Pharmacological activation of Nrf2: Cardioprotective effects of statins and metformin against dyslipidemia-induced oxidative stress

Abstract

Oxidative stress plays a central role in dyslipidemia-related cardiovascular complications, driving cellular damage and disease progression. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is a critical defense mechanism against oxidative stress, helping to protect cardiac function under pathological conditions. This review explores the potential of enhancing Nrf2 activation as a therapeutic strategy to mitigate oxidative damage in cardiovascular diseases associated with dyslipidemia. While statins and metformin are primarily known for their lipid- and glucose-lowering effects, emerging evidence suggests that they also influence Nrf2 activation. These drugs do not directly activate Nrf2 but rather modulate its activity by reducing oxidative stress and improving mitochondrial function, offering dual protection against cardiovascular dysfunction. By examining the relationship between oxidative stress, Nrf2 activation, and commonly used therapies, this review proposes a novel approach to enhance cardiovascular protection in patients with metabolic disorders, offering insights into new therapeutic avenues to improve outcomes in cardiovascular diseases associated with metabolic conditions.

Keywords: Antioxidants; Dyslipidemia; Metformin; Nrf2 activation; Oxidative stress; Statins.