Emesis-related biochemical and histopathological changes induced by cisplatin in the ferret.

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.