title: Anti-emetic mechanisms of Zingiber officinale against cisplatin induced emesis in the pigeon; behavioral and neurochemical correlates.
abstract: BACKGROUND
  Zingiber officinale (ZO, family Zingiberaceae) has been reported for its antiemetic activity against cancer chemotherapy induced emesis in animal models and in clinics. Current study was designed to investigate ZO for potential usefulness against cisplatin induced vomiting in pigeon and its effects on central and peripheral neurotransmitters involved in the act of vomiting.
  
  
  METHODS
  Zingiber officinale acetone fraction (ZO-ActFr) was investigated for attenuation of emesis induced by cisplatin in healthy pigeons. Neurotransmitters DA, 5HT and their metabolites DOPAC, HVA and 5HIAA were analyzed using High Performance Liquid Chromatography system coupled with electrochemical detector in area postrema, brain stem and intestine. Antiemetic effect of ZO-ActFr was correlated with central and intestinal neurotransmitters levels in pigeon.
  
  
  RESULTS
  Cisplatin (7 mg/kg i.v.) induced emesis without lethality upto the observation period. ZO-ActFr (25, 50 & 100 mg/kg) attenuated cisplatin induced emesis ~ 44.18%, 58.13% (P < 0.05) and 27.9%, respectively; the reference drug, metoclopramide (MCP; 30 mg/kg), produced ~ 48.83% reduction (P < 0.05). ZO-ActFr reduced (P < 0.05 - 0.001) 5-hydroxytryptamine (5HT) concentration in the area postrema, brain stem and intestine at 3(rd) hour of cisplatin administration, while at the 18(th) hour ZO treatments attenuated the dopamine upsurge (P < 0.001) caused by cisplatin in the area postrema and 5HT concentration (P < 0.01 - 0.001) in the brain stem and intestine. ZO treatments alone did not altered the basal neurotransmitters and their metabolites in the brain areas and intestine.
  
  
  CONCLUSIONS
  The behavioral study verify the antiemetic profile of ZO against cisplatin induced emesis in the pigeon, where central and peripheral neural evidences advocate the involvement of serotonergic mechanism at initial time point (3(rd) hr), while the later time point (18(th) hr) is associated with serotonergic and dopaminergic component in the mediation of its antiemetic effect.
authors.affiliation: Department of Pharmacy, University of Swabi, Swabi, Pakistan. Ihsanmkd@gmail.com.|Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. Ihsanmkd@gmail.com.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Ullah
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. Fazal_subhan@upesh.edu.pk.
authors.forename: Fazal
authors.initials: F
authors.lastname: Subhan
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir Lower, Pakistan. Ayazuop@gmail.com.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayaz
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. rehmatshah@upesh.edu.pk.|Hospital Pharmacist, Khyber Teaching Hospital, Peshawar, Pakistan. rehmatshah@upesh.edu.pk.
authors.forename: Rehmat
authors.initials: R
authors.lastname: Shah
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. gohar.pharmacist@gmail.com.
authors.forename: Gowhar
authors.initials: G
authors.lastname: Ali
authors.affiliation: National Institute of Health, Islamabad, Pakistan. Ikram_pharmacist@yahoo.com.
authors.forename: Ikram Ul
authors.initials: IU
authors.lastname: Haq
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. samiullah@upesh.edu.pk.
authors.forename: Sami
authors.initials: S
authors.lastname: Ullah
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects; D001522:Behavior, Animal; D002945:Cisplatin / Q000009:adverse effects*; D010856:Columbidae; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D020939:Zingiber officinale; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012701:Serotonin / Q000378:metabolism*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D010936:Plant Extracts; D012701:Serotonin; D002945:Cisplatin; D004298:Dopamine