title: Synthetic and natural antioxidants attenuate cisplatin-induced vomiting.
abstract: Synthetic and natural antioxidants including Bacopa monnieri (L.) Pennell (Scrophulariaceae) which also possess anti-dopaminergic properties, have been proposed to be useful for emetogenic chemotherapy. In this study, synthetic [N-(2-mercaptopropionyl) glycine (MPG), vitamin C (Vit-C)] and natural [grape seed proanthocyanidin (GP), B. monnieri n-butanolic fraction (BM-ButFr)] antioxidants and their combinations were evaluated against cisplatin-induced emesis in pigeons during a 24 h observation period.
  
  
  
  Emesis was induced using cisplatin (7.0 mg/kg, i.v). MPG (10, 20, 30 mg/kg), Vit-C (100, 200, 300 mg/kg), GP (50, 100, 150 mg/kg) and BM-ButFr (5, 10, 20 mg/kg) and their combinations were administered i.m., 15 min before cisplatin administration. The number of vomiting bouts, retching, emetic latency and % weight loss were recorded to assess antiemetic potential. Antioxidant activity was evaluated by the DPPH free radical scavenging assay (FRSA).
  
  
  
  Significant attenuation of vomiting bouts, retching, % weight loss along with an increase in latency was produced by all the antioxidants and their combinations compared to cisplatin alone and this is the first report of this activity of GP in pigeons. Low EC50values in the FRSA for MPG (67.66 μg/mL), Vit-C (69.42 μg/mL), GP (6.498 μg/mL) and BM-ButFr (55.61 μg/mL) compared to BHT standard (98.17 μg/mL) demonstrated their radical scavenging capacity. Correlation between the antioxidant activity and antiemetic efficacy disclosed a high degree of correlation for the tested antioxidants.
  
  
  
  The selected synthetic and natural antioxidants and their combinations were able to attenuate cisplatin-induced vomiting, which correlated with their potent in vitro antioxidant activity.
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Javaid
authors.initials: J
authors.lastname: Alam
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan. fazal_subhan@upesh.edu.pk.
authors.forename: Fazal
authors.identifier: 0000-0002-1976-8314
authors.initials: F
authors.lastname: Subhan
authors.affiliation: Department of Pharmacy, University of Swabi, Swabi, Pakistan.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Ullah
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Gowhar
authors.initials: G
authors.lastname: Ali
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, CF103NB, UK.
authors.forename: Robert D E
authors.initials: RD
authors.lastname: Sewell
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000302:isolation & purification / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000302:isolation & purification / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000302:isolation & purification / Q000627:therapeutic use; D034681:Bacopa; D002945:Cisplatin / Q000633:toxicity*; D010856:Columbidae; D005260:Female; D056604:Grape Seed Extract / Q000302:isolation & purification / Q000627:therapeutic use; D008297:Male; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use*; D044945:Proanthocyanidins / Q000302:isolation & purification / Q000627:therapeutic use; D008625:Tiopronin / Q000302:isolation & purification / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D000975:Antioxidants; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D010936:Plant Extracts; D044945:Proanthocyanidins; D008625:Tiopronin; D001205:Ascorbic Acid; D002945:Cisplatin
keywords: Antiemetic; Bacopa monnieri; Chemotherapy; Correlation; Emesis; Free radical scavenging assay; Grape seed proanthocyanidin; N-(2-mercaptopropionyl) glycine; Vitamin C