Antioxidants Protect against Arsenic Induced Mitochondrial Cardio-Toxicity

Arsenic is a potent cardiovascular toxicant associated with numerous biomarkers of cardiovascular diseases in exposed human populations. Arsenic is also a carcinogen, yet arsenic trioxide is used as a therapeutic agent in the treatment of acute promyelotic leukemia (APL). The therapeutic use of arsenic is limited due to its severe cardiovascular side effects. Many of the toxic effects of arsenic are mediated by mitochondrial dysfunction and related to arsenic's effect on oxidative stress. Therefore, we investigated the effectiveness of antioxidants against arsenic induced cardiovascular dysfunction. A growing body of evidence suggests that antioxidant phytonutrients may ameliorate the toxic effects of arsenic on mitochondria by scavenging free radicals. This review identifies 21 antioxidants that can effectively reverse mitochondrial dysfunction and oxidative stress in cardiovascular cells and tissues. In addition, we propose that antioxidants have the potential to improve the cardiovascular health of millions of people chronically exposed to elevated arsenic concentrations through contaminated water supplies or used to treat certain types of leukemias. Importantly, we identify conceptual gaps in research and development of new mito-protective antioxidants and suggest avenues for future research to improve bioavailability of antioxidants and distribution to target tissues in order reduce arsenic-induced cardiovascular toxicity in a real-world context.