Nephrology Division, Universidade Federal de São Paulo--Escola Paulista de Medicina, São Paulo, Brazil.
Nitric Oxide. 2011 Mar 15;24(2):77-83. doi: 10.1016/j.niox.2010.12.001. Epub 2010 Dec 16.
GENTA nephrotoxicity is likely to be caused, among other factors, by an increase of vasoconstrictors or a decrease of vasodilators such as NO. Few days after discontinuing GENTA treatment, the renal function is recovered, but if risk factors like advanced age, previous renal dysfunction, simultaneous use of other nephrotoxic drugs or dehydration are present, severe and progressive renal disease occurs. The aim of this study was to evaluate the renal function in rats during GENTA treatment and after its suspension as well as its relationship with NO. Rats were treated with water (vehicle, CTL) or GENTA (100 mg/kg BW) intraperitonially during 10 days; both n=24. Twelve animals of each group were sacrificed after blood and 24 h urine were collected, and their kidneys were removed for histology. In another rats this procedure underwent after 20 or 30 days of GENTA suspension. GENTA treated group developed a marked decrease in renal function, characterized by an increased serum urea and decreased creatinine clearance; NO was increased in the serum and decreased in the urine; all P < 0.01 vs CTL. Acute tubular necrosis was confirmed in GENTA treated group. After GENTA suspension we observed a normalization of urea, creatinine clearance and serum and urinary NO; the histological lesions were also attenuated. We suggest that NO could play a role in GENTA induced nephrotoxicity and recovery. The understanding of this physiopathology could be an useful tool to prevent or blunt the nephrotoxicity progression, mainly when risk factors are present.
氨基糖苷类药物的肾毒性可能是由于血管收缩剂的增加或血管扩张剂如一氧化氮（NO）的减少等因素引起的。在停止使用氨基糖苷类药物治疗后几天，肾功能会恢复，但如果存在年龄较大、先前肾功能不全、同时使用其他肾毒性药物或脱水等危险因素，则会发生严重且进行性的肾脏疾病。本研究旨在评估大鼠在氨基糖苷类药物治疗期间和停药后的肾功能及其与一氧化氮的关系。大鼠腹膜内注射水（载体，CTL）或氨基糖苷类（100mg/kgBW），每天 10 天；每组 n=24。每组 12 只动物在收集血液和 24 小时尿液后被处死，并取出肾脏进行组织学检查。在另一组大鼠中，在氨基糖苷类药物停药 20 或 30 天后进行了此程序。氨基糖苷类药物治疗组的肾功能明显下降，表现为血清尿素升高和肌酐清除率降低；血清中一氧化氮增加，尿液中一氧化氮减少；所有 P<0.01 与 CTL 相比。在氨基糖苷类药物治疗组中证实了急性肾小管坏死。在氨基糖苷类药物停药后，我们观察到尿素、肌酐清除率以及血清和尿液中一氧化氮的恢复正常；组织学损伤也减轻了。我们认为一氧化氮可能在氨基糖苷类药物引起的肾毒性和恢复中起作用。了解这种病理生理学可能是预防或减轻肾毒性进展的有用工具，特别是在存在危险因素时。
