Induction of renal metallothionein allows increasing dose of an extensively used antitumor drug, cis-diamminedichloroplatinum.
The effect of preadministration of bismuth, a specific potent inducer of renal metallothionein (MT), on the lethal and renal toxicity of cis-DDP, an extensively used antitumor drug containing heavy metal platinum, in mice was investigated. Pretreatment of mice with two s.c. doses of bismuth nitrate (BN; 30 mumol/kg/day) at 24-hr interval prevented the lethal toxicity, the increase in BUN value and the occurrence of diarrhea caused by cis-DDP (35 mumol/kg, s.c.). This protective effect of BN-pretreatment was significantly correlated with increased MT levels in the kidney. The pretreatment of tumor-bearing mice with BN also depressed the lethal and renal toxicity of cis-DDP without compromising its antitumor activity, and allowed the administration of relatively high dose of cis-DDP. Daily five consecutive p.o. preadministration of bismuth subnitrate (BSN), one of the bismuth compounds being in use as a protectant of the gastrointestinal lining, was also effective to depress the lethal toxicity of cis-DDP. Since the effective dose of BSN is not far from that commonly used for men, this treatment will allow the increase in cis-DDP dose, promising a clinical advantage in cancer chemotherapy.
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D001729:Bismuth / Q000494:pharmacology / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced; D008668:Metallothionein / Q000096:biosynthesis*; D051379:Mice; D009368:Neoplasm Transplantation
D008668:Metallothionein; C010804:bismuth subnitrate; D002945:Cisplatin; D001729:Bismuth