The role of oxidative stress in ischaemic heart disease has been thoroughly investigated in humans. Increased levels of ROS (reactive oxygen species) and RNS (reactive nitrogen species) have been demonstrated during ischaemia and post-ischaemic reperfusion in humans. Depending on their concentrations, these reactive species can act either as benevolent molecules that promote cell survival (at low-to-moderate concentrations) or can induce irreversible cellular damage and death (at high concentrations). Although high ROS levels can induce NF-κB (nuclear factor κB) activation, inflammation, apoptosis or necrosis, low-to-moderate levels can enhance the antioxidant response, via Nrf2 (nuclear factor-erythroid 2-related factor 2) activation. However, a clear definition of these concentration thresholds remains to be established. Although a number of experimental studies have demonstrated that oxidative stress plays a major role in heart ischaemia/reperfusion pathophysiology, controlled clinical trials have failed to prove the efficacy of antioxidants in acute or long-term treatments of ischaemic heart disease. Oral doses of vitamin C are not sufficient to promote ROS scavenging and only down-regulate their production via NADPH oxidase, a biological effect shared by vitamin E to abrogate oxidative stress. However, infusion of vitamin C at doses high enough to achieve plasma levels of 10 mmol/l should prevent superoxide production and the pathophysiological cascade of deleterious heart effects. In turn, n−3 PUFA (polyunsaturated fatty acid) exposure leads to enhanced activity of antioxidant enzymes. In the present review, we present evidence to support the molecular basis for a novel pharmacological strategy using these antioxidant vitamins plus n−3 PUFAs for cardioprotection in clinical settings, such as post-operative atrial fibrillation, percutaneous coronary intervention following acute myocardial infarction and other events that are associated with ischaemia/reperfusion.
Skip Nav Destination
Article navigation
Review Article|
September 07 2012
Cardioprotection against ischaemia/reperfusion by vitamins C and E plus n−3 fatty acids: molecular mechanisms and potential clinical applications
Ramón Rodrigo;
*Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile. Santiago, Chile
Dr Ramón Rodrigo (email [email protected]).
Search for other works by this author on:
Juan C. Prieto;
Juan C. Prieto
*Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile. Santiago, Chile
†Department of Cardiology, Clinical Hospital, University of Chile. Santiago, Chile
Search for other works by this author on:
Rodrigo Castillo
Rodrigo Castillo
‡Pathophysiology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
December 16 2011
Revision Received:
May 25 2012
Accepted:
June 08 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2013 Biochemical Society
2013
Clin Sci (Lond) (2013) 124 (1): 1–15.
Article history
Received:
December 16 2011
Revision Received:
May 25 2012
Accepted:
June 08 2012
Citation
Ramón Rodrigo, Juan C. Prieto, Rodrigo Castillo; Cardioprotection against ischaemia/reperfusion by vitamins C and E plus n−3 fatty acids: molecular mechanisms and potential clinical applications. Clin Sci (Lond) 1 January 2013; 124 (1): 1–15. doi: https://doi.org/10.1042/CS20110663
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |