Abstract
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.
Highlights
IntroductionExposure to arsenic through contaminated groundwater is widespread in certain regions of many countries including Bangladesh, India, and China [1]
acute promyelotic leukemia (APL) is a subtype of acute myeloid leukemia (AML) that is genetically characterized by a specific chromosomal translocation that yields the promyelotic leukemia/retinoic acid receptor alpha (PML/RARA) fusion gene—a DNA-binding transcription factor [8]
In light of arsenic’s demonstrated cardiovascular toxicity and the association between mitochondrial dysfunction and reactive oxygen species (ROS), the present study explores mechanisms of arsenic toxicity and the protective action of food-based antioxidants, many of which work by scavenging antioxidants
Summary
Exposure to arsenic through contaminated groundwater is widespread in certain regions of many countries including Bangladesh, India, and China [1]. Arsenic has been characterized as a strong carcinogen [5]. Arsenic-induced reactive oxygen species (ROS) cause genetic mutations and cancer by promoting DNA damage, activating oncogenic kinases, and activating lipids and proteins that inactivate DNA repair mechanisms [6,7]. Arsenic trioxide has been used as a therapeutic agent in the treatment of acute promyelotic leukemia (APL). APL is a subtype of acute myeloid leukemia (AML) that is genetically characterized by a specific chromosomal translocation that yields the promyelotic leukemia/retinoic acid receptor alpha (PML/RARA) fusion gene—a DNA-binding transcription factor [8].
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