Improved survival in intestinal ischemia by allopurinol not related to xanthine-oxidase inhibition. 1990

J Garcia Garcia, and C Martin Rollan, and M A Refoyo Enrinquez, and M Holgado Madruga, and E Mariño Hernandez, and J F Macias Nuñez, and A Gomez Alonso
Facultad de Medicina, Universidad de Salamanca, Spain.

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.

UI MeSH Term Description Entries
D007042 Hypoxanthines Purine bases related to hypoxanthine, an intermediate product of uric acid synthesis and a breakdown product of adenine catabolism.
D007422 Intestines The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE. Intestine
D007511 Ischemia A hypoperfusion of the BLOOD through an organ or tissue caused by a PATHOLOGIC CONSTRICTION or obstruction of its BLOOD VESSELS, or an absence of BLOOD CIRCULATION. Ischemias
D010117 Oxypurinol A xanthine oxidase inhibitor. Alloxanthine,Oxipurinol
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D000493 Allopurinol A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms. Allohexal,Allohexan,Alloprin,Allopurin,Allorin,Allpargin,Allural,Apulonga,Apurin,Atisuril,Bleminol,Caplenal,Capurate,Cellidrin,Embarin,Foligan,Hamarin,Jenapurinol,Lopurin,Lysuron,Milurit,Milurite,Novopurol,Pan Quimica,Progout,Pureduct,Purinol,Remid,Rimapurinol,Roucol,Suspendol,Tipuric,Uribenz,Uridocid,Uripurinol,Urosin,Urtias,Xanthomax,Xanturic,Zygout,Zyloprim,Zyloric
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014527 Uric Acid An oxidation product, via XANTHINE OXIDASE, of oxypurines such as XANTHINE and HYPOXANTHINE. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals URATE OXIDASE further oxidizes it to ALLANTOIN. 2,6,8-Trihydroxypurine,Ammonium Acid Urate,Monosodium Urate,Monosodium Urate Monohydrate,Potassium Urate,Sodium Acid Urate,Sodium Acid Urate Monohydrate,Sodium Urate,Sodium Urate Monohydrate,Trioxopurine,Urate,Acid Urate, Ammonium,Acid Urate, Sodium,Acid, Uric,Monohydrate, Monosodium Urate,Monohydrate, Sodium Urate,Urate Monohydrate, Monosodium,Urate Monohydrate, Sodium,Urate, Ammonium Acid,Urate, Monosodium,Urate, Potassium,Urate, Sodium,Urate, Sodium Acid
D014969 Xanthine Oxidase An iron-molybdenum flavoprotein containing FLAVIN-ADENINE DINUCLEOTIDE that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. Hypoxanthine Oxidase,Hypoxanthine Dehydrogenase,Hypoxanthine-Xanthine Oxidase,Purine-Xanthine Oxidase,Dehydrogenase, Hypoxanthine,Hypoxanthine Xanthine Oxidase,Oxidase, Hypoxanthine,Oxidase, Hypoxanthine-Xanthine,Oxidase, Purine-Xanthine,Oxidase, Xanthine,Purine Xanthine Oxidase

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