASD have cerebellar hypoplasia and developmental deficits associated with cerebellar injury. Choline is an essential nutrient but many diets in the USA are choline deficient. In rats, choline given with or following alcohol exposure reduces many alcohol-induced neurobehavioral deficits, but not those associated with cerebellar function. Our objective was to determine if choline supplementation prior to alcohol exposure would ameliorate the impact of ethanol on a cerebellar-associated behavioral test in mice. Pregnant C57Bl6/J mice were maintained on a choline deficient diet from embryonic day 4.5. On postnatal day 1 (P1), pups were assigned to one of 8 treatment groups: choline (C) or saline (S) pre-treatment from P1-5, ethanol (6 g/kg) or Intralipid® on P5, C or S post-treatment from P6-20. On P30, balance and coordination were tested using the dowel crossing test. Overall, there was a significant effect of treatment and females crossed longer distances than males. Ethanol exposure significantly reduced the total distance crossed. Choline pre-treatment increased the distance crossed by males, and both pre- and post-treatment with choline significantly increased total distance crossed for females and males. There was no effect of choline on Intralipid®-exposed animals. This is the first study to show that choline ameliorates ethanol-induced effects on balance and coordination when given before ethanol exposure. Choline fortification of common foodstuffs may reduce the effects of alcohol. PMID:26085462

  1. The Library Administrator's Automation Handbook.

    ERIC Educational Resources Information Center

    Boss, Richard W.

    One of the most significant decisions in a library administrator's career is the decision to automate one or more of a library's operations. This book describes the present state of local library automation; the planning, selection, and implementation process; and the library administrator's role in the process. The bulk of the text provides a…

  2. Mesenchymal stem cells ameliorate inflammatory cytokine-induced impairment of AT-II cells through a keratinocyte growth factor-dependent PI3K/Akt/mTOR signaling pathway

    PubMed Central

    LI, JIWEI; HUANG, SHA; ZHANG, JUNHUA; FENG, CHANGJIANG; GAO, DONGYUN; YAO, BIN; WU, XU; FU, XIAOBING

    2016-01-01

    Lung epithelium restoration subsequent to injury is of concern in association with the outcomes of diverse inflammatory lung diseases. Previous studies have demonstrated that mesenchymal stem cells (MSCs) may promote epithelial repair subsequent to inflammatory injury, however the mechanism that mediates this effect remains unclear. The current study examined the role of MSCs in alveolar type II epithelial cell (AT-II cell) restoration subsequent to an inflammatory insult. AT-II cells were firstly exposed to inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, then were co-cultured with MSCs in Transwell for 72 h. Cell proliferation, expression of surfactant protein A (SP-A) and expression of the α1 subunit were evaluated respectively by the Cell Counting Kit-8 assay, western blotting and semiquantitative reverse transcription-polymerase chain reaction. Keratinocyte growth factor (KGF) small interfering RNA (siRNA) was applied to knockdown the main cytoprotective factors in the MSCs. Subsequent to an inflammatory insult, AT-II cells were observed to be impaired, exhibiting the characteristics of injured cell morphology, reduced cell proliferation and reduced expression of SP-A and the α1 subunit. Co-culture with MSCs significantly ameliorated these cell impairments, while these benefits were weakened by the application of KGF siRNA. Simultaneously, expression levels of phosphorylated (p-) protein kinase B (AKT) and p-mammalian target of rapamycin (mTOR) in AT-II cells were upregulated by MSCs, suggesting activation of the phosphoinositide 3-kinase (PI3K) pathway. These data demonstrate that administration of MSCs to the inflammation-insulted AT-II cells may ameliorate the impairments through a KGF-dependent PI3K/AKT/mTOR signaling pathway. PMID:27035760

  3. Mesenchymal stem cells ameliorate inflammatory cytokine-induced impairment of AT-II cells through a keratinocyte growth factor-dependent PI3K/Akt/mTOR signaling pathway.

    PubMed

    Li, Jiwei; Huang, Sha; Zhang, Junhua; Feng, Changjiang; Gao, Dongyun; Yao, Bin; Wu, Xu; Fu, Xiaobing

    2016-05-01

    Lung epithelium restoration subsequent to injury is of concern in association with the outcomes of diverse inflammatory lung diseases. Previous studies have demonstrated that mesenchymal stem cells (MSCs) may promote epithelial repair subsequent to inflammatory injury, however the mechanism that mediates this effect remains unclear. The current study examined the role of MSCs in alveolar type II epithelial cell (AT‑II cell) restoration subsequent to an inflammatory insult. AT‑II cells were firstly exposed to inflammatory cytokines including tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑1β, then were co‑cultured with MSCs in Transwell for 72 h. Cell proliferation, expression of surfactant protein A (SP‑A) and expression of the α1 subunit were evaluated respectively by the Cell Counting Kit‑8 assay, western blotting and semiquantitative reverse transcription-polymerase chain reaction. Keratinocyte growth factor (KGF) small interfering RNA (siRNA) was applied to knockdown the main cytoprotective factors in the MSCs. Subsequent to an inflammatory insult, AT‑II cells were observed to be impaired, exhibiting the characteristics of injured cell morphology, reduced cell proliferation and reduced expression of SP‑A and the α1 subunit. Co‑culture with MSCs significantly ameliorated these cell impairments, while these benefits were weakened by the application of KGF siRNA. Simultaneously, expression levels of phosphorylated (p‑) protein kinase B (AKT) and p‑mammalian target of rapamycin (mTOR) in AT‑II cells were upregulated by MSCs, suggesting activation of the phosphoinositide 3‑kinase (PI3K) pathway. These data demonstrate that administration of MSCs to the inflammation-insulted AT-II cells may ameliorate the impairments through a KGF-dependent PI3K/AKT/mTOR signaling pathway. PMID:27035760

  4. Lettuce glycoside B ameliorates cerebral ischemia reperfusion injury by increasing nerve growth factor and neurotrophin-3 expression of cerebral cortex in rats

    PubMed Central

    Zhan, Heqin; Li, Shengying; Sun, Juan; Liu, Ruili; Yan, Fulin; Niu, Bingxuan; Zhang, Haifang; Wang, Xinyao

    2014-01-01

    Aims: The aim of the study was to investigate the effects of LGB on cerebral ischemia-reperfusion (I/R) injury in rats and the mechanisms of action of LGB. Materials and Methods: The study involved extracting LGB from P. laciniata, exploring affects of LGB on brain ischemia and action mechanism at the molecular level. The cerebral ischemia reperfusion injury of middle cerebral artery occlusion was established. We measured brain histopathology and brain infarct rate to evaluate the effects of LGB on brain ischemia injury. The expressions of nerve growth factor (NGF) and neurotrophin-3 (NT-3) were also measured to investigate the mechanisms of action by the real-time polymerase chain reaction and immunohistochemistry. Statistical analysis: All results were mentioned as mean ± standard deviation. One-way analysis of variance was used to determine statistically significant differences among the groups. Values of P < 0.05 were considered to be statistically significant. Results: Intraperitoneal injection of LGB at the dose of 12, 24, and 48 mg/kg after brain ischemia injury remarkably ameliorated the morphology of neurons and brain infarct rate (P < 0.05, P < 0.01). LGB significantly increased NGF and NT-3 mRNA (messenger RNA) and both protein expression in cerebral cortex at the 24 and 72 h after drug administration (P < 0.05, P < 0.01). Conclusions: LGB has a neuroprotective effect in cerebral I/R injury and this effect might be attributed to its upregulation of NGF and NT-3 expression ability in the brain cortex during the latter phase of brain ischemia. PMID:24550587

  5. The effects of diazinon on lipid peroxidation and antioxidant enzymes in rat heart and ameliorating role of vitamin E and vitamin C.

    PubMed

    Akturk, O; Demirin, H; Sutcu, R; Yilmaz, N; Koylu, H; Altuntas, I

    2006-11-01

    Diazinon is one of the most widely used organophosphate insecticides (OPIs) in agriculture and public health programs. Reactive oxygen species (ROS) caused by OPIs may be involved in the toxicity of various pesticides. The aim of this study was to investigate how diazinon affects lipid peroxidation (LPO) and the antioxidant defense system in vivo and the possible ameliorating role of vitamins E and C. For this purpose, experiments were done to study the effects of DI on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in adult rat heart. Experimental groups were: (1) control group, (2) diazinon treated (DI) group, (3) DI+vitamins E and C-treated (DI+Vit) group. The levels of malondialdehyde (MDA) and the activities of SOD and CAT increased significantly in the DI group compared with the control group. The activity of SOD and the levels of MDA decreased significantly in the DI+Vit group compared with the DI group. The differences between the DI+Vit and control groups according to the MDA levels and the activities of both SOD and CAT were statistically significant. These results suggest that treating rats with a single dose of diazinon increases LPO and some antioxidant enzyme activities in the rat myocardium and, in addition, that single-dose treatment with a combination of vitamins E and C after the administration of diazinon can reduce LPO caused by diazinon, though this treatment was not sufficiently effective to reduce the values to those in control group. PMID:16964585

  6. Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate production in the prefrontal cortex of rats exposed to blockade of N-methy-D-aspartate receptors; Toward the therapeutics of cognitive impairment of schizophrenia

    PubMed Central

    Uehara, Takashi; Matsuoka, Tadasu; Sumiyoshi, Tomiki

    2014-01-01

    Rationale: Augmentation therapy with serotonin-1A (5-HT1A) receptor partial agonists has been suggested to improve cognitive impairment in patients with schizophrenia. Decreased activity of prefrontal cortex may provide a basis for cognitive deficits of the disease. Lactate plays a significant role in the supply of energy to the brain, and glutamatergic neurotransmission contributes to lactate production. Objectives and methods: The purposes of this study were to examine the effect of repeated administration (once a daily for 4 days) of tandospirone (0.05 or 5 mg/kg) on brain energy metabolism, as represented by extracellular lactate concentration (eLAC) in the medial prefrontal cortex (mPFC) of a rat model of schizophrenia. Results: Four-day treatment with MK-801, an NMDA-R antagonist, prolonged eLAC elevation induced by foot-shock stress (FS). Co-administration with the high-dose tandospirone suppressed prolonged FS-induced eLAC elevation in rats receiving MK-801, whereas tandospirone by itself did not affected eLAC increment. Conclusions: These results suggest that stimulation of 5-HT1A receptors ameliorates abnormalities of energy metabolism in the mPFC due to blockade of NMDA receptors. These findings provide a possible mechanism, based on brain energy metabolism, by which 5-HT1A agonism improve cognitive impairment of schizophrenia and related disorders. PMID:25232308

  7. C-C chemokine receptor type 4 antagonist Compound 22 ameliorates experimental autoimmune encephalomyelitis.

    PubMed

    Moriguchi, Kota; Miyamoto, Katsuichi; Tanaka, Noriko; Ueno, Rino; Nakayama, Takashi; Yoshie, Osamu; Kusunoki, Susumu

    2016-02-15

    Chemokines and chemokine receptors play important roles in the immune response. We previously reported the pathogenic role of C-C chemokine receptor type 4 (CCR4) in experimental autoimmune encephalomyelitis (EAE). Here, we examined whether CCR4 antagonism modulates the disease course of EAE. Wild-type and CCR4-knockout mice were induced EAE and were administered Compound 22, an antagonist of CCR4. Compound 22 significantly ameliorated the severity of EAE in wild-type mice, but not in the CCR4-knockout mice. Compound 22 inhibited Th1 and Th17 polarization of antigen-induced T-cell responses. Therefore, CCR4 antagonists might be potential therapeutic agents for multiple sclerosis. PMID:26857495

  8. Arctigenin isolated from the seeds of Arctium lappa ameliorates memory deficits in mice.

    PubMed

    Lee, In-Ah; Joh, Eun-Ha; Kim, Dong-Hyun

    2011-09-01

    The seeds of Arctium lappa L. (AL, family Asteraceae), the main constituents of which are arctiin and arctigenin, have been used as an herbal medicine or functional food to treat inflammatory diseases. These main constituents were shown to inhibit acetylcholinesterase (AChE) activity. Arctigenin more potently inhibited AChE activity than arctiin. Arctigenin at doses of 30 and 60 mg/kg (p. o.) potently reversed scopolamine-induced memory deficits by 62 % and 73 %, respectively, in a passive avoidance test. This finding is comparable with that of tacrine (10 mg/kg p. o.). Arctigenin also significantly reversed scopolamine-induced memory deficits in the Y-maze and Morris water maze tests. On the basis of these findings, arctigenin may ameliorate memory deficits by inhibiting AChE. PMID:21308615

  9. Amelioration of laminin-alpha2-deficient congenital muscular dystrophy by somatic gene transfer of miniagrin.

    PubMed

    Qiao, Chunping; Li, Jianbin; Zhu, Tong; Draviam, Romesh; Watkins, Simon; Ye, Xiaojing; Chen, Chunlian; Li, Juan; Xiao, Xiao

    2005-08-23

    Congenital muscular dystrophy (CMD) is characterized by severe muscle wasting, premature death in early childhood, and lack of effective treatment. Most of the CMD cases are caused by genetic mutations of laminin-alpha2, which is essential for the structural integrity of muscle extracellular matrix. Here, we report that somatic gene delivery of a structurally unrelated protein, a miniature version of agrin, functionally compensates for laminin-alpha2 deficiency in the murine models of CMD. Adeno-associated virus-mediated overexpression of miniagrin restored the structural integrity of myofiber basal lamina, inhibited interstitial fibrosis, and ameliorated dystrophic pathology. Furthermore, systemic gene delivery of miniagrin into multiple vital muscles significantly improved whole body growth and motility and quadrupled the lifespan (50% survival) of the dystrophic mice. Thus, our study demonstrated the efficacy of somatic gene therapy in a mouse model of CMD. PMID:16103356

