In the
hepatopulmonary syndrome (HPS), a common complication of
liver cirrhosis, pulmonary endothelial
endothelin B (ETB) receptor overexpression, enhanced endothelial
nitric oxide (
NO) synthase (eNOS)-derived NO production, and increases in pulmonary inducible
NO synthase (iNOS) and
heme oxygenase (HO-1) are important factors in the development of vasodilatation. These changes may be influenced by redox-sensitive signaling pathways, including
nuclear factor-kappaB (
NF-kappaB). In this study, our aim was to evaluate the effects of the
flavonoid antioxidant quercetin on the development of HPS in rats with common bile duct
ligation (CBDL). Rats were divided into the following 4 groups: rats subjected to CBDL,
Sham (rats subjected to simulated CBDL),
quercetin-treated
sham, and
quercetin-treated CBDL.
Quercetin (50 mg/kg) was administered for 2 wk starting on d 14 after surgery. Increased NO production, overexpression of iNOS, eNOS, HO-1, and ETB-receptor and activation of
NF-kappaB were observed in lung of CBDL rats.
Quercetin inhibited oxidative stress,
NF-kappaB activation, and the expression of different pulmonary mediators involved in HPS.
Quercetin also ameliorated liver injury and reduced the expression of hepatic
endothelin-1 and HO-1 in untreated cirrhotic rats. Our findings suggest that
quercetin administered after the onset of hepatic injury significantly ameliorates pulmonary complications in CBDL rats and that limitation of cirrhotic evolution contributes to this effect.