Journal
JOURNAL OF TOXICOLOGICAL SCIENCES
Volume 45, Issue 11, Pages 661-671Publisher
JAPANESE SOC TOXICOLOGICAL SCIENCES
DOI: 10.2131/jts.45.661
Keywords
Ageratina adenophora; Euptox A; GO/G1 arrest; Apoptosis; Reactive oxygen species (ROS); Mitochondrial-related pathway
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Funding
- Key Research & development Project of Sichuan Province [2015SZ0201, 2020YFS0337]
- Science and Technology Support Program
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As a toxin of Ageratina adenophora (A. adenophora), euptox A (9-oxo-10, 11-dehy-droageraphorone) 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 AIR 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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