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Environ Toxicol Pharmacol. 2017 Jun;52:38-46. doi: 10.1016/j.etap.2017.03.007. Epub 2017 Mar 9.

Cadmium and α-lipoic acid activate similar de novo synthesis and recycling pathways for glutathione balance.

Author information

1
Department of Health Sciences, CUValles, University of Guadalajara, Guadalajara - Ameca Rd Km. 45.5, Ameca, Jalisco, 46600, Mexico; Laboratory of Immunology, Department of Physiology, CUCS, University of Guadalajara, 950 Sierra Mojada St., Guadalajara, Jalisco, 44340, Mexico. Electronic address: josemacias@valles.udg.mx.
2
Department of Medical and Life Sciences, CUCienega, University of Guadalajara, 1115 Universidad Ave., Ocotlán, Jalisco, 47820, Mexico.
3
Department of Microbiology and Pathology, CUCS, University of Guadalajara, 950 Sierra Mojada St., Guadalajara, Jalisco, 44340, Mexico.
4
Laboratory of Immunology, Department of Physiology, CUCS, University of Guadalajara, 950 Sierra Mojada St., Guadalajara, Jalisco, 44340, Mexico.

Abstract

Glutathione (GSH) protects cells against oxidative stress. Redox modifiers induce GSH biosynthesis and recycling to maintain reduced environment inside cells. Cadmium (Cd2+) is a heavy metal that activates redox-sensitive transcriptional factors. The antioxidant α-lipoic acid (ALA) has shown to modulate GSH pathways. This study aimed to investigate de novo synthesis and recycling pathways for GSH balance by different Cd2+ concentrations and ALA in HepG2 cells. ALA activates Nrf2 pathway leading to GSH increment. Pre-treatment with 1μM Cd2+ or ALA produces tolerance to 5μM Cd2+ toxic effects. 5μM Cd2+ exposure significantly augmented nuclear Nrf2, GSH and GCLC, GCLM, HMOX1, TNFα and IL-6 mRNA expression but not GSR, however these upsurges were significantly abrogated by ALA or 1μM Cd2+ pre-treatments. Exposure to low Cd2+ concentration generate timely protective responses, similar to that elicited by ALA, maintaining a normal redox balance inside the cell due to GSH replenishment.

KEYWORDS:

-γ-GCL; Cadmium; GSR; Glutathione; Nrf2; α-Lipoic acid

PMID:
28366867
DOI:
10.1016/j.etap.2017.03.007
[Indexed for MEDLINE]

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