title: Pre-treatment of BALB/c mice with a centrally acting serotonin antagonist (cyproheptadine) reduces mortality from Boophone disticha poisoning.
abstract: BACKGROUND
  Crude extracts of Boophone disticha are used in Southern African traditional medical practice for the management of various illnesses and conditions and have also been abused for their claimed euphoric and hallucinogenic effects. Unfortunately, ingestion of Boophone disticha has resulted in toxicity and death. The results of a recent acute toxicity study in a rat model insinuated that central nervous system (CNS) serotonin overdrive could be the cause of toxicity in B. disticha poisoning. The present work sought to test that hypothesis by investigating whether pre-treatment of B. disticha poisoned BALB/c mice with the CNS acting serotonin antagonist, cyproheptadine, has a dose-dependent protective effect on toxicity and mortality.
  
  
  METHODS
  A hydroethanolic extract of B. disticha was used in all the experiments. Five groups each with 10 animals were constituted as follows; a negative control group (received 10 ml/kg Normal Saline), a positive control group (received 375 mg/kg of the B. disticha extract), and three test groups each receiving 10 mg/kg, 15 mg/kg and 20 mg/kg cyproheptadine intraperitoneally 15 minutes before oral gavage administration of 375 mg/kg B. disticha extract respectively. The Functional Observational Battery was used to evaluate neurobehavioral and physiological changes resulting from toxicity of the plant extract. The mice were then placed in an open field for another five minutes and the number of rearings and border crossings were counted and recorded. Gait abnormalities, involuntary motor movements, mobility, arousal and stereotypical behavior were also scored according to predefined criteria. All open field investigations were recorded electronically using a LABTEC Webcam(®) and results were later analysed and recorded by one of the group members. All results were entered on data collection forms. Time to death (survival time) was considered as the time period from dosage with Boophone disticha to time of death. The study follow up period was 7 days and those mice that were alive at the end of the 7 day follow-up period were considered as having survived the poisoning episode. The Kaplan Meier plot and Log-rank test were used to compare differences in mortality and median time to death for mice in the 5 treatment groups.
  
  
  RESULTS
  We found that cyproheptadine pre-treatment led to a dose-dependent decrease in mortality from 80% in the group not pre-treated with cyproheptadine, to 30% in the 15 and 20 mg/kg cyproheptadine pre-treated groups (n = 10 per group, p < 0.05). There was also a dose-dependent increase in median survival times amongst the groups (p < 0.0001). Pre-treatment with cyproheptadine also resulted in a decrease of other toxic symptoms associated with Boophone disticha.
  
  
  CONCLUSIONS
  We conclude that cyproheptadine has a dose-dependent protective effect on mortality and toxicity produced by exposure to Boophone disticha in our mouse model of toxicity.
authors.affiliation: Drug and Toxicology Information Service (DaTIS), School of Pharmacy, College of Health Sciences, University of Zimbabwe, Avondale, Harare, Zimbabwe.
authors.forename: M
authors.initials: M
authors.lastname: Mutseura
authors.forename: D
authors.initials: D
authors.lastname: Tagwireyi
authors.forename: L L
authors.initials: LL
authors.lastname: Gadaga
mesh_terms: D000353:Africa, Southern; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003533:Cyproheptadine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D019669:Embryophyta / Q000737:chemistry* / Q000254:growth & development; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000517:prevention & control; D006213:Hallucinogens / Q000037:antagonists & inhibitors* / Q000506:poisoning; D008297:Male; D016488:Medicine, African Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000503:physiopathology / Q000517:prevention & control*; D010936:Plant Extracts / Q000037:antagonists & inhibitors* / Q000506:poisoning; D018517:Plant Roots / Q000737:chemistry / Q000254:growth & development; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D019956:Stereotypic Movement Disorder / Q000209:etiology / Q000517:prevention & control; D016019:Survival Analysis; D015030:Zimbabwe
chemical_list: D006213:Hallucinogens; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012702:Serotonin Antagonists; D003533:Cyproheptadine