Anti-emetic activity of ghrelin in ferrets exposed to the cytotoxic anti-cancer agent cisplatin

Emesis may be modulated via multiple mechanisms. The actions of ghrelin suggest an ability to couple an induction of hunger with preparation of the stomach for ingestion of food. Such a process might reduce any tendency to vomit, so an anti-emetic activity of ghrelin was investigated in the ferret cisplatin-induced emesis model. In controls, intra-peritoneal cisplatin (10 mg/kg) induced 41.4 +/- 8.4 episodes of emesis comprising 310.4 +/- 55.3 retches and 28.8 +/- 6.9 vomits during the 6 h observation; the latency to onset of the first emetic episode was 108.9 +/- 4.8 min. Intraperitoneal ghrelin (1 mg/kg, split as a 30 min pre- and 30 min-post dose) did not induce a change in behaviour or modify cisplatin-induced emesis (p > 0.05). Intracerebroventricular (i.c.v.) administration (third ventricle) was achieved via a pre-implanted cannula. At the first emetic episode following cisplatin, ghrelin or vehicle (20 mu l saline) was administered i.c.v. During the 30 min following the initial episode of emesis, control animals exhibited 18.0 +/- 2.6 emetic episodes comprising 160.3 +/- 24.1 retches and 13.8 +/- 2.7 vomits. Ghrelin 10 mu g i.c.v. reduced the number of retches by 61.5% (p < 0.05) and at a dose of 30 mu g i.c.v. ghrelin reduced the number of episodes, individual retches and vomits by 74.4 (P < 0.05), 80.4 (p < 0.01), and 72.5% (p < 0.05), respectively. At subsequent time periods there were no differences between g-hrelin- or saline-treated animals (p > 0.05). An ability of ghrelin to reduce emesis is consistent with a role in modulating gastro-intestinal functions and identifies a novel approach to the treatment of emesis. (C) 2005 Elsevier Ireland Ltd. All fights reserved.