Synthesis without Compromising Its Antitumor Activity in Mice -Diamminedichloroplatinum(II) by Induction of Metallothionein cis Prevention of Lethal and Renal Toxicity of Updated Version

نویسندگان

  • Akira Naganuma
  • Masahiko Satoh
  • Nobumasa Imura
چکیده

The participation of renal metallothionein (Ml) in the toxicity and antitumor activity of cii-diamminedichloroplatinum(II) (cw-DDP) in male mice was examined. Preinduction of MT in the kidney by the s.c. administration of bismuth compounds decreased the lethality and renal and gastrointestinal toxicity caused by a single s.c. injection of c/j-DDP. In the present study a correlation between the protective effect of pre treatment with bismuth nitrate against cw-DDP toxicity and the preinduced MT levels in the kidney was observed. Bismuth nitrate pretreat ment showed no effect on the antitumor activity of cii-DDP against several transplantable tumors, probably because it induces MT in the kidney but not in tumor tissues. The fact that p.o. preadministration of bismuth subnitrate, an antidiarrheal drug, also depressed the lethal toxicity of cis-DDP is promising for its prompt application in medical attention. Thus, bismuth pretreatment allows higher doses of ci's-DDP with no apparent toxicity, resulting in more efficient utilization of this anticancer drug.

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تاریخ انتشار 2006