Fructose induced metabolic syndrome in rats, a role for Glitazones, fibrates and statins

The metabolic syndrome is a constellation of symptoms and signs that include central obesity, insulin resistance, dysglycemia. dyslipidemia and hypertension. .The present work aimed to study the effect of a Peroxisome Proliferator Activated Receptor-alpha [PPAR-alpha] agonist [fenofibrate], two PPAR-gamma agonists [rosiglitazone and pioglitazone] and a statin [simvastatin] on glycemic control and lipid profile in fructose-induced metabolic syndrome in rats. The study also aimed to assess the benefits gained from the combination of these agents. The present study was carried out on one hundred and ten white male albino rats. Ten rats received normal laboratory chow. The remaining rats were fed a high fructose diet for induction of metabolic syndrome X. The current study showed that treatment of fructose induced metabolic syndrome [FMS] rats with fenofibrate, rosiglitazone or pioglitazone was associated with significant improvement in glycemic control Fenofibrate treatment was associated with significant decrease in body weight in comparison to rosiglitazone or pioglitazone-treated rats that showed a significant body weight gain. Fenofibrate and simvastatin treatment of FMS rats caused a significant decrease in serum triglycerides [TGs,], cholesterol as well as significant increase in serum high density lipoproteins [HDL]. Only simvastatin resulted in a significant decrease in serum low density lipoproteins [LDL]. The combination of fenofibrate with rosiglitazone or pioglitazone was associated with less body weight gain and a more marked improvement in glycemic control The addition of simvastatin to fenofibrate and rosiglitazone or pioglitazone was associated with a significant improvement in lipid profile when compared to the combination offenofibrate with rosiglitazone or pioglitazone. No further significant improvement in glycemic was control achieved by the addition of simvastatin to nfenofibrate and rosiglitazone or pioglitazone. Given the close relationship between PPAR activity and the metabolic syndrome, PPAR agonists are promising therapeutic agents for diseases including type 2 diabetes mellitus [DM2]. obesity, hypertension, hyperlipidemia and atherosclerosis. Combination drug therapy, which utilizes complementary mechanisms, can be advantageous in patients with significant combined or mixed dyslipidemias. The combination of glitazones and statins was associated with the utmost glycemic control and improvement in lipid profile

study of the potential role of aldose reductase inhibitors [Sorbinil, Tolrestat and Ponalrestat] in the amelioration of nephropathy in diabetic rats

This work included 90 male albino rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin [STZ] in a dose of 55 mg/kg body weight. One week after STZ injection, uninephrectomy was done and the study began one week after uninephrectomy operation and continued for eight months. The results revealed that oral administration of sorbinil, tolrestat or ponalrestat for eight months in uninephrectomized [UNE] diabetic rats produced significant decreases in sorbitol and fructose levels in RBCs, kidney sorbitol and aldose reductase activity in RBCs associated with significant increases in Na

Beneficial effects of angiotensin converting enzyme inhibitors captopril and enalapril on experimentally induced colitis in rats

Increasing evidence supports an association between inflammation and angiotensin converting enzyme [ACE]. The aim of this study was to examin the efficacy of ACE inhibitors [ACEIs] namely, captopril and enalapril on acetic acid induced colitis in rats. Colitis was induced by intracolonic injection of 2 ml of 3% acetic acid. Eighty rats were studied in this study, divided into: two main groups, group 1, 40 rats of long duration of inflammation and treatment and group II, 40 rats of short duration of inflammation and treatment. Each group was subdivided into 4 subgroups. 10 control rats, 10 rats injected intracolonic with acetic acid [acetic acid untreated rats], 10 rats injected intracolonic with acetic and plus oral administration of captopril [captopril treated rats], and 10 rats injected intracolonic with acetic acid plus oral administration of enalapril [enalapril treated rats]. Captopril and enalapril were given 2 days after induction of colitis and continued daily for 3 weeks in group I, and for 2 days before and 2 days after induction of colitis in group II. Intracolonic acetic acid injection produced a significant inflammation, assessed by the ulcer index score, the weight of the colon and the colonic tissue level of myeloperoxidase enzyme, in acetic acid untreated rats of both groups. These parameters were significantly improved by ACEIs administration. The effect of captopril in group I was more potent than enalapril, while in group II both ACEIs had the same effect. in group II captopril succeeded to inhibit the change in the weight of the colon or the tissue level of myeloperoxidase enzyme. The colonic tissue level of glutathione reductase was significantly reduced in acetic acid untreated rats of both groups. This reduction was significantly inhibited by ACEIs administration in both groups, with better results with captopril treated rats than enalapril ones in group I. Also the efficacy of captopril in group I was more significant than in group II in improving the glutathione reductase colonic tissue level. Captopril and enalapril also sigificantly improved the level of tissue lipid peroxides, which was significantly elevated in acetic acid untreated rats of both groups. However, the efficiency of captopril in reducing the lipid peroxides level was mor significant than enalapril in both groups. this study provides an evidence that the two ACEIs particularly captopril confers a good anti-inflammatory activity against colitis in rats leading to improvement of oxidative stress induced by the inflammatory insult

possible role for tamoxifen in the prevention of streptozotoain induced diabetes and its cardiovascular complications in rats

In this work the potential beneficial effects of nicotinamide, amino- guanidine, desferrioxamine and Tamoxifen in the prevention of streptozotocin induced diabetes and its vascular complications in rats were investigated. In the prophylaxis trial, nicotinamide, amino- guanidine, desferrioxamine and Tamoxifen all prevented or decreased the abnormalities in serum glucose, lipid profile, antioxidants enzymes and lipid peroxides observed in diabetic rats. Treatment of streptozotocin induced-diabetic rats by insulin corrected the observed abnormalities in serum glucose and lipid profile, still the changes in antioxidant enzymes and lipid peroxides were insignificant. Treatment of diabetic rats by insulin together with nicotinamide, amino- guanidine, desferrioxamine or Tamoxifen corrected the abnormalities in all these parameters as compared with the appropriate control groups