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Original communication| Volume 137, ISSUE 1, P85-91, January 2005

Apoptosis inhibition plays a greater role than necrosis inhibition in decreasing bacterial translocation in experimental intestinal transplantation

  • Daniel Azuara
    Affiliations
    From the Department of Surgery and Surgical Specialities, University of Barcelona School of Medicine, Campus Bellvitge, L'Hospitalet de Llobregat; Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC-IDIBAPS); and Department of Microbiology, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
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  • Anna Sola
    Affiliations
    From the Department of Surgery and Surgical Specialities, University of Barcelona School of Medicine, Campus Bellvitge, L'Hospitalet de Llobregat; Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC-IDIBAPS); and Department of Microbiology, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
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  • Georgina Hotter
    Affiliations
    From the Department of Surgery and Surgical Specialities, University of Barcelona School of Medicine, Campus Bellvitge, L'Hospitalet de Llobregat; Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC-IDIBAPS); and Department of Microbiology, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
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  • Laura Calatayud
    Affiliations
    From the Department of Surgery and Surgical Specialities, University of Barcelona School of Medicine, Campus Bellvitge, L'Hospitalet de Llobregat; Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC-IDIBAPS); and Department of Microbiology, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
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  • Javier de Oca
    Correspondence
    Reprint requests: Dr Javier de Oca, Departamento de Cirugía y Especialidades Quirúrgicas, Universidad de Barcelona, Campus de Bellvitge, Edificio Pavellon de Gobierno 4a planta, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
    Affiliations
    From the Department of Surgery and Surgical Specialities, University of Barcelona School of Medicine, Campus Bellvitge, L'Hospitalet de Llobregat; Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC-IDIBAPS); and Department of Microbiology, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
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      Background

      During small-bowel transplantation, necrosis and apoptosis are involved in the destruction of intestinal epithelial cells. This study was conducted to assess which mode of cell death plays a greater role as a trigger of the bacterial translocation (BT) associated with intestinal transplantation.

      Methods

      The following experimental groups were studied: sham, Tx (intestinal transplantation), Tx + poly (ADP-ribose) synthetase (PARS) inhibitor 3-aminobenzamide (3-AB), and Tx + caspase inhibitor Z-VAD-fmk. Histological analysis, caspase-3 activity, DNA fragmentation, and BT were measured in tissue samples after transplantation.

      Results

      During intestinal transplantation, apoptosis and necrosis both increased, showing graft injury and high levels of BT. Rats treated with 3-AB showed histological protection of the transplanted graft and a tendency toward lower BT despite the existence of high apoptosis levels. The rats treated with Z-VAD showed histological protection of the transplanted graft and decreased levels of caspase-3 and DNA fragmentation. The Tx + Z-VAD group showed the lowest levels of BT in all tissues.

      Conclusions

      In small intestinal transplantation, both apoptosis and cell necrosis give rise to histological injury and BT. Apoptosis inhibition and necrosis inhibition treatments protect intestinal grafts from ischemia/reperfusion injury; Z-VAD supplementation has a greater effect on BT prevention than does administration of the PARS inhibitor 3-AB.
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      References

