DETECTION OF CIRCULATING ANTIBODIES TO MALONDIALDEHYDE-ACETALDEHYDE ADDUCTS IN ETHANOL-FED RATS

Background & Aims: Malondialdehyde and acetaldehyde react together wit h proteins and form hybrid protein conjugates designated as MAA adduct s, which have been detected in livers of ethanol-fed rats. The aim of this study was to examine the immune response to MAA adducts and other aldehyde adducts during long-term ethanol exposure. Methods: Rats wer e pair-fed for 7 months with a liquid diet containing either ethanol o r isocaloric carbohydrate. Circulating antibody titers against MAA add ucts and acetaldehyde adducts were measured and characterized in these animals. Results: A significant increase in antibody titers against M AA-adducted proteins was observed in the ethanol-fed animals. Competit ive inhibitions of antibody binding indicated that the circulating ant ibodies against MAA-modified proteins in the ethanol-fed rats recogniz ed mainly a specific, chemically defined MAA epitope, Antibody titers to reduced and nonreduced acetaldehyde adducts were very low, and no s ignificant differences were observed between ethanol-fed and control a nimals. Significant plasma immunoreactivity to not only MAA-adducted b ut also unmodified rat liver proteins (cytosol, microsomes, and especi ally plasma membrane) were also observed in the ethanol-fed rats. Conc lusions: Long-term ethanol feeding generates circulating antibodies no t only against MAA epitopes but possibly also against unmodified, nati ve (self) protein epitopes, suggesting that MAA adducts could trigger harmful autoimmune responses.