Pravastatin modulates early diabetic nephropathy in an experimental model of diabetic renal disease

Abstract

Development of diabetes causes early functional (endothelial dysfunction) and morphological abnormalities in the kidney. If left untreated, these will ultimately progress to renal failure. Apart from strategies aimed at maintaining very tight glycemic control, attention has turned to the development of adjuvant therapy to maintain endothelial function in these patients. The agents receiving the most critical appraisal due to their endothelial protective effects are the 3-hydrox 3-methylglutaryl (HMG)-Co-enzyme A (CoA) reductase inhibitors. The aim of the study was to investigate: (1) the early alterations in the renal diabetic injury; and (2) to examine the protective role of Pravastatin in this end-organ diabetic model. Sprague Dawley rats (n = 21) were randomized into three groups: (1) control; (2) diabetic; and (3) diabetic treated with Pravastatin. Diabetic nephropathy was investigated with serum biochemical parameters (urea, creatinine), functional parameters (total urinary protein loss, glomerular filtration rate, renal cortical blood flow), and structural assessment (hemotoxylin and eosin staining). We demonstrated impairment in functional, biochemical, and structural parameters in the diabetic nephropathy group, which was diminished by treatment with Pravastatin. This was attributed to an up-regulation in endothelial constitutive nitric oxide synthase (ecNOS) expression in the treated diabetic group. We have shown that Pravastatin, in an experimental model of early diabetes nephropathy preserves microvascular endothelial function in the presence of hyperglycemia, thus inhibiting the early stage of diabetic microangiopathy.