The Expressions of iNOS and the Effects of iNOS Inhibitor in the Rats of Cisplatin Induced Nephrotoxicity

Lee, Doo Hyoung; Myoung, Soon Chul; Kim, Young Seon

Abstract

PURPOSE: This study was designed to investigate the role of NO in cisplatin induced nephrotoxicity of rats, especially in association with expressions of inducible nitric oxide synthase(iNOS) and the effects of iNOS inhibitor.
MATERIALS AND METHODS
Male, Sprague-Dawley rats weighing 170-190gm were used. Nephrotoxicity was induced by single intraperitoneal administration of cisplatin(10mg/kg). Aminoguanidine sulfate (300mg/kg), a relatively specific iNOS inhibitor, was administrated 30 minutes prior to cisplatin administration. Individual kidneys were obtained from control, cisplatin single treated and cisplatin combined with aminoguanidine treated rats at 6, 12, 24, 48, 72hours and 7days after cisplatin administration. Serum BUN/creatinine(mg/dl), the unit weight of rat kidney (kidney wet weight/body weight) were estimated. HE stain was performed for histologic evaluation of nephrotoxicity. The expressions of iNOS were assessed by Western blotting and RT-PCR.
RESULTS
Serum BUN/creatinine levels in aminoguanidine treated groups were suppressed its increment significantly at 12, 24 and 48 hours compared with cisplatin single treated groups (p<0.05). The unit weight of kidneys in aminoguanidine treated groups were decreased significantly at 24 and 48hours compared with cisplatin single treated groups (p<0.05). Western blotting represents intense iNOS protein bands (117KDa) at 24,48 and 72hours in cisplatin single treated groups. RT-PCR assay for iNOS mRNA (429bp) were weakly expressed in control groups and intense expressions were identified cisplatin single treated and cisplatin combined with aminoguanidine treated groups at 6, 12, 24 and 72hours.
CONCLUSIONS
From these results, it is suggested that cisplatin induced nephrotoxicity may be partly mediated by NO. Aminoguanidine may delay or suppress the cisplatin induced nephrotoxicity of rat kidney.