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1.
Toxicon ; 108: 126-33, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26410111

RESUMO

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.


Assuntos
Bothrops , Venenos de Crotalídeos/toxicidade , Túbulos Renais/efeitos dos fármacos , Rim/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 7/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cães , Células Epiteliais/efeitos dos fármacos , Citometria de Fluxo , Taxa de Filtração Glomerular/efeitos dos fármacos , Técnicas In Vitro , Células Madin Darby de Rim Canino , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade , Resistência Vascular/efeitos dos fármacos
2.
PLoS One ; 10(7): e0132569, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26193352

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 µg/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.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Apoptose/efeitos dos fármacos , Bothrops , Venenos de Crotalídeos/farmacologia , Rim/efeitos dos fármacos , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular , Rim/metabolismo , Rim/patologia , Necrose/metabolismo , Necrose/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo
3.
Toxicon ; 88: 107-14, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24874890

RESUMO

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.


Assuntos
Bothrops , Venenos de Crotalídeos/toxicidade , Túbulos Renais/efeitos dos fármacos , Animais , Caspases/metabolismo , Cães , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Túbulos Renais/patologia , Células Madin Darby de Rim Canino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Necrose , Espécies Reativas de Oxigênio/metabolismo
4.
J Exp Ther Oncol ; 9(3): 249-53, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22070057

RESUMO

BACKGROUND: Animal venoms are complex mixtures of proteins and non proteins components with several biological activities. Snake venoms represent an essentially unexplored source of bioactive compounds that may cure disease conditions which do not respond to currently available therapies. These venoms possess many pharmacological activities, as cytotoxic and/or lytic effects on tumor cells in vitro. Herein, were investigated the in vitro cytotoxicity of three Bothrops venoms in tumor cell lines. METHODS: Cytotoxic effect was evaluated in HCT-8 (colon - human), SF-295 (nervous system - human), HL-60 (human leukemia) and MDAMB-435 (breast - human). Cell density and membrane integrity were determined by the exclusion of propidium iodide. To determine whether Bothrops venoms treated cells were undergoing an apoptotic and/ or necrosis death, phosphatidylserine (PS) externalization was measured after the incubation with the venom. RESULTS: Botrhops venons showed significant cytotoxcity against all cell lines in study. Cell density and membrane integrity were determined by the exclusion of propidium iodide. The Bothrops venoms reduced the cell number and revealed the presence of a necrotic population when the cells was exposed to the B. pauloensis B. diporus and B. pirajai venoms. To determine whether Bothrops venoms treated cells were undergoing an apoptotic and/or necrosis death, PS externalization was measured after the incubation with the venom and it was observed necrotic and apoptotic cells. CONCLUSIONS: All Bothrops venoms tested showed cytotoxicity against tumor cell lines through inducing of necrosis and apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Bothrops , Linhagem Celular Tumoral/efeitos dos fármacos , Venenos de Crotalídeos/farmacologia , Animais , Neoplasias da Mama , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo , Feminino , Células HL-60 , Humanos , Necrose , Neoplasias do Sistema Nervoso
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