Endo T, Minami M, Monma Y, Saito H, Takeuchi M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
J Toxicol Sci. 1990 Nov;15(4):235-44. doi: 10.2131/jts.15.235.
Cisplatin is an effective antineoplastic agent that causes severe vomiting due to unknown mechanism. The ferret, an animal model useful in the determination of emetic activity, was used to clarify the emesis-related biochemical and histopathological changes that were induced by cisplatin. Cisplatin (5 to 10 mg/kg) was administered intraperitoneally and a 7-10 mg/kg i.p. dose evoked dose-dependent emesis in the ferret. Almost all cisplatin-vomiting episodes occurred within a 6 hour observation period. All ferrets receiving cisplatin in this study died within 3-5 days. Significant increases in ileal mucosal levels of serotonin and norepinephrine were observed in cisplatin-treated ferrets. There were no significant changes in the levels of serotonin and dopamine in the gastric mucosa. Also, karyorrhexis was observed in the epithelial cells of the ileum and in the lymph follicles of the spleen of cisplatin-treated ferrets. These significant biochemical and pathological changes in the ileum may play an important role in cisplatin-induced emesis.
顺铂是一种有效的抗肿瘤药物，但其导致严重呕吐的机制尚不清楚。雪貂是一种有助于确定催吐活性的动物模型，被用于阐明顺铂诱导的与呕吐相关的生化和组织病理学变化。腹腔注射顺铂（5至10mg/kg），7-10mg/kg的腹腔注射剂量在雪貂中引起剂量依赖性呕吐。几乎所有顺铂引起的呕吐发作都发生在6小时的观察期内。本研究中所有接受顺铂治疗的雪貂在3-5天内死亡。在接受顺铂治疗的雪貂中，观察到回肠黏膜中血清素和去甲肾上腺素水平显著升高。胃黏膜中血清素和多巴胺水平没有显著变化。此外，在接受顺铂治疗的雪貂的回肠上皮细胞和脾脏淋巴滤泡中观察到核碎裂。回肠中这些显著的生化和病理变化可能在顺铂诱导的呕吐中起重要作用。
