Natural and synthetic antioxidants targeting cardiac oxidative stress and redox signaling in cardiometabolic diseases

Free Radic Biol Med. 2021 Jun:169:446-477. doi: 10.1016/j.freeradbiomed.2021.03.045. Epub 2021 Apr 24.

Abstract

Cardiometabolic diseases (CMDs) are metabolic diseases (e.g., obesity, diabetes, atherosclerosis, rare genetic metabolic diseases, etc.) associated with cardiac pathologies. Pathophysiology of most CMDs involves increased production of reactive oxygen species and impaired antioxidant defense systems, resulting in cardiac oxidative stress (OxS). To alleviate OxS, various antioxidants have been investigated in several diseases with conflicting results. Here we review the effect of CMDs on cardiac redox homeostasis, the role of OxS in cardiac pathologies, as well as experimental and clinical data on the therapeutic potential of natural antioxidants (including resveratrol, quercetin, curcumin, vitamins A, C, and E, coenzyme Q10, etc.), synthetic antioxidants (including N-acetylcysteine, SOD mimetics, mitoTEMPO, SkQ1, etc.), and promoters of antioxidant enzymes in CMDs. As no antioxidant indicated for the prevention and/or treatment of CMDs has reached the market despite the large number of preclinical and clinical studies, a sizeable translational gap is evident in this field. Thus, we also highlight potential underlying factors that may contribute to the failure of translation of antioxidant therapies in CMDs.

Keywords: Antioxidant vitamins; Antioxidants; Cardiometabolic diseases (CMDs); Cardioprotection; Oxidative stress (OxS); Polyphenols; Synthetic antioxidants; Translational gaps.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antioxidants*
  • Cardiovascular Diseases* / drug therapy
  • Humans
  • Oxidation-Reduction
  • Oxidative Stress
  • Reactive Oxygen Species

Substances

  • Antioxidants
  • Reactive Oxygen Species