Fahad A. Al-Abbasi
Med Sci Monit 2012; 18(6): BR208-214
Available online: 2012-06-01
Background: Acrylonitrile (ACN) is an extensively produced aliphatic nitrile. The gastrointestinal tract is an important target organ for ACN toxicity. The objective of the present study was to investigate the role of xanthine oxidase (XO) in ACN-induced gastric toxicity in rats.
Material/Methods: We assessed the effect of ACN on oxidative stress parameters as xanthine oxidase (XO) and total xanthine dehydrogenase (XD)/ XO activity, superoxide anion (O2.–) production, reduced glutathione (GSH) levels and lipid peroxidation in gastric tissues.
Results: A single oral dose of ACN (25 mg/kg) caused a significant enhancement in XO activity. ACN also caused a significant depletion of GSH levels, enhanced O2.– production and increased lipid peroxidation in the time-course experiment. In the dose-response experiment, ACN accelerated the conversion of XD to XO, with a significant depletion of gastric GSH in a dose-related manner. A strong negative correlation existed between the levels of GSH and the percentage enhancement in XO activity (r =–0.997). (O2.–) production and malondialdehyde (MDA) formation were significantly elevated in a dose-related manner. Pretreatment with allopurinol (50 mg/kg) significantly protected against ACN-induced rise in XO activity, depletion of GSH, and elevated production of (O2.–). However, pretreatment with diethyl maleate (DEM; 100 mg/kg) significantly aggravated the ACN-induced GSH depletion and rise in XO activity. Furthermore, DEM significantly enhanced (O2.–) and MDA production.
Conclusions: The present study indicates that enhancement of XO activity could be implicated in ACN-induced gastric damage in rats.
Keywords: Thiobarbituric Acid Reactive Substances - metabolism, Stomach Diseases - enzymology, Stomach - pathology, Rats, Sprague-Dawley, Rats, Maleates - pharmacology, Glutathione - metabolism, Animals, Allopurinol - pharmacology, Acrylonitrile - toxicity, Time Factors, Xanthine Oxidase - metabolism