Effect of some hypolipidemic drugs on glycemic control, lipid profile and some oxidative indiced in experimental hyperlpidemic diabetic rats

Diabetic patients, especially those with type-2 diabetes, are at a higher risk of developing cardiovascular disease. The specific pattern of diabetic dyslipidaemia, hyperglycemia, hyperinsulinemia, increased oxidative stress and inflammatory cytokines are co-operative factors for increasing cardiovascular morbidity and mortality in these patients. The present study was conducted to investigate the impact of different antidyslipidemic agents on these risk factors in a rat model of diabetic dyslipidaemia with hyperinsulinemia. A total of 70 rats were involved in the study; 10 of which served as a normal control group. The remaining rats were lipid-fed and streptozotocin [STZ]-injected, and were randomly assigned to no treatment [control group] or to 2-month treatment with pravastatin, fenofibrate, cholestyramine, nicotinic acid or fish oil. The lipid-fed STZ-injected rats developed high fasting serum glucose and glycated hemoglobin [HbAlc] levels together with hyperinsulinemia. They also acquired the characteristic pattern of diabetic dyslipidemia, i.e. increased levels of low density lipoprotein-cholesterol [LDL-C] and triglycerides [TG], and decreased high density lipoprotein-cholesterol [HDL-C] level. This was associated with increased markers of oxidative stress and inflammation "increased serum levels of malondialdehyde [MDA] and tumor necrosis factor-alpha [TNF-c_ together with decreased concentration of reduced glutathione and superoxide dismutase [SOD] activity in liver and kidney' Both pravastatin and fenofibrate significantly decreased serum cholesterol, LDL-C and TG, and increased serum HDL-C. However, only fenofibrate could normalize serum levels of HDL-C and TG. Cholestyramine significantly decreased serum levels of total cholesterol and LDL-C but increased the serum level of TG. Nicotinic acid produced significant decreases in serum TG and LDL-C levels and a significant increase in serum HDL-C level. Fish oil only significantly decreased the serum TG level. Fenofibrate and fish oil produced significant decreases in serum glucose, HbAJc and serum insulin levels. Pravastatin only decreased serum insulin level significantly. Cholestyramine did not affect the glycemic control, Nicotinic acid, on the other hand, produced significant increases in serum glucose, HbAlc and serum insulin levels. .Pravastatin, fenofibrate and fish oil decreased the oxidative stress and serum level of TNF-a. On the other hand, cholestyramine and nicotinic acid did not significantly change any of the studied oxidative and inflammatory parameters. Major outcome clinical studies are required to compare the effect of the most promising agents, pravastatin, fenofibrte, fish oil and/or their possible combinations on the overall mortality and morbidity in diabetic dyslipidemic patients

modulatory effects of some drugs with potential influence on oxidative cell damage on experimental ulcerative colitis

Ulcerative colitis is a chronic inflammatory bowel disease [IBD] where reactive oxygen species [ROS] are produced in excess. There are comparatively low tissue levels of endogenous antioxidants in the colonic mucosa. Oxidative stress occurred in IBD may therefore easily overwhelm the endogenous defenses that regulate ROS production. Our aim was to assess the ability of vitamins C, deferoxamine [Dfx] and amlodipine [Amlo] to inhibit colonic inflammation in dextran sulphate sodium [DSS]-induced colitis in rats. We used thirty mature male albino rats assigned to Group I: normal control. Group II: received DSS+0.5 ml 0.9% normal saline daily. Group III: received DSS+vitamin C 100 mg/kg b.w./day. Group IV: received DSS+amlodipine 3 mg/kg/day. Group V: received DDS+Dfx 300 micro mol/kg/day. Acute colitis was induced by 3% DSS in drinking water for 7 days. Vitamin C, amlodipine, and deferoxamine were administered orally for 7 days before and a further 7 days during treatment with DSS. Rats without colitis received regular drinking water. On day 14 of drug treatment, colons were excised and opened longitudinally. Gross colonic mucosal injury were observed and scored. Colonic wet/dry weight ratios were calculated as an indirect index of the inflammatory reaction. Colonic myeloperoxidase [MPO] activity, glutathione [GSH] and Thiobarbituric acid-reactive substances were measured. The results of the present study showed that pretreatment of the rats with vitamin C, Amlo and Dfx reduced the gross mucosal injury developed after induction of colitis. These drugs prevented the increase in MPO activity produced in these cases of inflammation. Pretreatment of animals with vitamin C, Amlo or Dfx prevented the depletion of colonic GSH caused by DSS-induced colonic injury. All of the tested drugs were found also to decrease the enhanced lipid per oxidation observed in this model of DSS-induced colitis in rats. It can be concluded that pretreatment with vitamin C, amlodipine and deferoxamine can inhibit the inflammatory process in DSS-induced colitis in rats through their antioxidant properties

study on some pharmacologic manipulations of diet-induced obesity in rats

Aim: Obesity is a major health problem that represents an energy imbalance associated with complications, including cardiovascular disease, diabetes, and an increased mortality rate. The aim of the present work was to study some pharmacological manipulations of diet-induced obesity [DIO] in rats. Subjects and The study was conducted on 60 adult male albino rats that were divided into two groups; the DIO group fed high-calorie diet [HCD] [n=48] and the normal control group [n=12] fed normal laboratory diet. After 8 weeks, DIO rats were subdivided into four subgroups [each of 12 rats] that received the lipase inhibitor [orlistat], or the PPAR-gamma agonist [rosiglitazone], or the beta3-agonist [trecadrine] or a vehicle orally for 3 weeks. After the specified period, the following obesity variables were recorded: body weight, obesity index, food intake and rectal temperature. Blood samples were withdrawn for determination of serum metabolic parameters: glucose, triglycerides [TG], free fatty acids [FFA], leptin and insulin levels. Rats were sacrificed; and the remaining obesity variables were measured: retroperitoneal and interscapular fat as well as liver weight. The use of a HCD for 8 weeks resulted in a significant increase in all the measured obesity variables [except for rectal temperature] together with a significant increase in all the measured serum parameters as compared to rats that received normal laboratory diet. Orlistat administration for 3 weeks caused a significant decrease in all obesity variables with no significant change in food intake. A significant decrease in serum TG, FFA, insulin and leptin levels was also evident. Rosiglitazone-treated rats exhibited a significant decrease in liver weight together with a significant increase in fat pads weight and rectal temperature. Trecadrine produced significant reduction in obesity variables except for interscapular fat weight and rectal temperature that were significantly increased. Significant improvements in all serum metabolic parameters were noted with rosiglitazone and trecadrine treatment. Conclusions: From the current study, it can be concluded that lipase inhibitors and beta 3 agonists are effective in reducing body weight, while PPAR-gamma agonists are effective in improving insulin sensitivity and lipid abnormalities and so are rather effective as an adjuvant therapy to control the subsequent metabolic derangements relevant to obesity. Extrapolating these findings, especially the role of beta3-agonists, awaits further human trials before recommending it as a standard antiobesity drug