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Mentions: BUN and Cr were increased in all CP treated groups, but it was only statistically significant in male treated with CP and in female treated with CP+L-arginine (p < 0.05). L-arginine attenuates the levels of BUN and Cr in male but not in female when compared with control groups (the BUN reduction was significantly different, p < 0.05). The nitrite level increased in L-arginine treated animals (male, p < 0.1; female, p < 0.05), but at the end of the experiment, a significant difference in nitrite level was only detected between females groups (p < 0.05) (Figure 2). On the whole, these findings indicated that L-arginine provides different pattern of effect on BUN, Cr and nitrite levels in CP-induced nephrotoxicity model in male and female rats.
The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin-induced nephrotoxicity: Gender related differences in rat model
Bottom Line: 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).
Affiliation: Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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.