Antioxidant role of heme oxygenase-1 in prehepatic portal hypertensive rats.
OBJECTIVE
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 mumol/kg body weight) 24 h before the end of the experiment entirely prevented all these effects. Pretreatment with Sn-protoporphyrin IX (Sn-PPIX) (100 mug/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.


CONCLUSIONS
These results suggest a beneficial role of HO-1 overexpression in prehepatic portal hypertensive rats.
Gonzales
Soledad
S
School of Pharmacy and Biochemistry, University of Buenos Aires 1113, Ciudad Autonoma de Buenos Aires, Republica Argentina.
Perez
Maria-Julia
MJ
Perazzo
Juan-C
JC
Tomaro
Maria-Lujan
ML
D000818:Animals; D000975:Antioxidants / Q000502:physiology*; D001663:Bilirubin / Q000494:pharmacology / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002248:Carbon Monoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006975:Hypertension, Portal / Q000201:enzymology* / Q000503:physiopathology; D008099:Liver / Q000098:blood supply / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; D002248:Carbon Monoxide; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1; D001663:Bilirubin