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Resveratrol protects against arsenic trioxide‐induced oxidative damage through maintenance of glutathione homeostasis and inhibition of apoptotic progression
Author(s) -
Chen Chengzhi,
Jiang Xuejun,
Lai Yanhao,
Liu Yuan,
Zhang Zunzhen
Publication year - 2015
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.21919
Subject(s) - resveratrol , arsenic trioxide , glutathione , oxidative stress , reactive oxygen species , dna damage , apoptosis , chemistry , lipid peroxidation , pharmacology , biochemistry , biology , dna , enzyme
Arsenic trioxide (As 2 O 3 ) is commonly used to treat acute promyelocytic leukemia and solid tumors. However, the clinical application of the agent is limited by its cyto‐ and genotoxic effects on normal cells. Thus, relief of As 2 O 3 toxicity in normal cells is essentially necessary for improvement of As 2 O 3 ‐mediated chemotherapy. In this study, we have identified a series of protective effects of resveratrol against As 2 O 3 ‐induced oxidative damage in normal human bronchial epithelial (HBE) cells. We showed that treatment of HBE cells with resveratrol significantly reduced cellular levels of DNA damage, chromosomal breakage, and apoptosis induced by As 2 O 3 . The effect of resveratrol against DNA damage was associated with a decreased level of reactive oxygen species and lipid peroxidation in cells treated by As 2 O 3 , suggesting that resveratrol protects against As 2 O 3 toxicity via a cellular anti‐oxidative stress pathway. Further analysis of the roles of resveratrol demonstrated that it modulated biosynthesis, recycling, and consumption of glutathione (GSH), thereby promoting GSH homeostasis in HBE cells treated by As 2 O 3 . This was further supported by results showing that resveratrol prevented an increase in the activities and levels of caspases, Fas, Fas‐L, and cytochrome c proteins induced by As 2 O 3 . Our study indicates that resveratrol relieves As 2 O 3 ‐induced oxidative damage in normal human lung cells via maintenance of GSH homeostasis and suppression of apoptosis. Environ. Mol. Mutagen. 56:333–346, 2015. © 2014 Wiley Periodicals, Inc.