        • Haglund U.
        Gut ischaemia.
        Gut. 1994; 25: S73-S76
        • Shah K.A.
        • Shurey S.
        • Green C.J.
        Apoptosis after intestinal ischemia-reperfusion injury.
        Transplantation. 1997; 64: 1393-1397
        • Kong S.E.
        • Blennerhassett L.R.
        • Heel K.A.
        • McCauley R.D.
        • Hall J.C.
        Ischaemia-reperfusion injury to the intestine.
        Aust NZ J Surg. 1998; 68: 554-561
        • Cicalese L.
        • Sileri P.
        • Green M.
        • Abu-Elmagd K.
        • Kocoshis S.
        • Reyes J.
        Bacterial translocation in clinical intestinal transplantation.
        Transplantation. 2001; 71: 1414-1417
        • Wintersberger U.
        • Wintersberger E.
        Poly ADP-ribosylation: a cellular emergency reaction?.
        FEBS Lett. 1985; 188: 189-191
        • Schraufstatter I.U.
        • Hyslop P.A.
        • Hinshaw D.B.
        • Spragg R.G.
        • Sklar L.A.
        • Cochrane C.G.
        Hydrogen peroxide–induced injury of cells and its prevention by inhibitors of poly(ADP-ribose) polymerase.
        Proc Natl Acad Sci U S A. 1986; 83: 4908-4912
        • Cuzzocrea S.
        • Zingarelli B.
        • Costantino G.
        • Szabo A.
        • Salzman A.L.
        • Caputi A.P.
        • et al.
        Beneficial effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase in a rat model of splanchnic artery occlusion and reperfusion.
        Br J Pharmacol. 1997; 121: 1065-1074
        • Liaudet L.
        • Szabo A.
        • Soriano F.G.
        • Zingarelli B.
        • Szabo C.
        • Salzman A.L.
        Poly (ADP-ribose) synthetase mediates intestinal mucosal barrier dysfunction after mesenteric ischemia.
        Shock. 2000; 14: 134-141
        • Miller D.K.
        The role of caspase family of cysteine proteases in apoptosis.
        Semin Immunol. 1997; 9: 35-49
        • Farber A.
        • Connors J.P.
        • Friedlander R.M.
        • Wagner R.J.
        • Powell R.J.
        • Cronenwett J.L.
        A specific inhibitor of apoptosis decreases tissue injury after intestinal ischemia-reperfusion in mice.
        J Vasc Surg. 1999; 30: 752-760
        • Monchik G.J.
        • Russell P.S.
        Transplantation of small bowel in the rat: technical and immunological considerations.
        Surgery. 1971; 70: 693-702
        • Piguet P.F.
        • Vesin C.
        • Donati Y.
        • Barazzone C.
        TNF-induced enterocyte apoptosis and detachment in mice: induction of caspases and prevention by a caspase inhibitor, ZVAD-fmk.
        Lab Invest. 1999; 79: 495-500
        • Park P.O.
        • Wallander J.
        • Tufveson G.
        • Haglund U.
        Cold ischemic and reperfusion injury in a model of small bowel transplantation in the rat.
        Eur Surg Res. 1991; 23: 1-8
        • Sileri P.
        • Rastellini C.
        • Dicuonzo G.
        • Gaspari A.
        • Benedetti E.
        • Cicalese L.
        Transplantation of the intestines and bacterial translocation.
        G Chir. 2000; 21: 196-204
        • Fukuyama K.
        • Iwakiri R.
        • Noda T.
        • Kojima M.
        • Utsumi H.
        • Tsunada S.
        • et al.
        Apoptosis induced by ischemia-reperfusion and fasting in gastric mucosa compared to small intestinal mucosa in rats.
        Dig Dis Sci. 2001; 46: 545-549
        • Ikeda H.
        • Suzuki Y.
        • Suzuki M.
        • Koike M.
        • Tamura J.
        • Tong J.
        • et al.
        Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium.
        Gut. 1998; 42: 530-537
        • Majno G.
        • Joris I.
        Apoptosis, oncosis, and necrosis: an overview of cell death.
        Am J Pathol. 1995; 146: 3-15
        • Azuara D.
        • Sola A.
        • Hotter G.
        • Calatayud L.
        • Jaurrieta E.
        • de Oca J.
        Role of nitric oxide in apoptosis and cell necrosis for intestinal transplantation.
        Transplant Proc. 2003; 35: 1931-1932
        • Azuara D.
        • Sola A.
        • Hotter G.
        • Calatayud L.
        • Jaurrieta E.
        • de Oca J.
        Administration of nitric oxide with caspase inhibitors minimizes bacterial translocation in experimental intestinal transplantation.
        Transplantation. 2004; 77: 177-183
        • Banda M.A.
        • Granger D.N.
        Mechanism and protection from ischemic intestinal injury.
        Transplant Proc. 1996; 28: 2595-2597
        • Schraufstatter I.U.
        • Hinshaw D.B.
        • Hyslop P.A.
        • Hyslop P.A.
        • Spragg R.G.
        • Cochrane C.G.
        Oxidant injury of cells: DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide.
        J Clin Invest. 1986; 77: 1312-1320
        • Eguchi Y.
        • Shimizu S.
        • Tsujimoto Y.
        Intracellular ATP levels determine cell death fate by apoptosis or necrosis.
        Cancer Res. 1997; 57: 1835-1840
        • Leist M.
        • Single B.
        • Castoldi A.F.
        • Kuhnle S.
        • Nicotera P.
        Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis.
        J Exp Med. 1997; 185: 1481-1486
        • Bojarski C.
        • Bendfeldt K.
        • Gitter A.H.
        • Mankertz J.
        • Fromm M.
        • Wagner S.
        • et al.
        Apoptosis and intestinal barrier function.
        Ann N Y Acad Sci. 2000; 915: 270-274
        • Zhang C.
        • Sheng Z.Y.
        • Hu S.
        • Gao J.C.
        • Yu S.
        • Liu Y.
        The influence of apoptosis of mucosal epithelial cells on intestinal barrier integrity after scald in rats.
        Burns. 2002; 28: 731-737
        • Zech B.
        • Wilm M.
        • van Eldik R.
        • Brune B.
        Mass spectrometric analysis of nitric oxide–modified caspase-3.
        J Biol Chem. 1999; 274: 20931-20936