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Ephedrine-induced mitophagy via oxidative stress in human hepatic stellate cells

Cited 12 time in Web of Science Cited 12 time in Scopus
Authors
Lee, Ah Young; Jang, Yoonjeong; Hong, Seong-Ho; Chang, Seung-Hee; Park, Sungjin; Kim, Sanghwa; Kang, Kyung-Sun; Kim, Ji-Eun; Cho, Myung-Haing
Issue Date
2017-08
Citation
Journal of Toxicological Sciences, Vol.42 No.4, pp.461-473
Keywords
EphedrineMitophagyParkinMitochondrial oxidative stressHepatotoxicity
Abstract
The herb Ephedra sinica (also known as Chinese ephedra or Ma Huang), used in traditional Chinese medicine, contains alkaloids identical to ephedrine and pseudoephedrine as its principal active constituents. Recent studies have reported that ephedrine has various side effects in the cardiovascular and nervous systems. In addition, herbal Ephedra, a plant containing many pharmacologically active alkaloids, principally ephedrine, has been reported to cause acute hepatitis. Many studies reported clinical cases, however, the cellular mechanism of liver toxicity by ephedrine remains unknown. In this study, we investigated hepatotoxicity and key regulation of mitophagy in ephedrine-treated LX-2 cells. Ephedrine triggered mitochondrial oxidative stress and depolarization. Mitochondrial swelling and autolyso-some were observed in ephedrine-treated cells. Ephedrine also inhibited mitochondrial biogenesis, and the mitochondrial copy number was decreased. Parkin siRNA recovered the ephedrine-induced mitochondrial damage. Excessive mitophagy lead to cell death through imbalance of autophagic flux. Moreover, antioxidants and reducing Parkin level could serve as therapeutic targets for ephedrine-induced hepatotoxicity.
ISSN
0388-1350
URI
https://hdl.handle.net/10371/172448
DOI
https://doi.org/10.2131/jts.42.461
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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