Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xanthine oxidase

Background: Intestinal ischemia-reperfusion (IR) injury results in cell des truction, which may be mediated by the generation of reactive oxygen specie s, potentially toxic metabolites of xanthine oxidase. Pentoxifylline (PTX) possesses a variety of biochemical and antioxidant properties that can impr ove capillary now and tissue oxygenation. Because of these combined effects , it has been hypothesized that pentoxifylline would protect against intest inal IR. Methods: Young adult rats were randomly assigned to one of four experimenta l groups: IR/Placebo (n = 12) in which superior and inferior mesenteric art eries were clamped for 45 minutes and then reopened; IR/PTX (n = 11) in whi ch IR was induced as in the Placebo group, but with 25 mg/kg PTX at 0, 30, and 60 minutes; No IR/Placebo (n = 12); and No IR/PTX (n = 6) in which plac ebo and PTX were applied with no IR. Blood and intestinal samples were take n for serial thiobarbituric acid-reducing substances (TBARS; index of lipid peroxidation), for xanthine oxidase-xanthine dehydrogenase ratios, glutath ione, myeloperoxidase, and histopathology. Results: Animals in the IR/PTX group had lower TEARS and the least severe h istopathologic injury. Xanthine oxidase-xanthine dehydrogenase ratios were elevated only in IR/ Placebo (0.67 +/- 0.22 vs. 0.45 +/- 0.14 in IR/PTX; 0. 42 +/- 0.22 in No IR/Placebo; and 0.40 +/- 0.11 in No IR/PTX; p = 0.0009). Reduced glutathione was diminished in IR/PTX animals (38.9 +/- 1.35 vs. 46. 1 +/- 7.0 in IR/Placebo; 41.1 +/- 2.5 in No IR/ Placebo; 43.6 +/- 1.0 in No IR/PTX; p = 0.048). No differences were recorded in myeloperoxidase levels among groups. Conclusions: Pentoxifylline ameliorates histopathologic signs of injury and decreases lipid peroxidation (TBARS). Normal xanthine oxidase-xanthine deh ydrogenase ratios in the treated compared with IR-only animals imply that t he protective effect of PTX is at least partially mediated through inhibiti on of xanthine oxidase.