  10. Amelioration of Muscular Dystrophy by Transgenic Expression of Niemann-Pick C1

    PubMed Central

    Steen, Michelle S.; Adams, Marvin E.; Tesch, Yan

    2009-01-01

    Duchenne muscular dystrophy (DMD) and other types of muscular dystrophies are caused by the loss or alteration of different members of the dystrophin protein complex. Understanding the molecular mechanisms by which dystrophin-associated protein abnormalities contribute to the onset of muscular dystrophy may identify new therapeutic approaches to these human disorders. By examining gene expression alterations in mouse skeletal muscle lacking α-dystrobrevin (Dtna−/−), we identified a highly significant reduction of the cholesterol trafficking protein, Niemann-Pick C1 (NPC1). Mutations in NPC1 cause a progressive neurodegenerative, lysosomal storage disorder. Transgenic expression of NPC1 in skeletal muscle ameliorates muscular dystrophy in the Dtna−/− mouse (which has a relatively mild dystrophic phenotype) and in the mdx mouse, a model for DMD. These results identify a new compensatory gene for muscular dystrophy and reveal a potential new therapeutic target for DMD. PMID:18946078

  11. Preterm white matter brain injury is prevented by early administration of umbilical cord blood cells.

    PubMed

    Li, Jingang; Yawno, Tamara; Sutherland, Amy; Loose, Jan; Nitsos, Ilias; Bischof, Robert; Castillo-Melendez, Margie; McDonald, Courtney A; Wong, Flora Y; Jenkin, Graham; Miller, Suzanne L

    2016-09-01

    Infants born very preterm are at high risk for neurological deficits including cerebral palsy. In this study we assessed the neuroprotective effects of umbilical cord blood cells (UCBCs) and optimal administration timing in a fetal sheep model of preterm brain injury. 50 million allogeneic UCBCs were intravenously administered to fetal sheep (0.7 gestation) at 12h or 5d after acute hypoxia-ischemia (HI) induced by umbilical cord occlusion. The fetal brains were collected at 10d after HI. HI (n=7) was associated with reduced number of oligodendrocytes (Olig2+) and myelin density (CNPase+), and increased density of activated microglia (Iba-1+) in cerebral white matter compared to control fetuses (P<0.05). UCBCs administered at 12h, but not 5d after HI, significantly protected white matter structures and suppressed cerebral inflammation. Activated microglial density showed a correlation with decreasing oligodendrocyte number (P<0.001). HI caused cell death (TUNEL+) in the internal capsule and cell proliferation (Ki-67+) in the subventricular zone compared to control (P<0.05), while UCBCs at 12h or 5d ameliorated these effects. Additionally, UCBCs at 12h induced a significant systemic increase in interleukin-10 at 10d, and reduced oxidative stress (malondialdehyde) following HI (P<0.05). UCBC administration at 12h after HI reduces preterm white matter injury, via anti-inflammatory and antioxidant actions. PMID:27317990

  12. Candesartan and glycyrrhizin ameliorate ischemic brain damage through downregulation of the TLR signaling cascade.

    PubMed

    Barakat, Waleed; Safwet, Nancy; El-Maraghy, Nabila N; Zakaria, Mohamed N M

    2014-02-01

    Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. The final outcome of stroke is determined not only by the volume of the ischemic core, but also by the extent of secondary brain damage inflicted to penumbral tissues by brain swelling, impaired microcirculation, and inflammation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (rt-PA). The current study was designed to investigate the protective effects of candesartan (0.15 mg/kg, orally) and glycyrrhizin (30 mg/kg, orally) experimentally-induced ischemic brain damage in C57BL/6 mice (middle cerebral artery occlusion, MCAO) in comparison to the effects of a standard neuroprotective drug (cerebrolysin, 7.5 mg/kg, IP). All drugs were administered 30 min before and 24h after MCAO. Both candesartan and glycyrrhizin ameliorated the deleterious effects of MCAO as indicated by the improvement in the performance of the animals in behaviour tests, reduction in brain infarction, neuronal degeneration, and leukocyte infiltration. In addition, MCAO induced a significant upregulation in the different elements of the TLR pathway including TLR-2 and TLR-4, Myd88, TRIF and IRF-3 and the downstream effectors TNF-α, IL-1β, IL-6 and NF-kB. All these changes were significantly ameliorated by treatment with candesartan and glycyrrhizin. The results of the current study represent a new indication for both candesartan and glycyrrhizin in the management of ischemic stroke with effects comparable to those of the standard neuroprotective drug cerebrolysin. PMID:24378346

  13. Short-term peripheral nerve stimulation ameliorates axonal dysfunction after spinal cord injury

    PubMed Central

    Kiernan, Matthew C.; Macefield, Vaughan G.; Lee, Bonne B.; Lin, Cindy S.-Y.

    2015-01-01

    There is accumulating evidence that peripheral motor axons deteriorate following spinal cord injury (SCI). Secondary axonal dysfunction can exacerbate muscle atrophy, contribute to peripheral neuropathies and neuropathic pain, and lead to further functional impairment. In an attempt to ameliorate the adverse downstream effects that developed following SCI, we investigated the effects of a short-term peripheral nerve stimulation (PNS) program on motor axonal excitability in 22 SCI patients. Axonal excitability studies were undertaken in the median and common peroneal nerves (CPN) bilaterally before and after a 6-wk unilateral PNS program. PNS was delivered percutaneously over the median nerve at the wrist and CPN around the fibular head, and the compound muscle action potential (CMAP) from the abductor pollicis brevis and tibialis anterior was recorded. Stimulus intensity was above motor threshold, and pulses (450 μs) were delivered at 100 Hz with a 2-s on/off cycle for 30 min 5 days/wk. SCI patients had consistently high thresholds with a reduced CMAP consistent with axonal loss; in some patients the peripheral nerves were completely inexcitable. Nerve excitability studies revealed profound changes in membrane potential, with a “fanned-in” appearance in threshold electrotonus, consistent with membrane depolarization, and significantly reduced superexcitability during the recovery cycle. These membrane dysfunctions were ameliorated after 6 wk of PNS, which produced a significant hyperpolarizing effect. The contralateral, nonstimulated nerves remained depolarized. Short-term PNS reversed axonal dysfunction following SCI, may provide an opportunity to prevent chronic changes in axonal and muscular function, and may improve rehabilitation outcomes. PMID:25787956

  14. Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

    PubMed

    Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

    2015-04-01

    Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats. PMID:24905340

  15. Liposomes ameliorate Crizotinib- and Nilotinib-induced inhibition of the cardiac IKr channel and QTc prolongation.

    PubMed

    Shopp, George M; Helson, Lawrence; Bouchard, Annie; Salvail, Dany; Majeed, Muhammad

    2014-09-01

    Crizotinib (Xalkori®) and nilotinib (Tasigna®) are tyrosine kinase inhibitors approved for the treatment of non-small cell lung cancer and chronic myeloid leukemia, respectively. Both have been shown to result in electrocardiogram rate-corrected Q-wave T-wave interval (QTc) prolongation in humans and animals. Liposomes have been shown to ameliorate drug-induced effects on the cardiac-delayed rectifier K(+) current (IKr, KV11.1), coded by the human ether-a-go-go-related gene (hERG). This study was undertaken to determine if liposomes would also decrease the effect of crizotinib and nilotinib on the IKr channel. Crizotinib and nilotinib were tested in an in vitro IKr assay using human embryonic kidney (HEK) 293 cells stably transfected with the hERG. Dose-responses were determined and the 50% inhibitory concentrations (IC50s) were calculated. When the HEK 293 cells were treated with crizotinib or nilotinib that were mixed with liposomes, there was a significant decrease in the IKr channel inhibitory effects of these two drugs. When isolated, rabbit hearts were exposed to crizotinib or nilotinib, there were significant increases in QTc prolongation. Mixing either of the drugs with liposomes ameliorated the effects of the drugs. Rabbits dosed intravenously (IV) with crizotinib or nilotinib showed QTc prolongation. When liposomes were injected prior to crizotinib or nilotinib, the liposomes decreased the effects on the QTc interval. The use of liposomal encapsulated QT-prolongation agents, or giving liposomes in combination with drugs, may decrease their cardiac liability. PMID:25202051

  16. Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice

    PubMed Central

    2013-01-01

    Introduction N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). Methods CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35. Results Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment. Conclusions We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA. PMID:24246048

  17. Ketamine Inhalation Ameliorates Ovalbumin-Induced Murine Asthma by Suppressing the Epithelial-Mesenchymal Transition

    PubMed Central

    Song, Li; Sen, Shi; Sun, Yuhong; Zhou, Jun; Mo, Liqun; He, Yanzheng

    2016-01-01

    Background Asthma accounts for 0.4% of all deaths worldwide, a figure that increases annually. Ketamine induces bronchial smooth muscle relaxation, and increasing evidence suggests that its anti-inflammatory properties might protect against lung injury and ameliorate asthma. However, there is a lack of evidence of the usefulness and mechanism of ketamine in acute asthma exacerbation. This study aimed to analyze the therapeutic effects and mechanism of action of ketamine on acute ovalbumin (OVA)-induced murine asthma. Material/Methods In vivo, BALB/c mice with OVA-induced asthma were treated with or without ketamine (25 or 50 mg/mL). Serum, lung sections, and mononuclear cell suspensions from the lung were collected for histological, morphometric, immunofluorescence, microRNA, quantitative polymerase chain reaction, regulatory T cell identification, cytokine, and Western blotting analyses. In vitro, bronchial epithelial cells were cultured to analyze the effect and mechanism of ketamine on epithelial-mesenchymal transition (EMT) and transforming growth factor-β (TGF-β) signaling. Results The inhalation of ketamine 25 or 50 mg/mL markedly suppressed OVA-induced airway hyper-responsiveness and airway inflammation, significantly increased the percentage of CD4+CD25+ T cells, and significantly decreased OVA-induced up-regulation of TGF-β1 and the EMT. MiR-106a was present at higher amounts in OVA-induced lung samples and was suppressed by ketamine treatment. The in vitro results showed that TGF-β1-induced EMT was suppressed by ketamine via miR-106a level regulation. Conclusions Ketamine ameliorates lung fibrosis in OVA-induced asthmatic mice by suppressing EMT and regulating miR-106a level, while ketamine inhalation might be a new therapeutic approach to the treatment of allergic asthma. PMID:27418244

  18. Ketamine Inhalation Ameliorates Ovalbumin-Induced Murine Asthma by Suppressing the Epithelial-Mesenchymal Transition.

    PubMed

    Song, Li; Sen, Shi; Sun, Yuhong; Zhou, Jun; Mo, Liqun; He, Yanzheng

    2016-01-01

    BACKGROUND Asthma accounts for 0.4% of all deaths worldwide, a figure that increases annually. Ketamine induces bronchial smooth muscle relaxation, and increasing evidence suggests that its anti-inflammatory properties might protect against lung injury and ameliorate asthma. However, there is a lack of evidence of the usefulness and mechanism of ketamine in acute asthma exacerbation. This study aimed to analyze the therapeutic effects and mechanism of action of ketamine on acute ovalbumin (OVA)-induced murine asthma. MATERIAL AND METHODS In vivo, BALB/c mice with OVA-induced asthma were treated with or without ketamine (25 or 50 mg/mL). Serum, lung sections, and mononuclear cell suspensions from the lung were collected for histological, morphometric, immunofluorescence, microRNA, quantitative polymerase chain reaction, regulatory T cell identification, cytokine, and Western blotting analyses. In vitro, bronchial epithelial cells were cultured to analyze the effect and mechanism of ketamine on epithelial-mesenchymal transition (EMT) and transforming growth factor-β (TGF-β) signaling. RESULTS The inhalation of ketamine 25 or 50 mg/mL markedly suppressed OVA-induced airway hyper-responsiveness and airway inflammation, significantly increased the percentage of CD4+CD25+ T cells, and significantly decreased OVA-induced up-regulation of TGF-β1 and the EMT. MiR-106a was present at higher amounts in OVA-induced lung samples and was suppressed by ketamine treatment. The in vitro results showed that TGF-β1-induced EMT was suppressed by ketamine via miR-106a level regulation. CONCLUSIONS Ketamine ameliorates lung fibrosis in OVA-induced asthmatic mice by suppressing EMT and regulating miR-106a level, while ketamine inhalation might be a new therapeutic approach to the treatment of allergic asthma. PMID:27418244

  19. 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

  20. Short-term peripheral nerve stimulation ameliorates axonal dysfunction after spinal cord injury.

    PubMed

    Lee, Michael; Kiernan, Matthew C; Macefield, Vaughan G; Lee, Bonne B; Lin, Cindy S-Y

    2015-05-01

    There is accumulating evidence that peripheral motor axons deteriorate following spinal cord injury (SCI). Secondary axonal dysfunction can exacerbate muscle atrophy, contribute to peripheral neuropathies and neuropathic pain, and lead to further functional impairment. In an attempt to ameliorate the adverse downstream effects that developed following SCI, we investigated the effects of a short-term peripheral nerve stimulation (PNS) program on motor axonal excitability in 22 SCI patients. Axonal excitability studies were undertaken in the median and common peroneal nerves (CPN) bilaterally before and after a 6-wk unilateral PNS program. PNS was delivered percutaneously over the median nerve at the wrist and CPN around the fibular head, and the compound muscle action potential (CMAP) from the abductor pollicis brevis and tibialis anterior was recorded. Stimulus intensity was above motor threshold, and pulses (450 μs) were delivered at 100 Hz with a 2-s on/off cycle for 30 min 5 days/wk. SCI patients had consistently high thresholds with a reduced CMAP consistent with axonal loss; in some patients the peripheral nerves were completely inexcitable. Nerve excitability studies revealed profound changes in membrane potential, with a "fanned-in" appearance in threshold electrotonus, consistent with membrane depolarization, and significantly reduced superexcitability during the recovery cycle. These membrane dysfunctions were ameliorated after 6 wk of PNS, which produced a significant hyperpolarizing effect. The contralateral, nonstimulated nerves remained depolarized. Short-term PNS reversed axonal dysfunction following SCI, may provide an opportunity to prevent chronic changes in axonal and muscular function, and may improve rehabilitation outcomes. PMID:25787956

  1. Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.

