Renoprotective effect of atorvastatin on STZ-diabetic rats through attenuating kidney-associated dysmetabolism.Eur J Pharmacol. 2014 Oct 05; 740:9-14.EJ
Atorvastatin (AT) has been alternatively used for managing diabetic complications in clinic. However, AT-related therapeutic potentiality remains relatively unexplored, especially in diabetic nephropathy. This study aimed to investigate the underlying potentiality that AT exerted on anti-diabetic nephropathy role against streptozotocin (STZ)-induced kidney injury in rats. STZ-diabetic rats were intragastrically administered with AT (10, 20 mg/kg/d) for consecutive 8 weeks. The effects of AT on body weight, levels of blood glucose, lipometabolism, redox state, cellular metabolism, regulator factor and kidney morphological changes were monitored by routine measurement, biochemistry assay, PT-PCR analysis, ultrastructural and pathological observations, respectively. Compared with the diabetic nephropathy rats, AT elevated the body weight of diabetic nephropathy rats (P<0.01), effectively reduced the blood glucose level (P<0.01), increased the levels of insulin and high-density lipoprotein cholesterol (HDL-C) in plasma (P<0.01), and decreased the 24 h urine protein content and serum concentrations of low-density lipoprotein cholesterol (LDL-C) (P<0.01). Meanwhile, increase in kidney tissue, the intrarenal activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced, while the malonaldehyde (MDA) content was reduced (P<0.01). In addition, the expression of transforming growth factor beta 1 (TGF-β1) mRNA in kidney tissue was notably down-regulated (P<0.01). Furthermore, AT contributed to alleviating STZ-induced nephritic damages in rats. These results demonstrate that atorvastatin exerts the effective protective role against kidney injuries of STZ-induced diabetic nephropathy rat, which the underlying mechanisms are associated with ameliorating glyco, lipometabolism, enhancing antioxidant ability, and mitigating renal damage.