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J Toxicol Sci. 2017;42(4):461-473. doi: 10.2131/jts.42.461.

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

Lee AY1, Jang Y1, Hong SH1,2, Chang SH1, Park S1,3, Kim S1,4, Kang KS5, Kim JE1,6, Cho MH1,7,4,8,9.

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Laboratory of Toxicology, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Korea.
Present address: New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Korea.
Present address: Department of Pharmacology and Medical Science, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Korea.
Graduate Group of Tumor Biology, Seoul National University, Korea.
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Korea.
Present address: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Canada.
Graduate School of Convergence Science and Technology, Seoul National University, Korea.
Advanced Institute of Convergence Technology, Seoul National University, Korea.
Institute of GreenBio Science Technology, Seoul National University, Korea.


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 autolysosome 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.


Ephedrine; Hepatotoxicity; Mitochondrial oxidative stress; Mitophagy; Parkin

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