Cytoprotective Effect of Alpha-Lipoic Acid on Paraquat-Exposed Human Bronchial Epithelial Cells <i>via</i> Activation of Nuclear Factor Erythroid Related Factor-2 Pathway

Abstract

Alpha-lipoic acid (LA), a metabolic antioxidant, is a natural compound and its biological function has been well studied in various human diseases. The present study was designed to investigate the cytoprotective effect and the molecular mechanisms of LA in paraquat (PQ)-induced oxidative stress injury using BEAS-2B human bronchial epithelial cells. LA co-treatment prevented PQ-induced BEAS-2B cell death. LA also prevented PQ-induced increases in total reactive oxygen species (ROS), lactate dehydrogenase (LDH) and malondialdehyde (MDA). LA also increased the expression of detoxifying phase II enzyme encoding genes and antioxidant genes including HO-1, NQO1, CAT, GPX3 and GPX4, resulting in the attenuation of the decreases of antioxidants during PQ-induced oxidative stress. Nuclear factor erythroid related factor 2 (Nrf2) was induced by LA. Additionally, translocation of Nrf2 from the cytoplasm to the nucleus was promoted by LA treatment. While LA was responsible for the upregulation of Nrf2, it also activated and up-regulated the downstream proteins heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) quinone oxidoreductase 1 (NQO1). The data collectively suggest that the beneficial effect of LA involving the activation of cytoprotective antioxidant genes make LA a potential candidate in the prevention of PQ-induced oxidative stress-related bronchial cell death, pending clinically relevant studies.

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

“…Lipoic acid protects against the effects of Bisphenol A or Bi-n-butyl phthalate on testicular mitochondrial toxicity [210,211]. In various other models it also protects against the toxic effects of acetaminophen [212], acrolein [213], cyclosporine [214], indomethacin [215], paraquat [216] and rotenone [217] as well as cypermethrin [218], dimethoate, glyphosate and zineb [219],chrysene [220] lindane [221] and Tetrachlorodibenzodioxin [222]. Lipoic acid and other antioxidants have also been used in the clinical management and prevention of heavy metal intoxication [223].…”

Paeonol extracted from Paeonia suffruticosa Andr. ameliorated UVB‐induced skin photoaging via DLD/Nrf2/ARE and MAPK/AP‐1 pathway

“…Reports also showed that DLD could convert dihydrolipoic acid into α‐lipoic acid in cell culture (Bratic & Trifunovic, ). Interestingly, α‐lipoic acid activates two major regulators of cytoprotective response to oxidative stress, Nrf2 and HO‐1 (Y. S. Kim et al, ), which suggests that DLD not only acts as a target of ROS but also plays an important role in the cellular defense against oxidative stress. In this study, DLD was investigated as a potential target by which UVB radiation could impact the Nrf2/ARE pathway.…”

“…DLD is an integral component of the multienzyme complex, which is composed of pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and α-keto acid dehydrogenase (Patel & Hong, 1998). This is particularly noteworthy, as α-keto acid dehydrogenase has been identified as a potential primary target of ROS (Y. S. Kim, Podder, & Song, 2013). Reports also showed that DLD could convert dihydrolipoic acid into α-lipoic acid in cell culture (Bratic & Trifunovic, 2010).…”

Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage

“…injection in old rats was able to enhance nuclear Nrf2 levels and to induce Nrf2 binding to ARE, with the resulting increase of GSH levels [32]. An array of studies and researches with different experimental models confirmed that ALA is an effective chemoprotective agent and that its action is mediated by Nrf2 in many contexts [48][49][50][51][52].…”