ROLE OF NITRIC OXIDE DONOR AND PHOSPHODIESTERASE-II INHIBITOR IN A STREPTOZOTOCIN INDUCED DIABETIC NEPHROPATHY IN RATS

Abstract

The aim of the present study was to investigate the role of Sodium Nitroprusside (SNP), a nitric oxide donor alone or combination with erythro-9-(2-
hydroxy-3-nonyl) adenine, (EHNA), a Phosphodiesterase-II specific inhibitor in the reduction of various markers of nephropathy, reactive oxygen
species (ROS) and endogenous antioxidants enzymes activity. The serum creatinine, blood urea nitrogen (BUN), proteinuria, cholesterol level,
absolute kidney weight, kidney hypertrophy, renal collagen content, nitrite/ nitrate concentration, ROS were assessed by estimating Thiobarbituric
Acid Reactive Substances (TABRS) level and endogenous antioxidants enzymatic activities (SOD, Catalase and GSH) were examined in 80 male
Wistar rats that were allocated in ten groups (n=8). The experimental protocol includes normal and diabetic control groups, SNP per se, Aldosterone
per se group, SNP-1mg, SNP-2mg treated diabetic rats alone or in combination with EHNA and Aldosterone for 2 weeks after 6 weeks of STZ
administration. Significant increase in serum creatinine, BUN, proteinuria, cholesterol level, absolute kidney weight, kidney hypertrophy, renal
collagen content, TBARS and significant decrease in serum nitrite/nitrate, endogenous antioxidant enzymes activity was detected in serum and kidney
homogenate in the diabetic groups. Intraperitoneal administration of SNP alone and in combination with EHNA groups was found statistically
significant for reducing the markers of nephropathy, ROS and antioxidants activities. There was statistical difference observed when Aldosterone was
administered in combination with SNP 1 & 2 mg in diabetic rats. Diabetes induced renal injury was found to be reduced by the intraperitoneal
administration of SNP in dose dependent manner, even in the presence of EHNA. However beneficial effects were attenuated when Aldosterone was
administered in combination with SNP in diabetic rats