Department of Pharmacy
Permanent URI for this collectionhttp://localhost:4000/handle/123456789/1931
Browse
8 results
Search Results
Item Tannic acid prevents azidothymidine (AZT) induced hepatotoxicity and genotoxicity along with change in expression of PARG and histone H3 acetylation(Elsevier, 2008-03) Gaikwad, Anil BhanudasAzidothymidine (AZT) is known to decrease HIV virus replication and is one of the most frequently prescribed antiretroviral drugs used for AIDS treatment. Dose-limiting toxicities are the major curse associated with AZT therapy. Recently, we have reported that tannic acid; a PARG inhibitor prevents cisplatin induced nephrotoxicity. The present work was conceived to study the effect of tannic acid on AZT induced hepatotoxicity and genotoxicity. AZT induces increase in plasma levels of ALT, AST and alkaline phosphatase along with increase in micronucleus (MN) count in peripheral blood. Suggesting, AZT is hepatotoxic and genotoxic to mice. Treatment of tannic acid protects AZT induced hepatotoxicity by decreasing the ALT, AST and alkaline phosphatase levels. It also significantly reduces the oxidative damage by preventing reduction in glutathione and decreasing the level of malondialdehyde in liver of AZT treated mice. In addition, tannic acid decreases the PARG expression, PARP cleavage and histone H3 acetylation in liver of AZT treated mice. Moreover, treatment of tannic acid also decreases MN count in peripheral blood, suggesting its anti-mutagenic effect. In light of these findings we suggest the potential role of tannic acid treatment in preventing AZT induced toxicity.Item Gallotannin ameliorates the development of streptozotocin‐induced diabetic nephropathy by preventing the activation of PARP(Wiley, 2008-08) Gaikwad, Anil BhanudasPoly(ADP-ribose) polymerase (PARP) is known to be activated under conditions of oxidative stress and/or radiation exposure. The role of this enzyme has been well demonstrated in the streptozotocin (STZ) induced model of diabetes. Inhibition of PARP by specific inhibitors is known to prevent the development of STZ induced diabetic nephropathy by reduction in oxidative stress induced apoptosis. This study shows for the first time the role of poly(ADP-ribose) glycohydrolase (PARG) inhibitors as an alternative approach for inhibition of PARP. Gallotannin (20 mg/kg/day, i.p.) treatment for 4 weeks led to a significant reduction in the levels of plasma creatinine which is a well known marker for diabetic nephropathy. Treatment with gallotannin resulted in protection up to a certain level of glomerular damage, suggesting compensatory glomerular hypertrophy. As a PARG inhibitor gallotannin treatment also showed protection in PARP cleavage which is a hallmark for apoptotic cell death signifying the protective role of gallotannin in cell death signaling.Item PPARγ agonists partially restores hyperglycemia induced aggravation of vascular dysfunction to angiotensin II in thoracic aorta isolated from rats with insulin resistance(Elsevier, 2007-05) Gaikwad, Anil BhanudasAltered vascular responses to various vasopressors in animal models of insulin resistance (IR) and diabetes have been well documented. However, the precise mechanisms about vascular responses in IR with or without frank hyperglycemia (prediabetic state) are not available. Moreover, recently the role of peroxisome proliferators activated receptor-γ (PPARγ) has been linked to influence the vascular responses in hypertensive and diabetic state. Hence, the present study was conceived to determine the role of hyperglycemia on angiotensin II (Ang II) mediated vascular responses in the high fat diet (HFD) induced insulin resistance either with mild or frank hyperglycemia [induced by injection of low dose streptozotocin (STZ) to HFD fed rats (HFD + STZ)]. In addition, insulin-sensitizing agent such as rosiglitazone and pioglitazone were also studied on biochemical and vascular responses. Ang II-induced contractions were studied isometrically in thoracic aortic rings isolated from 4 weeks of normal pellet diet (NPD) fed control, HFD and HFD + STZ fed insulin resistant rats. Specific binding of Ang II receptors were carried out using radioligand ([3H]–Ang II) binding studies. After 4 weeks of HFD feeding, rats exhibited characteristics features of insulin resistance such as mild hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia and hypertension; whereas HFD + STZ treated rats showed all above parameters along with frank hyperglycemia. Maximal contractile response (Emax) to Ang II is increased in HFD fed rats as compared to control rats. Moreover, Emax values are further elevated in HFD + STZ group where the frank hyperglycemia was induced by low dose of streptozotocin. Rosiglitazone (5 mg kg−1, p.o.) and pioglitazone (10 mg kg−1, p.o.) treatment significantly lowered the plasma glucose, triglycerides, insulin and cholesterol levels in insulin resistance rats. In addition, it also restored the elevated systolic, mean arterial, diastolic blood pressure and attenuated the enhanced contractile responses to Ang II in thoracic aortic rings obtained from both HFD and HFD + STZ treated rats. Specific binding of [3H]–Ang II is upregulated in HFD-fed and HFD + STZ treated rats. Treatment with pioglitazone and rosiglitazone significantly decreased the AT1R specific binding in HFD fed rats. Our results indicate the role of hyperglycemia in the elevation of Ang II induced vascular responses in thoracic aorta isolated from insulin resistant rats and PPARγ agonists can