Yasumasu T, Ueda T, Uozumi J, Mihara Y, Koikawa Y, Kumazawa J
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Pharm Pharmacol. 1992 Nov;44(11):885-7. doi: 10.1111/j.2042-7158.1992.tb03229.x.
To clarify the difference in nephrotoxicity between cisplatin and carboplatin, ultrastructural alterations and DNA synthesis of renal cell nuclei were studied in Sprague-Dawley rats which had received intravenously either cisplatin or carboplatin at an equitoxic dose. Twelve hours after cisplatin injection, nucleolar segregation accompanied by aggregated nuclear heterochromatin was observed in the third segment of the proximal tubules. Seventy-two hours after cisplatin injection, nuclear damage was more widespread while regenerative cells were also observed. Nuclear damage was not observed in the carboplatin-treated rats. Nuclear DNA synthesis of renal cells was suppressed at 8, 12 and 24 h and was accelerated at 72 h after cisplatin injection. Carboplatin did not suppress nuclear DNA synthesis at any time. The results indicate that cisplatin, but not carboplatin, can affect the renal cell nuclei. Cisplatin-induced nephrotoxicity is related to its effects on renal cell nuclei.
为阐明顺铂和卡铂肾毒性的差异,在接受等毒性剂量顺铂或卡铂静脉注射的Sprague-Dawley大鼠中,研究了肾细胞核的超微结构改变和DNA合成。顺铂注射12小时后,在近端小管的第三段观察到核仁分离并伴有聚集的核异染色质。顺铂注射72小时后,核损伤更为广泛,同时也观察到再生细胞。在接受卡铂治疗的大鼠中未观察到核损伤。顺铂注射后8、12和24小时肾细胞核DNA合成受到抑制,72小时后加速。卡铂在任何时候都不会抑制核DNA合成。结果表明,顺铂而非卡铂可影响肾细胞核。顺铂诱导的肾毒性与其对肾细胞核的作用有关。