Myricetin protects natural killer cells from arsenite induced DNA damage by attenuating oxidative stress and retaining poly(ADP-Ribose) polymerase 1 activity

Huijuan Ma; Xiaodong Song; Ping Huang; Weiwei Zhang; Xinyue Ling; Xiaoning Yang; Wenwei Wu; Huan Xu; Wei Wang

doi:10.1016/j.mrgentox.2021.503337

Myricetin protects natural killer cells from arsenite induced DNA damage by attenuating oxidative stress and retaining poly(ADP-Ribose) polymerase 1 activity

Mutat Res Genet Toxicol Environ Mutagen. 2021 May:865:503337. doi: 10.1016/j.mrgentox.2021.503337. Epub 2021 Feb 19.

Authors

Huijuan Ma¹, Xiaodong Song², Ping Huang¹, Weiwei Zhang¹, Xinyue Ling¹, Xiaoning Yang¹, Wenwei Wu¹, Huan Xu³, Wei Wang⁴

Affiliations

¹ East China University of Science and Technology, State Key Laboratory of Bioreactor Engineering, Shanghai, 200237, China; East China University of Science and Technology, School of Pharmacy, Department of Pharmaceutical Sciences, Shanghai, 200237, China.
² Medical Laboratory Department, Hua Shan Hospital North, Fudan University, Shanghai, 201907, China.
³ East China University of Science and Technology, State Key Laboratory of Bioreactor Engineering, Shanghai, 200237, China; East China University of Science and Technology, School of Pharmacy, Department of Pharmaceutical Sciences, Shanghai, 200237, China. Electronic address: xuhuan@ecust.edu.cn.
⁴ East China University of Science and Technology, State Key Laboratory of Bioreactor Engineering, Shanghai, 200237, China; East China University of Science and Technology, School of Pharmacy, Department of Pharmaceutical Sciences, Shanghai, 200237, China; Department of Pharmacology and Toxicology and BIO5 Institute, University of Arizona, Tucson, AZ, 85721-0207, USA. Electronic address: wwang@pharmacy.arizona.edu.

PMID: 33865543
DOI: 10.1016/j.mrgentox.2021.503337

Abstract

Environmental exposure to arsenite (As⁺³) is known to induce immunotoxicity. Natural killer (NK) cells are innate lymphoid cells act as professional killers of tumor cells. Our previous report indicated that 500 ppb As⁺³ drinking water exposure induced significant DNA damage in the NK cells of C57BL/6 mice. Myricetin is a plant-derived flavonoid known as a strong antioxidant. In this study, daily administration of myricetin at 20 mg/kg was found to alleviate the cell population decrease and DNA damage in the NK cells of BALB/c mice exposed to 500 and 1000 ppb As⁺³ via drinking water. Oxidative stress and poly(ADP-ribose) polymerase 1 (PARP-1) inhibition were induced by As⁺³ at 1 and 2 μM in isolated mouse NK cells in vitro, which were attenuated by 20 μM myricetin. The mitigatory effect of myricetin on the PARP-1 inhibition in NK cells treated with As⁺³ was also found to be the result of its prevention of the zinc loss induced by As⁺³ on PARP-1. Collectively, these results demonstrated, for the first time, that myricetin could protect NK cells from As⁺³ induced DNA through attenuating oxidative stress and retaining PARP-1 activity, indicating that myricetin may be utilized for the prevention of the immunotoxicity induced by As⁺³ in NK cells.

Keywords: DNA damage; Genotoxicity; Myricetin; NK cells; Oxidative stress; PARP-1.

Publication types

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

MeSH terms

Animals
Arsenites / toxicity*
Cells, Cultured
Cytoprotection / drug effects
Cytoprotection / immunology
DNA Damage / drug effects
DNA Repair / drug effects
DNA Repair / genetics
Flavonoids / pharmacology*
Immunity, Innate / drug effects
Killer Cells, Natural / drug effects*
Killer Cells, Natural / metabolism
Killer Cells, Natural / pathology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Oxidative Stress / drug effects*
Oxidative Stress / genetics
Poly(ADP-ribose) Polymerases / metabolism*

Substances

Arsenites
Flavonoids
myricetin
Poly(ADP-ribose) Polymerases
arsenite