Differential Contribution of Clinical Amounts of Acetaldehyde to Skeletal and Cardiac Muscle Dysfunction in Alcoholic Myopathy

Acute intoxication due to alcohol consumption has been known to elicit reversible skeletal and cardiac muscle dysfunction, or “alcoholic myopathy and cardiomyopathy”. Sometimes, irreversible muscle damage can be induced after heavy alcohol drinking. Many researchers have proposed that acetaldehyde, the major oxidised product of alcohol, may be a primary factor underlying alcohol-induced muscle dysfunction. Because acetaldehyde is rapidly metabolised to acetate by aldehyde dehydrogenase (ALDH) mainly in the liver, blood concentration of acetaldehyde is maintained at a low level even after heavy alcohol intoxication. In alcoholics, blood acetaldehyde level is relatively high, probably due to hepatic inhibition of ALDH activity. Several mM of acetaldehyde have been used for studies of cardiac muscle contraction, the intracellular calcium transient, and the L-type calcium channel. In skeletal muscle, the calcium release channel/ryanodine receptor activity has been reported to be inhibited by exposure to 1 mM acetaldehyde. However, these observations were made using potentially lethal concentrations of acetaldehyde, so the hypothesis that acetaldehyde plays a crucial role on alcoholic myopathy is questionable. In this review, we will summarise the effect of alcohol and its major oxidised product, acetaldehyde, on skeletal and heart muscles and propose a toxic contribution of clinical concentrations of acetaldehyde to alcoholic myopathy. In addition, this review will include briefly the effect of acetaldehyde on diabetic cardiomyopathy.