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A tungsten supplemented diet attenuates bacterial translocation in chronic portal hypertensive and cholestatic rats: role of xanthine dehydrogenase and xanthine oxidase
  1. G Schimpla,
  2. M A Pabstb,
  3. G Feierlc,
  4. A Kuesza,
  5. H Özbeya,
  6. S Takahashia,
  7. M E Höllwartha
  1. aDepartment of Paediatric Surgery, University of Graz, Medical School, Austria, bInstitute of Histology, University of Graz, Medical School, Austria, cInstitute of Hygiene, University of Graz, Medical School, Austria
  1. Dr G Schimpl, Department of Paediatric Surgery, Auenbruggerplatz 34, A-8036 Graz, Austria.

Abstract

BACKGROUND Bacterial translocation (BT) plays a major role in the pathophysiological process of spontaneous infections in portal hypertension (PH) and cholestatic jaundice. The major mechanisms promoting BT in experimental animal models are the disruption of the intestinal ecological equilibrium and disruption of the intestinal mucosal barrier. The enzymes xanthine dehydrogenase (XD) and xanthine oxidase (XO) are often implicated as a significant source of oxidants which have a major impact on the impairment of intestinal barrier function.

AIM To investigate the incidence of BT in rats with PH and obstructive jaundice, and to evaluate the impact of XD and XO.

METHODS Animals were subjected to sham laparotomy (SL), PH by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). They were fed either a standard pellet diet or a tungsten supplemented molybdenum-free diet. Four weeks after the operative procedure, intestinal colonisation and 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 PH and CBDL groups compared with the SL group. In normally fed animals after SL, BT occurred in 12%. In PH and after CBDL, the rate of BT increased significantly (p<0.05) to 28% and 54% respectively. In the jejunum of normally fed animals subjected to PH or CBDL, a significant increase in XO was observed (p<0.01). Animals fed a tungsten supplemented diet showed a significant attenuation of BT to 14% in PH and 22% after CBDL (p<0.05). Tungsten treatment completely suppressed jejunal XD and XO activities.

CONCLUSIONS Significant intestinal bacterial overgrowth, BT, and XD to XO conversion occurred in PH and after CBDL. XD and XO inactivation by a tungsten supplemented molybdenum-free diet significantly reduced the incidence of BT without affecting intestinal bacterial overgrowth. These data strongly support the hypothesis that increased XD to XO conversion may contribute to intestinal barrier failure in PH and after CBDL.

  • bacterial translocation
  • portal hypertension
  • chronic cholestasis
  • xanthine oxidase
  • xanthine dehydrogenase
  • Abbreviations used in this paper

    BT
    bacterial translocation
    SL
    sham laparotomy
    PH
    portal hypertension
    CBDL
    common bile duct ligation
    XO
    xanthine oxidase
    XD
    xanthine dehydrogenase
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  • Abbreviations used in this paper

    BT
    bacterial translocation
    SL
    sham laparotomy
    PH
    portal hypertension
    CBDL
    common bile duct ligation
    XO
    xanthine oxidase
    XD
    xanthine dehydrogenase
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