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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doaj-2602c31eb4be43ba9166f522f28b0bab2021-07-23T13:32:21ZengMDPI AGBiomolecules2218-273X2021-07-01111054105410.3390/biom11071054Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in RatsTorsten R. Goesch0Nancy A. Wilson1Weifeng Zeng2Bret M. Verhoven3Weixiong Zhong4Maya M. Coumbe Gitter5William E. Fahl6Obvia Pharmaceuticals Ltd., Madison, WI 53719, USADepartment of Surgery, Division of Organ Transplant, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Surgery, Division of Organ Transplant, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Surgery, Division of Organ Transplant, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Surgery, Division of Organ Transplant, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Oncology, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, Madison, WI 53706, USAObvia Pharmaceuticals Ltd., Madison, WI 53719, USAAllograft 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.https://www.mdpi.com/2218-273X/11/7/1054kidney allograftkidney rejectionischemia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Torsten R. Goesch Nancy A. Wilson Weifeng Zeng Bret M. Verhoven Weixiong Zhong Maya M. Coumbe Gitter William E. Fahl |
spellingShingle |
Torsten R. Goesch Nancy A. Wilson Weifeng Zeng Bret M. Verhoven Weixiong Zhong Maya M. Coumbe Gitter William E. Fahl Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats Biomolecules kidney allograft kidney rejection ischemia |
author_facet |
Torsten R. Goesch Nancy A. Wilson Weifeng Zeng Bret M. Verhoven Weixiong Zhong Maya M. Coumbe Gitter William E. Fahl |
author_sort |
Torsten R. Goesch |
title |
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_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_sort |
suppression of inflammation-associated kidney damage post-transplant using the new prc-210 free radical scavenger in rats |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2021-07-01 |
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. |
topic |
kidney allograft kidney rejection ischemia |
url |
https://www.mdpi.com/2218-273X/11/7/1054 |
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