ultimately, excreted from the body in urine Additionally, the aldehyde moiety of HNE can either be reduced into alcohol or oxidized into acid in reactions catalyzed by alcohol dehydrogenase, aldo–keto reductases and aldehyde dehydrogenase, respectively. Specifically, alcohol dehydrogenase and aldo–keto reductases (AKRs) catalyze the reduction of 4-hydroxyalkenals and their GSH-conjugates to 1,4-ihydroxy-2- nonene (DHN) or GSH-DHN,which are less toxic and able to be efficiently cleared from the cell [21–26]. Reduction of GSH-HNE stabilizes the Michael adduct and improves its likelihood of clearance. Aldo–keto reductases have been shown to be upregulated in response to oxidative damage, emphasizing the importance of AKRs in detoxification during oxidative stress [33,34]. Alternatively, aldehyde dehydrogenases catalyze the oxidation of HNE to form 4-hydroxy-2-nonenoic acid (HNEA). Cytochrome P450 can also contribute to the clearance of reactive aldehydes [27,28]. At low levels, α,β-unsaturated aldehydes are oxidized by mammalian P450 enzymes to their carboxylic acid derivatives [27]. Additionally, P450 has been shown to catalyze the reduction of α,β-unsaturated aldehydes to their alcohol form in vivo [28]. Thus, redundantmechanisms for the detoxification and clearance of reactive lipid electrophiles exist to efficiently scavenge such reactive species and prevent cytotoxicity