Torii Y, Mutoh M, Saito H, Matsuki N
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Eur J Pharmacol. 1993 Aug 2;248(2):131-5. doi: 10.1016/0926-6917(93)90034-n.
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.
在臭鼩（Suncus murinus）中研究了自由基在顺铂诱导呕吐中的作用。用顺铂（20mg/kg，腹腔注射）处理60分钟后，脑、肝和小肠中硫代巴比妥酸（TBA）值（表明脂质过氧化程度）显著升高。此外，自由基清除剂N-（2-巯基丙酰基）甘氨酸（MPG）腹腔注射（ID50值为130mg/kg）可预防顺铂（20mg/kg，腹腔注射）诱导的呕吐。然而，MPG并不阻断硫酸铜（40mg/kg，口服）、藜芦碱（0.5mg/kg，皮下注射）或5-羟色胺（10mg/kg，腹腔注射）诱导的呕吐。我们还研究了与聚乙二醇偶联的超氧化物歧化酶和过氧化氢酶的作用，但在顺铂给药前30分钟或给药后20分钟腹腔注射这些药物时，呕吐发作次数和潜伏期没有显著变化。MPG不影响体外试验中顺铂的抗肿瘤作用。这些结果表明，自由基介导顺铂引起的呕吐，自由基清除剂可能成为一类新的预防癌症化疗药物诱导呕吐的药物。
