Sadzuka Y, Shoji T, Takino Y
School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Toxicol Lett. 1991 Jul;57(2):159-66. doi: 10.1016/0378-4274(91)90142-s.
cis-Diamminedichloroplatinum(II) (cisplatin) is one of the most effective antitumor agents currently available for cancer chemotherapy. Unfortunately, its clinical use is severely limited by its dose-dependent nephrotoxicity. Recently, it has been reported that this nephrotoxicity is associated with an increase in lipid peroxides in the rat kidney. However, it is not clear if the specific nephrotoxicity is related to the increase in lipid peroxides induced by cisplatin since the increase in lipid peroxides in the kidney has not been compared with that in other tissues. We examined the changes in lipid peroxide levels in rat tissues after cisplatin administration to clarify the relationship between lipid peroxides and cisplatin nephrotoxicity. After cisplatin administration (5 mg/kg i.p.), the relative weight of the rat liver decreased, but that of the kidney increased. The increase in lipid peroxide levels in the kidney and liver of cisplatin-treated rats was significant. The percent change from control was greatest in the kidney on the 5th day after administration among all tissues examined. Cisplatin did not affect enzymatic or non-enzymatic lipid peroxidation in microsomes of rat kidney or liver in vitro. It appears that the increase in lipid peroxides in the kidney was not a direct consequence of cisplatin administration.
顺二氯二氨合铂（II）（顺铂）是目前可用于癌症化疗的最有效的抗肿瘤药物之一。不幸的是，其临床应用因剂量依赖性肾毒性而受到严重限制。最近，有报道称这种肾毒性与大鼠肾脏中脂质过氧化物的增加有关。然而，由于尚未将肾脏中脂质过氧化物的增加与其他组织中的增加进行比较，所以尚不清楚特定的肾毒性是否与顺铂诱导的脂质过氧化物增加有关。我们检查了顺铂给药后大鼠组织中脂质过氧化物水平的变化，以阐明脂质过氧化物与顺铂肾毒性之间的关系。顺铂给药（腹腔注射5mg/kg）后，大鼠肝脏的相对重量下降，但肾脏的相对重量增加。顺铂处理的大鼠肾脏和肝脏中脂质过氧化物水平的增加是显著的。在给药后第5天，在所检查的所有组织中，肾脏中相对于对照的变化百分比最大。顺铂在体外不影响大鼠肾脏或肝脏微粒体中的酶促或非酶促脂质过氧化。看来肾脏中脂质过氧化物的增加不是顺铂给药的直接后果。
