Eshraghi-Jazi Fatemeh, Nematbakhsh Mehdi, Nasri Hamid, Talebi Ardeshir, Haghighi Maryam, Pezeshki Zahra, Safari Tahereh, Ashrafi Farzaneh
Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
J Res Med Sci. 2011 Nov;16(11):1389-96.
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.
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.
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).
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.
顺铂（CP）作为一种治疗实体瘤的潜在药物，会产生肾毒性并干扰内皮功能。CP诱导的肾毒性可能与性别有关。一氧化氮在内皮功能中起关键作用，而L-精氨酸作为内源性一氧化氮供体可促进内皮功能。本研究探讨了L-精氨酸在CP诱导的肾毒性模型中的作用及其与性别的关系。
将33只Wistar大鼠随机分为四组。第1组（雄性，n = 6）和第2组（雌性，n = 11）接受单剂量的L-精氨酸（300 mg/kg，腹腔注射），次日，它们接受单剂量的CP（7 mg/kg）。第3组（雄性，n = 9）和第4组（雌性，n = 7）采用相同的给药方案，但用生理盐水代替L-精氨酸。所有动物在给予CP一周后处死。测量血尿素氮（BUN）、肌酐和亚硝酸盐水平。同时取出肾脏进行病理检查。
5只动物死亡。所有接受CP治疗的动物体重均减轻。在接受CP + L-精氨酸治疗的动物中，雄性和雌性的体重减轻标准化值存在显著差异（p < 0.05）。接受CP治疗的雄性和接受CP + L-精氨酸治疗的雌性的BUN和肌酐显著升高（p < 0.05）。与对照组相比，L-精氨酸降低了雄性的BUN（雌性未降低）（p < 0.05）。接受L-精氨酸治疗的动物亚硝酸盐水平显著升高。接受CP + L-精氨酸治疗的雌性的肾组织损伤评分和肾脏重量标准化值高于仅接受CP治疗的雌性（p < 0.05）。
L-精氨酸可能对雄性CP诱导的肾毒性具有保护作用，但对雌性则会促进诱导损伤。确切机制有待确定。
