Myricitrin protects against peroxynitrite-mediated DNA damage and cytotoxicity in astrocytes

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.