Molecular and Cellular Events in Alcohol‐Induced Muscle Disease

Abstract

Alcohol consumption induces a dose-dependent noxious effect on skeletal muscle, leading to progressive functional and structural damage of myocytes, with concomitant reductions in lean body mass. Nearly half of high-dose chronic alcohol consumers develop alcoholic skeletal myopathy. The pathogenic mechanisms that lie between alcohol intake and loss of muscle tissue involve multiple pathways, making the elucidation of the disease somewhat difficult. This review discusses the recent advances in basic and clinical research on the molecular and cellular events involved in the development of alcohol-induced muscle disease. The main areas of recent research interest on this field are as follows: (i) molecular mechanisms in alcohol exposed muscle in the rat model; (ii) gene expression changes in alcohol exposed muscle; (iii) the role of trace elements and oxidative stress in alcoholic myopathy; and (iv) the role of apoptosis and preapoptotic pathways in alcoholic myopathy. These aforementioned areas are crucial in understanding the pathogenesis of this disease. For example, there is overwhelming evidence that both chronic alcohol ingestion and acute alcohol intoxication impair the rate of protein synthesis of myofibrillar proteins, in particular, under both postabsorptive and postprandial conditions. Perturbations in gene expression are contributory factors to the development of alcoholic myopathy, as ethanol-induced alterations are detected in over 400 genes and the protein profile (i.e., the proteome) of muscle is also affected. There is supportive evidence that oxidative damage is involved in the pathogenesis of alcoholic myopathy. Increased lipid peroxidation is related to muscle fibre atrophy, and reduced serum levels of some antioxidants may be related to loss of muscle mass and muscle strength. Finally, ethanol induces skeletal muscle apoptosis and increases both pro- and antiapoptotic regulatory mechanisms.

Is Alcohol Drinking Associated with Renal Impairment in the General Population of South Korea?

“…Fourth, we used GFR estimation with the MDRD study equation using serum creatinine levels for evaluating renal function. In fact, serum creatinine is affected by a number of factors, such as diet, malnutrition, and muscle wasting, which may be related to alcohol consumption [39], so that it could induce some degree of measurement bias in eGFR. Additionally, albuminuria may be an early marker of renal dysfunction, independently of eGFR [28,40], however, there was a critical measurement issue that the ascertainment of albuminuria as urine ACR was made at a single point in time [29].…”

Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats

“…When the excessive alcohol consumption is longstanding, a nonischemic cardiomyopathy develops, which is referred to as alcoholic cardiomyopathy (59). Whereas the etiology of this distinct disease entity is poorly understood, it is most certainly influenced by both genetic and environmental components (13,33) and is more symptomatic in individuals where alcohol consumption is increased with regard to amount and duration (71). Gender may also be a factor as women develop an asymptomatic form of alcoholic cardiomyopathy with a lower total lifetime consumption of alcohol (12,70).…”

External and Internal Influences on Muscle Pathology

“…The patient's glycosylated hemoglobin A1c was within reference range. Alcoholic neuropathy is a possibility in this case, but alcohol-induced type-2 fiber atrophy, muscle necrosis, or alcoholic myopathy 5 was not evident in the biopsy. Less-common causes of bilaterally symmetric denervation include hereditary motor and sensory neuropathies include Charcot-Marie-Tooth disease, spinal muscular atrophy, and motor neuron disease, such as amyotrophic lateral sclerosis (ALS).…”