Horinouchi Takahiro, Mazaki Yuichi, Miwa Soichi
Department of Cellular Pharmacology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.
Department of Cellular Pharmacology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.
J Pharmacol Sci. 2025 May;158(1):8-12. doi: 10.1016/j.jphs.2025.02.010. Epub 2025 Feb 27.
In this study, we aimed to determine the cytotoxic factors involved in ferroptosis induced by nicotine- and tar-free cigarette smoke extract (CSE) from heated tobacco products (HTPs) in vascular smooth muscle cells. CSE decreased mitochondrial metabolic activity and increased lactate dehydrogenase leakage. These cytotoxic effects completely disappeared after removing the carbonyls from the mainstream smoke. α, β-Unsaturated carbonyl compounds (acrolein, methyl vinyl ketone, crotonaldehyde, and methacrolein) in the mainstream smoke of HTPs and CSE caused cell damage, which was inhibited by a ferroptosis inhibitor, UAMC-3203. These results suggest that α, β-unsaturated carbonyl compounds might be involved in CSE-induced ferroptosis.
在本研究中，我们旨在确定加热烟草制品（HTPs）中不含尼古丁和焦油的香烟烟雾提取物（CSE）诱导血管平滑肌细胞铁死亡所涉及的细胞毒性因子。CSE降低了线粒体代谢活性并增加了乳酸脱氢酶泄漏。从主流烟雾中去除羰基后，这些细胞毒性作用完全消失。HTPs主流烟雾和CSE中的α，β-不饱和羰基化合物（丙烯醛、甲基乙烯基酮、巴豆醛和异丁烯醛）导致细胞损伤，铁死亡抑制剂UAMC-3203可抑制这种损伤。这些结果表明，α，β-不饱和羰基化合物可能参与CSE诱导的铁死亡。
