The underlying mechanisms involved in arsenic-induced cardiovascular toxicity

Introduction: Heavy metals exposure can effect different parts of the body, such as the cardiovascular system. Cardiovascular dysfunction is one of the leading causes of morbidity and mortality around the world. One of the most commonly associated with the toxicity of the cardiovascular system is arsenic. This review provides an updated summary of the underlying pathobiology of arsenic cardiotoxicity and provides information about cardiac health effects associated with some medicinal plants in arsenic toxicity. Methods: Appropriate keywords were used to search through PubMed, Google Scholar, and Scopus. All relevant results published from 1990 to date were chosen for final review. Results: The most important mechanisms of arsenic cardiotoxicity is oxidative stress, DNA damage, apoptosis and ion channels dysfunction. Numerous studies have shown the interference of MAPK signaling pathways, caspase activation, mitochondrial disruption and p53 in arsenic induced apoptosis. Arsenic trioxide as an effective and potent antitumor agent has major limitations such as T wave changes, QT prolongation and sudden death in humans. Discussion: Arsenic is a trace metalloid found in the environment. Many people are chronically exposed to arsenic contamination. Arsenic toxicity is well documented as it severely affects human health. Cardiotoxicity is an essential consideration in the evaluation of As2O3 because myocardial damage might be irreversible and lethal. Multiple studies have reported that arsenic exposure decreases GSH levels, especially cardiac glutathione. It also reduces total thiol contents and increases the levels of oxidized glutathione (GSSG), DNA damage, lipid peroxidation, and protein carbonyl content. Several investigations have provided experimental evidence that arsenic binds to the SH-group of GSH or proteins with high cysteine content, which may lead to the accumulation of ROS. Importantly, ROS-mitochondrial disruption, caspase activation, MAPK signaling, and p53 are the pathways for arsenic-induced apoptosis. Arsenic may induce atherosclerosis directly by increasing mRNA transcripts of growth factors such as GMCSF, TGF, and the inflammatory cytokines like tumor necrosis factor-a and interleukin-6. Importantly, arsenic exposure enhances the aggregation of platelets and increases plasminogen activator inhibitor type-1 (PAI-1) expression and thus leading to reduced fibrinolysis. Moreover, arsenic increases the levels of intracellular oxidized glutathione (GSSG) in endothelial cells to induce oxidative stress, which may cause atherosclerosis. Besides, the activations of NF- kB were increased in mice and human aortic endothelial cells exposed to arsenic.

کلیدواژه ها:

heavy metals ، arsenic ، cardiovascular toxicity ، apoptosis