Ghrelin alleviates cancer chemotherapy-associated dyspepsia in rodents.
OBJECTIVE
Chemotherapy treatment may lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS).


METHODS
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.x2) 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).


CONCLUSIONS
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.
Liu
Y-L
YL
Division of Basic Medical Sciences, St. George's University of London Tooting, UK.
Malik
N M
NM
Sanger
G J
GJ
Andrews
P L R
PL
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D004326:Drinking / Q000187:drug effects; D004334:Drug Administration Schedule; D004415:Dyspepsia / Q000139:chemically induced / Q000517:prevention & control*; D004435:Eating / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D054439:Ghrelin; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D036361:Peptide Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D000970:Antineoplastic Agents; D005765:Gastrointestinal Agents; D054439:Ghrelin; D036361:Peptide Hormones; D002945:Cisplatin