title: Determination of Toxic Activities in Bothrops spp. Snake Venoms Using Animal-Free Approaches: Correlation Between In Vitro Versus In Vivo Assays.
abstract: The main purpose of this study is to investigate the in vitro toxic effects of 5 Bothrops spp. snake venoms, which are part of the antigenic mixture used for the production of Brazilian antivenom, and evaluate their correlation with the in vivo toxic activities of Bothrops spp. venoms. The correlation analysis could be helpful for the replacement of living animals experimentation for in vitro bioassay. Cytotoxicity, L-amino acid oxidase (LAAO), proteolitic (serine and metalloproteinase), hyaluronidase (Hyal), and phospholipase A2 (PLA2) activities were estimated and the correlation coefficient was determined for each activity in relation to lethality, edema, hemorrhage and necrosis induced in live animals by B. jararaca, B. alternatus, B. jararacussu, B. neuwiedi, and B. moojeni venoms. The lethal activity in mice was highly related to Hyal activity (r = 0.94, p < .05), edema related to PLA2 activity (r = 0.94, p < .05), whereas the necrotizing activity showed high correlation with LAAO activity (r = 0.83, p < .05). A very significant correlation between in vitro cytotoxicity and LAAO activities was also observed (r = 0.97, p < .05).
authors.affiliation: *Departamento de Bioquímica e Imunologia, and.
authors.forename: Letícia Lopes
authors.initials: LL
authors.lastname: de Souza
authors.affiliation: *Departamento de Bioquímica e Imunologia, and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Stransky
authors.affiliation: *Departamento de Bioquímica e Imunologia, and.
authors.forename: Clara
authors.initials: C
authors.lastname: Guerra-Duarte
authors.affiliation: *Departamento de Bioquímica e Imunologia, and.
authors.forename: Ana
authors.initials: A
authors.lastname: Flor-Sá
authors.affiliation: *Departamento de Bioquímica e Imunologia, and.
authors.forename: Francisco Santos
authors.initials: FS
authors.lastname: Schneider
authors.affiliation: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, CEP:31270-901, Brazil.
authors.forename: Evanguedes
authors.initials: E
authors.lastname: Kalapothakis
authors.affiliation: *Departamento de Bioquímica e Imunologia, and olortegi@icb.ufmg.br.
authors.forename: Carlos
authors.initials: C
authors.lastname: Chávez-Olórtegui
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D016824:Antigens, Human Platelet / Q000187:drug effects / Q000378:metabolism; D000997:Antivenins / Q000494:pharmacology; D017837:Bothrops; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003435:Crotalid Venoms / Q000633:toxicity*; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D050830:L-Amino Acid Oxidase / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D059748:Proteolysis / Q000187:drug effects
chemical_list: D016824:Antigens, Human Platelet; D000997:Antivenins; D003435:Crotalid Venoms; D050830:L-Amino Acid Oxidase; D006821:Hyaluronoglucosaminidase
keywords: Bothrops venoms; cytotoxic activity; hyaluronidase activity; in vitro assays; lethal activity