Experimental heart muscle damage in alcohol feeding is associated with increased amounts of reduced- and unreduced-acetaldehyde and malondialdehyde-acetaldehyde protein adducts.
Chronic and excessive alcohol consumption induces defined myocardial lesions characterized by impaired structural, mechanical and biochemical features. The pathogenic mechanisms are unknown, although it is possible that protein adduct formation by reactive metabolites of ethanol may be a contributory process. Hitherto, this has only been tested with respect to antibodies against reduced-acetaldehyde protein adducts in clinical studies, despite the fact that during alcohol toxicity the formation of reduced-acetaldehyde, unreduced-acetaldehyde, malondialdehyde, malondialdehyde-acetaldehyde and hydroxyethyl protein adducts have been reported in non-cardiac tissues. It was our hypothesis that the heart is particularly sensitive to the formation of protein adducts in alcohol toxicity.To test this hypothesis, we analysed hearts from rats fed nutritionally complete liquid diets containing ethanol as 35% of total calories for 6 weeks, using the Lieber-DeCarli pair-feeding protocol. Control rats were treated identically and fed the same diet in which ethanol was replaced by isocaloric glucose. At the end of the feeding period, the hearts were dissected and ventricular muscle analysed. After 6 weeks' ethanol feeding, ELISA analysis showed increased amounts of reduced-acetaldehyde protein adducts (p < 0.01) unreduced-acetaldehyde (p < 0.01) and malondialdehyde-acetaldehyde (p= 0.01) protein adducts. However, malondialdehyde and alpha-hydroxyethyl-protein adducts were not significantly increased in hearts of ethanol-fed rats compared to pair-fed control (p > 0.1 in both instances). This is the first report of acetaldehyde adduct formation in alcoholic cardiomyopathy. This suggests that either immune process may develop or functional impairment of affected proteins may occur.
Worrall
S
S
Alcohol Research Unit, Department of Biochemistry, The University of Queensland, Brisbane, Queensland, Australian. worrall@biosci.uq.edu.au
Richardson
P J
PJ
Preedy
V R
VR