L-Aminoacid Oxidase from Bothrops leucurus Venom Induces Nephrotoxicity via Apoptosis and Necrosis

Autor(es)

Morais, Isabel C. O. ^[1] ; Pereira, Gustavo J. S. ^[2] ; Orzaez, M. ^[3] ; Jorge, Roberta J. B. ^[1] ; Bincoletto, Claudia ^[2] ; Toyama, Marcos H. ^[4] ; Monteiro, Helena S. A. ^[1] ; Smaili, Soraya S. ^[2] ; Perez-Paya, Enrique ^[3] ; Martins, Alice M. C. ^[5]

Afiliação do(s) autor(es)

^[1] Univ Fed Ceara, Fac Med, Dept Physiol & Pharmacol, Fortaleza, Ceara - Brazil

^[2] Univ Fed Sao Paulo, Dept Pharmacol, Sao Paulo - Brazil

^[3] Ctr Invest Principe Felipe, Dept Med Chem, Valencia - Spain

^[4] Univ Estadual Paulista, Sao Vicente Unit, Sao Paulo - Brazil

^[5] Univ Fed Ceara, Dept Clin & Toxicol Anal, Fortaleza, Ceara - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 7 JUL 20 2015.
• Citações Web of Science: 11

Resumo

Acute renal failure is a common complication caused by Bothrops viper envenomation. In this study, the nefrotoxicity of a main component of B. leucurus venom called L-aminoacid oxidase (LAAO-Bl) was evaluated by using tubular epithelial cell lines MDCK and HK-2 and perfused kidney from rats. LAAO-Bl exhibited cytotoxicity, inducing apoptosis and necrosis in MDCK and HK-2 cell lines in a concentration-dependent manner. MDCK apoptosis induction was accompanied by Ca2+ release from the endoplasmic reticulum, reactive oxygen species (ROS) generation and mitochondrial dysfunction with enhanced expression of Bax protein levels. LAAO-Bl induced caspase-3 and caspase-7 activation in both cell lines. LAAO-Bl (10 mu g/mL) exerts significant effects on the isolated kidney perfusion increasing perfusion pressure and urinary flow and decreasing the glomerular filtration rate and sodium, potassium and chloride tubular transport. Taken together our results suggest that LAAO-Bl is responsible for the nephrotoxicity observed in the envenomation by snakebites. Moreover, the cytotoxic of LAAO-Bl to renal epithelial cells might be responsible, at least in part, for the nephrotoxicity observed in isolated kidney. (AU)

• Processo FAPESP: 08/11515-3 - Mecanismos de sinalização de cálcio intracelular na Modulação da Apoptose e da Autofagia
• Beneficiário: Soraya Soubhi Smaili
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/51647-6 - Atividade antitumoral de compostos paladaciclos em linhagem celular estabelecida de osteossarcoma humano: vias de sinalizacao de calcio na morte celular programada e autofagia.
• Beneficiário: Claudia Bincoletto Trindade
• Modalidade de apoio: Auxílio à Pesquisa - Regular