    PubMed

    Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro; Yokota, Takashi; Matsushima, Shouji; Suga, Tadashi; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Mizushima, Wataru; Masaki, Yoshihiro; Furihata, Takaaki; Katsuyama, Ryoichi; Okita, Koichi; Tsutsui, Hiroyuki

    2014-10-01

    We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin-sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, HFD+vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND+vehicle group. Pioglitazone normalized the insulin levels in HFD-fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP-dependent mitochondrial respiration, complex I and III activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondrial function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus. PMID:24964389

  2. Processed Aloe vera Gel Ameliorates Cyclophosphamide-Induced Immunotoxicity

    PubMed Central

    Im, Sun-A; Kim, Ki-Hyang; Kim, Hee-Suk; Lee, Ki-Hwa; Shin, Eunju; Do, Seon-Gil; Jo, Tae Hyung; Park, Young In; Lee, Chong-Kil

    2014-01-01

    The effects of processed Aloe vera gel (PAG) on cyclophosphamide (CP)-induced immunotoxicity were examined in mice. Intraperitoneal injection of CP significantly reduced the total number of lymphocytes and erythrocytes in the blood. Oral administration of PAG quickly restored CP-induced lymphopenia and erythropenia in a dose-dependent manner. The reversal of CP-induced hematotoxicity by PAG was mediated by the functional preservation of Peyer’s patch cells. Peyer’s patch cells isolated from CP-treated mice, which were administered PAG, produced higher levels of T helper 1 cytokines and colony-stimulating factors (CSF) in response to concanavalin A stimulation as compared with those isolated from CP-treated control mice. PAG-derived polysaccharides directly activated Peyer’s patch cells isolated from normal mice to produce cytokines including interleukin (IL)-6, IL-12, interferon-γ, granulocyte-CSF, and granulocyte-macrophage-CSF. The cytokines produced by polysaccharide-stimulated Peyer’s patch cells had potent proliferation-inducing activity on mouse bone marrow cells. In addition, oral administration of PAG restored IgA secretion in the intestine after CP treatment. These results indicated that PAG could be an effective immunomodulator and that it could prevent CP-induced immunotoxic side effects. PMID:25347273

  3. 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

  4. 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

  5. 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

  6. Repeated administration of a mutant cocaine esterase: effects on plasma cocaine levels, cocaine-induced cardiovascular activity, and immune responses in rhesus monkeys.

    PubMed

    Collins, Gregory T; Brim, Remy L; Noon, Kathleen R; Narasimhan, Diwahar; Lukacs, Nicholas W; Sunahara, Roger K; Woods, James H; Ko, Mei-Chuan

    2012-07-01

    Previous studies have demonstrated the capacity of a long-acting mutant form of a naturally occurring bacterial double mutant cocaine esterase (DM CocE) to antagonize the reinforcing, discriminative, convulsant, and lethal effects of cocaine in rodents and reverse the increases in mean arterial pressure (MAP) and heart rate (HR) produced by cocaine in rhesus monkeys. This study was aimed at characterizing the immunologic responses to repeated dosing with DM CocE and determining whether the development of anti-CocE antibodies altered the capacity of DM CocE to reduce plasma cocaine levels and ameliorate the cardiovascular effects of cocaine in rhesus monkeys. Under control conditions, intravenous administration of cocaine (3 mg/kg) resulted in a rapid increase in the plasma concentration of cocaine (n = 2) and long-lasting increases in MAP and HR (n = 3). Administration of DM CocE (0.32 mg/kg i.v.) 10 min after cocaine resulted in a rapid hydrolysis of cocaine with plasma levels below detection limits within 5 to 8 min. Elevations in MAP and HR were significantly reduced within 25 and 50 min of DM CocE administration, respectively. Although slight (10-fold) increases in anti-CocE antibodies were observed after the fourth administration of DM CocE, these antibodies did not alter the capacity of DM CocE to reduce plasma cocaine levels or ameliorate cocaine's cardiovascular effects. Anti-CocE titers were transient and generally dissipated within 8 weeks. Together, these results suggest that highly efficient cocaine esterases, such as DM CocE, may provide a novel and effective therapeutic for the treatment of acute cocaine intoxication in humans. PMID:22518021

  7. Amelioration of soil PAH and heavy metals by combined application of fly ash and biochar

    NASA Astrophysics Data System (ADS)

    Masto, Reginald; George, Joshy; Ansari, Md; Ram, Lal

    2016-04-01

    Generation of electricity through coal combustion produces huge quantities of fly ash. Sustainable disposal and utilization of these fly ash is a major challenge. Fly ash along with other amendments like biochar could be used for amelioration of soil. In this study, fly ash and biochar were used together for amelioration of polycyclic aromatic hydrocarbon (PAH) contaminated soil. Field experiment was conducted to investigate the effects of fly ash and biochar on the amelioration of soil PAH, and the yield of Zea mays. The treatments were control, biochar (4 t/ha), fly ash (4 t/ha), ash + biochar ( 2 + 2 t/ha). Soil samples were collected after the harvest of maize crop and analysed for chemical and biological parameters. Thirteen PAHs were analysed in the postharvest soil samples. Soil PAHs were extracted in a microwave oven at 120 °C using hexane : acetone (1:1) mixture. The extracted solutions were concentrated, cleaned and the 13 PAHs [Acenaphthene (Ace), fluorene (Flr), phenanthrene (Phn), anthracene(Ant), pyrene(Pyr), benz(a)anthracene (BaA), chrysene (Chy), benzo(b)fluoranthene (BbF), benzo(k)fluoranthene (BkF), benzo(a)pyrene, benzo(g,h,i)perylene (BghiP), dibenzo(a,h)anthracene, and indeno(1,2,3-cd)pyrene)(Inp)] were analysed using GC-MS. The mean pH increased from 6.09 in control to 6.64 and 6.58 at biochar and fly ash treated soils, respectively. N content was not affected, whereas addition of biochar alone and in combination with fly ash, has significantly increased the soil organic carbon content. P content was almost double in combined (9.06 mg/kg) treatment as compared to control (4.32 mg/kg). The increase in K due to biochar was 118%, whereas char + ash increased soil K by 64%. Soil heavy metals were decreased: Zn (‑48.4%), Ni (‑41.4%), Co (‑36.9%), Cu (‑35.7%), Mn (‑34.3%), Cd (‑33.2%), and Pb (‑30.4%). Soil dehydrogenase activity was significantly increased by ash and biochar treatments and the maximum activity was observed for the

  8. Anti-B7-H3 monoclonal antibody ameliorates the damage of acute experimental pancreatitis by attenuating the inflammatory response.

    PubMed

    Zhuang, Xiaohui; Shen, Jiaqing; Jia, Zhengyu; Wu, Airong; Xu, Ting; Shi, Yuqi; Xu, Chunfang

    2016-06-01

    B7-H3, a recently discovered B7 family member, is documented as a regulator in the inflammatory response as well as T cell-mediated immune responses. In this paper, we find that patients with acute pancreatitis revealed overwhelming levels of serum soluble B7-H3 (sB7-H3) associated with the clinical outcomes. Furthermore, B7-H3 protein was marked increased in l-arginine-induced acute experimental pancreatitis. Anti-B7-H3 monoclonal antibody treatment attenuated the proinflammatory cytokine production, downregulated the activation of the NF-κB signaling pathway, and ameliorated the pancreas disruption in l-arginine-induced pancreatitis. In addition, although l-arginine alone failed to induce the production of proinflammatory cytokine and anti-B7-H3 mAb had no effect on the proinflammatory cytokine production of acinar cells, administration of anti-B7-H3 mAb in the coculture model of acinar cells and macrophages stimulated by l-arginine displayed the similar effects. On the whole, B7-H3 participates in the development of acute pancreatitis, and anti-B7-H3 monoclonal antibody ameliorates severity of acute experimental pancreatitis via attenuation of the inflammatory response. PMID:27003113

  9. ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice

    PubMed Central

    Yildirim, Emre; Connor, David A.; Gould, Thomas J.

    2015-01-01

    Nicotine withdrawal produces cognitive deficits that can predict relapse. Amelioration of these cognitive deficits emerges as a target in current smoking cessation therapies. In rodents, withdrawal from chronic nicotine disrupts contextual fear conditioning (CFC), whereas acute nicotine enhances this hippocampus-specific learning and memory. These modifications are mediated by β2-subunit-containing (β2*) nicotinic acetylcholine receptors in the hippocampus. We aimed to test ABT-089, a partial agonist of α4β2*, and ABT-107, an α7 nicotinic acetylcholine receptor agonist, for amelioration of cognitive deficits induced by withdrawal from chronic nicotine in mice. Mice underwent chronic nicotine administration (12.6 mg/kg/day or saline for 12 days), followed by 24 h of withdrawal. At the end of withdrawal, mice received 0.3 or 0.6 mg/kg ABT-089 or 0.3 mg/kg ABT-107 (doses were determined through initial dose–response experiments and prior studies) and were trained and tested for CFC. Nicotine withdrawal produced deficits in CFC that were reversed by acute ABT-089, but not ABT-107. Cued conditioning was not affected. Taken together, our results suggest that modulation of hippocampal learning and memory using ABT-089 may be an effective component of novel therapeutic strategies for nicotine addiction. PMID:25426579

  10. BPOZ-2 Gene Delivery Ameliorates Alpha-Synucleinopathy in A53T Transgenic Mouse Model of Parkinson’s Disease

    PubMed Central

    Roy, Avik; Rangasamy, Suresh Babu; Kundu, Madhuchhanda; Pahan, Kalipada

    2016-01-01

    Ankyrin-rich BTB/POZ domain containing protein-2 or BPOZ-2, a scaffold protein, has been recently shown to control the degradation of many biological proteins ranging from embryonic development to tumor progression. However, its role in the process of neuronal diseases has not been properly explored. Since, abnormal clearance of metabolic proteins contributes to the development of alpha-synuclein (α-syn) pathologies in Parkinson’s disease (PD), we are interested to explore if BPOZ-2 participates in the amelioration of α-syn in vivo in basal ganglia. Here we report that lentiviral administration of bpoz-2 gene indeed lowers the burden of α-syn in DA neurons in the nigra of A53T transgenic (A53T-Tg) mouse. Our detailed immunological analyses have shown that the overexpression of bpoz-2 dramatically improves both somatic and neuritic α-syn pathologies in the nigral DA neurons. Similarly, the specific ablation of bpoz-2 by lentiviral-shRNA stimulates the load of monomeric and polymeric forms of α-syn in the nigral DA neurons of A53T-Tg. While investigating the mechanism, we observed that BPOZ-2 was involved in a protein-protein association with PINK1 and therefore could stimulate PINK1-dependent autophagic clearance of α-syn. Our results have demonstrated that bpoz-2 gene delivery could have prospect in the amelioration of alpha-synucleinopathy in PD and other Lewy body diseases. PMID:26916519

  11. Combination of angiotensin-(1–7) with perindopril is better than single therapy in ameliorating diabetic cardiomyopathy

    PubMed Central

    Hao, Panpan; Yang, Jianmin; Liu, Yanping; Zhang, Mingxiang; Zhang, Kai; Gao, Fei; Chen, Yuguo; Zhang, Cheng; Zhang, Yun

    2015-01-01

    We recently found that overexpression of angiotensin (Ang)-converting enzyme 2, which metabolizes Ang-II to Ang-(1–7) and Ang-I to Ang-(1–9), may improve left ventricular remodeling in diabetic cardiomyopathy. Here we aimed to test whether chronic infusion of Ang-(1–7) can dose-dependently ameliorate left ventricular remodeling and function in a rat model of diabetic cardiomyopathy and whether the combination of Ang-(1–7) and Ang-converting enzyme inhibition may be superior to single therapy. Our results showed that Ang-(1–7) treatment dose-dependently ameliorated left ventricular remodeling and dysfunction in diabetic rats by attenuating myocardial fibrosis, myocardial hypertrophy and myocyte apoptosis via both the Mas receptor and angiotensin II type 2 receptor. Furthermore, combining Ang-(1–7) with perindopril provided additional cardioprotection relative to single therapy. Ang-(1–7) administration provides a novel and promising approach for treatment of diabetic cardiomyopathy. PMID:25740572

  12. Long-Term Consumption of Platycodi Radix Ameliorates Obesity and Insulin Resistance via the Activation of AMPK Pathways.

