TY - JOUR
T1 - Sodium sulfite exacerbates allograft vasculopathy and affects tryptophan breakdown in murine heterotopic aortic transplantation
AU - Sucher, Robert
AU - Hautz, Theresa
AU - Mohr, Elisabeth
AU - Mackowitz, Maximilian
AU - Mellitzer, Vanessa
AU - Steger, Christina
AU - Cardini, Benno
AU - Resch, Thomas
AU - Margreiter, Christian
AU - Schneeberger, Stefan
AU - Brandacher, Gerald
AU - Fuchs, Dietmar
AU - Oberhuber, Rupert
AU - Gostner, Johanna M.
N1 - Publisher Copyright:
Copyright © 2019 Robert Sucher et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
PY - 2019
Y1 - 2019
N2 - Graft vasculopathy is the main feature of chronic rejection in organ transplantation, with oxidative stress being a major trigger. Inflammation-associated prooxidant processes may be controlled by antioxidants; however, interference with redox-regulated mechanisms is a complex endeavor. An essential feature of the cellular immune response is the acceleration of tryptophan (Trp) breakdown, leading to the formation of several bioactive catabolites. Long-term activation of this immunobiochemical pathway contributes to the establishment of a tolerogenic environment, thereby supporting allograft survival. Herein, the impact of the antioxidant sodium sulfite on the development of graft vasculopathy was assessed in murine aortic transplantation. Allogeneic (BALB/c to C57BL/6) heterotopic murine aortic transplantations were performed. Animals were left untreated or were treated with 10 µl of 0.1 M, of 0.01 M sodium sulfite, or of 0.1 M sodium sulfate, intraperitoneally once/day, until postoperative day (POD) 100. Grafts were assessed by histology, immunohistochemistry, and adhesion molecule gene expression. Serum concentrations of tryptophan and its catabolite kynurenine (Kyn) were measured. On day 100, graft vasculopathy was significantly increased upon treatment with 0.1 M sodium sulfite, compared to allogeneic untreated controls (p = 0 004), which correlated with a significant increase of a-smooth-muscle-actin, Vcam-1, and P-selectin. Serum Kyn concentrations increased in the allogeneic control group over time (p < 0 05, POD = 50), while low-dose sodium sulfite treatment (0.01 M) treatment resulted in a decrease in Kyn levels over time (p < 0 05, POD = 10), compared to the respective baselines (p < 0 05). Longitudinal analysis of serum metabolite concentrations in the different treatment groups further identified an overall effect of sodium sulfite on Kyn concentrations. Antioxidative treatment may result in ambivalent consequences. Our data reveal that an excess of antioxidants like sodium sulfite can aggravate allograft vasculopathy, which further highlights the challenges associated with interventions that interfere with the complex interplay of redox-regulated inflammatory processes.
AB - Graft vasculopathy is the main feature of chronic rejection in organ transplantation, with oxidative stress being a major trigger. Inflammation-associated prooxidant processes may be controlled by antioxidants; however, interference with redox-regulated mechanisms is a complex endeavor. An essential feature of the cellular immune response is the acceleration of tryptophan (Trp) breakdown, leading to the formation of several bioactive catabolites. Long-term activation of this immunobiochemical pathway contributes to the establishment of a tolerogenic environment, thereby supporting allograft survival. Herein, the impact of the antioxidant sodium sulfite on the development of graft vasculopathy was assessed in murine aortic transplantation. Allogeneic (BALB/c to C57BL/6) heterotopic murine aortic transplantations were performed. Animals were left untreated or were treated with 10 µl of 0.1 M, of 0.01 M sodium sulfite, or of 0.1 M sodium sulfate, intraperitoneally once/day, until postoperative day (POD) 100. Grafts were assessed by histology, immunohistochemistry, and adhesion molecule gene expression. Serum concentrations of tryptophan and its catabolite kynurenine (Kyn) were measured. On day 100, graft vasculopathy was significantly increased upon treatment with 0.1 M sodium sulfite, compared to allogeneic untreated controls (p = 0 004), which correlated with a significant increase of a-smooth-muscle-actin, Vcam-1, and P-selectin. Serum Kyn concentrations increased in the allogeneic control group over time (p < 0 05, POD = 50), while low-dose sodium sulfite treatment (0.01 M) treatment resulted in a decrease in Kyn levels over time (p < 0 05, POD = 10), compared to the respective baselines (p < 0 05). Longitudinal analysis of serum metabolite concentrations in the different treatment groups further identified an overall effect of sodium sulfite on Kyn concentrations. Antioxidative treatment may result in ambivalent consequences. Our data reveal that an excess of antioxidants like sodium sulfite can aggravate allograft vasculopathy, which further highlights the challenges associated with interventions that interfere with the complex interplay of redox-regulated inflammatory processes.
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U2 - 10.1155/2019/8461048
DO - 10.1155/2019/8461048
M3 - Article
C2 - 31089419
AN - SCOPUS:85066829542
SN - 1942-0900
VL - 2019
JO - Oxidative medicine and cellular longevity
JF - Oxidative medicine and cellular longevity
M1 - 8461048
ER -