Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 14, 2006; 12(26): 4149-4155
Published online Jul 14, 2006. doi: 10.3748/wjg.v12.i26.4149
Antioxidant role of heme oxygenase-1 in prehepatic portal hypertensive rats
Soledad Gonzales, María Julia Pérez, Juan C Perazzo, María Luján Tomaro
Soledad Gonzales, María Luján Tomaro, Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires 1113, Argentina
María Julia Pérez, Juan C Perazzo, Laboratory of Portal Hypertension, Department of Biological Science, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires 1113, Argentina
Co-first-authors: María Julia Pérez, Juan C Perazzo
Supported by Grants from the University of Buenos Aires, Buenos Aires, Argentina and CONICET, Buenos Aires, Argentina
Correspondence to: Professor Juan C Perazzo, Laboratory of Portal Hypertension, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, CP 1113, Ciudad Autónoma de Buenos Aires, Republica Argentina. jperazzo@ffyb.uba.ar
Received: January 25, 2006
Revised: February 10, 2006
Accepted: February 18, 2006
Published online: July 14, 2006
Abstract

AIM: To study the effect of bilirubin on the oxidative liver status and the activity and expression of heme oxygenase-1 (HO-1) in rat liver injury induced by prehepatic portal hypertension.

METHODS: Wistar male rats, weighing 200-250 g, were divided at random into two groups: one group with prehepatic portal hypertension (PH) induced by regulated prehepatic portal vein ligation (PPVL) and the other group corresponded to sham operated rats. Portal pressure, oxidative stress parameters, antioxidant enzymes, HO-1 activity and expression and hepatic sinusoidal vasodilatation were measured.

RESULTS: In PPVL rats oxidative stress was evidenced by a marked increase in thiobarbituric acid reactive substances (TBARS) content and a decrease in reduced glutathione (GSH) levels. The activities of liver antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were also diminished while activity and expression of HO-1 were enhanced. Administration of bilirubin (5 μmol/kg body weight) 24 h before the end of the experiment entirely prevented all these effects. Pretreatment with Sn-protoporphyrin IX (Sn-PPIX) (100 μg/kg body weight, i.p.), a potent inhibitor of HO, completely abolished the oxidative stress and provoked a slight decrease in liver GSH levels as well as an increase in lipid peroxidation. Besides, carbon monoxide, another heme catabolic product, induced a significant increase in sinusoidal hepatic areas in PPVL group. Pretreatment of PPVL rats with Sn-PPIX totally prevented this effect.

CONCLUSION: These results suggest a beneficial role of HO-1 overexpression in prehepatic portal hypertensive rats.

Keywords: Heme oxygenase-1, Portal hypertensive rats, Liver oxidative stress