    PubMed

    Lee, Chae Eun; Hur, Haeng Jeon; Hwang, Jin-Taek; Sung, Mi Jeong; Yang, Hye Jeong; Kim, Hyun-Jin; Park, Jae Ho; Kwon, Dae Young; Kim, Myung-Sunny

    2012-01-01

    This study was designed to evaluate the effects and mechanism of Platycodi radix, having white balloon flower (Platycodon grandiflorum for. albiflorum (Honda) H. Hara) on obesity and insulin resistance. The extracts of Platycodi radix with white balloon flower were tested in cultured cells and administered into mice on a high-fat diet. The Platycodi radix activated the AMPK/ACC phosphorylation in C2C12 myotubes and also suppressed adipocyte differentiation in 3T3-L1 cells. In experimental animal, it suppressed the weight gain of obese mice and ameliorated obesity-induced insulin resistance. It also reduced the elevated circulating mediators, including triglyceride (TG), T-CHO, leptin, resistin, and monocyte chemotactic protein (MCP)-1 in obesity. As shown in C2C12 myotubes, the administration of Platycodi radix extracts also recovered the AMPK/ACC phosphorylation in the muscle of obese mice. These results suggest that Platycodi radix with white balloon flower ameliorates obesity and insulin resistance in obese mice via the activation of AMPK/ACC pathways and reductions of adipocyte differentiation. PMID:22829857

  13. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

    SciTech Connect

    Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

    2014-10-01

    Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD{sub 50}) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo

  14. NF-kappaB inhibition ameliorates angiotensin II-induced inflammatory damage in rats.

    PubMed

    Muller, D N; Dechend, R; Mervaala, E M; Park, J K; Schmidt, F; Fiebeler, A; Theuer, J; Breu, V; Ganten, D; Haller, H; Luft, F C

    2000-01-01

    We recently reported that the activation of nuclear factor-kappaB (NF-kappaB) promotes inflammation in rats harboring both human renin and angiotensinogen genes (double-transgenic rats [dTGR]). We tested the hypothesis that the antioxidant pyrrolidine dithiocarbamate (PDTC) inhibits NF-kappaB and ameliorates renal and cardiac end-organ damage. dTGR feature hypertension, severe renal and cardiac damage, and a 40% mortality rate at 7 weeks. Electrophoretic mobility shift assay showed increased NF-kappaB DNA binding activity in hearts and kidneys of dTGR. Chronic PDTC (200 mg/kg SC) treatment decreased blood pressure (162+/-8 versus 190+/-7 mm Hg; P=0.02) in dTGR compared with dTGR controls. The cardiac hypertrophy index was also significantly reduced (4.90+/-0.1 versus 5.77+/-0.1 mg/g; P<0. 001). PDTC reduced 24-hour albuminuria by >95% (2.5+/-0.8 versus 57. 1+/-8.7 mg/d; P<0.001) and prevented death. Vascular injury was ameliorated in small renal and cardiac vessels. Electrophoretic mobility shift assay showed that PDTC inhibited NF-kappaB binding activity in heart and kidney, whereas AP-1 activity in the kidney was not decreased. dTGR exhibited increased left ventricular c-fos and c-jun mRNA expression. PDTC treatment reduced c-fos but not c-jun mRNA. Immunohistochemistry showed increased p65 NF-kappaB subunit expression in the endothelium and smooth muscle cells of damaged small vessels, as well as infiltrating cells in glomeruli, tubules, and collecting ducts of dTGR. PDTC markedly reduced the immunoreactivity of p65. PDTC also prevented the NF-kappaB-dependent transactivation of the intercellular adhesion molecule ICAM-1 and inducible nitric oxide synthase. Monocyte infiltration was markedly increased in dTGR kidneys and hearts. Chronic treatment reduced monocyte/macrophage infiltration by 72% and 64%, respectively. Thus, these results demonstrate that PDTC inhibits NF-kappaB activity, ameliorates inflammation, and protects against angiotensin II-induced end

  15. Sparassis crispa (Hanabiratake) ameliorates skin conditions in rats and humans.

    PubMed

    Kimura, Takashi; Hashimoto, Mamiko; Yamada, Munenori; Nishikawa, Yoshihiro

    2013-01-01

    Sparassis crispa (SC) is an edible mushroom with various medicinal properties. In this study, we investigated to determine whether SC would affect skin conditions in rats and humans. Oral administration of SC increased both turnover of the stratum corneum and dermal soluble collagen content in collagen synthetic activity-reduced model rats. To investigate the effects of oral intake of SC in humans, we performed a randomized, double-blind, placebo-controlled study. We found that cheek transepidermal water loss was significantly lower in the experimental group than in the control group at 4 weeks of ingestion. This study suggests that SC is effective and safe for the improvement of skin conditions. PMID:24018675

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. Activation of Aryl Hydrocarbon Receptor (AhR) Leads to Reciprocal Epigenetic Regulation of FoxP3 and IL-17 Expression and Amelioration of Experimental Colitis

    PubMed Central

    Singh, Balwan; Price, Robert L.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2011-01-01

    Background Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3+ Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis. Methodology/Principal Findings Dextran sodium sulphate (DSS) administration induced acute colitis in C57BL/6 mice, as shown by significant weight loss, shortening of colon, mucosal ulceration, and increased presence of CXCR3+ T cells as well as inflammatory cytokines. Interestingly, a single dose of TCDD (25 µg/kg body weight) was able to attenuate all of the clinical and inflammatory markers of colitis. Analysis of T cells in the lamina propria (LP) and mesenteric lymph nodes (MLN), during colitis, revealed decreased presence of Tregs and increased induction of Th17 cells, which was reversed following TCDD treatment. Activation of T cells from AhR+/+ but not AhR -/- mice, in the presence of TCDD, promoted increased differentiation of Tregs while inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD treatment. Conclusions/Significance These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation. PMID:21858153

  1. Ocotillol, a Majonoside R2 Metabolite, Ameliorates 2,4,6-Trinitrobenzenesulfonic Acid-Induced Colitis in Mice by Restoring the Balance of Th17/Treg Cells.

    PubMed

    Lee, Sang-Yun; Jeong, Jin-Ju; Le, Thi Hong Van; Eun, Su-Hyeon; Nguyen, Minh Duc; Park, Jeong Hill; Kim, Dong-Hyun

    2015-08-12

    In a preliminary experiment, majonoside R2 (MR2), isolated from Vietnamese ginseng (Panax vietnamensis Ha et Grushv.), inhibited differentiation to Th17 cells and was metabolized to ocotillol via pseudoginsenoside RT4 (PRT4) by gut microbiota. Therefore, we examined the inhibitory effects of MR2 and its metabolites PRT4 and ocotillol against Th17 cell differentiation. These ginsenosides significantly suppressed interleukin (IL)-6/tumor growth factor beta-induced differentiation of splenic CD4(+) T cells into Th17 cells and expression of IL-17 in vitro. Among these ginsenosides, ocotillol showed the highest inhibitory effect. We also examined the anti-inflammatory effect of ocotillol in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Oral administration of ocotillol significantly suppressed TNBS-induced colon shortening, macroscopic score, myeloperoxidase activity, and production of nitric oxide and prostaglandin E2. Ocotillol treatment increased TNBS-suppressed expression of tight junction proteins ZO-1, occludin, and claudin-1 in the colon. Treatment with ocotillol inhibited TNBS-induced expression of tumor necrosis factor (TNF)-α and IL-1β, as well as activation of NF-κB and MAPKs. Moreover, treatment with ocotillol inhibited TNBS- induced differentiation to Th17 cells in the lamina propria of colon, as well as expression of T-bet, RORγt, IL-17, and IL-23. Ocotillol treatment also increased Treg cell differentiation and Foxp3 and IL-10 expression. These findings suggest that orally administered MR2 may be metabolized to ocotillol in the intestine by gut microbiota and the transformed ocotillol may ameliorate inflammatory diseases such as colitis by restoring the balance of Th17/Treg cells. PMID:26194345

  2. Study of Glycine and Folic Acid Supplementation to Ameliorate Transfusion Dependence in Congenital SLC25A38 Mutated Sideroblastic Anemia.

    PubMed

    LeBlanc, Marissa A; Bettle, Amanda; Berman, Jason N; Price, Victoria E; Pambrun, Chantale; Yu, Zhijie; Tiller, Marilyn; McMaster, Christopher R; Fernandez, Conrad V

    2016-07-01

    Congenital sideroblastic anemia (CSA) is a hematological disorder characterized by the presence of ringed sideroblasts in bone marrow erythroid precursors. Mutations in the erythroid-specific glycine mitochondrial transporter gene SLC25A38 have been found in a subset of patients with transfusion-dependent congenital CSA. Further studies in a zebrafish model identified a promising ameliorative strategy with combined supplementation with glycine and folate. We tested this combination in three individuals with SLC25A38 CSA, with a primary objective to decrease red blood cell transfusion requirements. No significant impact was observed on transfusion requirements or any hematologic parameters. PMID:27038157

  3. Inhibition of prolyl hydroxylase 3 ameliorates cardiac dysfunction in diabetic cardiomyopathy.

    PubMed

    Xia, Yanfei; Gong, Luwei; Liu, Hui; Luo, Beibei; Li, Bo; Li, Rui; Li, Beibei; Lv, Mei; Pan, Jinyu; An, Fengshuang

    2015-03-01

    Prolyl hydroxylase 3 (PHD3) is a member of the prolyl hydroxylases (PHDs) family and is induced by hypoxia. It plays a critical role in regulating the abundance of hypoxia-inducible factor (HIF). Its expression is increased in diabetic rat hearts; however, its role remains unclear. We investigated the potential role and mechanism of action of PHD3 in the setting of diabetes-induced myocardial dysfunction in rats. In vivo, type 2 diabetic rat model was induced via a high-fat diet and intraperitoneal injection of streptozotocin. PHD3 expression was knocked down using lentivirus-mediated short-hairpin RNA (shRNA). In vitro, primary neonatal cardiomyocytes and H9c2 cardiomyoblasts were cultured in 33.3 mM glucose (high glucose, HG) and 5.5 mM glucose (normal glucose, NG), the latter of which was used as a control. PHD3-siRNA was used to inhibit the expression of PHD3 and to investigate the role of PHD3 in HG-induced apoptosis in H9c2 cardiomyoblasts. Rats with diabetic cardiomyopathy (DCM) exhibited severe left ventricular dysfunction as well as myocardial apoptosis and fibrosis. PHD3 expression was increased in the myocardial tissues of diabetic rats, and inhibition of PHD3 ameliorated the disease. Additionally, the inhibition of PHD3 significantly decreased HG-induced apoptosis and MAPK activation in H9c2 cardiomyoblasts. Our results suggest that PHD3 inhibition ameliorates myocardial dysfunction in the setting of diabetic cardiomyopathy. PMID:25595486

  4. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation.

    PubMed

    Mayo, Lior; Cunha, Andre Pires Da; Madi, Asaf; Beynon, Vanessa; Yang, Zhiping; Alvarez, Jorge I; Prat, Alexandre; Sobel, Raymond A; Kobzik, Lester; Lassmann, Hans; Quintana, Francisco J; Weiner, Howard L

    2016-07-01

    SEE WINGER AND ZAMVIL DOI101093/BRAIN/AWW121 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The innate immune system plays a central role in the chronic central nervous system inflammation that drives neurological disability in progressive forms of multiple sclerosis, for which there are no effective treatments. The mucosal immune system is a unique tolerogenic organ that provides a physiological approach for the induction of regulatory T cells. Here we report that nasal administration of CD3-specific antibody ameliorates disease in a progressive animal model of multiple sclerosis. This effect is IL-10-dependent and is mediated by the induction of regulatory T cells that share a similar transcriptional profile to Tr1 regulatory cells and that suppress the astrocyte inflammatory transcriptional program. Treatment results in an attenuated inflammatory milieu in the central nervous system, decreased microglia activation, reduced recruitment of peripheral monocytes, stabilization of the blood-brain barrier and less neurodegeneration. These findings suggest a new therapeutic approach for the treatment of progressive forms of multiple sclerosis and potentially other types of chronic central nervous system inflammation. PMID:27246324

  5. Psoralen and Isopsoralen Ameliorate Sex Hormone Deficiency-Induced Osteoporosis in Female and Male Mice

    PubMed Central

    Yuan, Xiaomei; Bi, Yanan; Yan, Zeman; Pu, Weiling; Li, Yuhong; Zhou, Kun

    2016-01-01

    Osteoporosis is a systemic skeletal disease, which is characterized by a systemic destruction of bone mass and microarchitecture. With life standard improved, the treatment of osteoporosis attracted more attention. The aim of this study is to verify the osteoprotective effect of psoralen and isopsoralen in females and males. Female and male mice were divided into 7 groups in this study: control group (sham-operation), model group (by ovariectomy or orchidectomy), positive control group (females given estradiol valerate; males given alendronate sodium), psoralen groups (10 mg/kg and 20 mg/kg), and isopsoralen groups (10 mg/kg and 20 mg/kg). After administration of psoralen and isopsoralen for 8 weeks, osteoporosis was ameliorated with increasing bone strength and improving trabecular bone microstructure as indicated by CT scan and pathology. Serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRACP), osteocalcin (OC), and C-terminal cross-linking telopeptides of type I collagen (CTX-1) were examined. Decreased TRACP and increased ALP/TRACP suggested restoring from bone destruction. These results suggest that psoralen and isopsoralen may be used as good natural compounds for the treatment of osteoporosis in males, as well as females. PMID:27239473

