Cardiovascular Toxicology

, Volume 10, Issue 2, pp 73–86

Protective Role of Antioxidants in Diabetes-Induced Cardiac Dysfunction

Article

Abstract

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.

Keywords

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

Abbreviations

6PGD

6-Phosphogluconate dehydrogenase

AGEs

Advanced glycation end products

ACE

Angiotensin converting enzyme

AngII

Angiotensin II

AR

Aldose reductase

AT1

Angiotensin II type 1 receptor

CAT

Catalase

eNOS

Endothelial nitric oxide synthase

G6PD

Glucose-6-phosphate dehydrogenase

GR

Glutathione reductase

GSH

Glutathione

GSH-Px

Glutathione peroxidase

GSSG

Oxidized glutathione

GSSH

Reduced glutathione

GST

Glutathione-S-transferase

OH

Hydroxyl radical

H2O2

Hydrogen peroxide

iNOS

Inducible nitric oxide synthase

LV

Left ventricular

MMPs

Matrix metalloproteinases

MnSOD/SOD2

Manganese superoxide dismutase

MT

Metallothionein

NAC

N-acetyl-l-cysteine

NADPH

Nicotinamide adenine dinucleotide phosphate

NO

Nitric oxide radical

NOS

Nitric oxide synthase

NOX

Nicotinamide adenine dinucleotide phosphate oxidase

NF-κB

Nuclear factor-kappa B

O2

Oxygen ion

O2

Superoxide radical

PARP

Poly(ADP-ribose) polymerase

PGC-1α

PPARγ coactivator-1α

PKA

Protein kinase A

PKC

Protein kinase C

PPARs

Peroxisome proliferator–activated receptors

PPARα, γ

Peroxisome proliferator–activated receptor α, γ

ROS

Reactive oxygen species

RNS

Reactive nitrogen species

RAS

Renin–angiotensin system

RyR2

Ryanodine receptor type 2

SR

Sarcoplasmic reticulum

SERCA

Sarco/endoplasmic reticulum Ca2+ ATPase

SOD

Superoxide dismutase

STZ

Streptozotocin

TBARS

Thiobarbituric acid-reactive substances

Trx

Thioredoxin

Trx-R

Thioredoxine reductase

Trx-P

Thioredoxine peroxidase

UCP

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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