4.1 Article

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

期刊

JOURNAL OF TOXICOLOGICAL SCIENCES
卷 42, 期 4, 页码 461-473

出版社

JAPANESE SOC TOXICOLOGICAL SCIENCES
DOI: 10.2131/jts.42.461

关键词

Ephedrine; Mitophagy; Parkin; Mitochondrial oxidative stress; Hepatotoxicity

资金

  1. BK21 PLUS Program for Creative Veterinary Science Research

向作者/读者索取更多资源

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.

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