Induction of Hemoxygenase 1 prevents acute hepatic cholestasis produced by oxidative stress in the rat

Here,we studied the effect of HO1 induction andconsequent increase in endogenous levels of bilirubin (BR) on OS-induced cholestasis.Wistar rats were treated with Hemin (H)and biliary concentrations of BR were determined, finding that it increased 6-8h post i. p. injection of 20 mg/kg H (12.6±2.5 vs...

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Autores principales:	Martín, Pamela L., Ceccatto, Paula, Arriaga, Sandra Mónica María, Sánchez Pozzi, Enrique J., Roma, Marcelo Gabriel, Basiglio, Cecilia Lorena
Otros Autores:	Sociedad Argentina de Investigación Clínica
Formato:	conferenceObject documento de conferencia acceptedVersion
Lenguaje:	Inglés
Publicado:	Fundación Revista Medicina 2018
Materias:	HO1 Oxidative Stress Cholestasis Bilirrubin
Acceso en línea:	http://hdl.handle.net/2133/10510 http://hdl.handle.net/2133/10510
Aporte de:	Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario

id	I15-R121-2133-10510
record_format	dspace
institution	Universidad Nacional de Rosario
institution_str	I-15
repository_str	R-121
collection	Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language	Inglés
orig_language_str_mv	eng
topic	HO1 Oxidative Stress Cholestasis Bilirrubin
spellingShingle	HO1 Oxidative Stress Cholestasis Bilirrubin Martín, Pamela L. Ceccatto, Paula Arriaga, Sandra Mónica María Sánchez Pozzi, Enrique J. Roma, Marcelo Gabriel Basiglio, Cecilia Lorena Induction of Hemoxygenase 1 prevents acute hepatic cholestasis produced by oxidative stress in the rat
topic_facet	HO1 Oxidative Stress Cholestasis Bilirrubin
description	Here,we studied the effect of HO1 induction andconsequent increase in endogenous levels of bilirubin (BR) on OS-induced cholestasis.Wistar rats were treated with Hemin (H)and biliary concentrations of BR were determined, finding that it increased 6-8h post i. p. injection of 20 mg/kg H (12.6±2.5 vs 5.3±0.6 for vehicle, p<0.001;n=4). Oxidative cholestatic injury was induced by tert-butyl hydroperoxide (tBOOH,440 μmol/kg, i.p.) and bile flow (μl/min/g liver) was monitored finding that it decreased 4-6h post treatment (p<0.05 vs control; n=6). Pretreatment with Hcompletely prevented reduction of bile flow (1.65±0.04 and 1.30±0.03, respectively; p<0.01;n=6). Redox state was evaluated by measuring levels of lipid peroxidation (LP), oxidized glutathione/total glutathione ratio (GSSG/GSHt) and activity of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). We found that tBOOH caused an increase in LP (0.170±0.022nmol MDA/mg proteínvs C, 0.090±0.005nmol MDA/mg protein p<0.05;n=6) while pretreatment with H prevented this increase (0.082±0.001nmol MDA/mg protein 0.05 vstBOOH; n=6). GSSG/GSHt ratio increased after treatment with tBOOH (0.40±0.09 vs C, 0.14±0.12, p<0.05;n=6) while pretreatment with H prevented this increase (0.20±0.01, p<0.05;n=6). CAT and SOD activities were increased in tBOOH group (p<0.05 vs C, n=3, for both enzymes) while pre-treatment with H completely prevented these increases (p<0.05 vstBOOH,n=3). We also studied the function of two key hepatocanalicular transporters, Bsep and Mrp2, by determining biliary excretion of their specific substrates, bile salts (BS) and GSHt, respectively. Biliary excretion of both BS and GSHt decreased after treatment with tBOOH, and pretreatment with H prevented these decreases (p<0.05 vstBOOH, n=4).We conclude that induction of HO1 and consequent elevation of BR protect the liver from oxidative injury and contribute to limit the progression of cholestatic liver diseases concurring with OS.
author2	Sociedad Argentina de Investigación Clínica
author_facet	Sociedad Argentina de Investigación Clínica Martín, Pamela L. Ceccatto, Paula Arriaga, Sandra Mónica María Sánchez Pozzi, Enrique J. Roma, Marcelo Gabriel Basiglio, Cecilia Lorena
format	conferenceObject documento de conferencia acceptedVersion
author	Martín, Pamela L. Ceccatto, Paula Arriaga, Sandra Mónica María Sánchez Pozzi, Enrique J. Roma, Marcelo Gabriel Basiglio, Cecilia Lorena
author_sort	Martín, Pamela L.
title	Induction of Hemoxygenase 1 prevents acute hepatic cholestasis produced by oxidative stress in the rat
title_short	Induction of Hemoxygenase 1 prevents acute hepatic cholestasis produced by oxidative stress in the rat
title_full	Induction of Hemoxygenase 1 prevents acute hepatic cholestasis produced by oxidative stress in the rat
title_fullStr	Induction of Hemoxygenase 1 prevents acute hepatic cholestasis produced by oxidative stress in the rat
title_full_unstemmed	Induction of Hemoxygenase 1 prevents acute hepatic cholestasis produced by oxidative stress in the rat
title_sort	induction of hemoxygenase 1 prevents acute hepatic cholestasis produced by oxidative stress in the rat
publisher	Fundación Revista Medicina
publishDate	2018
url	http://hdl.handle.net/2133/10510 http://hdl.handle.net/2133/10510
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bdutipo_str	Repositorios
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Induction of Hemoxygenase 1 prevents acute hepatic cholestasis produced by oxidative stress in the rat

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