Allopurinol, oxidative stress and intestinal permeability in patients with cirrhosis: an open-label pilot study.
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.


OBJECTIVE
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.
Spahr
Laurent
L
Gastroenterology and Hepatology, University Hospital, Geneva, Switzerland. Laurent.Spahr@hcuge.ch
Bresson-Hadni
Solange
S
Amann
Pauline
P
Kern
Ilse
I
Golaz
Olivier
O
Frossard
Jean-Louis
JL
Hadengue
Antoine
A
D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy; D007422:Intestines / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects*; D010865:Pilot Projects
D004791:Enzyme Inhibitors; D008315:Malondialdehyde; D000493:Allopurinol