  6. 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

  7. Ameliorative Effects of Pomegranate Peel Extract against Dietary-Induced Nonalcoholic Fatty Liver in Rats.

    PubMed

    Al-Shaaibi, Siham N K; Waly, Mostafa I; Al-Subhi, Lyutha; Tageldin, Mohamed H; Al-Balushi, Nada M; Rahman, Mohammad S

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is associated with oxidative stress. In this study, we investigated the potential protective effect of pomegranate (Punica granatum L.) peel extract (PPE) against oxidative stress in the liver of rats with NAFLD. Sprague-Dawley rats were fed a high fat diet (HFD), 20% corn oil, or palm oil for 8 weeks in the presence or absence of PPE. The control group was fed a basal diet. The progression of NAFLD was evaluated histologically and by measuring liver enzymes (alanine transaminase and aspartate transaminase), serum lipids (triglycerides and total cholesterol), and oxidative stress markers. The HFD feeding increased the body weight and caused NAFLD, liver steatosis, hyperlipidemia, oxidative stress, and elevated liver enzymes. Administration of PPE ameliorated the hepatic morphology, reduced body weight, improved liver enzymes, and inhibited lipogenesis. Furthermore, PPE enhanced the cellular redox status in the liver tissue of rats with NAFLD. Our findings suggest that PPE could improve HFD-induced NAFLD via abolishment of hepatic oxidative damage and hyperlipidemia. PPE might be considered as a potential lead material in the treatment of NAFLD and obesity through the modulation of lipid metabolism. PMID:27069901

  8. Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice

    PubMed Central

    Chrisam, Martina; Pirozzi, Marinella; Castagnaro, Silvia; Blaauw, Bert; Polishchuck, Roman; Cecconi, Francesco; Grumati, Paolo; Bonaldo, Paolo

    2015-01-01

    Autophagy is a self-degradative process responsible for the clearance of damaged or unnecessary cellular components. We have previously found that persistence of dysfunctional organelles due to autophagy failure is a key event in the pathogenesis of COL6/collagen VI-related myopathies, and have demonstrated that reactivation of a proper autophagic flux rescues the muscle defects of Col6a1-null (col6a1−/−) mice. Here we show that treatment with spermidine, a naturally occurring nontoxic autophagy inducer, is beneficial for col6a1−/− mice. Systemic administration of spermidine in col6a1−/− mice reactivated autophagy in a dose-dependent manner, leading to a concurrent amelioration of the histological and ultrastructural muscle defects. The beneficial effects of spermidine, together with its being easy to administer and the lack of overt side effects, open the field for the design of novel nutraceutical strategies for the treatment of muscle diseases characterized by autophagy impairment. PMID:26565691

  9. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

    PubMed Central

    Kim, Joo Wan; Ku, Sae-Kwang; Kim, Ki Young; Kim, Sung Goo; Han, Min Ho; Kim, Gi-Young; Hwang, Hye Jin; Kim, Byung Woo; Kim, Cheol Min

    2015-01-01

    The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation. PMID:26064425

  10. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation

    PubMed Central

    Mayo, Lior; Cunha, Andre Pires Da; Madi, Asaf; Beynon, Vanessa; Yang, Zhiping; Alvarez, Jorge I.; Prat, Alexandre; Sobel, Raymond A.; Kobzik, Lester; Lassmann, Hans; Quintana, Francisco J.

    2016-01-01

    See Winger and Zamvil (doi:10.1093/brain/aww121) for a scientific commentary on this article. The innate immune system plays a central role in the chronic central nervous system inflammation that drives neurological disability in progressive forms of multiple sclerosis, for which there are no effective treatments. The mucosal immune system is a unique tolerogenic organ that provides a physiological approach for the induction of regulatory T cells. Here we report that nasal administration of CD3-specific antibody ameliorates disease in a progressive animal model of multiple sclerosis. This effect is IL-10-dependent and is mediated by the induction of regulatory T cells that share a similar transcriptional profile to Tr1 regulatory cells and that suppress the astrocyte inflammatory transcriptional program. Treatment results in an attenuated inflammatory milieu in the central nervous system, decreased microglia activation, reduced recruitment of peripheral monocytes, stabilization of the blood–brain barrier and less neurodegeneration. These findings suggest a new therapeutic approach for the treatment of progressive forms of multiple sclerosis and potentially other types of chronic central nervous system inflammation. PMID:27246324

  11. Ameliorative Effects of Pomegranate Peel Extract against Dietary-Induced Nonalcoholic Fatty Liver in Rats

    PubMed Central

    Al-Shaaibi, Siham N. K.; Waly, Mostafa I.; Al-Subhi, Lyutha; Tageldin, Mohamed H.; Al-Balushi, Nada M.; Rahman, Mohammad S.

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is associated with oxidative stress. In this study, we investigated the potential protective effect of pomegranate (Punica granatum L.) peel extract (PPE) against oxidative stress in the liver of rats with NAFLD. Sprague-Dawley rats were fed a high fat diet (HFD), 20% corn oil, or palm oil for 8 weeks in the presence or absence of PPE. The control group was fed a basal diet. The progression of NAFLD was evaluated histologically and by measuring liver enzymes (alanine transaminase and aspartate transaminase), serum lipids (triglycerides and total cholesterol), and oxidative stress markers. The HFD feeding increased the body weight and caused NAFLD, liver steatosis, hyperlipidemia, oxidative stress, and elevated liver enzymes. Administration of PPE ameliorated the hepatic morphology, reduced body weight, improved liver enzymes, and inhibited lipogenesis. Furthermore, PPE enhanced the cellular redox status in the liver tissue of rats with NAFLD. Our findings suggest that PPE could improve HFD-induced NAFLD via abolishment of hepatic oxidative damage and hyperlipidemia. PPE might be considered as a potential lead material in the treatment of NAFLD and obesity through the modulation of lipid metabolism. PMID:27069901

  12. Ameliorative effect of Matricaria chamomilla .L on paraquat: Induced oxidative damage in lung rats

    PubMed Central

    Ranjbar, Akram; Mohsenzadeh, Fariba; Chehregani, Abdolkarim; Khajavi, Farzad; Zijoud, Seyed-Mostafa Hossini; Ghasemi, Hassan

    2014-01-01

    Background: Herbal medicines have been long used for antioxidant properties. The purpose of this study was to investigate the effect of hydroalcholic extract Matricaria chamomilla. L (M. chamomilla) against Paraquat (PQ) induced pulmonary injury in association with its antioxidant activity. Materials and Methods: Effective doses of PQ (5 mg/kg/day) and M. chamomilla (50 mg/kg/day) were administered alone or in combination for 7 days. At the end of the experiment, lung tissue of the animals was separated. The activity of enzymatic scavengers such as glutathione peroxidase (GPx) and superoxide dismutase (SOD), lipid peroxidation (LPO) and total antioxidant power (TAP) were measured. Results: In these samples, the LPO, SOD, and GPx were higher in the PQ group as compared with controls. M. chamomilla extract ameliorated LPO, SOD, GPx and increased TAP in plasma and lung tissue of PQ induced changes. Co administration of PQ with M. chamomilla improved LPO and SOD, and GPx. Conclusion: M. chamomilla as natural antioxidant may be considered beneficial for the protection oxidative lung injury in PQ poisoning. PMID:25002799

  13. Sodium aescinate ameliorates liver injury induced by methyl parathion in rats.

    PubMed

    DU, Yuan; Wang, Tian; Jiang, Na; Ren, Ru-Tong; Li, Chong; Li, Chang-Kun; Fu, Feng-Hua

    2012-05-01

    Methyl parathion, a highly cytotoxic insecticide, has been used in agricultural pest control for several years. The present study investigated the protective effect of sodium aescinate (SA, the sodium salt of aescin) against liver injury induced by methyl parathion. Forty male Sprague-Dawley rats were randomly divided into 5 groups of 8 animals: the control group; the methyl parathion (15 mg/kg) poisoning (MP) group; and the MP plus SA at doses of 0.45, 0.9 and 1.8 mg/kg groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and acetylcholinesterase (AChE) in the plasma were assayed. Nitric oxide (NO) and antioxidative parameters were measured. Histopathological examination of the liver was also performed. The results revealed that SA had no effect on AChE. Treatment with SA decreased the activities of ALT and AST, and the levels of malondialdehyde and NO. Treatment with SA also increased the level of glutathione and the activities of superoxide dismutase and glutathione peroxidase. SA administration also ameliorated liver injury induced by methyl parathion poisoning. The findings indicate that SA protects against liver injury induced by methyl parathion and that the mechanism of action is related to the antioxidative and anti-inflammatory effects of SA. PMID:22969975

  14. Capsaicin Ameliorates Cisplatin-Induced Renal Injury through Induction of Heme Oxygenase-1

    PubMed Central

    Jung, Sung-Hyun; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Subin; Choe, Seong-Kyu; Park, Raekil; So, Hong-Seob

    2014-01-01

    Cisplatin is one of the most potent chemotherapy agents. However, its use is limited due to its toxicity in normal tissues, including the kidney and ear. In particular, nephrotoxicity induced by cisplatin is closely associated with oxidative stress and inflammation. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in the heme metabolism, has been implicated in a various cellular processes, such as inflammatory injury and anti-oxidant/oxidant homeostasis. Capsaicin is reported to have therapeutic potential in cisplatin-induced renal failures. However, the mechanisms underlying its protective effects on cisplatin-induced nephrotoxicity remain largely unknown. Herein, we demonstrated that administration of capsaicin ameliorates cisplatin-induced renal dysfunction by assessing the levels of serum creatinine and blood urea nitrogen (BUN) as well as tissue histology. In addition, capsaicin treatment attenuates the expression of inflammatory mediators and oxidative stress markers for renal damage. We also found that capsaicin induces HO-1 expression in kidney tissues and HK-2 cells. Notably, the protective effects of capsaicin were completely abrogated by treatment with either the HO inhibitor ZnPP IX or HO-1 knockdown in HK-2 cells. These results suggest that capsaicin has protective effects against cisplatin-induced renal dysfunction through induction of HO-1 as well as inhibition oxidative stress and inflammation. PMID:24642709

  15. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis

    PubMed Central

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y.; Fong, Guo-Hua; Sakmar, Thomas P.; Rafii, Shahin; Ding, Bi-Sen

    2016-01-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin–dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladaptbed hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis. PMID:26779814

  16. Antagonism of CRTH2 ameliorates chronic epicutaneous sensitization-induced inflammation by multiple mechanisms.

    PubMed

    Boehme, Stefen A; Chen, Edward P; Franz-Bacon, Karin; Sásik, Roman; Sprague, L James; Ly, Tai Wei; Hardiman, Gary; Bacon, Kevin B

    2009-01-01

    Prostaglandin D(2) (PGD(2)) and its receptor chemoattractant receptor homologous molecule expressed on T(h)2 cells (CRTH2) have been implicated in the pathogenesis of numerous allergic diseases. We investigated the role of PGD(2) and CRTH2 in allergic cutaneous inflammation by using a highly potent and specific antagonist of CRTH2. Administration of this antagonist ameliorated cutaneous inflammation caused by either repeated epicutaneous ovalbumin or FITC sensitization. Gene expression and ELISA analysis revealed that there was reduced pro-inflammatory cytokine mRNA or protein produced. Importantly, the CRTH2 antagonist reduced total IgE, as well as antigen-specific IgE, IgG1 and IgG2a antibody levels. This reduction in antibody production correlated to reduced cytokines produced by splenocytes following in vitro antigen challenge. An examination of skin CD11c(+) dendritic cells (DC) showed that in mice treated with the CRTH2 antagonist, there was a decrease in the number of these cells that migrated to the draining lymph nodes in response to FITC application to the skin. Additionally, naive CD4(+) T lymphocytes co-cultured with skin-derived DC from CRTH2 antagonist-treated mice showed a reduced ability to produce a number of cytokines compared with DC from vehicle-treated mice. Collectively, these findings suggest that CRTH2 has a pivotal role in mediating the inflammation and the underlying immune response following epicutaneous sensitization. PMID:19066315

  17. VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats

    PubMed Central

    Farkas, Laszlo; Farkas, Daniela; Ask, Kjetil; Möller, Antje; Gauldie, Jack; Margetts, Peter; Inman, Mark; Kolb, Martin

    2009-01-01

    Idiopathic pulmonary fibrosis (IPF) can lead to the development of secondary pulmonary hypertension (PH) and ultimately death. Despite this known association, the precise mechanism of disease remains unknown. Using a rat model of IPF, we explored the role of the proangiogenic and antiapoptotic growth factor VEGF in the vascular remodeling that underlies PH. In this model, adenoviral delivery of active TGF-β1 induces pulmonary arterial remodeling, loss of the microvasculature in fibrotic areas, and increased pulmonary arterial pressure (PAP). Immunohistochemistry and mRNA analysis revealed decreased levels of VEGF and its receptor, which were inversely correlated with PAP and endothelial cell apoptosis in both the micro- and macrovasculature. Treatment of IPF rats with adenoviral delivery of VEGF resulted in reduced endothelial apoptosis, increased vascularization, and improved PAP due to reduced remodeling but worsened PF. These data show that experimental pulmonary fibrosis (PF) leads to loss of the microvasculature through increased apoptosis and to remodeling of the pulmonary arteries, with both processes resulting in PH. As administration of VEGF ameliorated the PH in this model but concomitantly aggravated the fibrogenic process, VEGF-based therapies should be used with caution. PMID:19381013

