Bothropoides pauloensis venom effects on isolated perfused kidney and cultured renal tubular epithelial cells

• Published in: Toxicon (Oxford) Vol. 108; pp. 126 - 133
• Main Authors: Marinho, Aline D., Morais, Isabel C.O., Lima, Dânya B., Jorge, Antônio R.C., Jorge, Roberta J.B., Menezes, Ramon R.P.P.B., Mello, Clarissa P., Pereira, Gustavo J.S., Silveira, João A.M., Toyama, Marcos H., Orzáez, Mar, Martins, Alice M.C., Monteiro, Helena S.A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-12-2015
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Bothropoides pauloensis; Bothrops; Caspase 3 - metabolism; Caspase 7 - metabolism; Cell death; Cell Survival - drug effects; Crotalid Venoms - toxicity; Dogs; Epithelial Cells - drug effects; Flow Cytometry; Glomerular Filtration Rate - drug effects; In Vitro Techniques; Iodides; Kidney - drug effects; Kidney Tubules - drug effects; Kidneys; Madin Darby Canine Kidney Cells; Male; Membrane Potential, Mitochondrial - drug effects; Mortality; Rats, Wistar; Reactive Oxygen Species - metabolism; Renal effects; Sodium; Toxicity Tests; Transportation; Vascular Resistance - drug effects; Bothropoides pauloensis; Cell death; Renal effects
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2015.09.031

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.
•Bothropoides pauloensis venom induced apoptosis and necrosis in MDCK cells.•The venom induced caspases 3 and 7 activation, mitochondrial depolarization and ROS overproduction in MDCK cells.•B. pauloensis venom induced alterations in rat isolated kidney.