title: Bothropoides pauloensis venom effects on isolated perfused kidney and cultured renal tubular epithelial cells.
abstract: Snake envenomation (Bothrops genus) is common in tropical countries and acute kidney injury is one of the complications observed in Bothrops snakebite with relevant morbidity and mortality. Here, we showed that Bothropoides pauloensis venom (BpV) decreased cell viability (IC50 of 7.5 μg/mL). Flow cytometry with annexin V and propidium iodide showed that cell death occurred predominantly by apoptosis and late apoptosis, through caspases 3 and 7 activation, mitochondrial membrane potential collapse and ROS overproduction. BpV reduced perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate, percentage of sodium, chloride or potassium tubular transportation. These findings demonstrated that BpV cytotoxicity on renal epithelial cells might be responsible for the nephrotoxicity observed in isolated kidney.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, 60430-270, Fortaleza, Ceará, Brazil. Electronic address: alinediogo_marinho@hotmail.com.
authors.forename: Aline D
authors.initials: AD
authors.lastname: Marinho
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, 60430-270, Fortaleza, Ceará, Brazil.
authors.forename: Isabel C O
authors.initials: IC
authors.lastname: Morais
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Dânya B
authors.initials: DB
authors.lastname: Lima
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, 60430-270, Fortaleza, Ceará, Brazil.
authors.forename: Antônio R C
authors.initials: AR
authors.lastname: Jorge
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, 60430-270, Fortaleza, Ceará, Brazil.
authors.forename: Roberta J B
authors.initials: RJ
authors.lastname: Jorge
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, 60430-270, Fortaleza, Ceará, Brazil.
authors.forename: Ramon R P P B
authors.initials: RR
authors.lastname: Menezes
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Clarissa P
authors.initials: CP
authors.lastname: Mello
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil.
authors.forename: Gustavo J S
authors.initials: GJ
authors.lastname: Pereira
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, 60430-270, Fortaleza, Ceará, Brazil.
authors.forename: João A M
authors.initials: JA
authors.lastname: Silveira
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 Medicinal Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Orzáez
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Alice M C
authors.initials: AM
authors.lastname: Martins
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, 60430-270, Fortaleza, Ceará, Brazil.
authors.forename: Helena S A
authors.initials: HS
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017837:Bothrops; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003435:Crotalid Venoms / Q000633:toxicity*; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects; D005434:Flow Cytometry; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects*; D007684:Kidney Tubules / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018675:Toxicity Tests; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D003435:Crotalid Venoms; D017382:Reactive Oxygen Species; D053148:Caspase 3; D053179:Caspase 7
keywords: Bothropoides pauloensis; Cell death; Renal effects