Sequestration and Elimination of Toxic Aldehydes.

Abstract

It is well-known that aldehydes resulting from the in vivo oxidation of primary alcohols are toxic. Here, we experimentally demonstrate in rat models that the dipeptide cysteinylglycine (CG), formed in vivo from its oxidized product, cystinyl-bis-glycine (CbG), will sequester acetaldehyde and isoamyl aldehyde, two model aldehydes resulting from the oxidation of ethanol and isoamyl alcohol, respectively, and excrete them in urine as their respective conjugation products with CG. These data suggest that a whole series of toxic aldehydes can be sequestered and detoxified by CG and may prevent the flushing syndrome exhibited by individuals with a defective enzyme that converts acetaldehyde to acetate. The data also suggest the possibility of alleviating the hangover syndrome we believe to be caused by aldehydes, such as isoamyl aldehyde derived from short, branched-chain alcohols, present as congeners in certain alcoholic beverages. The sequestration of other toxic agents, such as cyanide, that can react with CG can also be envisioned.