attenuate these responses.Item Differential effects of tannic acid on cisplatin induced nephrotoxicity in rats(Elsevier, 2007-05) Gaikwad, Anil BhanudasCisplatin is a widely used antineoplastic drug. Major drawback of cisplatin therapy is its nephrotoxicity. The objective of this study was to check the effect of tannic acid on cisplatin induced nephrotoxicity. Post-treatment of tannic acid prevents cisplatin (5 mg/kg) induced nephrotoxicity and decreases poly(ADP-ribose) polymerase cleavage, phosphorylation of p38 and hypoacetylation of histone H4. In contrast, co-treatment of tannic acid potentiates the nephrotoxicity. Comparative nephrotoxicity studies show that co-treatment of tannic acid with reduced dose of cisplatin (1.5 mg/kg) developed almost similar nephrotoxicity. MALDI protein profiling of plasma samples provides indirect evidence that tannic acid co-treatment increases bioavailability of cisplatin.Item Change in histone H3 phosphorylation, MAP kinase p38, SIR 2 and p53 expression by resveratrol in preventing streptozotocin induced type I diabetic nephropathy(Taylor & Francis, 2009-07) Gaikwad, Anil BhanudasResveratrol has been reported to have a wide variety of biological effects. However, little is known regarding its role on phosphorylation of histone H3, MAP kinase p38, SIR2 and p53 in type I diabetic nephropathy (DN). Hence, the present study was undertaken to examine changes in the above said parameters by resveratrol treatment. Male Sprague-Dawley rats were rendered diabetic using a single dose of streptozotocin (55 mg/kg, i.p.). DN was assessed by measurements of blood urea nitrogen and creatinine levels. Phosphorylation of histone H3, SIR2, p53 and MAP kinase p38 expression were examined by western blotting. This study reports that treatment of resveratrol prevents the decrease in the expression of SIR2 in diabetic kidney. It also prevents increase in p38, p53 expression and dephosphorylation of histone H3 in diabetic kidney. This is the first report which suggests that protection against development of diabetic nephropathy by resveratrol treatment involves change in phosphorylation of histone H3, expression of Sir-2, p53 and p38 in diabetic kidneyItem Rosiglitazone attenuates the cognitive deficits induced by high fat diet feeding in rats(Elsevier, 2008-07) Gaikwad, Anil BhanudasThe present study was designed to test the hypothesis that insulin resistance plays a role in high fat diet feeding induced cognitive deficits. Rats consuming the high fat diet exhibited characteristic features of insulin resistance viz. mild hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and hyperinsulinemia. Further, these rats showed a severe deficit in learning and memory. In contrast, rosiglitazone at the dose of 5 mg/kg, p.o. for 7 days prior to biochemical and behavioral testing significantly lowered the plasma glucose, triglycerides, cholesterol, and insulin levels. These animals also performed better on Morris water maze task, suggesting improved spatial memory. Our data demonstrate that the insulin sensitizers can overcome the cognitive deficits arising from high fat diet feeding, which may be in part mediated through the development of peripheral insulin resistance.Item Change in post-translational modifications of histone H3, heat-shock protein-27 and MAP kinase p38 expression by curcumin in streptozotocin-induced type I diabetic nephropathy(Wiley, 2009-01) Gaikwad, Anil BhanudasCurcumin has been used to treat cancer, diabetes and other pathologies. However, little is known regarding its role in altering post-translational modifications of histone H3. A recent report suggests that acute hyperglycaemia induces a global down-regulation of gene expression in human tissues and epigenetic regulation of gene expression could be a novel mechanism underlying the pathological processes of hyperglycaemia. The present study was undertaken to examine changes in histone modification by curcumin treatment which prevents development of type I diabetic nephropathy.Item Intermittent fasting prevents the progression of type I diabetic nephropathy in rats and changes the expression of Sir2 and p53(Elsevier, 2007-03) Gaikwad, Anil BhanudasDiabetic nephropathy (DN) is one of the main causes of end stage renal disease (ESRD) and a leading cause of diabetes mellitus related morbidity and mortality. Recently, sirtuin are reported to have emerging pathogenetic roles in cancer, muscle differentiation, heart failure, neurodegeneration, diabetes and aging. The aim of the present study was to study the role of intermittent fasting (IF) on DN and studying the expression of Sir2 and p53. At biochemical level, we found that IF causes significant improvement in blood urea nitrogen (BUN), creatinine, albumin and HDL cholesterol, parameters that are associated with the development of DN. Diabetic rats on IF also show significant improvement in onset of hypertension. Interestingly, the expression of Sir2, a NAD dependent histone deacetylase, decreases in diabetic rat kidney and this decrease is overcome by IF. Moreover, we provide evidence for involvement of mitogen activated protein kinases (MAPK) cascade in mediating the effects of IF as there is reduction in the expression of p38 which gets induced under diabetic condition. This was further accompanied by the concomitant decrease in cleavage of caspase3 and p53 expression. These findings suggest that IF significantly improves biochemical parameters associated with development of DN and changes the expression of Sir2 and p53.