2.2. Mechanisms to detoxify lipid electrophiles in vivo
The extent and severity of cellular damage elicited by electrophilic lipids are highly dependent on the ability of cells to clear and detoxify these aldehydes. Once formed, the cell attempts to clear electrophiles
through mechanisms involving glutathione (GSH), aldehyde dehydrogenases, aldo–keto reductases and P450 enzymes [19–28]. The first line of defense that cells utilize to eliminate reactive aldehydes
is conjugationwith glutathione (GSH) [21]. HNE is able to spontaneously form Michael adducts with GSH to form GSH conjugates. Alternatively, the conjugation of GSH to the α,β-unsaturated carbonyl can be catalyzed by glutathione-S-transferases (GSTs), including hGSTA4-4 and hGST5.8, in a reaction that proceeds several hundred times faster than the spontaneous reaction