In vitroandin vivogenotoxic evaluation ofBothrops moojenisnake venom

Abstract

Context: 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). Material and 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 (CC 50 ) on Vero cells of 4.09 mg/mL. Vero cells treated with 4 mg/mL for 90 min and 6 h presented significant (p50.05, ANOVA/NewmanKeuls 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 mg/animal presented significant genotoxicity (p50.05, 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 mg/animal. Discussion and conclusion: 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.

A Review on Genotoxic and Genoprotective Effects of Biologically Active Compounds of Animal Origin

“…The venom of Bothrops moojeni , popularly known as “caiçaca” or “jararacão”, at a concentration close to IC 50 4 (μg/mL) produced DNA breaks in Vero cells in vitro ; the breaks were repaired in 6 h, and the alkaline comet assay was used. However, when injected into Swiss mice, the venom produced non-reparable lesions [ 85 ]. Bothrops brazili , Bothrops jararacussu and Bothrops atrox crude venoms also presented genotoxic potential in human lymphocytes, and the latter two increased DNA breakage 5-fold compared with the negative controls in the alkaline comet assay [ 86 ].…”