Beneficial effects of spironolactone on glomerular injury in streptozotocin-induced diabetic rats.

INTRODUCTION: To investigate the beneficial effects of spironolactone (SPL) on glomerular injury in streptozotocin (STZ)-induced diabetic rats and the possible mechanism.

METHODS AND RESULTS: STZ-induced diabetic rats were divided into control group, STZ group, and SPL group. Glomerular morphology was observed by light microscopy after the rats were sacrificed after 30 days treatment. The mRNA expressions of transforming growth factor-beta 1 (TGF-beta1) and type-1 plasminogen activator inhibitor (PAI-1) in renal cortex were measured by transcription-polymerase chain reaction (RT-PCR). The protein expressions of PAI-1, fibronectin (FN) and TGF-beta1 were detected by western blotting and immunohistochemistry respectively. In addition, levels of malondialdehyde (MDA) and the activity of antioxidants including superoxide diamutase (SOD), glutathione peroxidase (GSH-PX) in the cortex of kidney were measured.

RESULTS: In untreated diabetic rats, the glomerular volume, the expression of FN and the urinary albumin excretion increased. The mRNA and protein expression of PAI-1 and TGF-beta1 significantly increased in the STZ group. Treatment with SPL partially reversed these changes. Meanwhile, elevated MDA levels as well as decreased SOD and GSH-PX activities in the cortex of kidney were significantly ameliorated in the treated group.

CONCLUSION: SPL ameliorates the glomerular injury in STZ-induced early diabetic renal injury, which is closely related with the reduction of PAI-1 and TGF-beta1 expression and the attenuation of oxidative stress.