Improved survival in intestinal ischemia by allopurinol not related to xanthine-oxidase inhibition.
Allopurinol, a xanthine-oxidase (XO) inhibitor, has been used to improve the resistance to ischemia with disappointing results that have been attributed to administration regimen of the drug. Our aim was to investigate the effect of different administration schedules of allopurinol on the survival in rats undergoing intestinal ischemia testing the blockade of XO. Intestinal ischemia was achieved by 90 min of clamping the superior mesenteric artery (SMA) close to its origin from the aorta. Three groups of animals were evaluated: A-group: only the allopurinol solvent was given; B-group: the full dose of allopurinol (100 mg/k b.w.) was given iv and C-group: the 75% dose was administered orally 24 hr before and the remaining 25% was administered 30 min before. Survival was evaluated at 48 hr and the blockade of XO was assayed by High Efficacy Liquid Chromatography (HELC) in homogenate of intestinal wall. Survival was only improved in the C-group (P = 0.02). Levels of hypoxanthine were significantly increased both in B-group and C-group (P = 0.003) when compared with the A-group. Levels of uric acid in B-group (P = 0.0003) and C-group (P = 0.0009) were significantly decreased with respect to A-group. That means that an effective blockade of XO is achieved whichever the regimen of administration. Allopurinol and oxypurinol levels were significantly increased (P = 0.05 and P = 0.008) in C-group when compared with B-group. We conclude that the protective effect of allopurinol on survival in intestinal ischemia in rats is not related to the blockade of XO but rather to the allopurinol and oxypurinol levels in intestinal wall.
Garcia Garcia
J
J
Facultad de Medicina, Universidad de Salamanca, Spain.
Martin Rollan
C
C
Refoyo Enrinquez
M A
MA
Holgado Madruga
M
M
Mariño Hernandez
E
E
Macias Nuñez
J F
JF
Gomez Alonso
A
A
D000493:Allopurinol / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D002853:Chromatography, Liquid; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000032:analysis; D007422:Intestines / Q000032:analysis / Q000098:blood supply*; D007511:Ischemia / Q000401:mortality; D010117:Oxypurinol / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014527:Uric Acid / Q000032:analysis; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D007042:Hypoxanthines; D014527:Uric Acid; D019271:Hypoxanthine; D000493:Allopurinol; D014969:Xanthine Oxidase; D010117:Oxypurinol