  18. Smart Soup, a Traditional Chinese Medicine Formula, Ameliorates Amyloid Pathology and Related Cognitive Deficits

    PubMed Central

    Li, Xiaohang; Cui, Jin; Ding, Jianqing; Wang, Ying; Zeng, Xianglu; Ling, Yun; Shen, Xiaoheng; Chen, Shengdi; Huang, Chenggang; Pei, Gang

    2014-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe disease-modifying treatment and symptomatic intervention alternatives against AD. Smart Soup (SS), a Chinese medicine formula composed of Rhizoma Acori Tatarinowii (AT), Poria cum Radix Pini (PRP) and Radix Polygalae (RP), is a typical prescription against memory deficits. Here, we assessed the efficacy of SS against AD. Oral administration of SS ameliorated the cognitive impairment of AD transgenic mice, with reduced Aβ levels, retarded Aβ amyloidosis and reduced Aβ-induced gliosis and neuronal loss in the brains of AD mice. Consistently, SS treatment reduced amyloid-related locomotor dysfunctions and premature death of AD transgenic Drosophila. Mechanistic studies showed that RP reduced Aβ generation, whereas AT and PRP exerted neuroprotective effects against Aβ. Taken together, our study indicates that SS could be effective against AD, providing a practical therapeutic strategy against the disease. PMID:25386946

  19. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

    PubMed

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

    2016-02-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis. PMID:26779814

  20. Salvianolic acid B ameliorates CNS autoimmunity by suppressing Th1 responses.

    PubMed

    Dong, Zhihui; Ma, Dihui; Gong, Ye; Yu, Tingmin; Yao, Gang

    2016-04-21

    Experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), is a Th1 and Th17 cell-mediated CNS autoimmune disease. Therefore, immune regulation is a key target for therapy. Salvianolic acid B (Sal B) is a major water-soluble bioactive component of the famous traditional Chinese medicine Salvia miltiorrhiza, which is notable for its anti-oxidative and anti-inflammatory effects. Thus Sal B, by impairing Th1 or Th17 responses in EAE/MS, might ameliorate the crippling symptoms. Here we show that the intraperitoneal administration of 30mg/kg Sal B daily for 14 days after the onset of MOG-induced EAE in mice effectively reduced its severity. Additionally, Sal B treatment downgraded the infiltration of inflammatory cells, limited astrogliosis and blocked Th1 responses other than that of Th17. These results indicated that Sal B may serve as an effective therapeutic agent for MS/EAE by inhibiting Th1 cell responses. PMID:26777627

  1. Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis

    PubMed Central

    Hiramitsu, Masanori; Shimada, Yasuhito; Kuroyanagi, Junya; Inoue, Takashi; Katagiri, Takao; Zang, Liqing; Nishimura, Yuhei; Nishimura, Norihiro; Tanaka, Toshio

    2014-01-01

    Lemon (Citrus limon) contains various bioactive flavonoids, and prevents obesity and obesity-associated metabolic diseases. We focused on eriocitrin (eriodictyol 7-rutinoside), a powerful antioxidative flavonoid in lemon with lipid-lowering effects in a rat model of high-fat diet. To investigate the mechanism of action of eriocitrin, we conducted feeding experiments on zebrafish with diet-induced obesity. Oral administration of eriocitrin (32 mg/kg/day for 28 days) improved dyslipidaemia and decreased lipid droplets in the liver. DNA microarray analysis revealed that eriocitrin increased mRNA of mitochondrial biogenesis genes, such as mitochondria transcription factor, nuclear respiratory factor 1, cytochrome c oxidase subunit 4, and ATP synthase. In HepG2 cells, eriocitrin also induced the corresponding orthologues, and reduced lipid accumulation under conditions of lipid loading. Eriocitrin increased mitochondrial size and mtDNA content, which resulted in ATP production in HepG2 cells and zebrafish. In summary, dietary eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis. PMID:24424211

  2. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

    SciTech Connect

    Zhang, Ying; Li, Jianguo

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  3. Senior Administrators Should Have Administrative Contracts.

    ERIC Educational Resources Information Center

    Posner, Gary J.

    1987-01-01

    Recognizing that termination is viewed by the employee as the equivalent to capital punishment of a career, an administrative contract can reduce the emotional and financial entanglements that often result. Administrative contracts are described. (MLW)

  4. Toll-like receptor 4 knockout ameliorates neuroinflammation due to lung-brain interaction in mechanically ventilated mice.

    PubMed

    Chen, Ting; Chen, Chang; Zhang, Zongze; Zou, Yufeng; Peng, Mian; Wang, Yanlin

    2016-08-01

    Toll-like receptor 4 (TLR4) is a crucial receptor in the innate immune system, and increasing evidence supports its role in inflammation, stress, and tissue injury, including injury to the lung and brain. We aimed to investigate the effects of TLR4 on neuroinflammation due to the lung-brain interaction in mechanically ventilated mice. Male wild-type (WT) C57BL/6 and TLR4 knockout (TLR4 KO) mice were divided into three groups: (1) control group (C): spontaneous breathing; (2) anesthesia group (A): spontaneous breathing under anesthesia; and (3) mechanical ventilation group (MV): 6h of MV under anesthesia. The behavioral responses of mice were tested with fear conditioning tests. The histological changes in the lung and brain were assessed using hematoxylin-eosin (HE) staining. The level of TLR4 mRNA in tissue was measured using reverse transcription-polymerase chain reaction (RT-PCR). The levels of inflammatory cytokines were measured with an enzyme-linked immunosorbent assay (ELISA). Microgliosis, astrocytosis, and the TLR4 immunoreactivity in the hippocampus were measured by double immunofluorescence. MV mice exhibited impaired cognition, and this impairment was less severe in TLR4 KO mice than in WT mice. In WT mice, MV increased TLR4 mRNA expression in the lung and brain. MV induced mild lung injury, which was prevented in TLR4 KO mice. MV mice exhibited increased levels of inflammatory cytokines, increased microglia and astrocyte activation. Microgliosis was alleviated in TLR4 KO mice. MV mice exhibited increased TLR4 immunoreactivity, which was expressed in microglia and astrocytes. These results demonstrate that TLR4 is involved in neuroinflammation due to the lung-brain interaction and that TLR4 KO ameliorates neuroinflammation due to lung-brain interaction after prolonged MV. In addition, Administration of a TLR4 antagonist (100μg/mice) to WT mice also significantly attenuated neuroinflammation of lung-brain interaction due to prolonged MV. TLR4 antagonism

  5. Novice Administrators: Personality and Administrative Style Changes.

    ERIC Educational Resources Information Center

    Schmidt, Linda J.; Kosmoski, Georgia J.; Pollack, Dennis R.

    Since the advent of effective-schools research findings, educational administration experts have advocated a democratic and collegial leadership style for school administrators. This paper provides the findings of a study that examined 43 beginning administrators (25 females, 32 Caucasians, 9 African-Americans, 2 Hispanics) to determine what…

  6. Fatty Acid Synthase Inhibitor C75 Ameliorates Experimental Colitis

    PubMed Central

    Matsuo, Shingo; Yang, Weng-Lang; Aziz, Monowar; Kameoka, Shingo; Wang, Ping

    2014-01-01

    Abnormalities of lipid metabolism through overexpression of fatty acid synthase (FASN), which catalyzes the formation of long-chain fatty acids, are associated with the development of inflammatory bowel disease (IBD). C75 is a synthetic α-methylene-γ-butyrolactone compound that inhibits FASN activity. We hypothesized that C75 treatment could effectively reduce the severity of experimental colitis. Male C57BL/6 mice were fed 4% dextran sodium sulfate (DSS) for 7 d. C75 (5 mg/kg body weight) or dimethyl sulfoxide (DMSO) (vehicle) was administered intraperitoneally from d 2 to 6. Clinical parameters were monitored daily. Mice were euthanized on d 8 for histological evaluation and measurements of colon length, chemokine, cytokine and inflammatory mediator expression. C75 significantly reduced body weight loss from 23% to 15% on d 8, compared with the vehicle group. The fecal bleeding, diarrhea and colon histological damage scores in the C75-treated group were significantly lower than scores in the vehicle animals. Colon shortening was significantly improved after C75 treatment. C75 protected colon tissues from DSS-induced apoptosis by inhibiting caspase-3 activity. Macrophage inflammatory protein 2, keratinocyte-derived chemokine, myeloperoxidase activity and proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β and IL-6) in the colon were significantly downregulated in the C75-treated group, compared with the vehicle group. Treatment with C75 in colitis mice inhibited the elevation of FASN, cyclooxygenase-2 and inducible nitric oxide synthase expression as well as IκB degradation in colon tissues. C75 administration alleviates the severity of colon damage and inhibits the activation of inflammatory pathways in DSS-induced colitis. Thus, inhibition of FASN may represent an attractive therapeutic potential for treating IBD. PMID:24306512

  7. 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

  8. 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

  9. 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

  10. Amelioration by catalpol of atherosclerotic lesions in hypercholesterolemic rabbits.

    PubMed

    Liu, Jiang-yue; Zhang, Dai-juan

    2015-02-01

    The aim of the present study was to evaluate the effects of catalpol administration on atherosclerosis. Atherogenesis was induced by a high-cholesterol chow in male New Zealand White rabbits that were randomly assigned to receive atorvastatin (5 mg/kg/day), catalpol (5 mg/kg/day), or vehicle by oral gavage for 12 weeks. The rabbits were sacrificed after 12 weeks, and the thoracic aorta and serum were collected for further pathological and molecular biological analysis. Catalpol administration resulted in significantly attenuated atherosclerotic lesions. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol were remarkably reduced, and high-density lipid cholesterol was elevated in the catalpol-treated group. Catalpol reduced the levels of tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule-1, and soluble intercellular adhesion molecule-1 in the serum, as well as vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-α protein, inducible nitric oxide synthase, matrix metalloproteinases-9, and nuclear factor-κB protein65 in the aortic arch. In addition, catalpol treatment reduced the lipid peroxidation levels, while elevating antioxidant capacity. Catolpol pretreatment inhibited the nuclear translocation and DNA binding activity of nuclear factor-κB protein in oxygenized low-density lipoprotein-stimulated EA.hy926 cells. Furthermore, catolpol pretreatment activated nuclear factor erythroid 2-related factor 2 and upregulated the expression of its downstream antioxidant enzyme heme oxygenase. In summary, catalpol attenuated atherosclerotic lesions by the inhibition of inflammatory cytokines and oxidative stress status in a rabbit atherosclerotic model and enhanced the antioxidant capacity in oxygenized low-density lipoprotein-stimulated EA.hy926 cells. These results suggest that catalpol may be used to prevent and attenuate atherosclerosis

  11. 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

  12. 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

  13. 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

  14. Coffee bean polyphenols ameliorate postprandial endothelial dysfunction in healthy male adults.

    PubMed

    Ochiai, Ryuji; Sugiura, Yoko; Otsuka, Kazuhiro; Katsuragi, Yoshihisa; Hashiguchi, Teruto

    2015-05-01

    To reveal the effect of coffee bean polyphenols (CBPs) on blood vessels, this study aimed to investigate the effect of CBPs on acute postprandial endothelial dysfunction. Thirteen healthy non-diabetic men (mean age, 44.9 ± 1.4 years) consumed a test beverage (active: containing CBPs, placebo: no CBPs) before a 554-kcal test meal containing 14 g of protein, 30 g of fat and 58 g of carbohydrates. Then, a crossover analysis was performed to investigate the time-dependent changes in flow-mediated dilation (FMD) in the brachial artery. In the active group, the postprandial impairment of FMD was significantly improved, the two-hour postprandial nitric oxide metabolite levels were significantly increased and the six-hour postprandial urinary 8-epi-prostaglandin F2α levels were significantly reduced compared to the placebo group. The test meal increased the levels of blood glucose, insulin and triglycerides in both groups with no significant intergroup differences. These findings indicate that CBPs intake ameliorates postprandial endothelial dysfunction in healthy men. PMID:25666414

  15. Ameliorative Influence of Green Tea Extract on Copper Nanoparticle-Induced Hepatotoxicity in Rats

    NASA Astrophysics Data System (ADS)

    Ibrahim, Marwa A.; Khalaf, A. A.; Galal, Mona K.; Ogaly, Hanan A.; H. M. Hassan, Azza

    2015-09-01

    The potential toxicity of copper nanoparticles (CNPs) to the human health and environment remains a critical issue. In the present study, we investigated the protective influence of an aqueous extract of green tea leaves (GTE) against CNPs-induced (20-30 nm) hepatotoxicity. Four different groups of rats were used: group I was the control, group II received CNPs (40 mg/kg BW), group III received CNPs plus GTE, and group IV received GTE alone. We highlighted the hepatoprotective effect of GTE against CNPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, histopathological alterations, and DNA damage evaluation. The rats that were given CNPs only had a highly significant elevation in liver enzymes, alteration in oxidant-antioxidant balance, and severe pathological changes. In addition, we detected a significant elevation of DNA fragmentation percentage, marked DNA laddering, and significance over expression of both caspase-3 and Bax proteins. The findings for group III clarify the efficacy of GTE as a hepatoprotectant on CNPs through improving the liver enzyme activity, antioxidant status, as well as suppressing DNA fragmentation and the expression of the caspase-3 and Bax proteins. In conclusion, GTE was proved to be a potential hepatoprotective additive as it significantly ameliorates the hepatotoxicity and apoptosis induced by CNPs.

