Abstract
Hyperglycemia-induced oxidative stress is usually found in diabetic condition. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, statins, are widely used as cholesterol-lowering medication with several “pleiotropic” effects in diabetic patients. This study aims to evaluate whether the protective effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 (Oat3) function involve the modulation of oxidative stress and pancreatic function in type 1 diabetic rats. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg BW). Atorvastatin and insulin as single or combined treatment were given for 4 weeks after diabetic condition had been confirmed. Diabetic rats demonstrated renal function and renal Oat3 function impairment with an increased MDA level and decreased SOD protein expression concomitant with stimulation of renal Nrf2 and HO-1 protein expression. Insulin plus atorvastatin (combined) treatment effectively restored renal function as well as renal Oat3 function which correlated with the decrease in hyperglycemia and oxidative stress. Moreover, pancreatic inflammation and apoptosis in diabetic rats were ameliorated by the combined drugs treatment. Therefore, atorvastatin plus insulin seems to exert the additive effect in improving renal functionby alleviating hyperglycemiaand the modulation of oxidative stress, inflammation and apoptosis.
Highlights
Type 1 diabetes (T1D) is an autoimmune disease characterized by low plasma insulin due to a destruction of the pancreatic β-cells which synthesize insulin[1] leading to the development of hyperglycemia
We demonstrated that renal inflammation, endoplasmic reticulum (ES) stress and apoptosis were ameliorated by atorvastatin in gentamicin-induced nephrotoxicity in rats[12]
Cholesterol, triglyceride, urine glucose and urine volume were significantly increased in diabetic rats when compared with control or control plus atorvastatin-treated rats (p < 0.05)
Summary
Type 1 diabetes (T1D) is an autoimmune disease characterized by low plasma insulin due to a destruction of the pancreatic β-cells which synthesize insulin[1] leading to the development of hyperglycemia. AGE activates the polyol pathway resulting in the activation of Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase causing cell damage and dysfunction[3,4,5] These conditions can lead to diabetic nephropathy and diabetic-induced complications in several organs including the pancreas. DN is characterized by various ultrastructural changes of nephrons including basement membrane thickening, glomerular and tubular hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis[6] This pathology markedly affects the secretory and excretory capacities of transporters in renal proximal tubules. In this study we have evaluated the renoprotective effects of atorvastatin plus low dose insulin treatment on renal function and the function of the important renal transport protein, renal Oat[3], in modulation of the renal oxidative stress pathway, and its effect on the inflammation and apoptosis of the pancreas in streptozotocin (STZ)-induced diabetic rats
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