[4] The topic has since been often reviewed,[5] and one source describes the compound as "the most studied LPO (lipid peroxidation) product with pleiotropic capabilities".

[17] Special attention must also be paid to cooking oils used repeatedly in catering and households because in those processes very high amounts of OαβUAs are generated and they can be easily absorbed through the diet.

While there are other GSTs capable of this conjugation reaction (notably in the alpha class), these other isoforms are much less efficient and their production is not induced by the stress events which cause the formation of 4-HNE (such as exposure to hydrogen peroxide, ultraviolet light, heat shock, cancer drugs, etc.

This result strongly suggests that hGSTA4-4 and hGST5.8 are specifically adapted by human cells for the purpose of detoxifying 4-HNE to abrogate the downstream effects which such a buildup would cause.

Increased activity of the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) has been shown to have a protective effect against cardiac ischemia in animal models, and the postulated mechanism given by the investigators was 4-hydroxynonenal metabolism.

[19] GS-HNE is a potent inhibitor of the activity of glutathione S-transferase, and therefore must be shuttled out of the cell to allow conjugation to occur at a physiological rate.