  16. 4,4'-Diisothiocyanostilbene-2,2'-disulfonic Acid (DIDS) Ameliorates Ischemia-Hypoxia-Induced White Matter Damage in Neonatal Rats through Inhibition of the Voltage-Gated Chloride Channel ClC-2

    PubMed Central

    Zhao, Baixiong; Quan, Hongyu; Ma, Teng; Tian, Yanping; Cai, Qiyan; Li, Hongli

    2015-01-01

    Chronic cerebral hypoperfusion is believed to cause white matter lesions (WMLs), leading to cognitive impairment. Previous studies have shown that inflammation and apoptosis of oligodendrocytes (OLs) are involved in the pathogenesis of WMLs, but effective treatments have not been studied. In this study, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a chloride (Cl−) channel blocker, was injected into chronic cerebral ischemia-hypoxia rat models at different time points. Our results showed that DIDS significantly reduced the elevated mRNA levels and protein expression of chloride channel 2 (ClC-2) in neonatal rats induced by ischemia-hypoxia. Meanwhile, DIDS application significantly decreased the concentrations of reactive oxygen species (ROS); and the mRNA levels of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha TNF-α in neonatal rats with hypoxic-ischemic damage. Myelin staining was weaker in neonatal rats with hypoxic-ischemic damage compared to normal controls in corpus callosum and other white matter, which was ameliorated by DIDS. Furthermore, the elevated number of caspase-3 and neural/glial antigen 2 (NG-2) double-labeled positive cells was attenuated by DIDS after ischemia anoxic injury. Administration of DIDS soon after injury alleviated damage to OLs much more effectively in white matter. In conclusion, our study suggests that early application of DIDS after ischemia-hypoxia injury may partially protect developing OLs. PMID:25961953

  17. Intravenous administration of Honokiol provides neuroprotection and improves functional recovery after traumatic brain injury through cell cycle inhibition.

    PubMed

    Wang, Haiquan; Liao, Zhengbu; Sun, Xiaochuan; Shi, Quanhong; Huo, Gang; Xie, Yanfeng; Tang, Xiaolan; Zhi, Xinggang; Tang, Zhaohua

    2014-11-01

    Recently, increasing evidence has shown that cell cycle activation is a key factor of neuronal death and neurological dysfunction after traumatic brain injury (TBI). This study aims to investigate the effects of Honokiol, a cell cycle inhibitor, on attenuating the neuronal damage and facilitating functional recovery after TBI in rats, in an attempt to unveil its underlying molecular mechanisms in TBI. This study suggested that delayed intravenous administration of Honokiol could effectively ameliorate TBI-induced sensorimotor and cognitive dysfunctions. Meanwhile, Honokiol treatment could also reduce the lesion volume and increase the neuronal survival in the cortex and hippocampus. The neuronal degeneration and apoptosis in the cortex and hippocampus were further significantly attenuated by Honokiol treatment. In addition, the expression of cell cycle-related proteins, including cyclin D1, CDK4, pRb and E2F1, was significantly increased and endogenous cell cycle inhibitor p27 was markedly decreased at different time points after TBI. And these changes were significantly reversed by post-injury Honokiol treatment. Furthermore, the expression of some of the key cell cycle proteins such as cyclin D1 and E2F1 and the associated apoptosis in neurons were both remarkably attenuated by Honokiol treatment. These results show that delayed intravenous administration of Honokiol could effectively improve the functional recovery and attenuate the neuronal cell death, which is probably, at least in part, attributed to its role as a cell cycle inhibitior. This might give clues to developing attractive therapies for future clinical trials. PMID:24973706

  18. Naringin ameliorates cognitive deficits via oxidative stress, proinflammatory factors and the PPARγ signaling pathway in a type 2 diabetic rat model.

    PubMed

    Qi, Zhonghua; Xu, Yinghui; Liang, Zhanhua; Li, Sheng; Wang, Jie; Wei, Yi; Dong, Bin

    2015-11-01

    Naringenin is a flavonoid polyphenolic compound, which facilitates the removal of free radicals, oxidative stress and inflammation. The present study aimed to obtain a better understanding of the effects of curcumin on the regulation of diabetes‑associated cognitive decline, and its underlying mechanisms. An experimental diabetes mellitus (DM) rat model was induced by streptozoticin (50 mg/kg). Following treatment with naringin (100 and 200 mg/kg) for 16 weeks, the body weight and blood glucose levels of the DM rats were measured. A morris water maze test was used to analyze the effects of naringin on the cognitive deficit of the DM rats. The levels of oxidative stress, proinflammatory factors, caspase‑3 and caspase‑9, and the protein expression of peroxisome proliferator‑activated receptor γ (PPARγ) were quantified in the DM rats using a commercially‑available kit and western blot assay, respectively. In addition, a GW9662 PPARγ inhibitor (0.3 mg/kg) was administered to the DM rats to determine whether PPARγ affected the effects of naringin on the cognitive deficit of the DM rats. The results demonstrated that naringin increased the body weight, blood glucose levels, and cognitive deficits of the DM rats. The levels of oxidative stress and proinflammatory factors in the naringin‑treated rats were significantly lower, compared with those of the DM rats. In addition, naringin activated the protein expression of PPARγ, and administration of the PPARγ inhibitor decreased the protein expression of PPARγ, and attenuated the effects of naringin on cognitive deficit. The results also demonstrated that naringin decreased the expression levels of caspase‑3 and caspase‑9 in the DM rats. These results suggested that naringin ameliorated cognitive deficits via oxidative stress, proinflammatory factors and the PPARγ signaling pathway in the type 2 diabetic rat model. Furthermore, oxidative stress, proinflammatory factors and PPARγ signaling may be

  19. Neuropeptide S ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 through activation of cognate receptor-expressing neurons in the subiculum complex.

    PubMed

    Shao, Yu-Feng; Wang, Can; Xie, Jun-Fan; Kong, Xiang-Pan; Xin, Le; Dong, Chao-Yu; Li, Jing; Ren, Wen-Ting; Hou, Yi-Ping

    2016-07-01

    Our previous studies have demonstrated that neuropeptide S (NPS), via selective activation of the neurons bearing NPS receptor (NPSR) in the olfactory cortex, facilitates olfactory function. High level expression of NPSR mRNA in the subiculum complex of hippocampal formation suggests that NPS-NPSR system might be involved in the regulation of olfactory spatial memory. The present study was undertaken to investigate effects of NPS on the scopolamine- or MK801-induced impairment of olfactory spatial memory using computer-assisted 4-hole-board spatial memory test, and by monitoring Fos expression in the subiculum complex in mice. In addition, dual-immunofluorescence microscopy was employed to identify NPS-induced Fos-immunereactive (-ir) neurons that also bear NPSR. Intracerebroventricular administration of NPS (0.5 nmol) significantly increased the number of visits to switched odorants in recall trial in mice suffering from odor-discriminating inability induced by scopolamine, a selective muscarinic cholinergic receptor antagonist, or MK801, a N-methyl-D-aspartate receptor antagonist, after training trials. The improvement of olfactory spatial memory by NPS was abolished by the NPSR antagonist [D-Val(5)]NPS (40 nmol). Ex vivo c-Fos and NPSR immunohistochemistry revealed that, as compared with vehicle-treated mice, NPS markedly enhanced Fos expression in the subiculum complex encompassing the subiculum (S), presubiculum (PrS) and parasubiculum (PaS). The percentages of Fos-ir neurons that also express NPSR were 91.3, 86.5 and 90.0 % in the S, PrS and PaS, respectively. The present findings demonstrate that NPS, via selective activation of the neurons bearing NPSR in the subiculum complex, ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 in mice. PMID:26323488

  20. Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice

    PubMed Central

    Zeng, Hong-liang; Huang, Su-ling; Xie, Fu-chun; Zeng, Li-min; Hu, You-hong; Leng, Ying

    2015-01-01

    Aim: Defects in fatty acid metabolism contribute to the pathogenesis of insulin resistance and obesity. In this study, we investigated the effects of a novel compound yhhu981 on fatty acid metabolism in vitro and in vivo. Methods: The capacity to stimulate fatty acid oxidation was assessed in C2C12 myotubes. The fatty acid synthesis was studied in HepG2 cells using isotope tracing. The phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) was examined with Western blot analysis. For in vivo experiments, ob/ob mice were orally treated with yhhu981 acutely (300 mg/kg) or chronically (150 or 300 mg·kg−1·d−1 for 22 d). On the last day of treatment, serum and tissue samples were collected for analysis. Results: Yhhu981 (12.5–25 μmol/L) significantly increased fatty acid oxidation and the expression of related genes (Sirt1, Pgc1α and Mcad) in C2C12 myotubes, and inhibited fatty acid synthesis in HepG2 cells. Furthermore, yhhu981 dose-dependently increased the phosphorylation of AMPK and ACC in both C2C12 myotubes and HepG2 cells. Compound C, an AMPK inhibitor, blocked fatty acid oxidation in yhhu981-treated C2C12 myotubes and fatty acid synthesis decrease in yhhu981-treated HepG2 cells. Acute administration of yhhu981 decreased the respiratory exchange ratio in ob/ob mice, whereas chronic treatment with yhhu981 ameliorated the lipid abnormalities and ectopic lipid deposition in skeletal muscle and liver of ob/ob mice. Conclusion: Yhhu981 is a potent compound that stimulates fatty acid oxidation, and exerts pleiotropic effects on lipid metabolism by activating AMPK. PMID:25732571

  1. YiQiFuMai powder injection ameliorates blood–brain barrier dysfunction and brain edema after focal cerebral ischemia–reperfusion injury in mice

    PubMed Central

    Cao, Guosheng; Ye, Xinyi; Xu, Yingqiong; Yin, Mingzhu; Chen, Honglin; Kou, Junping; Yu, Boyang

    2016-01-01

    YiQiFuMai powder injection (YQFM) is a modern preparation derived from the traditional Chinese medicine Sheng-Mai-San. YQFM is widely used in clinical practice in the People’s Republic of China, mainly for the treatment of microcirculatory disturbance-related diseases. However, little is known about its role in animals with ischemic stroke. The aim of this study was to examine the effect of YQFM on brain edema and blood–brain barrier (BBB) dysfunction induced by cerebral ischemia–reperfusion (I/R) injury. Male C57BL/6J mice underwent right middle cerebral artery occlusion for 1 hour with a subsequent 24-hour reperfusion to produce I/R injury. YQFM (three doses: 0.336, 0.671, and 1.342 g/kg) was then given intraperitoneally (IP). The results demonstrated that YQFM significantly decreased infarct size, improved neurological deficits, reduced brain water content, and increased cerebral blood flow after I/R injury. 18F-fluorodeoxyglucose micro-positron emission tomography imaging and hematoxylin and eosin staining results indicated that YQFM is able to ameliorate brain metabolism and histopathological damage after I/R. Moreover, YQFM administration reduced BBB leakage and upregulated the expression of zona occludens-1 (ZO-1) and occludin, which was confirmed by Evans Blue extravasation, Western blotting, and immunofluorescence assay. Our findings suggest that YQFM provides protection against focal cerebral I/R injury in mice, possibly by improving BBB dysfunction via upregulation of the expression of tight junction proteins. PMID:26834461

  2. Comparison of the relative propensities of isoamyl nitrite and sodium nitrite to ameliorate acute cyanide poisoning in mice and a novel antidotal effect arising from anesthetics.

    PubMed

    Cambal, Leah K; Weitz, Andrew C; Li, Hui-Hua; Zhang, Yang; Zheng, Xi; Pearce, Linda L; Peterson, Jim

    2013-05-20

    Isoamyl nitrite has previously been considered acceptable as an inhaled cyanide antidote; therefore, the antidotal utility of this organic nitrite compared with sodium nitrite was investigated. To facilitate a quantitative comparison, doses of both sodium nitrite and isoamyl nitrite were given intraperitoneally in equimolar amounts to sublethally cyanide-challenged mice. Righting recovery from the knockdown state was clearly compromised in the isoamyl nitrite-treated animals, the effect being attributable to the toxicity of the isoamyl alchol produced during hydrolysis of the isoamyl nitrite to release nitrite anion. Subsequently, inhaled aqueous sodium nitrite aerosol was demonstrated to ameliorate sublethal cyanide toxicity, when provided to mice after the toxic dose, by the more rapid recovery of righting ability compared to that of the control animals given only the toxicant. Aerosolized sodium nitrite has thus been shown by these experiments to have promise as a better alternative to organic nitrites for development as an inhaled cyanide antidote. The inhaled sodium nitrite led to the production of NO in the bloodstream as determined by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin. The aerosol delivery was performed in an unmetered inhalation chamber, and in this study, no attempt was made to optimize the procedure. It is argued that administration of an effective inhaled aqueous sodium nitrite dose in humans is possible, though just beyond the capability of current individual metered-dose inhaler designs, such as those used for asthma. Finally, working at slightly greater than LD50 NaCN doses, it was fortuitously discovered that (i) anesthesia leads to significantly prolonged survival compared to that of unanesthetized animals and that (ii) the antidotal activity of nitrite anion was completely abolished under anesthesia. Plausible explanations for these effects in mice and their practical consequences in relation to

  3. Gingko biloba extract (Ginaton) ameliorates dextran sulfate sodium (DSS)-induced acute experimental colitis in mice via reducing IL-6/STAT3 and IL-23/IL-17

