Allopurinol, oxidative stress and intestinal permeability in patients with cirrhosis: an open-label pilot study.
Résumé
BACKGROUND: Cirrhosis is associated with intestinal barrier failure, related in part to enterocytes oxidative damage via xanthine oxidase overactivity. Experimentally, allopurinol, a xanthine oxidase inhibitor, reduces enterocytes' damage and bacterial translocation. AIM: To assess the short-term effects of allopurinol on intestinal permeability, oxidative stress and endotoxin-dependent cytokines in patients with cirrhosis. METHODS: Nineteen patients with cirrhosis, in a stable condition (age: 56 years; Child A/B/C: 6/7/6; ascites: 12; alcoholic cirrhosis: 16/19; abstinence >2 weeks), were included. At baseline and day 10 of allopurinol 400 mg/day, intestinal permeability [lactulose/mannitol (Lac/Man) ratio test], oxidative stress (serum malondialdehyde), as well as TNF-soluble receptor-1, IL-6 and lipopolysaccharide-binding protein (which reflects exposition to endotoxin) were measured. RESULTS: Malondialdehyde decreased significantly (-23%, P<0.05), whereas no effects were seen on intestinal permeability and the endotoxin-associated systemic inflammatory response. At baseline, portal pressure correlated to the Lac/Man ratio (r=0.55, P<0.02). At day 10, changes in malondialdehyde correlated to changes in the Lac/Man ratio (r=0.51, P<0.05). CONCLUSIONS: A 10-day course of allopurinol in patients with cirrhosis is associated with a significant reduction in oxidative stress but no effect on intestinal permeability and inflammatory markers. Whether intestinal damage in cirrhosis can be accessible to antioxidant therapy requires further study.