Cardiovascular Toxicology

, Volume 10, Issue 2, pp 73–86

Protective Role of Antioxidants in Diabetes-Induced Cardiac Dysfunction



Cardiac dysfunction occurs during type 1 and type 2 diabetes and results from multiple parameters including glucotoxicity, lipotoxicity, fibrosis and mitochondrial uncoupling. Oxidative stress arises from an imbalance between the production of ROS and the biological system’s ability to readily detoxify the reactive intermediates. It is involved in the etiology of diabetes-induced downregulation of heart function. Several studies have reported beneficial effects of a therapy with antioxidant agents, including trace elements and other antioxidants, against the cardiovascular system consequences of diabetes. Antioxidants act through one of three mechanisms to prevent oxidant-induced cell damages. They can reduce the generation of ROS, scavenge ROS, or interfere with ROS-induced alterations. Modulating mitochondrial activity is an important possibility to control ROS production. Hence, the use of PPARα agonist to reduce fatty acid oxidation and of trace elements such as zinc and selenium as antioxidants, and physical exercise to induce mitochondrial adaptation, contribute to the prevention of diabetes-induced cardiac dysfunction. The paradigm that inhibiting the overproduction of superoxides and peroxides would prevent cardiac dysfunction in diabetes has been difficult to verify using conventional antioxidants like vitamin E. That led to use of catalytic antioxidants such as SOD/CAT mimetics. Moreover, increases in ROS trigger a cascade of pathological events, including activation of MMPs, PPARs and protein O-GlcNAcation. Multiple tools have been developed to counteract these alterations. Hence, well-tuned, balanced and responsive antioxidant defense systems are vital for proper prevention against diabetic damage. This review aims to summarize our present knowledge on various strategies to control oxidative stress and antagonize cardiac dysfunction during diabetes.


Oxidative stress Reactive oxygen species Reactive nitrogen species Selenium Doxycycline Hyperglycemia Intracellular calcium ion Heart function 



6-Phosphogluconate dehydrogenase


Advanced glycation end products


Angiotensin converting enzyme


Angiotensin II


Aldose reductase


Angiotensin II type 1 receptor




Endothelial nitric oxide synthase


Glucose-6-phosphate dehydrogenase


Glutathione reductase




Glutathione peroxidase


Oxidized glutathione


Reduced glutathione




Hydroxyl radical


Hydrogen peroxide


Inducible nitric oxide synthase


Left ventricular


Matrix metalloproteinases


Manganese superoxide dismutase






Nicotinamide adenine dinucleotide phosphate


Nitric oxide radical


Nitric oxide synthase


Nicotinamide adenine dinucleotide phosphate oxidase


Nuclear factor-kappa B


Oxygen ion


Superoxide radical


Poly(ADP-ribose) polymerase


PPARγ coactivator-1α


Protein kinase A


Protein kinase C


Peroxisome proliferator–activated receptors

PPARα, γ

Peroxisome proliferator–activated receptor α, γ


Reactive oxygen species


Reactive nitrogen species


Renin–angiotensin system


Ryanodine receptor type 2


Sarcoplasmic reticulum


Sarco/endoplasmic reticulum Ca2+ ATPase


Superoxide dismutase




Thiobarbituric acid-reactive substances




Thioredoxine reductase


Thioredoxine peroxidase


Uncoupling protein


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.INSERM U-637, Physiopathologie Cardiovasculaire, CHU Arnaud de VilleneuveMontpellierFrance
  2. 2.Department of Biophysics, Faculty of MedicineAnkara UniversityAnkaraTurkey

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