l-Carnitine protects against 1,4-benzoquinone-induced apoptosis and DNA damage by suppressing oxidative stress and promoting fatty acid oxidation in K562 cells.

Abstract:

:Widespread occupational and environmental exposure to benzene is unavoidable and poses a public health threat. Studies of potential interventions to prevent or relieve benzene toxicity are, thus, essential. Research has shown l-carnitine (LC) has beneficial effects against various pathological processes and diseases. LC possesses antioxidant activities and participates in fatty acid oxidation (FAO). In this study, we investigated whether 1,4-benzoquinone (1,4-BQ) affects LC levels and the FAO pathway, as well as analyzed the influence of LC on the cytotoxic effects of 1,4-BQ. We found that 1,4-BQ significantly decreased LC levels and downregulated Cpt1a, Cpt2, Crat, Hadha, Acaa2, and Acadvl mRNA expression in K562 cells. Subsequent assays confirmed that 1,4-BQ decreased cell viability and increased apoptosis and caspase-3, -8, and -9 activities. It also induced obvious oxidative stress and DNA damage, including an increase in the levels of reactive oxygen species and malondialdehyde, tail DNA%, and olive tail moment. Additionally, the mitochondrial membrane potential was significantly reduced. Cotreatment with LC (500 μmol/L) relieved these alterations by reducing oxidative stress and increasing the protein expression levels of Cpt1a and Hadha, particularly in the 20 μmol/L 1,4-BQ group. Thus, our results demonstrate that 1,4-BQ causes cytotoxicity, reduces LC levels, and downregulates the FAO genes. In contrast, LC exhibits protective effects against 1,4-BQ-induced apoptosis and DNA damage by decreasing oxidative stress and promoting the FAO pathway.

journal_name

Environ Toxicol

journal_title

Environmental toxicology

authors

Sun R,Man Z,Ji J,Ji S,Xu K,Pu Y,Yu L,Zhang J,Yin L,Pu Y

doi

10.1002/tox.22939

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

1033-1042

issue

10

eissn

1520-4081

issn

1522-7278

journal_volume

35

pub_type

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