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Allopurinol, oxidative stress and intestinal permeability in patients with cirrhosis: an open‐label pilot study
Author(s) -
Spahr Laurent,
BressonHadni Solange,
Amann Pauline,
Kern Ilse,
Golaz Olivier,
Frossard JeanLouis,
Hadengue Antoine
Publication year - 2007
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2006.01382.x
Subject(s) - malondialdehyde , xanthine oxidase , cirrhosis , intestinal permeability , allopurinol , oxidative stress , medicine , lactulose , xanthine oxidase inhibitor , gastroenterology , pharmacology , endocrinology , chemistry , biochemistry , enzyme
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.