Gender Difference in the Serum Levels of Total Nitric Oxide Metabolites, Nitrite, and Nitrate in Cisplatin-induced Nephrotoxicity in Rats

Document Type : Original Article (s)

Authors

1 Professor, Water and Electrolytes Research Center AND Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Student of Medicine, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

3 Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

4 Associate Professor, Water and Electrolytes Research Center AND Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

5 Assistant Professor, Water and Electrolytes Research Center AND Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Nephrotoxicity is the most common adverse effect of cisplatin therapy in clinic, which also disturbs the nitric oxide system. Cisplatin-induced nephrotoxicity may be gender-related; nevertheless, no information has been well documented regarding the gender-specific influences of cisplatin on nitric oxide metabolites. In order to narrow this gap, this study was designed to determine the gender difference in the serum levels of total nitric oxide metabolites (NOx), nitrite, and nitrate in cisplatin-induced nephrotoxicity in rats. Methods: 25 male and female rats were randomly divided into 4 groups. The male groups 1 and 3 were received saline (control) and a single dose of cisplatin (7 mg/kg), respectively. The female groups 2 and 4 also received similar treatments.  One week later, the blood samples were obtained and the animals were sacrificed for pathological investigation. Findings: The serum levels of NOx (group 1 = 22.43 ± 3 mmole/liter, group 3 = 50.71 ± 7.52, P < 0.05), and nitrite (group 1 = 13.2 ± 2.1 mmole/liter, group 3 = 37.7 ± 4, P < 0.05) in male animals treated with cisplatin was significantly higher than the control group. Such finding was not seen in female rats. The intensity of kidney tissue damage in male rats was also more marked compared with the female animals. Conclusion: The effect of cisplatin on nitric oxide metabolites could be gender related, and nitrite is more influenced by cisplatin than nitrate. More studies may be needed for clarifying the exact mechanisms. Keywords: Cisplatin, Adverse effects, Nitric oxide, Sex, Rats