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Generation of protein adducts with malondialdehyde and acetaldehyde in muscles with predominantly type I or type II fibers in rats exposed to ethanol and the acetaldehyde dehydrogenase inhibitor cyanamide^1,2,3

¹ From the Department of Clinical Chemistry, Anatomy and Cell Biology, University of Oulu, Oulu, Finland (ON and SP); EP Central Hospital Laboratory, Seinäjoki, Finland (ON); and the Department of Nutrition and Dietetics, King’s College London (MK and VRP).

Background: Alcoholic myopathy is known to primarily affect type II muscle fibers (glycolytic, fast-twitch, anaerobic), whereas type I fibers (oxidative, slow-twitch, aerobic) are relatively protected.

Objective: We investigated whether aldehyde-derived adducts of proteins with malondialdehyde and acetaldehyde are formed in muscle of rats as a result of acute exposure to ethanol and acetaldehyde. The differences between type I muscle, type II muscle, and liver tissue were also assessed.

Design: The formation and distribution of malondialdehyde- and acetaldehyde-protein adducts were studied with immunohistochemistry in soleus (type I) muscle, plantaris (type II) muscle, and liver in 4 groups of rats. The different groups were administered saline (control), cyanamide (an acetaldehyde dehydrogenase inhibitor), ethanol, and cyanamide + ethanol.

Results: Treatment of rats with ethanol and cyanamide + ethanol increased the amount of aldehyde-derived protein adducts in both soleus and plantaris muscle. The greatest responses in malondialdehyde-protein and acetaldehyde-protein adducts were observed in plantaris muscle, in which the effect of alcohol was further potentiated by cyanamide pretreatment. Malondialdehyde- and acetaldehyde-protein adducts were also found in liver specimens from rats treated with ethanol and ethanol + cyanamide; the most abundant amounts were found in rats given cyanamide pretreatment.

Conclusions: Acute ethanol administration increases protein adducts with malondialdehyde and acetaldehyde, primarily in type II muscle. This may be associated with the increased susceptibility of anaerobic muscle to alcohol toxicity. Higher acetaldehyde concentrations exacerbate adduct formation, especially in type II–predominant muscles. The present findings are relevant to studies on the pathogenesis of alcohol-induced myopathy.

Key Words: Alcohol • myopathy • skeletal muscle • ethanol metabolism • acetaldehyde • lipid peroxidation • alcoholic myopathy • alcoholism • muscle • fast-twitch muscle • slow-twitch muscle • type I muscle fiber • type II muscle fiber • protein adduct • malondialdehyde

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				V. B. PATEL, S. WORRALL, P. W. EMERY, and V. R. PREEDY PROTEIN ADDUCT SPECIES IN MUSCLE AND LIVER OF RATS FOLLOWING ACUTE ETHANOL ADMINISTRATION Alcohol Alcohol., November 1, 2005; 40(6): 485 - 493. [Abstract] [Full Text] [PDF]