title: Effect of Gingerol on Cisplatin-Induced Pica Analogous to Emesis Via Modulating Expressions of Dopamine 2 Receptor, Dopamine Transporter and Tyrosine Hydroxylase in the Vomiting Model of Rats.
abstract: BACKGROUND
  Gingerol, the generic term for pungent constituents in ginger, has been used for treating vomiting in China. We are going to investigate the mechanisms of inhibitive effect of gingerol on cisplatin-induced pica behaviour by studying on both peripheral and central levels, and the effects of gingerol on homeostasis of dopamine (DA) transmission: dopamine D2 receptor (D2R), dopamine transporter (DAT) and tyrosine hydroxylase (TH).
  
  
  METHODS
  The antiemetic effect of gingerol was investigated on a vomiting model in rats induced by cisplatin 3 mg·kg(-1) intraperitoneal injection (i.p.). Rats were randomly divided into the normal control group (C), simple gingerol control group (CG), cisplatin control group (V), cisplatin + metoclopramide group (M), cisplatin + low-dose gingerol group (GL), cisplatin + middle-dose gingerol group (GM) and cisplatin + high-dose gingerol group (GH). In observation period, rats in Groups C and V were pretreated with sterile saline 3 mL i.g.; rats in Group CG were pretreated with gingerol 40 mg·kg(-1) i.g.; rats in Group M were pretreated with metoclopramide 2.5 mg·kg(-1) i.g.; rats in Groups GL, GM and GH were pretreated with gingerol 10, 20 and 40 mg·kg(-1) i.g. for 3 days, respectively. Cisplatin (3 mg·kg(-1), i.p.) was administered one time after each treatment with the antiemetic agent or its vehicle except the Groups C and CG. The distribution of D2R, DAT and TH in the area postrema and ileum were measured by immunohistochemistry and quantitated based on the image analysis, and the expression of DAT and TH in the area postrema and ileum were measured by RT-PCR. The weights of kaolin eaten of the remaining rats were observed in every 6 h continuously for 72 h.
  
  
  RESULTS
  The weight of kaolin eaten in rats induced by cisplatin was significantly reduced by pretreatment with gingerol in a dose-dependent manner during the 0-24 h and 24-72 h periods (P < 0.05). Gingerol markedly improved gastric emptying induced by cisplatin in a dose-dependent manner (P < 0.05), and exhibited effective dose-dependent inhibition on the increase of expression levels of D2R and TH and the decrease of expression levels of DAT in both the ileum and area postrema (P < 0.05).
  
  
  CONCLUSIONS
  Gingerol is effective on cisplatin-induced emesis in rats possibly by inhibiting central or peripheral increase of DA by inhibiting D2R, TH and accelerating DAT.
authors: Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan; †Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, China.
authors: Weibin
authors: W
authors: Qian
authors: ‡Shandong Academy Occupational Health and Occupational Medicine, Shandong Academy of Medical Sciences, Jinan 250002, Shandong, China.
authors: Xinrui
authors: X
authors: Cai
authors: §Jinan Shizhong People's Hospital, Jinan 250002, Shandong, China.
authors: Yingying
authors: Y
authors: Wang
authors: †Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, China.
authors: Xinying
authors: X
authors: Zhang
authors: ||Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou 061000, Hebei, China.
authors: Hongmin
authors: H
authors: Zhao
authors: †Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, China.
authors: Qiuhai
authors: Q
authors: Qian
authors: ¶Pharmic Department, Medical College of Qingdao University, Qingdao 266021, Shandong, China.
authors: Zhihong
authors: Z
authors: Yang
authors: ¶Pharmic Department, Medical College of Qingdao University, Qingdao 266021, Shandong, China.
authors: Zhantao
authors: Z
authors: Liu
authors: Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors: Junichi
authors: J
authors: Hasegawa
keywords: dopamine 2 receptor; dopamine transport; gingerol; tyrosine hydroxylase; vomiting