title: Myricitrin protects against peroxynitrite-mediated DNA damage and cytotoxicity in astrocytes.
abstract: Peroxynitrite, a potent oxidising and nitrating species, has been implicated in the pathogenesis of neurodegenerative diseases. This study was undertaken to investigate the protective effect of myricitrin on peroxynitrite-mediated toxicity and the underlying mechanism. Our results showed that the presence of myricitrin was found to significantly inhibit peroxynitrite-mediated DNA damage. EPR spectroscopy demonstrated that myricitrin potently diminished the DMPO-hydroxyl radical adduct signal from peroxynitrite. Further study showed that glutathione (GSH) depletion caused by peroxynitrite can be effectively prevented by pre-incubation of astrocytes with myricitrin. Moreover, co-incubation of astrocytes with myricitrin and buthionine sulfoximine (BSO) eliminated the myricitrin-induced GSH increase. In contrast, co-incubation of myricitrin with BSO slightly protected astrocytes against cytotoxicity and DNA damage mediated by peroxynitrite. These results revealed that myricitrin can protect against peroxynitrite-induced DNA damage and cytotoxicity, which might have implications for myricitrin-mediated neuroprotection.
authors.affiliation: Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China. zjuchenwei@zju.edu.cn
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhuang
authors.forename: Ya
authors.initials: Y
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D031641:Myrica / Q000737:chemistry*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D018696:Neuroprotective Agents; D030421:Peroxynitrous Acid; C008577:myricitrin; D005978:Glutathione