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Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats

Allograft kidney transplantation, which triggers host cellular- and antibody-mediated rejection of the kidney, is a major contributor to kidney damage during transplant. Here, we asked whether PrC-210 would suppress damage seen in allograft kidney transplant. Brown Norway (BN) rat kidneys were perfu...

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Autores principales: Goesch, Torsten R., Wilson, Nancy A., Zeng, Weifeng, Verhoven, Bret M., Zhong, Weixiong, Coumbe Gitter, Maya M., Fahl, William E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301928/
https://www.ncbi.nlm.nih.gov/pubmed/34356678
http://dx.doi.org/10.3390/biom11071054
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author Goesch, Torsten R.
Wilson, Nancy A.
Zeng, Weifeng
Verhoven, Bret M.
Zhong, Weixiong
Coumbe Gitter, Maya M.
Fahl, William E.
author_facet Goesch, Torsten R.
Wilson, Nancy A.
Zeng, Weifeng
Verhoven, Bret M.
Zhong, Weixiong
Coumbe Gitter, Maya M.
Fahl, William E.
author_sort Goesch, Torsten R.
collection PubMed
description Allograft kidney transplantation, which triggers host cellular- and antibody-mediated rejection of the kidney, is a major contributor to kidney damage during transplant. Here, we asked whether PrC-210 would suppress damage seen in allograft kidney transplant. Brown Norway (BN) rat kidneys were perfused in situ (UW Solution) with or without added 30 mM PrC-210, and then immediately transplanted into Lewis (LEW) rats. 20 h later, the transplanted BN kidneys and LEW rat plasma were analyzed. Kidney histology, and kidney/serum levels of several inflammation-associated cytokines, were measured to assess mismatch-related kidney pathology, and PrC-210 protective efficacy. Twenty hours after the allograft transplants: (i) significant histologic kidney tubule damage and mononuclear inflammatory cell infiltration were seen in allograft kidneys; (ii) kidney function metrics (creatinine and BUN) were significantly elevated; (iii) significant changes in key cytokines, i.e., TIMP-1, TNF-alpha and MIP-3A/CCL20, and kidney activated caspase levels were seen. In PrC-210-treated kidneys and recipient rats, (i) kidney histologic damage (Banff Scores) and mononuclear infiltration were reduced to untreated background levels; (ii) creatinine and BUN were significantly reduced; and (iii) activated caspase and cytokine changes were significantly reduced, some to background. In conclusion, the results suggest that PrC-210 could provide broadly applicable organ protection for many allograft transplantation conditions; it could protect transplanted kidneys during and after all stages of the transplantation process—from organ donation, through transportation, re-implantation and the post-operative inflammation—to minimize acute and chronic rejection.
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spelling pubmed-83019282021-07-24 Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats Goesch, Torsten R. Wilson, Nancy A. Zeng, Weifeng Verhoven, Bret M. Zhong, Weixiong Coumbe Gitter, Maya M. Fahl, William E. Biomolecules Article Allograft kidney transplantation, which triggers host cellular- and antibody-mediated rejection of the kidney, is a major contributor to kidney damage during transplant. Here, we asked whether PrC-210 would suppress damage seen in allograft kidney transplant. Brown Norway (BN) rat kidneys were perfused in situ (UW Solution) with or without added 30 mM PrC-210, and then immediately transplanted into Lewis (LEW) rats. 20 h later, the transplanted BN kidneys and LEW rat plasma were analyzed. Kidney histology, and kidney/serum levels of several inflammation-associated cytokines, were measured to assess mismatch-related kidney pathology, and PrC-210 protective efficacy. Twenty hours after the allograft transplants: (i) significant histologic kidney tubule damage and mononuclear inflammatory cell infiltration were seen in allograft kidneys; (ii) kidney function metrics (creatinine and BUN) were significantly elevated; (iii) significant changes in key cytokines, i.e., TIMP-1, TNF-alpha and MIP-3A/CCL20, and kidney activated caspase levels were seen. In PrC-210-treated kidneys and recipient rats, (i) kidney histologic damage (Banff Scores) and mononuclear infiltration were reduced to untreated background levels; (ii) creatinine and BUN were significantly reduced; and (iii) activated caspase and cytokine changes were significantly reduced, some to background. In conclusion, the results suggest that PrC-210 could provide broadly applicable organ protection for many allograft transplantation conditions; it could protect transplanted kidneys during and after all stages of the transplantation process—from organ donation, through transportation, re-implantation and the post-operative inflammation—to minimize acute and chronic rejection. MDPI 2021-07-19 /pmc/articles/PMC8301928/ /pubmed/34356678 http://dx.doi.org/10.3390/biom11071054 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Goesch, Torsten R.
Wilson, Nancy A.
Zeng, Weifeng
Verhoven, Bret M.
Zhong, Weixiong
Coumbe Gitter, Maya M.
Fahl, William E.
Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats
title Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats
title_full Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats
title_fullStr Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats
title_full_unstemmed Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats
title_short Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats
title_sort suppression of inflammation-associated kidney damage post-transplant using the new prc-210 free radical scavenger in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301928/
https://www.ncbi.nlm.nih.gov/pubmed/34356678
http://dx.doi.org/10.3390/biom11071054
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