The Pathogenesis of Xenobiotic-Induced Oxidative Stress in the Cardiac Microenvironment
Journal Title: Advances in Clinical Toxicology - Year 2019, Vol 4, Issue 3
Abstract
The heart functions to ensure optimal perfusion of every organ while maintaining elasticity and compliance. Mainly composed of cardiac myocytes, fibroblasts, endothelial and vascular cells, the heart has the highest energy demand of all organs. Thus, it requires a high rate of adenosine triphosphate (ATP) production to maintain normal physiological function. Using oxidative phosphorylation, the heart produces ATP and concomitantly produces reactive oxidative species (ROS). Therefore, normal homeostasis and mitochondrial metabolism make the heart extremely susceptible to intrinsic and extrinsic oxidative stress. Exogenous foreign agents or aberrantly expressed endogenous molecules are characterized as cardiac xenobiotics (CX) which promote cardiac-specific toxicity. CX enter the body via nutritional and drug intake or environmental exposure and cause an imbalance in ROS production and antioxidant protection within the cardiac microenvironment. Chronic ROS exposure alters the cellular and molecular physiology of key detoxifying enzymes which modify cardiovascular structure and function. The heart has a tightly controlled antioxidant system that manages ROS and maintains homeostasis within the cardiac microenvironment. This strictly regulated system consists of endogenous enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and exogenous antioxidants such as vitamins, minerals, polyphenols and carotenoids derived from nutritional sources. Sustained levels of cardiac xenobiotics can result in chronically imbalanced ROS production that outpaces the antioxidant system. Over time this imbalanced system results in irreversible cellular and subcellular damage, altering cardiac structure and function and increasing the risk of cardiac dysfunctions such as maladaptive left ventricular hypertrophy, cardiac fibrosis and heart failure.
Authors and Affiliations
Thomas SH, Gipson N, Vaughn J, Omeler C, Dawkins NL and Bradford CN1*
Keywords
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- EP ID EP751669
- DOI 10.23880/act-16000165
- Views 21
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