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 nephrotoxicity 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.