Acetaldehyde and malondialdehyde react together to generate distinct protein adducts in the liver during long-term ethanol administration

✍ Scribed by D J Tuma; G M Thiele; D Xu; L W Klassen; M F Sorrell

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 276 KB
• Volume: 23
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510230431

✦ Synopsis

and generate hybrid adducts (MAA-adducts) and further Acetaldehyde and the lipid peroxidation-derived aldesuggest that MAA adducts may represent a major species hyde malondialdehyde (MDA), are reactive compounds of adducts formed in the liver during ethanol metabothat are generated during ethanol metabolism in the lism in vivo. (HEPATOLOGY 1996;23:872-880.) liver, and both aldehydes have been shown to be capable of binding to proteins and forming stable adducts. Because similar concentrations of MDA and acetaldehyde Numerous studies have shown that acetaldehyde can can coexist in the liver during ethanol oxidation, protein covalently react with proteins in vitro under physiologiadduct formation in the presence of both of these aldecal conditions to form both stable and unstable adhydes was studied under both in vitro and in vivo condiducts. Because of this chemical reactivity, the covations. When proteins were incubated in the presence of lent binding of acetaldehyde to hepatic proteins has both MDA and acetaldehyde, MDA caused a marked and been proposed as a key event leading to alcohol-induced concentration-dependent increase in the stable binding liver injury. Many groups have demonstrated by imof acetaldehyde to proteins. Maximum stimulation of binding occurred at approximately a fourfold molar ex-munoassays, using antibodies directed against acetalcess of MDA relative to acetaldehyde when concentradehyde-modified proteins, the presence of acetaldehyde tions of 1.0 mmol/L and 0.1 mmol/L were tested. The foradducts in the livers of rats, 5-7 guinea pigs, 8 and humation of highly fluorescent product or products was mans 9 chronically consuming ethanol. However, the associated with the MDA stimulation of acetaldehyde nature or chemical structures of these adducts that binding, indicating that new and distinct products were form in vivo have not been characterized, and conflictbeing generated. These hybrid adducts of MDA and aceting results in the literature concerning the nature, subaldehyde have been designated as MAA adducts. An afcellular distribution, and identity of these adducts have finity-purified polyclonal antibody was produced that been reported. 10 specifically recognized MAA epitopes on proteins and Several studies have suggested that chronic ethanol did not cross-react with carrier proteins or proteins modified with either acetaldehyde or MDA alone. A consumption induces hepatic lipid peroxidation, which quantitative competitive enzyme-linked immunosorin turn generates another reactive aldehyde, malondibent assay (ELISA) was developed and detected the presaldehyde (MDA). 11-13 MDA-protein adducts have been ence of MAA-modified proteins in liver cytosol from ethdetected in the liver after administration of agents that anol-fed rats but not in pair-fed controls. Quantification promote lipid peroxidation such as carbon tetrachloof the data from the competitive ELISA indicated the ride, 14 iron overload, 15 and, more recently, long-term presence of approximately 75 pmoles protein-bound ethanol feeding. Because similar concentrations of ac-MAA per milligram liver cytosol proteins of the ethanoletaldehyde and MDA can coexist in the liver during fed animals. These results indicate that acetaldehyde ethanol metabolism, 17 it is not surprising that both and MDA can react together in a synergistic manner acetaldehyde and MDA adducts have been detected in livers of ethanol-fed animals. Although both aldehydes alone are capable of adduct formation with pro-Abbreviations: MDA, malondialdehyde; BSA, bovine serum albumin; teins, the influence of the presence of both acetalde-ELISA, enzyme-linked immunosorbent assay; MAA, malondialdehyde-acetaldehyde adducts.