Possible involvement of α, β-unsaturated carbonyl compounds in ferroptosis induced by the cigarette smoke extract of heated tobacco products in vascular smooth muscle cells.

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.