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Nutrition and Disease

Quercetin Administration Ameliorates Pulmonary Complications of Cirrhosis in Rats^1–3,

⁴ Laboratory of Experimental Hepatology and Physiology, Porto Alegre Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035903, Brazil; ⁵ Laboratory of Oxidative Stress, Lutheran University of Brazil, Canoas 92425900, Brazil; and ⁶ Institute of Biomedicine, University of León and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, León 24071 Spain

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-B (NF-B). 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-B were observed in lung of CBDL rats. Quercetin inhibited oxidative stress, NF-B 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.

^* To whom correspondence should be addressed. E-mail: jgonga{at}unileon.es.

Manuscript received 2 February 2009. Initial review completed 9 March 2009. Revision accepted 14 May 2009.

Published online 3 June 2009.