Involvement of free radicals in cisplatin-induced emesis in Suncus murinus.
The participation of free radicals in cisplatin-induced emesis was investigated in the house musk shrew, Suncus murinus. Thiobarbituric acid (TBA) values, which indicate the degree of lipid peroxidation, in brain, liver and small intestine were increased significantly 60 min after the treatment with cisplatin (20 mg/kg, i.p.). Moreover, cisplatin (20 mg/kg, i.p.)-induced emesis was prevented by intraperitoneal injection of N-(2-mercaptopropionyl)glycine (MPG), a radical scavenging agent, with ID50 value of 130 mg/kg. However, MPG did not block the emesis induced by copper sulfate (40 mg/kg, p.o.), veratrine (0.5 mg/kg, s.c.) or serotonin (10 mg/kg, i.p.). We also investigated the effects of superoxide dismutase conjugated to polyethylene glycol and catalase, but the number of vomiting episodes and latency did not change significantly when these agents were intraperitoneally injected 30 min prior to or 20 min after the administration of cisplatin. MPG did not affect the antitumor effect of cisplatin tested in vitro. These results suggest that free radicals mediate emesis caused by cisplatin and that radical scavengers may become a new class of prophylactic drug against cancer-chemotherapeutic drug-induced emesis.
Torii
Y
Y
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Mutoh
M
M
Saito
H
H
Matsuki
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D005260:Female; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D012788:Shrews; D013858:Thiobarbiturates / Q000378:metabolism; D008625:Tiopronin / Q000494:pharmacology*; D000077526:Tropisetron; D014407:Tumor Cells, Cultured; D014839:Vomiting / Q000139:chemically induced*
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D007211:Indoles; D013858:Thiobarbiturates; D000077526:Tropisetron; D008625:Tiopronin; C029684:thiobarbituric acid; D002945:Cisplatin