title: Bothropoides insularis venom cytotoxicity in renal tubular epithelia cells.
abstract: Bothropoides insularis (jararaca-ilhoa) is a native endemic snake limited to the specific region of Queimada Island, on São Paulo coast. Several local and systemic effects have been described due to envenomation caused by it, such as edema, tissue necrosis, hemorrhage and acute renal failure. Our previous studies have shown that Bothropoides insularis venom (BinsV) demonstrated important functional and morphologic alterations in rat isolated kidney, especially decrease in tubular electrolyte transport, osmotic clearance and tubular necrosis. In order to elucidate the direct nephrotoxicity mechanism, the aim of the present study was to investigate BinsV cytotoxicity effect on renal epithelial cells. The treatment with BinsV over MDCK culture decreased cell viability in all concentrations tested with IC50 of 9 μg/mL. BinsV was able to induce membrane rupture and cell death with phosphatidilserine externalization. Furthermore, BinsV induced ROS overproduction and mitochondrial membrane potential collapse, as well as Bax translocation and caspases 3 and 7 expression. Therefore, these events might be responsible by BinsV-induced cell death caused by mitochondrial dysfunction and ROS overproduction in the direct cytotoxicity process.
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza 60430370, Ceará, Brazil.
authors.forename: Clarissa P
authors.initials: CP
authors.lastname: Mello
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Isabel C O
authors.initials: IC
authors.lastname: Morais
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Ramon R P P B
authors.initials: RR
authors.lastname: Menezes
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP/EPM), Brazil.
authors.forename: Gustavo J S
authors.initials: GJ
authors.lastname: Pereira
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza 60430370, Ceará, Brazil.
authors.forename: Alba F C
authors.initials: AF
authors.lastname: Torres
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza 60430370, Ceará, Brazil.
authors.forename: Dânya B
authors.initials: DB
authors.lastname: Lima
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza 60430370, Ceará, Brazil.
authors.forename: Ticiana P
authors.initials: TP
authors.lastname: Pereira
authors.affiliation: São Vicente Unit, Paulista Coastal Campus, São Paulo State University (UNESP), São Paulo, Brazil.
authors.forename: Marcos H
authors.initials: MH
authors.lastname: Toyama
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Helena S A
authors.initials: HS
authors.lastname: Monteiro
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP/EPM), Brazil.
authors.forename: Soraya S
authors.initials: SS
authors.lastname: Smaili
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza 60430370, Ceará, Brazil. Electronic address: martinsalice@gmail.com.
authors.forename: Alice M C
authors.initials: AM
authors.lastname: Martins
mesh_terms: D000818:Animals; D017837:Bothrops; D020169:Caspases / Q000378:metabolism; D003435:Crotalid Venoms / Q000633:toxicity*; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D061985:Madin Darby Canine Kidney Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009336:Necrosis; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D003435:Crotalid Venoms; D017382:Reactive Oxygen Species; D020169:Caspases
keywords: Bothropoides insularis venom; Cell death; Nephrotoxicity