    PubMed Central

    Sun, Yan; Lin, Lian-Jie; Lin, Yan; Sang, Li-Xuan; Jiang, Min; Zheng, Chang-Qing

    2015-01-01

    This study explored the underlying mechanism of Gingko biloba extract (Ginaton) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice. 40 male C57BL/6 mice were randomly divided into four groups: normal control group, Ginaton group, Ginaton treatment group, and DSS group. After 7 days administration, mice were sacrificed and colons were collected for H-E staining, immunohistochemistry, real-time PCR and Western blot. By observing clinical disease activity and histological damage, we assessed the effect of Ginaton on DSS-induced acute experimental colitis in mice and observed the effect of Ginaton on normal mice. We also explored the specific mechanism of Ginaton on DSS-induced acute experimental colitis in mice through examining the expression of inflammatory related mediators (gp130, STAT3, p-STAT3, ROR-γt) and cytokines (IL-6, IL-17, IL-23). Ginaton-treated DSS mice showed significant improvement over untreated DSS mice. Specifically, Ginaton improved clinical disease activity (DAI score, weight closs, colon shortening, and bloody stool) and histological damage, and reduced the expression of inflammatory-related mediators (p-STAT3, gp130, ROR-γt) and cytokines (IL-6, IL-17, IL-23). In addition, clinical disease activity, histological damage, the expression of inflammatory related mediators (STAT3, p-STAT3, gp130, ROR-t) and cytokines (IL-6, IL-17, IL-23) in mice of Ginaton group were similar to normal control group. In conclusion, Ginaton ameliorates DSS-induced acute experimental colitis in mice by reducing IL-17 production, which is at least partly involved in inhibiting IL-6/STAT3 signaling pathway and IL-23/IL-17 axis. Moreover, Ginaton itself does not cause inflammatory change in normal mice. These results support that Ginaton can be as a potential clinical treatment for ulcerative colitis (UC). PMID:26770316

  4. Treadmill exercise ameliorates ischemia-induced brain edema while suppressing Na⁺/H⁺ exchanger 1 expression.

    PubMed

    Nishioka, Ryutaro; Sugimoto, Kana; Aono, Hitomi; Mise, Ayano; Choudhury, Mohammed E; Miyanishi, Kazuya; Islam, Afsana; Fujita, Takahiro; Takeda, Haruna; Takahashi, Hisaaki; Yano, Hajime; Tanaka, Junya

    2016-03-01

    Exercise may be one of the most effective and sound therapies for stroke; however, the mechanisms underlying the curative effects remain unclear. In this study, the effects of forced treadmill exercise with electric shock on ischemic brain edema were investigated. Wistar rats were subjected to transient (90 min) middle cerebral artery occlusion (tMCAO). Eighty nine rats with substantially large ischemic lesions were evaluated using magnetic resonance imaging (MRI) and were randomly assigned to exercise and non-exercise groups. The rats were forced to run at 4-6m/s for 10 min/day on days 2, 3 and 4. Brain edema was measured on day 5 by MRI, histochemical staining of brain sections and tissue water content determination (n=7, each experiment). Motor function in some rats was examined on day 30 (n=6). Exercise reduced brain edema (P<0.05-0.001, varied by the methods) and ameliorated motor function (P<0.05). The anti-glucocorticoid mifepristone or the anti-mineralocorticoid spironolactone abolished these effects, but orally administered corticosterone mimicked the ameliorating effects of exercise. Exercise prevented the ischemia-induced expression of mRNA encoding aquaporin 4 (AQP4) and Na(+)/H(+) exchangers (NHEs) (n=5 or 7, P<0.01). Microglia and NG2 glia expressed NHE1 in the peri-ischemic region of rat brains and also in mixed glial cultures. Corticosterone at ~10nM reduced NHE1 and AQP4 expression in mixed glial and pure microglial cultures. Dexamethasone and aldosterone at 10nM did not significantly alter NHE1 and AQP4 expression. Exposure to a NHE inhibitor caused shrinkage of microglial cells. These results suggest that the stressful short-period and slow-paced treadmill exercise suppressed NHE1 and AQP4 expression resulting in the amelioration of brain edema at least partly via the moderate increase in plasma corticosterone levels. PMID:26724742

  5. Telmisartan ameliorates fibrocystic liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease.

    PubMed

    Yoshihara, Daisuke; Kugita, Masanori; Sasaki, Mai; Horie, Shigeo; Nakanishi, Koichi; Abe, Takaaki; Aukema, Harold M; Yamaguchi, Tamio; Nagao, Shizuko

    2013-01-01

    Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys which are massively enlarged due to multiple cysts, hypertension, and congenital hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial fibrosis developed in the liver. We previously reported that a peroxisome proliferator activated receptor (PPAR)-γ full agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and shows partial PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of drug-induced hepatotoxicity and hepatic fibrosis. In the present study, we determined whether telmisartan ameliorates progression of polycystic kidney and fibrocystic liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase and urea nitrogen were unaffected by telmisartan treatment. There was no effect on kidney disease progression, but liver weight relative to body weight, liver cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial fibrosis in PCK rats. The present results support the potential therapeutic use of ARBs for the

  6. Endurance exercise ameliorates low birthweight developed catch-up growth related metabolic dysfunctions in a mouse model.

    PubMed

    Ju, Liping; Tong, Wenxin; Qiu, Miaoyan; Shen, Weili; Sun, Jichao; Chen, Ying; Li, Zhen; Wang, Weiqing; Tian, Jingyan

    2016-03-31

    Low birthweight is known to predict high risk of metabolic diseases in adulthood, while regular endurance exercises are believed sufficient to improve metabolic dysfunction. In this study, we established a mouse model to determine whether long-term exercise training could ameliorate catch-up growth, and we explored the possible underlying mechanisms. By restricting maternal food intake during the last week of gestation, we successfully produced low birthweight pups. Further, normal birthweight mice and low birthweight mice were randomly distributed into one of three groups receiving either a normal fat diet, high fat diet, or high fat diet with exercise training. The growth/metabolism, mitochondrial content and functions were assessed at 6 months of age. Through group comparisons and correlation analyses, the 4th week was demonstrated to be the period of crucial growth and chosen to be the precise point of intervention, as the growth rate at this point is significantly correlated with body weight, intraperitoneal glucose tolerance test (IPGTT), Lee's index and fat mass in adulthood. In addition, regular endurance exercises when started from 4 weeks remarkably ameliorated low birthweight outcomes and induced catch-up growth and glucose intolerance in the 25th week. Furthermore, real-time PCR and western blot results indicated that the effect of long-term exercise on mitochondrial functions alleviated catch-up related metabolic dysfunction. To conclude, long-term exercise training from the 4th week is sufficient to ameliorate catch-up growth and related metabolic disturbances in adulthood by promoting mitochondrial functions in skeletal muscle. PMID:26842396

  7. Telmisartan Ameliorates Fibrocystic Liver Disease in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

    PubMed Central

    Yoshihara, Daisuke; Kugita, Masanori; Sasaki, Mai; Horie, Shigeo; Nakanishi, Koichi; Abe, Takaaki; Aukema, Harold M.; Yamaguchi, Tamio; Nagao, Shizuko

    2013-01-01

    Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys which are massively enlarged due to multiple cysts, hypertension, and congenital hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial fibrosis developed in the liver. We previously reported that a peroxisome proliferator activated receptor (PPAR)-γ full agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and shows partial PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of drug-induced hepatotoxicity and hepatic fibrosis. In the present study, we determined whether telmisartan ameliorates progression of polycystic kidney and fibrocystic liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase and urea nitrogen were unaffected by telmisartan treatment. There was no effect on kidney disease progression, but liver weight relative to body weight, liver cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial fibrosis in PCK rats. The present results support the potential therapeutic use of ARBs for the

  8. 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

  9. Amelioration of Atherosclerosis by the New Medicinal Mushroom Grifola gargal Singer.

    PubMed

    Harada, Etsuko; D'Alessandro-Gabazza, Corina N; Toda, Masaaki; Morizono, Toshihiro; Chelakkot-Govindalayathil, Ayshwarya-Lakshmi; Roeen, Ziaurahman; Urawa, Masahito; Yasuma, Taro; Yano, Yutaka; Sumiya, Toshimitsu; Gabazza, Esteban C

    2015-08-01

    The beneficial effects of edible mushrooms for improving chronic intractable diseases have been documented. However, the antiatherogenic activity of the new medicinal mushroom Grifola gargal is unknown. Therefore, we evaluated whether Grifola gargal can prevent or delay the progression of atherosclerosis. Atherosclerosis was induced in ApoE lipoprotein-deficient mice by subcutaneous infusion of angiotensin II. Grifola gargal extract (GGE) was prepared and intraperitoneally injected. The weight of heart and vessels, dilatation/atheroma formation of thoracic and abdominal aorta, the percentage of peripheral granulocytes, and the blood concentration of MCP-1/CCL2 were significantly reduced in mice treated with GGE compared to untreated mice. By contrast, the percentage of regulatory T cells and the plasma concentration of SDF-1/CXCL12 were significantly increased in mice treated with the mushroom extract compared to untreated mice. In vitro, GGE significantly increased the secretion of SDF-1/CXCL12, VEGF, and TGF-β1 from fibroblasts compared to control. This study demonstrated for the first time that Grifola gargal therapy can enhance regulatory T cells and ameliorate atherosclerosis in mice. PMID:25799023

  10. Ameliorative Effect of Recombinant Human Erythropoietin and Ischemic Preconditioning on Renal Ischemia Reperfusion Injury in Rats

    PubMed Central

    Elshiekh, Mohammed; Kadkhodaee, Mehri; Seifi, Behjat; Ranjbaran, Mina; Ahghari, Parisa

    2015-01-01

    Background: Ischemia-reperfusion (IR) injury is one of the most common causes of renal dysfunction. There is increasing evidence about the role of the reactive oxygen species (ROS) in these injuries and endogenous antioxidants seem to have an important role in decreasing the renal tissue injury. Objectives: The aim of this study was to compare the effect of recombinant human erythropoietin (EPO) and ischemic preconditioning (IPC) on renal IR injury. Materials and Methods: Twenty four male Wistar rats were allocated into four experimental groups: sham-operated, IR, EPO + IR, and IPC + IR. Rats were underwent 50 minutes bilateral ischemia followed by 24 hours reperfusion. Erythropoietin (5000 IU/kg, i.p) was administered 30 minutes before onset of ischemia. Ischemic preconditioning was performed by three cycles of 3 minutes ischemia followed by 3 minutes reperfusion. Plasma concentrations of urea and creatinine were measured. Kidney samples were taken for reactive oxidative species (ROS) measurement including superoxide dismutase (SOD) activity, glutathione (GSH) contents, and malondialdehyde (MDA) levels. Results: Compared to the sham group, IR led to renal dysfunction as evidenced by significantly higher plasma urea and creatinine. Treatment with EPO or IPC decreased urea, creatinine, and renal MDA levels and increased SOD activity and GSH contents in the kidney. Conclusions: Pretreatment with EPO and application of IPC significantly ameliorated the renal injury induced by bilateral renal IR. However, both treatments attenuated renal dysfunction and oxidative stress in kidney tissues. There were no significant differences between pretreatment with EPO or application of IPC. PMID:26866008

  11. Nigerian Honey Ameliorates Hyperglycemia and Dyslipidemia in Alloxan-Induced Diabetic Rats.

    PubMed

    Erejuwa, Omotayo O; Nwobodo, Ndubuisi N; Akpan, Joseph L; Okorie, Ugochi A; Ezeonu, Chinonyelum T; Ezeokpo, Basil C; Nwadike, Kenneth I; Erhiano, Erhirhie; Abdul Wahab, Mohd S; Sulaiman, Siti A

    2016-03-01

    Diabetic dyslipidemia contributes to an increased risk of cardiovascular disease. Hence, its treatment is necessary to reduce cardiovascular events. Honey reduces hyperglycemia and dyslipidemia. The reproducibility of these beneficial effects and their generalization to honey samples of other geographical parts of the world remain controversial. Currently, data are limited and findings are inconclusive especially with evidence showing honey increased glycosylated hemoglobin in diabetic patients. It was hypothesized that this deteriorating effect might be due to administered high doses. This study investigated if Nigerian honey could ameliorate hyperglycemia and hyperlipidemia. It also evaluated if high doses of honey could worsen glucose and lipid abnormalities. Honey (1.0, 2.0 or 3.0 g/kg) was administered to diabetic rats for three weeks. Honey (1.0 or 2.0 g/kg) significantly (p < 0.05) increased high density lipoprotein (HDL) cholesterol while it significantly (p < 0.05) reduced hyperglycemia, triglycerides (TGs), very low density lipoprotein (VLDL) cholesterol, non-HDL cholesterol, coronary risk index (CRI) and cardiovascular risk index (CVRI). In contrast, honey (3.0 g/kg) significantly (p < 0.05) reduced TGs and VLDL cholesterol. This study confirms the reproducibility of glucose lowering and hypolipidemic effects of honey using Nigerian honey. However, none of the doses deteriorated hyperglycemia and dyslipidemia. PMID:26927161

  12. Nigerian Honey Ameliorates Hyperglycemia and Dyslipidemia in Alloxan-Induced Diabetic Rats

    PubMed Central

    Erejuwa, Omotayo O.; Nwobodo, Ndubuisi N.; Akpan, Joseph L.; Okorie, Ugochi A.; Ezeonu, Chinonyelum T.; Ezeokpo, Basil C.; Nwadike, Kenneth I.; Erhiano, Erhirhie; Abdul Wahab, Mohd S.; Sulaiman, Siti A.

    2016-01-01

    Diabetic dyslipidemia contributes to an increased risk of cardiovascular disease. Hence, its treatment is necessary