Renoprotective effects of fenofibrate in diabetic rats are achieved by suppressing kidney plasminogen activator inhibitor-1

To investigate mechanisms of protective effects of fenofibrate on the diabetic kidney, male Wistar rats were divided into control, untreated diabetes, and fenofibrate-treated (32mg kg(-1) d(-1), 8weeks) diabetes groups. Diabetes induced by streptozotocin (25mg/kg) and a high-fat diet was characterized by the disorders of plasma glucose and lipids. In untreated diabetic rats, there were increases in glomerular volume, matrix content, expressions of laminin and urinary albumin excretion. These nephropathies were associated with the upregulations of plasminogen activator inhibitor 1 (PAI-1) mRNA expression and its protein activity in the renal cortex, and a significant increase in transforming growth factor beta 1 (TGF-beta 1) expression. Treatment with fenofibrate suppressed the expression of PAI-I mRNA and its protein activity, and inhibited TGF-beta 1 overexpression. It also partially reversed metabolic disorders and pathophysiologic changes associated with diabetic nephropathy. Our results indicate that fenofibrate delays the progression of diabetic nephropathy in rats to some extent. These renoprotective effects are likely to be achieved through suppression of PAI-1 and TGF-beta 1 in the renal cortex, and consequently less extracellular matrix deposition. (c) 2006 Elsevier Inc. All rights reserved.