Prevention of lethal and renal toxicity of cis-diamminedichloroplatinum(II) by induction of metallothionein synthesis without compromising its antitumor activity in mice. 1987

A Naganuma, and M Satoh, and N Imura

The participation of renal metallothionein (MT) in the toxicity and antitumor activity of cis-diamminedichloroplatinum(II) (cis-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 cis-DDP. In the present study a correlation between the protective effect of pretreatment with bismuth nitrate against cis-DDP toxicity and the preinduced MT levels in the kidney was observed. Bismuth nitrate pretreatment showed no effect on the antitumor activity of cis-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 cis-DDP with no apparent toxicity, resulting in more efficient utilization of this anticancer drug.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007941 Leukemia P388 An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene. P388D(1) Leukemia,P388, Leukemia
D008297 Male Males
D008668 Metallothionein A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. Isometallothionein,Metallothionein A,Metallothionein B,Metallothionein I,Metallothionein II,Metallothionein IIA
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D001729 Bismuth A metallic element that has the atomic symbol Bi, and atomic number 83. Its principal isotope is Bismuth 209.
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D004064 Digestive System A group of organs stretching from the MOUTH to the ANUS, serving to breakdown foods, assimilate nutrients, and eliminate waste. In humans, the digestive system includes the GASTROINTESTINAL TRACT and the accessory glands (LIVER; BILIARY TRACT; PANCREAS). Ailmentary System,Alimentary System
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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