Uozumi J, Koikawa Y, Yasumasu T, Tokuda N, Ueda T, Kumazawa J
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Res Exp Med (Berl). 1996;196(4):211-7. doi: 10.1007/BF02576843.
In order to evaluate the mechanism of the protective action of methylprednisolone against cisplatin-induced nephrotoxicity, platinum kinetics and urinary enzyme excretion following intravenous cisplatin, with or without methylprednisolone, were studied in vivo. The growth inhibition of LLC-PK1 cells by cisplatin in the presence or absence of methylprednisolone was studied in vitro. Rats intravenously injected with cisplatin combined with subcutaneous methylprednisolone 4 h prior to the cisplatin injection excreted more platinum in urine than rats treated with cisplatin alone. Both plasma and kidney platinum concentrations in rats injected with both cisplatin and methylprednisolone were significantly lower than those in rats given cisplatin alone at 4 h after cisplatin injection. However, there was no significant difference in urinary excretion of lactate dehydrogenase, gamma-glutamyl transpeptidase or N-acetyl-beta-D-glucosaminidase between methylprednisolone-treated rats and control rats. Methylprednisolone did not affect the inhibitory effects of cisplatin on the cell growth of LLC-PK1. These findings indicate that methylprednisolone-induced increase in urinary platinum excretion, accompanied by a decrease in plasma and kidney platinum concentrations following cisplatin injection in rats, may be one of the mechanisms responsible for the protective action of methylprednisolone.
为了评估甲泼尼龙对顺铂诱导的肾毒性的保护作用机制，在体内研究了静脉注射顺铂（有或无甲泼尼龙）后的铂动力学和尿酶排泄情况。在体外研究了顺铂在有或无甲泼尼龙存在的情况下对LLC-PK1细胞生长的抑制作用。在顺铂注射前4小时静脉注射顺铂并皮下注射甲泼尼龙的大鼠，其尿中排出的铂比单独用顺铂治疗的大鼠更多。在顺铂注射后4小时，同时注射顺铂和甲泼尼龙的大鼠血浆和肾脏中的铂浓度均显著低于单独给予顺铂的大鼠。然而，甲泼尼龙治疗组大鼠与对照组大鼠在乳酸脱氢酶、γ-谷氨酰转肽酶或N-乙酰-β-D-氨基葡萄糖苷酶的尿排泄方面没有显著差异。甲泼尼龙不影响顺铂对LLC-PK1细胞生长的抑制作用。这些发现表明，甲泼尼龙诱导大鼠顺铂注射后尿铂排泄增加，同时血浆和肾脏铂浓度降低，可能是甲泼尼龙发挥保护作用的机制之一。
