The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Original Article
Euptox A Induces G0 /GI arrest and apoptosis of hepatocyte via ROS, mitochondrial dysfunction and caspases-dependent pathways in vivo
Samuel Kumi OkyereQuan MoGao PeiZhihua RenJunliang DengYanchun Hu
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2020 年 45 巻 11 号 p. 661-671

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As a toxin of Ageratina adenophora (A. adenophora), euptox A (9-oxo-10, 11-dehydroageraphorone) is known to cause hepatotoxicity in animals. In this study, we examined the effects of euptox A on mouse liver cells and its underlying mechanisms for the first time. We found that euptox A induced liver cell cycle arrest and apoptosis in a dose-dependent manner mainly by mitochondria -related pathways, with the affected cells characterized by the appearance of DNA fragmentation, membrane blebbing, and chromatin condensation. The results showed that euptox A similarly induced hepatocyte G0 /GI arrest and apoptosis mainly by ROS accumulation and mitochondria-mediated and caspase-dependent pathways, elucidated by the loss of mitochondrial membrane potential, release of cytochrome C and AIF, activation of caspase-3/-9, Bax, as well as suppression of Bcl-2. This paper will provide new insights into the mechanisms involved in liver toxicity caused by euptox A in mice.

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© 2020 The Japanese Society of Toxicology
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