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

Morais IC, Pereira GJ, Orzáez M, Jorge RJ, Bincoletto C, Toyama MH, Monteiro HS, Smaili SS, Pérez-Payá E, Martins AM - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

LAAO-Bl induced alterations in rat isolated kidney.Effects of LAAO isolated of Bothrops leucurus venom on perfusion pressure (A), glomerular filtration rate (B), urinary flow (C), sodium, potassiun and chloride (D, E, F) tubular transport percentage. LAAO-Bl was added to the system 30 min after the beginning of each perfusion. The data represent the mean ± S.E.M of at least six independent experiments. *Significantly different from control group (p<0.05, one way ANOVA, Bonferroni post-test).
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pone.0132569.g004: LAAO-Bl induced alterations in rat isolated kidney.Effects of LAAO isolated of Bothrops leucurus venom on perfusion pressure (A), glomerular filtration rate (B), urinary flow (C), sodium, potassiun and chloride (D, E, F) tubular transport percentage. LAAO-Bl was added to the system 30 min after the beginning of each perfusion. The data represent the mean ± S.E.M of at least six independent experiments. *Significantly different from control group (p<0.05, one way ANOVA, Bonferroni post-test).

Mentions: Consistently with previous data, we used this experimental model in order to clarify the involvement of the LAAO-Bl in the renal effects of Bothrops leucurus venom. LAAO-Bl (10 μg/mL) increased perfusion pressure at 60 min and returned to normal at 90 min of perfusion (Fig 4A). There were no significant differences in the renal vascular resistance (RVR) after the infusion of LAAO-Bl when compared with control group. The glomerular filtration rate (GFR) decreased at 60 and 90 min of infusion and normalized at 120 min (Fig 4B). Urinary flow (UF) increased in the period of 120 min (Fig 4C). LAAO-Bl reduced significantly sodium, potassium and chloride tubular transport in the periods of 60, 90 and 120 min (Fig 4D–4F).


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

Morais IC, Pereira GJ, Orzáez M, Jorge RJ, Bincoletto C, Toyama MH, Monteiro HS, Smaili SS, Pérez-Payá E, Martins AM - PLoS ONE (2015)

LAAO-Bl induced alterations in rat isolated kidney.Effects of LAAO isolated of Bothrops leucurus venom on perfusion pressure (A), glomerular filtration rate (B), urinary flow (C), sodium, potassiun and chloride (D, E, F) tubular transport percentage. LAAO-Bl was added to the system 30 min after the beginning of each perfusion. The data represent the mean ± S.E.M of at least six independent experiments. *Significantly different from control group (p<0.05, one way ANOVA, Bonferroni post-test).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508040&req=5

pone.0132569.g004: LAAO-Bl induced alterations in rat isolated kidney.Effects of LAAO isolated of Bothrops leucurus venom on perfusion pressure (A), glomerular filtration rate (B), urinary flow (C), sodium, potassiun and chloride (D, E, F) tubular transport percentage. LAAO-Bl was added to the system 30 min after the beginning of each perfusion. The data represent the mean ± S.E.M of at least six independent experiments. *Significantly different from control group (p<0.05, one way ANOVA, Bonferroni post-test).
Mentions: Consistently with previous data, we used this experimental model in order to clarify the involvement of the LAAO-Bl in the renal effects of Bothrops leucurus venom. LAAO-Bl (10 μg/mL) increased perfusion pressure at 60 min and returned to normal at 90 min of perfusion (Fig 4A). There were no significant differences in the renal vascular resistance (RVR) after the infusion of LAAO-Bl when compared with control group. The glomerular filtration rate (GFR) decreased at 60 and 90 min of infusion and normalized at 120 min (Fig 4B). Urinary flow (UF) increased in the period of 120 min (Fig 4C). LAAO-Bl reduced significantly sodium, potassium and chloride tubular transport in the periods of 60, 90 and 120 min (Fig 4D–4F).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus