PMID- 10400107 OWN - NLM STAT- MEDLINE DCOM- 19990817 LR - 20190817 IS - 0277-2116 (Print) IS - 0277-2116 (Linking) VI - 29 IP - 1 DP - 1999 Jul TI - Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xanthine oxidase. PG - 69-74 AB - BACKGROUND: Intestinal ischemia-reperfusion (IR) injury results in cell destruction, which may be mediated by the generation of reactive oxygen species, potentially toxic metabolites of xanthine oxidase. Pentoxifylline (PTX) possesses a variety of biochemical and antioxidant properties that can improve capillary flow and tissue oxygenation. Because of these combined effects, it has been hypothesized that pentoxifylline would protect against intestinal IR. METHODS: Young adult rats were randomly assigned to one of four experimental groups: IR/Placebo (n = 12) in which superior and inferior mesenteric arteries were clamped for 45 minutes and then reopened; IR/PTX (n = 11) in which 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 placebo and PTX were applied with no IR. Blood and intestinal samples were taken for serial thiobarbituric acid-reducing substances (TBARS; index of lipid peroxidation), for xanthine oxidase-xanthine dehydrogenase ratios, glutathione, myeloperoxidase, and histopathology. RESULTS: Animals in the IR/PTX group had lower TBARS and the least severe histopathologic injury. Xanthine oxidasexanthine 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 dehydrogenase ratios in the treated compared with IR-only animals imply that the protective effect of PTX is at least partially mediated through inhibition of xanthine oxidase. FAU - Hammerman, C AU - Hammerman C AD - Shaare Zedek Medical Center and the Hebrew University-Hadassah Medical School, Jerusalem, Israel. FAU - Goldschmidt, D AU - Goldschmidt D FAU - Caplan, M S AU - Caplan MS FAU - Kaplan, M AU - Kaplan M FAU - Schimmel, M S AU - Schimmel MS FAU - Eidelman, A I AU - Eidelman AI FAU - Branski, D AU - Branski D FAU - Hochman, A AU - Hochman A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Pediatr Gastroenterol Nutr JT - Journal of pediatric gastroenterology and nutrition JID - 8211545 RN - 0 (Free Radical Scavengers) RN - EC 1.17.3.2 (Xanthine Oxidase) RN - SD6QCT3TSU (Pentoxifylline) SB - IM MH - Animals MH - Evaluation Studies as Topic MH - Free Radical Scavengers/*pharmacology MH - Intestines/*blood supply/pathology MH - Lipid Peroxidation MH - Pentoxifylline/*pharmacology MH - Random Allocation MH - Rats MH - Reperfusion Injury/pathology/physiopathology/*prevention & control MH - Xanthine Oxidase/*antagonists & inhibitors EDAT- 1999/07/10 00:00 MHDA- 1999/07/10 00:01 CRDT- 1999/07/10 00:00 PHST- 1999/07/10 00:00 [pubmed] PHST- 1999/07/10 00:01 [medline] PHST- 1999/07/10 00:00 [entrez] AID - 10.1097/00005176-199907000-00017 [doi] PST - ppublish SO - J Pediatr Gastroenterol Nutr. 1999 Jul;29(1):69-74. doi: 10.1097/00005176-199907000-00017.