Antiemetic role of thalidomide in a rat model of cisplatin-induced emesis.
The efficacy of thalidomide to attenuate cisplatin-induced emesis was evaluated in a rat model. Four groups were utilized: control group (peritoneal injection and gastric lavage with normal saline), cisplatin group (peritoneal injection of cisplatin at 10 mg/kg and gastric lavage with normal saline), thalidomide group (cisplatin as above and gastric lavage with thalidomide at 10 mg/kg), and granisetron group (positive control for antiemetic effects; cisplatin given as above and gastric lavage done with granisetron at 0.5 mg/kg). The cisplatin-induced kaolin consumption (pica behavior) was used as a model of emesis in patients. The animals' kaolin and food intakes were measured. Further, medulla and gastric tissues were obtained 5 and 33 h after peritoneal injections to quantify the levels of Substance P and Neurokinin-1 receptor (NK-1R). The cisplatin-induced kaolin consumption was significantly (p < 0.05 vs. cisplatin group) attenuated by thalidomide 72 h after the injection. The levels of Substance P in the medulla and gastric tissue were increased 5 h after the injection in both cisplatin and thalidomide groups, however, returned faster to normal levels in the thalidomide group (p < 0.05 vs. cisplatin group). Further, levels of NK-1R in the cisplatin, thalidomide, and granisetron group were significantly increased at both 5 and 33 h (p < 0.05 vs. control group), with no obvious difference among these three groups. In conclusion, thalidomide attenuates animal equivalent of cisplatin-induced emesis, and this beneficial effect is associated with decreased levels of Substance P levels in the medulla and gastric tissue.
Department of Oncology, The Affiliated Hospital of Xuzhou Medical College, No. 99 West Huaihai Road, Xuzhou, 221002, People's Republic of China, cnhzxyq@xzmc.edu.cn.
Zheng-xiang
ZX
Han
Jie
J
Xu
Hong-mei
HM
Wang
Jan
J
Ma
Xuan
X
Sun
Xiu-ping
XP
Du
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D007616:Kaolin / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism
D000932:Antiemetics; D000970:Antineoplastic Agents; D018040:Receptors, Neurokinin-1; D007616:Kaolin; D013373:Substance P; D013792:Thalidomide; D002945:Cisplatin