Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation

Abstract

Oxygen radicals derived from xanthine oxidase (XO) are important mediators of the cellular injury associated with reperfusion of ischemic intestine, stomach, liver, kidney, and pancreas. XO exists in nonischemic tissue predominantly as xanthine dehydrogenase (XDH) and converts to oxygen radical-producing XO with ischemia. Grinding intestine under liquid nitrogen and placing the powder in phosphate buffer (pH 7.0) containing thiol reductants and protease inhibitors adequately preserved total XDH + XO activity and the percentage in the oxidase form (%XO) for 24 h. Total activity in nonischemic intestine ranged from 374 nmol.min-1.g-1 in duodenum to 138 nmol.min-1.g-1 in ileum, while XO activity was approximately 19% of total activity throughout the entire small intestine. The rate of XDH conversion to XO during normothermic ischemia varied only slightly throughout the intestine, increasing 13% per hour to 34, 46, and 61% XO after 1, 2, and 3 h of ischemia, respectively. Our results contrast with previous reports where XDH conversion to XO occurred within 60 s ischemia but are consistent with physiological and morphological evidence of ischemic injury and provide further support for involvement of XO in intestinal injury associated with ischemia.

Nitrite confers protection against myocardial infarction: Role of xanthine oxidoreductase, NADPH oxidase and KATP channels

“…The activity of xanthine dehydrogenase in the rat hearts we studied accounts for approximately 80% of total enzymatic activity with the balance contributed by xanthine oxidase. This distribution in catalytic activity between the two forms of the enzyme is in agreement with previous studies on xanthine oxidoreductase activity [26,27]. The protective effects of nitrite against infarction and decreased post-ischemic ventricular dysfunction were abolished by oxypurinol, an inhibitor of the molybdo-pterin sites of xanthine oxidoreductase.…”

Intraluminal injection of short chain fatty acids diminishes intestinal mucosa injury in experimental ischemia-reperfusion

“…Both at the jejunum (control = 2 [0-4]; saline = 3 [1][2][3][4]) and at the ileum segments (control = 2 [0-4]; saline = 4 [1][2][3][4][5]), the attributed score of the mucosal injury was higher in the saline sac than in control sacs (p=0.02 for both jejunum The SCFA treated sacs showed lesser score at the ileum (p=0.03) but were not significantly different at the jejunum (p=0.83) when compared with saline sacs (Figures 2 and 3). …”

“…In brief, large amounts of xanthine dehydrogenase are converted to xanthine oxidase during ischemia by a calcium-dependent proteolytic process. Superoxide, hydrogen peroxide, and hydroxyl radical are formed and may then cause mucosal injury both by direct action and by secondary activation of PMN 1,3 . Other consequence of the ischemic bowel injury is the disruption of the gut mucosal barrier predisposing the egress of harmful microorganisms and/or their toxins in a phenomenon called bacterial translocation.…”

Modulation of the Xanthine Oxidase/Xanthine Dehydrogenase Ratio by Reaction of Malondialdehyde with NH2-Groups

“…The we assume that NH 2 -groups are important for the oxirelevance of xanthine oxidoreductase äs an oxygen rad-dase activity but not for the dehydrogenase activity of ical source (depending on the xanthine dehydrogenase/ xanthine oxidoreductase. To test this hypothesis, we anaxanthine oxidase rätio) under in vivo cohditions (8)(9)(10)(11)(12)) ^8 (1 is presently under discussion, together with questions 1. the reaction of malondialdehyde with NH 2 -and SHconcerning the mechanism of the modulation of the xan-groups in the xanthine oxidoreductase, 2. the xanthine dehydrogenase and xanthine oxidase activities of the dithiothreitol-treated enzyme after incubation with malondialdehyde and 3. the ability to reactivate malondialdehyde-modified xanthine oxidoreductase by dithiothreitol treatment.…”