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

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

dc.citation.title	Medicina (Buenos Aires)	es
dc.citation.title	Reunión Conjunta de Sociedades de Biociencias (2017)
dc.contributor.organizer	Sociedad Argentina de Investigación Clínica	es
dc.creator	Martín, Pamela L.
dc.creator	Ceccatto, Paula
dc.creator	Arriaga, Sandra Mónica María
dc.creator	Sánchez Pozzi, Enrique J.
dc.creator	Roma, Marcelo Gabriel
dc.creator	Basiglio, Cecilia Lorena
dc.date.accessioned	2018-02-06T21:08:17Z
dc.date.available	2018-02-06T21:08:17Z
dc.date.issued	2017-11
dc.description.abstract	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.	eng
dc.description.fil	Fil: Martín, Pamela L. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); Argentina.	es
dc.description.fil	Fil: Ceccatto, Paula. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); Argentina.	es
dc.description.fil	Fil: Arriaga, Sandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; Argentina.	es
dc.description.fil	Fil: Sánchez Pozzi, Enrique J. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); Argentina.	es
dc.description.fil	Fil: Roma, Marcelo Gabriel. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); Argentina.	es
dc.description.fil	Fil: Basiglio, Cecilia Lorena. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica. Instituto de Fisiología Experimental (IFISE-CONICET); Argentina.	es
dc.format	application/octet-stream
dc.identifier.uri	http://hdl.handle.net/2133/10510
dc.language.iso	eng	es
dc.publisher	Fundación Revista Medicina	es
dc.rights	openAccess	es
dc.rights.holder	Universidad Nacional de Rosario	es
dc.rights.holder	Martín, Pamela L.	es
dc.rights.holder	Ceccatto, Paula	es
dc.rights.holder	Arriaga, Sandra Mónica María	es
dc.rights.holder	Sánchez Pozzi, Enrique J.	es
dc.rights.holder	Roma, Marcelo Gabriel	es
dc.rights.holder	Basiglio, Cecilia Lorena	es
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/2.5/ar/	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/2.5/ar/	*
dc.subject	HO1	es
dc.subject	Oxidative Stress	es
dc.subject	Cholestasis	es
dc.subject	Bilirrubin	es
dc.title	Induction of Hemoxygenase 1 prevents acute hepatic cholestasis produced by oxidative stress in the rat	es
dc.type	conferenceObject
dc.type	documento de conferencia
dc.type	acceptedVersion
dc.type.collection	comunicaciones
dc.type.version	acceptedVersion	es