title: In vitro and in vivo genotoxic evaluation of Bothrops moojeni snake venom.
abstract: BACKGROUND
  Bothrops moojeni Hoge (Viperidae) venom is a complex mixture of compounds with therapeutic potential that has been included in the research and development of new drugs. Along with the biological activity, the pharmaceutical applicability of this venom depends on its toxicological profile.
  
  
  OBJECTIVE
  This study evaluates the cytotoxicity and genotoxicity of the Bothrops moojeni venom (BMV).
  
  
  METHODS
  The in vitro cytotoxicity and genotoxicity of a pooled sample of BMV was assessed by the MTT and Comet assay, respectively. Genotoxicity was also evaluated in vivo through the micronucleus assay.
  
  
  RESULTS
  BMV displayed a 50% cytotoxic concentration (CC50) on Vero cells of 4.09 µg/mL. Vero cells treated with 4 µg/mL for 90 min and 6 h presented significant (p < 0.05, ANOVA/Newman-Keuls test) higher DNA damage than the negative control in the Comet assay. The lower DNA damage found after 6 h compared with the 90 min treatment suggests a DNA repair effect. Mice intraperitoneally treated with BMV at 10, 30, or 80 µg/animal presented significant genotoxicity (p < 0.05, ANOVA/Newman-Keuls test) in relation to the negative control after 24 h of treatment. Contrary to the in vitro results, no DNA repair seemed to occur in vivo up to 96 h post-venom inoculation at a dose of 30 µg/animal.
  
  
  CONCLUSIONS
  The results show that BMV presents cyto- and genotoxicity depending on the concentration/dose used. These findings emphasize the importance of toxicological studies, including assessment of genotoxicity, in the biological activity research of BMV and/or in the development of BMV-derived products.
authors.affiliation: Laboratory of Mutagenesis, Universidade Católica Dom Bosco , Campo Grande - MS , Brazil .
authors.forename: Nathalia
authors.initials: N
authors.lastname: Novak Zobiole
authors.forename: Thiago
authors.initials: T
authors.lastname: Caon
authors.forename: Jéssica
authors.initials: J
authors.lastname: Wildgrube Bertol
authors.forename: Cintia Alves de Souza
authors.initials: CA
authors.lastname: Pereira
authors.forename: Brunna Mary
authors.initials: BM
authors.lastname: Okubo
authors.forename: Susana Elisa
authors.initials: SE
authors.lastname: Moreno
authors.forename: Francielle Tramontini Gomes de Sousa
authors.initials: FT
authors.lastname: Cardozo
mesh_terms: D000818:Animals; D017837:Bothrops; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D014709:Vero Cells; D014757:Viper Venoms / Q000633:toxicity*
chemical_list: D009153:Mutagens; D014757:Viper Venoms
keywords: Comet assay; MTT assay; cytotoxicity; genotoxicity; micronucleus assay