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Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury
Overproduction of hydrogen peroxide (H(2)O(2)) causes oxidative stress and is the main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury. Suppression of oxidative stress is therefore critical in the treatment of I/R injury. Here, we report H(2)O(2)-activatable antioxidant prodrug (BRA...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643254/ https://www.ncbi.nlm.nih.gov/pubmed/26563741 http://dx.doi.org/10.1038/srep16592 |
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author | Lee, Dongwon Park, Seunggyu Bae, Soochan Jeong, Dahee Park, Minhyung Kang, Changsun Yoo, Wooyoung Samad, Mohammed A. Ke, Qingen Khang, Gilson Kang, Peter M. |
author_facet | Lee, Dongwon Park, Seunggyu Bae, Soochan Jeong, Dahee Park, Minhyung Kang, Changsun Yoo, Wooyoung Samad, Mohammed A. Ke, Qingen Khang, Gilson Kang, Peter M. |
author_sort | Lee, Dongwon |
collection | PubMed |
description | Overproduction of hydrogen peroxide (H(2)O(2)) causes oxidative stress and is the main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury. Suppression of oxidative stress is therefore critical in the treatment of I/R injury. Here, we report H(2)O(2)-activatable antioxidant prodrug (BRAP) that is capable of specifically targeting the site of oxidative stress and exerting anti-inflammatory and anti-apoptotic activities. BRAP with a self-immolative boronic ester protecting group was designed to scavenge H(2)O(2) and release HBA (p-hydroxybenzyl alcohol) with antioxidant and anti-inflammatory activities. BRAP exerted potent antioxidant and anti-inflammatory activity in lipopolysaccharide (LPS)- and H(2)O(2)-stimulated cells by suppressing the generation of ROS and pro-inflammatory cytokines. In mouse models of hepatic I/R and cardiac I/R, BRAP exerted potent antioxidant, anti-inflammatory and anti-apoptotic activities due to the synergistic effects of H(2)O(2)-scavenging boronic esters and therapeutic HBA. In addition, administration of high doses of BRAP daily for 7 days showed no renal or hepatic function abnormalities. Therefore BRAP has tremendous therapeutic potential as H(2)O(2)-activatable antioxidant prodrug for the treatment of I/R injuries. |
format | Online Article Text |
id | pubmed-4643254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46432542015-11-20 Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury Lee, Dongwon Park, Seunggyu Bae, Soochan Jeong, Dahee Park, Minhyung Kang, Changsun Yoo, Wooyoung Samad, Mohammed A. Ke, Qingen Khang, Gilson Kang, Peter M. Sci Rep Article Overproduction of hydrogen peroxide (H(2)O(2)) causes oxidative stress and is the main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury. Suppression of oxidative stress is therefore critical in the treatment of I/R injury. Here, we report H(2)O(2)-activatable antioxidant prodrug (BRAP) that is capable of specifically targeting the site of oxidative stress and exerting anti-inflammatory and anti-apoptotic activities. BRAP with a self-immolative boronic ester protecting group was designed to scavenge H(2)O(2) and release HBA (p-hydroxybenzyl alcohol) with antioxidant and anti-inflammatory activities. BRAP exerted potent antioxidant and anti-inflammatory activity in lipopolysaccharide (LPS)- and H(2)O(2)-stimulated cells by suppressing the generation of ROS and pro-inflammatory cytokines. In mouse models of hepatic I/R and cardiac I/R, BRAP exerted potent antioxidant, anti-inflammatory and anti-apoptotic activities due to the synergistic effects of H(2)O(2)-scavenging boronic esters and therapeutic HBA. In addition, administration of high doses of BRAP daily for 7 days showed no renal or hepatic function abnormalities. Therefore BRAP has tremendous therapeutic potential as H(2)O(2)-activatable antioxidant prodrug for the treatment of I/R injuries. Nature Publishing Group 2015-11-13 /pmc/articles/PMC4643254/ /pubmed/26563741 http://dx.doi.org/10.1038/srep16592 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Lee, Dongwon Park, Seunggyu Bae, Soochan Jeong, Dahee Park, Minhyung Kang, Changsun Yoo, Wooyoung Samad, Mohammed A. Ke, Qingen Khang, Gilson Kang, Peter M. Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury |
title | Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury |
title_full | Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury |
title_fullStr | Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury |
title_full_unstemmed | Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury |
title_short | Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury |
title_sort | hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643254/ https://www.ncbi.nlm.nih.gov/pubmed/26563741 http://dx.doi.org/10.1038/srep16592 |
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