Ghrelin alleviates cancer chemotherapy-associated dyspepsia in rodents

Purpose: Chemotherapy treatment may lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Method: We examined the effects of ghrelin in rodent models of CADS induced by treatment with cisplatin. Results: In rats, increased gastric contents and reduced feeding were observed 48 h after injection with cisplatin (6 mg/kg, i.p.). Ghrelin (0.5 mg/kg, i.p.) caused a 16-fold increase in food intake over 1 h in cisplatin/ghrelin-treated rats compared to cisplatin/vehicle-treated rats. A single dose of ghrelin also restored the decreased locomotor activity in rats induced by cisplatin to almost the same level of saline-treated rats. In mice, daily food intake was significantly decreased at 24 h (60%) and 48 h (74%) after cisplatin (20 mg/kg, i.p.). Ghrelin (1 mg/kg, i.p.×2) significantly increased food intake measured at the 48 h time-point in both saline/ghrelin-treated and cisplatin/ghrelin-treated mice, with this effect being most marked in the cisplatin-treated group, where a twofold increase in feeding was observed. In cisplatin-treated mice, delayed gastric emptying was indicated by a 7.7-fold increase in the wet weight of gastric contents and ghrelin improved the gastric emptying index (GEI) by 31% (P<0.01). Conclusion: Together, these results suggest that it is possible to model cancer chemotherapy-induced dyspepsia in rodents and that ghrelin can greatly alleviate the behaviours associated with this syndrome. Agonists at the ghrelin receptor may, therefore, become a useful human therapeutic for this disorder.