Genotoxic effect of Bothrops snake venoms and isolated toxins on human lymphocyte DNA

Abstract

In the present study, micronucleus with cytokinesis blocking and comet assays were used to evaluate the genotoxic potential of Bothrops jararacussu, Bothrops atrox, Bothrops moojeni, Bothrops alternatus (Rhinocerophis alternatus) and Bothrops brazili snake venoms, and also of some isolated toxins (MjTX-I, BthTX-I and II myotoxins, BjussuMP-II metalloprotease, and BatxLAAO l-amino acid oxidase) on human lymphocytes. Significant DNA damages were observed, indicating genotoxic potential after exposure of the lymphocytes to the toxins BthTX-I, II and BatxLAAO compared to untreated and Cisplatin-treated controls, which were able to induce greater formation of micronuclei. B. brazili, B. jararacussu and B. atrox crude venoms also presented genotoxic potential, and the latter two induced DNA breakage 5 times more often than in normal environmental conditions (control without treatment). B. jararacussu venom and its isolated toxins, as well as an LAAO from B. atrox, were able to cause lymphocyte DNA breakage in the comet test with more than 85% damage levels. The DNA damage evaluation allows a widening of the toxic-pharmacological characterization of snake venoms and their toxins and also contributes to the understanding of the mechanisms of action of these molecules in several human pathologies.

In vitroandin vivogenotoxic evaluation ofBothrops moojenisnake venom

“…Moreover, cells treated with different concentrations of BMV (4, 2, or 1 mg/mL) or H 2 O 2 (positive control) for 90 min had higher damage frequency than those treated for 6 h. This effect might be associated with cellular DNA repair mechanisms, as described by Purschke et al (2002), who observed that human fibroblasts displayed repair ability of hydrogen peroxide-induced DNA damage. Differing from our results, Marcussi et al (2013) found no significant genotoxicity for BMV at 7.5 mg/mL by the Comet assay. The diverse obtained results might be related to the differences in the experimental parameters.…”

“…The diverse obtained results might be related to the differences in the experimental parameters. Marcussi et al (2013) used a different cell line (human lymphocytes) incubated with the venom for 4 h. In this work, we analyzed the in vitro genotoxicity in Vero cells treated for 90 min and 6 h.…”

l-amino acid oxidase from Bothrops marajoensis causes nephrotoxicity in isolated perfused kidney and cytotoxicity in MDCK renal cells

“…Re-oxidation of FAD by molecular O 2 results, in turn, in the production of keto acids, ammonia and hydrogen peroxide (H 2 O 2 ) (Moustafa et al, 2006;Tan and Fung, 2009). The generated H 2 O 2 can induce (St abeli et al, 2004) and inhibit platelet aggregation (Sakurai et al, 2003;Naumann et al, 2011), induce endothelial injury (Du and Clemetson, 2002) and are involved in the apoptosis of various cell cells due to DNA damage Marcussi et al, 2013;Lee et al, 2014). Bothrops marajoensis is found in the plains of Maraj o Island in the State of Par a, Brazil and possibly along the coastal lowlands of the Amazon Delta, in Brazil (Cavalcante et al, 2011).…”

Snake venom L-amino acid oxidases: an overview on their antitumor effects

“…Apoptotic processes and cell damage are some of the action mechanisms proposed for many SV-LAAOs, suggesting that these enzymes could be used as models for the development of more effective chemotherapeutic and other antitumor agents [2,13,23,24]. …”