Allopurinol reduces bacterial translocation, intestinal mucosal lipid peroxidation, and neutrophil-derived myeloperoxidase activity in chronic portal hypertensive and common bile duct-ligated growing rats.
Bacterial translocation (BT) from the gastrointestinal tract has been thought to play a role in the pathogenesis of septic complications in patients with chronic portal hypertension (PH) and obstructive jaundice. The purpose of this study was to investigate the incidence of BT and to assess the role of intestinal mucosal malondialdehyde (MDA) levels as an indicator of lipid peroxidation and polymorphonuclear neutrophil-derived myeloperoxidase (MPO) in chronic portal hypertensive and common bile duct-ligated rats. Twenty male rats were subjected to sham laparotomy (SL), 20 rats to calibrated portal vein constriction (PH), 20 rats to common bile duct ligation (CBDL), and 10 rats served as a nonoperated control group (NOP). After 4 wk, 10 animals of each operated group received 50 mg/kg allopurinol intraperitoneally, at 24 h, and again 2 h prior to estimation of BT, intestinal mucosal MDA, and MPO activities. In the NOP and SL groups, BT to the mesenteric lymph nodes (MLN) and spleen was present. In PH and in CBDL rats, BT to liver, portal vein, peritoneum, and caval vein occurred. Allopurinol treatment attenuated the frequence of BT in PH and decreased BT in CBDL rats significantly (p < 0.05). Ileal mucosal MDA levels (nanomoles/g) in untreated rats increased from 45.1 +/- 7.9 in SL to 98.2 +/- 9.1 in PH and to 102.2 +/- 11 in CBDL rats (p < 0.01). In the allopurinol groups the increase of MDA to 49.1 +/- 1.3 in PH, and 66.2 +/- 2.2 in CBDL was significantly lower (p < 0.01). MPO activity (units/g) in the ileal mucosa increased in untreated rats from 319 +/- 129 after SL to 866 +/- 104 after PH and to 1016 +/- 104 after CBDL (p < 0.01). Allopurinol significantly attenuated MPO activity to 369 +/- 44 in PH, and to 372 +/- 60 in CBDL animals (p < 0.01). In PH and CBDL rats significant BT, intestinal mucosal lipid peroxidation, and polymorphonuclear neutrophil-derived MPO activity occurred. Allopurinol reduced BT and improved intestinal mucosal MDA and MPO activities, suggesting that there might be an association between BT and intestinal mucosal lipid peroxidation.
Schimpl
G
G
Department of Pediatric Surgery, University of Graz, Medical School, Austria.
Pesendorfer
P
P
Steinwender
G
G
Feierl
G
G
Ratschek
M
M
Höllwarth
M E
ME
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects*; D003137:Common Bile Duct Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003250:Constriction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D009195:Peroxidase / Q000097:blood / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D008315:Malondialdehyde; D000493:Allopurinol; D009195:Peroxidase; D014969:Xanthine Oxidase