Document Detail


Suppression of nitrosative and oxidative stress to reduce cardiac allograft vasculopathy.
MedLine Citation:
PMID:  19168728     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-kappaB 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.
Authors:
Tomomi Hasegawa; Koichiro Iwanaga; Donald E Hultquist; Hui Liao; Scott H Visovatti; David J Pinsky
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-01-23
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  296     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-31     Completed Date:  2009-06-10     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1007-16     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Graft Survival / drug effects
Heart Transplantation / adverse effects*,  physiology
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
NF-kappa B / metabolism
Nitric Oxide Synthase Type II / metabolism
Nitrosation / drug effects
Oxidative Stress / drug effects
Reactive Nitrogen Species / antagonists & inhibitors*,  metabolism
Reactive Oxygen Species / antagonists & inhibitors*,  metabolism
Reperfusion Injury / etiology,  metabolism,  prevention & control
Riboflavin / pharmacology
Transplantation, Homologous
Vascular Diseases / etiology*,  metabolism,  prevention & control*
Grant Support
ID/Acronym/Agency:
P01HL089407/HL/NHLBI NIH HHS; R01HL055397/HL/NHLBI NIH HHS; R01HL085149/HL/NHLBI NIH HHS; T32-HL-007853/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/NF-kappa B; 0/Reactive Nitrogen Species; 0/Reactive Oxygen Species; 83-88-5/Riboflavin; EC 1.14.13.39/Nitric Oxide Synthase Type II
Comments/Corrections

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