L-arginine is a semi-essential amino acid that found naturally in food. hours after the last dose rats were sacrificed and their blood was collected from heart for biochemical analysis. Pancreatic tissues were obtained for analysis of glutathione peroxidase (GPx) glutathione s-transferase (GST) lipid peroxide levels (MDA) and histology analysis was examined for pancreas. Results indicated that treatment with simvastatin significantly enhanced levels of GPx and GST and decreased lipid peroxide levels induced by L-arginine compared to the vehicle. Moreover histopathological analysis further confirmed that administration of simvastatin relatively prevented pancreatic acinar cell damage compared to those animals received L-arginine only. These findings pointed out the protective SM13496 part of simvastatin against acute pancreatitis induced by high doses of L-arginine. Keywords: L-arginine acute pancreatitis simvastatin lipid peroxidation antioxidant enzymes Intro Acute pancreatitis (AP) is an acute inflammatory disorder of the pancreas with variable involvement of additional regional cells . The most common symptoms of AP are acute abdominal pain and improved concentration of serum lipase and amylase . AP is definitely a reversible inflammatory disorder that varies in severity ranging from focal edema and excess fat necrosis to common hemorrhagic parenchymal necrosis [3 4 It is relatively common with an annual incidence of 10 to 20 per 100 0 people in the Western world. Approximately 80% of instances are attributed to either SM13496 biliary tract disease or alcoholism. The basic alterations in AP include microvascular disturbances causing edema excess fat necrosis acute inflammatory reaction damage of pancreatic parenchyma and damage of blood vessels leading to interstitial hemorrhage [4 5 These alterations are largely due to activation of digestive proteases proinflammatory cell infiltration launch of inflammatory cytokines and generation of free radicals. In milder forms histological alterations SM13496 include interstitial edema and focal areas of excess fat necrosis in the pancreatic compound and peripancreatic excess fat. Fat necrosis results from enzymatic damage of excess fat cells where the released fatty acids combine with calcium to form insoluble salts that precipitate in situ [4 5 Like a model it has been demonstrated that Rat monoclonal to CD4.The 4AM15 monoclonal reacts with the mouse CD4 molecule, a 55 kDa cell surface receptor. It is a member of the lg superfamily,primarily expressed on most thymocytes, a subset of T cells, and weakly on macrophages and dendritic cells. It acts as a coreceptor with the TCR during T cell activation and thymic differentiation by binding MHC classII and associating with the protein tyrosine kinase, lck. large doses of L-arginine induce acute pancreatitis . A single dose of 500 mg/kg L-arginine is known to induce necrotizing pancreatitis in rats and it is found that such dose can selectively induce pancreatic acinar cell damage without any morphological changes in the islets of Langerhans [6 7 L-arginine-induced AP model is definitely highly reproducible and generates selective dose-dependent acinar cell necrosis . L-arginine is the precursor for the endogenous synthesis of nitric oxide (NO). NO is definitely a highly reactive radical gas and an important messenger molecule that is involved in functions such as neurotransmission swelling and rules of gene manifestation. Additionally NO is definitely a powerful vasodilator and may increase blood flow. The mechanism by which L-arginine causes AP is still unknown but it has been proposed that oxygen/nitric oxide and inflammatory cytokines may be involved in the development of the disease . HMG-CoA reductase is the enzyme that catalyses the conversion of HMG-CoA in mevalonate and this is the limiting step in the cholesterol synthesis. Statins are HMG-CoA reductase inhibitors used clinically in treatment of hyperlipidemia . You will find five statins in medical use including lovastatin simvastatin pravastatin atorvastatin and fluvastatin . In addition to their antihyperlipidemic effect statins have antioxidant activity against lipid peroxidation anti-inflammatory effects induce nitric oxide levels impeding thrombogenesis by inhibiting activation of extrinsic coagulation produce beneficial effects in hypertension improving endothelial dysfunction and provide additional cardioprotective SM13496 effects . The purpose of the present study was to evaluate the protective effect of simvastatin against large dose L-arginine-induced acute toxicity of pancreas. Materials and methods Animals and animal’s methods Male Sprague Dawley rats weighing 160-210 g aged 8-12 weeks from the central animal SM13496 house of Jordan University or college of Technology & Technology were used in this study. Animals were managed at a constant heat (23 ± 2°C) with light-dark cycles of 12/12 hour and free access to water.