The Open Nitric Oxide Journal


ISSN: 1875-0427 ― Volume 4, 2014

Role of Oxidative Stress in the Colonic Complications of Murine Syngeneic Graft-versus-host Disease

The Open Nitric Oxide Journal, 2011, 3: 72-80

Jacqueline Perez, J. Anthony Brandon , Donald A. Cohen , C. Darrell Jennings, Alan. M. Kaplan , J. Scott Bryson

Department of Internal Medi-cine, Division of Hematology and Blood & Marrow Transplantation, Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexing-ton, Kentucky 40536.

Electronic publication date 30/12/2011
[DOI: 10.2174/1875042701103010072]

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Syngeneic graft-versus-host disease (SGVHD) develops in mice following lethal irradiation, reconstitution with syngeneic bone marrow (BM) and treatment with a short course of the immunosuppressive agent cyclosporine A (CsA). The development of SGVHD is a complex process resulting from the cooperative interaction of multiple effector cell populations and inflammatory mediators contributing to the pathogenesis of this inducible disease. Using gene ex-pression analysis, flow cytometric analysis and immunohistochemistry, time course studies revealed increased reactive oxygen and nitrogen species in the tissues of CsA-treated animals compared to bone marrow transplantation (BMT) con-trols during the induction of SGVHD (d0-21 post-BMT). Studies were undertaken to determine the effect of CsA-induced oxidative stress on the induction of SGVHD. In vivo treatment with the superoxide dismutase mimetic, manganese (III) meso-tetrakis (4-benzoic acid) porphyrin (MnTBAP), during (d0-21 post BMT), or after CsA therapy (>d21 post-BMT), caused a reduction in the development of clinical symptoms of SGVHD (weight loss, diarrhea). Interestingly, treatment with MnTBAP resulted in a significant reduction in the deposition of peroxynitrite in the colons of CsA-MnTBAP-treated versus control CsA-treated SGVHD animals. These studies suggest a role for oxidative stress in the development of mur-ine SGVHD.

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