A tungsten supplemented diet attenuates bacterial translocation in chronicportal hypertensive and cholestatic rats: role of xanthine dehydrogenase and xanthine oxidase

Background-Bacterial translocation (BT) plays a major role in the pathophys iological process of spontaneous infections in portal hypertension (PII) an d cholestatic jaundice. The major mechanisms promoting BT in experimental a nimal models: are the disruption of the intestinal ecological equilibrium a nd disruption of the intestinal mucosal barrier. The enzymes xanthine dehyd rogenase (XD) and xanthine oxidase (XO) are often implicated as a significa nt source of oxidants which have a major impact on the impairment of intest inal barrier function. Aim-To investigate the incidence of BT in rats with PEI and obstructive jau ndice, and to evaluate the impact of XD and XO. Methods-Animals were subjected to sham laparotomy (SL), PH by calibrated st enosis of the portal vein, and common bile duct ligation (CBDL). They were fed either a standard pellet diet or a tungsten supplemented molybdenum-fre e diet. Four weeks after the operative procedure, intestinal colonisation a nd BT to portal vein, vena cava, mesenteric lymph nodes, liver, and spleen were determined. Intestinal XD and XO activity were measured enzymatically and histochemically. Results-Significant (p<0.01) intestinal bacterial overgrowth was present in all PII and CBDL groups compared with the SL group. In normally fed animal s after SL, BT occurred in 12%. In PN and after CBDL, the rate of BT increa sed significantly (p<0.05) to 28% and 54% respectively. In the jejunum of n ormally fed animals subjected to PII or CBDL, a significant increase in XO was observed (p<0.01). Animals fed a tungsten supplemented diet showed a si gnificant attenuation of BT to 14% in PH and 22% after CBDL (p<0.05). Tungs ten treatment completely suppressed jejunal IU) and XO activities. Conclusions-Significant intestinal bacterial overgrowth, BT, and XD to XO c onversion occurred in PH and after CBDL. XD and XO inactivation by a tungst en supplemented molybdenum-free diet significantly reduced, the incidence o f BT without affecting intestinal bacterial overgrowth, These data strongly support the hypothesis that increased XD to XO conversion may contribute t o intestinal barrier failure in PII and after CBDL.