Suppression of nitrosative and oxidative stress to reduce cardiac allograft vasculopathy

Author:

Hasegawa Tomomi,Iwanaga Koichiro,Hultquist Donald E.,Liao Hui,Visovatti Scott H.,Pinsky David J.

Abstract

Oxidant injury occurs when an organ is severed from its native blood supply and then reperfused and continues during subsequent periods of immune attack. Experiments here test the hypothesis that an antioxidant given only in the peri-reperfusion period protects against not only oxidative but also nitrosative stress, leading to reduced vasculopathy long after cardiac allotransplantation. Experiments were performed using a murine heterotopic cardiac transplantation model. An antioxidant, in the form of intraperitoneal high-dose riboflavin, was given to recipients during the initial 3 days after transplantation. Antioxidant-treated mice showed significantly longer graft survival than control mice. At 4 h after transplantation, antioxidant treatment significantly reduced graft lipid peroxidation and oxidized DNA and preserved antioxidant enzyme activity. At day 6 posttransplantation, the redox-sensitive transcription factor nuclear factor-κB and inducible nitric oxide synthase were significantly reduced following antioxidant treatment, with concomitant reduction of nitrotyrosine. Despite the limited duration of antioxidant treatment, both acute and chronic rejection were significantly suppressed. In vitro experiments confirmed suppression of nitrosative and oxidative stress and cardiomyocyte damage in antioxidant-treated cardiac allografts. Collectively, antioxidant administration during the initial 3 days after transplantation significantly reduces nitrosative and oxidative stress in cardiac allografts, modulates immune responses, and protects against vasculopathy.

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3