The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin-induced nephrotoxicity: Gender related differences in rat model

Background: cisplatin (cp) as a potential drug for solid tumors produces nephrotoxicity and disturbs endothelial function. cp induced nephrotoxicity may be gender related. nitric oxide plays a pivotal role in endothelial function and l-arginine as endogenous no donor promotes endothelial function. the role of l-arginine in cp induced nephrotoxici- ty model and its gender related was investigated in this study. methods: thirty three wistar rats were randomly assigned to four groups. the groups 1 (male, n = 6) and 2 (female, n = 11) received a single dose of l-arginine (300 mg/kg, ip), and the day after, they received a single dose of cp (7 mg/kg). the group 3 (male, n = 9) and 4 (female, n = 7) were assigned to the same regimen except for saline instead of l-arginine. all animals were sacrificed one week after cp administration. the levels of blood urea nitrogen (bun), creatinine and nitrite were measured. the kidneys were also removed for pathological investigations. results: five animals died. all cp treated animals lost weight. the normalized weigh loss was significantly different between male and female in cp+l-arginine treated animals (p < 0.05). bun and creatinine were increased significantly in male treated with cp and in female treated with cp+l-arginine (p < 0.05). l-arginine reduced bun in male (not in female) when compared with control groups (p < 0.05). the level of nitrite was increased significantly in l-arginine treated animals. kidney tissue damage score and normalized kidney weight were greater in females treated with cp+ l-arginine than female received cp alone (p < 0.05). conclusions: l-arginine may protect against cp induced nephrotoxicity in male, but it promotes the induced damage in female. the exact mechanism need to be defined.