Febuxostat improves the local and remote organ changes induced by intestinal ischemia/reperfusion in rats.

Abstract

BACKGROUND:

Xanthine oxidase has been implicated in the pathogenesis of a wide spectrum of diseases, and is thought to be the most important source of oxygen-free radicals and cell damage during re-oxygenation of hypoxic tissues.

AIMS:

The present study was undertaken to demonstrate whether febuxostat is superior to allopurinol in prevention of the local and remote harmful effects of small intestinal ischemia/reperfusion injury in rats.

METHODS:

Intestinal ischemia was induced by superior mesenteric artery ligation. The rats were assigned to five groups: the sham control; the intestinal ischemia/reperfusion; the allopurinol; and the febuxostat 5 and 10 mg/kg pretreated ischemia/reperfusion groups. Treatment was administered from 7 days before ischemia induction. After the reperfusion, the serum and tissues were obtained for biochemical, pharmacological, and histological studies.

RESULTS:

Intestinal reperfusion led to an elevation in the serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, malondialdehyde, and xanthine oxidase as well as intestinal myeloperoxidase, malonadialdehyde, and xanthine oxidase/xanthine dehydrogenase activity. Furthermore, the ischemia/reperfusion induced a reduction in the contractile responsiveness to acetylcholine. These changes were significantly regulated by the pretreatment with febuxostat compared to allopurinol. The degree of pathological impairment in the intestinal mucosa, liver, and lung tissues were lighter in the pretreated groups.

CONCLUSIONS:

Febuxostat may offer advantages over allopurinol in lessening local intestinal injury as well as remote hepatic and lung injuries induced by small intestinal ischemia/reperfusion.

• Authors: Amani Nabil Shafik
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 58 Issue 3 Pg. 650-9 (Mar 2013) ISSN: 1573-2568 [Electronic] United States
• PMID: 23010742 (Publication Type: Journal Article)

Chemical References

• Gout Suppressants
• Thiazoles
• Tumor Necrosis Factor-alpha
• Febuxostat
• Malondialdehyde
• Allopurinol
• Peroxidase
• Xanthine Dehydrogenase
• Xanthine Oxidase
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Allopurinol (pharmacology)
• Animals
• Aspartate Aminotransferases (blood)
• Dose-Response Relationship, Drug
• Febuxostat
• Gout Suppressants (administration & dosage, pharmacology)
• Intestinal Mucosa (pathology)
• Lipid Peroxidation
• Lung (pathology)
• Male
• Malondialdehyde (blood, metabolism)
• Muscle Contraction (drug effects, physiology)
• Muscle, Smooth (drug effects, physiology)
• Peroxidase (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy)
• Thiazoles (administration & dosage, pharmacology)
• Tumor Necrosis Factor-alpha (blood, metabolism)
• Xanthine Dehydrogenase (metabolism)
• Xanthine Oxidase (antagonists & inhibitors, metabolism)