+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Neuro, cardio, and reno protective activities of rosuvastatin in streptozotocin-induced type 2 diabetic rats undergoing treatment with metformin and glimepiride

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Diabetes is associated with complications like neuropathy, nephropathy, cardiomyopathy, and retinopathy due to increased oxidative stress and serum lipids. In the present study, rosuvastatin, a HMG-CoA inhibitor, was investigated for its protective effect in neuropathy, nephropathy, and cardiomyopathy based on the lipid-lowering property along with its pleiotropic effects such as improved blood flow to the organ and antioxidant defense. Type 2 diabetes was induced in Wistar rats by single i.p. administration of streptozotocin (50 mg/kg). These diabetic rats were treated with daily doses of rosuvastatin (10 mg/kg) alone, metformin (120 mg/kg) and glimepiride (1 mg/kg) and rosuvastatin in combination with metformin (120 mg/kg) and glimepiride (1 mg/kg) for a period of 6 weeks. The biochemical parameters involved in neuropathy, renopathy, and cardiopathy were estimated. Treatment resulted in significant ( P < 0.05) decrease in thiobarbituric acid reactive substances (TBARS) and increase in levels of glutathione peroxidise and catalase in brain and kidney homogenates. Significant ( P < 0.05) increase in high-density lipoproteins and decrease in creatinine kinase, triglycerides, total serum cholesterol represents the cardioprotective action, whereas significant ( P < 0.05) increase in the latency in the hotplate model shows the neuroprotective activity, and significant ( P < 0.05) decrease in blood urea nitrogen, creatinine levels and increase in serum total protein levels suggested the renoprotective actions. The unique properties of rosuvastatin such as antioxidant defense and lipid-lowering nature might have resulted in cardio, neuro, and renoprotective activity in type 2 diabetic rats treated with metformin and glimepiride.

          Related collections

          Most cited references 21

          • Record: found
          • Abstract: found
          • Article: not found

          Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.

          Sulfonylurea drugs have been the only oral therapy available for patients with non-insulin-dependent diabetes mellitus (NIDDM) in the United States. Recently, however, metformin has been approved for the treatment of NIDDM. We performed two large, randomized, parallel-group, double-blind, controlled studies in which metformin or another treatment was given for 29 weeks to moderately obese patients with NIDDM whose diabetes was inadequately controlled by diet (protocol 1: metformin vs. placebo; 289 patients), or diet plus glyburide (protocol 2: metformin and glyburide vs. metformin vs. glyburide; 632 patients). To determine efficacy we measured plasma glucose (while the patients were fasting and after the oral administration of glucose), lactate, lipids, insulin, and glycosylated hemoglobin before, during, and at the end of the study. In protocol 1, at the end of the study the 143 patients in the metformin group, as compared with the 146 patients in the placebo group, had lower mean (+/- SE) fasting plasma glucose concentrations (189 +/- 5 vs. 244 +/- 6 mg per deciliter [10.6 +/- 0.3 vs. 13.7 +/- 0.3 mmol per liter], P < 0.001) and glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.6 +/- 0.2 percent, P < 0.001). In protocol 2, the 213 patients given metformin and glyburide, as compared with the 210 patients treated with glyburide alone, had lower mean fasting plasma glucose concentrations (187 +/- 4 vs. 261 +/- 4 mg per deciliter [10.5 +/- 0.2 vs. 14.6 +/- 0.2 mmol per liter], P < 0.001) and glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.7 +/- 0.1 percent, P < 0.001). The effect of metformin alone was similar to that of glyburide alone. Eighteen percent of the patients given metformin and glyburide had symptoms compatible with hypoglycemia, as compared with 3 percent in the glyburide group and 2 percent in the metformin group. In both protocols the patients given metformin had statistically significant decreases in plasma total and low-density lipoprotein cholesterol and triglyceride concentrations, whereas the values in the respective control groups did not change. There were no significant changes in fasting plasma lactate concentrations in any of the groups. Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone.
            • Record: found
            • Abstract: found
            • Article: not found

            Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy.

            Diabetes mellitus is a major cause of peripheral neuropathy, commonly manifested as distal symmetrical polyneuropathy. This review examines evidence for the importance of vascular factors and their metabolic substrate from human and animal studies. Diabetic neuropathy is associated with risk factors for macrovascular disease and with other microvascular complications such as poor metabolic control, dyslipidaemia, body mass index, smoking, microalbuminuria and retinopathy. Studies in human and animal models have shown reduced nerve perfusion and endoneurial hypoxia. Investigations on biopsy material from patients with mild to severe neuropathy show graded structural changes in nerve microvasculature including basement membrane thickening, pericyte degeneration and endothelial cell hyperplasia. Arterio-venous shunting also contributes to reduced endoneurial perfusion. These vascular changes strongly correlate with clinical defects and nerve pathology. Vasodilator treatment in patients and animals improves nerve function. Early vasa nervorum functional changes are caused by the metabolic insults of diabetes, the balance between vasodilation and vasoconstriction is altered. Vascular endothelium is particularly vulnerable, with deficits in the major endothelial vasodilators, nitric oxide, endothelium-derived hyperpolarising factor and prostacyclin. Hyperglycaemia and dyslipidaemia driven oxidative stress is a major contributor, enhanced by advanced glycation end product formation and polyol pathway activation. These are coupled to protein kinase C activation and omega-6 essential fatty acid dysmetabolism. Together, this complex of interacting metabolic factors accounts for endothelial dysfunction, reduced nerve perfusion and function. Thus, the evidence emphasises the importance of vascular dysfunction, driven by metabolic change, as a cause of diabetic neuropathy, and highlights potential therapeutic approaches.
              • Record: found
              • Abstract: not found
              • Article: not found

              Inhibition of proinflammatory cytokine production by pravastatin.


                Author and article information

                J Adv Pharm Technol Res
                J Adv Pharm Technol Res
                Journal of Advanced Pharmaceutical Technology & Research
                Medknow Publications & Media Pvt Ltd (India )
                Apr-Jun 2014
                : 5
                : 2
                : 78-83
                Department of Pharmacology, St. Peter's Institute of Pharmaceutical Sciences, Warangal, Andhra Pradesh, India
                [1 ]Department of Pharmaceutical Analysis, Chaitanya College of Pharmacy Education and Research, Warangal, Andhra Pradesh, India
                Author notes
                Address for correspondence: Dr. Raj Kumar Venisetty, Department of Pharmaceutical Analysis, Chaitanya College of Pharmacy Education and Research, Kishanpura, Warangal, Andhra Pradesh, India. E-mail: vrk10@
                Copyright: © Journal of Advanced Pharmaceutical Technology & Research

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Original Article


                Comment on this article