Chronic α-tocopherol supplementation in rats does not ameliorate either chronic or acute alcohol-induced changes in muscle protein metabolism

Abstract

Chronic alcohol muscle disease is characterized by reduced skeletal muscle mass precipitated by acute reduction in protein synthesis. The pathogenic mechanisms remain obscure, but several lines of evidence suggest that increased oxidative stress occurs in muscle in response to alcohol and this may be associated with impaired alpha-tocopherol status. Potentially, this implies a therapeutic role for alpha-tocopherol, especially as we have shown that supplemental alpha-tocopherol may increase the rate of protein synthesis in normal rats [Reilly, Patel, Peters and Preedy (2000) J. Nutr. 130, 3045-3049]. We investigated the therapeutic effect of alpha-tocopherol on plantaris muscle protein synthesis in rats treated either acutely, chronically or chronically+acutely with ethanol. Protein synthesis rates were measured with a flooding dose of L-[4-(3)H]phenylalanine. Protein, RNA and DNA contents were determined by standard laboratory methods. Ethanol caused defined metabolic changes in muscle, including decreased protein, RNA and DNA contents in chronically treated rats. In acute or chronic+acute studies, ethanol suppressed fractional rates of protein synthesis. alpha-Tocopherol supplementation did not ameliorate the effects of either acute, chronic or chronic+acute alcohol on plantaris muscle protein content or rates of protein synthesis. In control animals (not treated with alcohol), alpha-tocopherol supplementation decreased muscle protein content owing to increases in protein turnover (both synthesis and degradation). alpha-Tocopherol supplementation is not protective against the deleterious effects of alcohol on protein metabolism in skeletal muscle.

Procysteine Stimulates Expression of Key Anabolic Factors and Reduces Plantaris Atrophy in Alcohol‐Fed Rats

“…The negative effects of chronic alcohol ingestion on skeletal muscle redox state have been well‐documented (Adachi et al., 2000; Fernández‐Solà et al., 2002; Koo‐Ng et al., 2000; Otis et al., 2007; Preedy et al., 2001). However, most alcohol studies that attempted to attenuate alcohol‐induced oxidant stress with antioxidant or antioxidant cofactor supplementation have reported limited successes (Durán Castellón et al., 2005;Koll et al., 2003; Reilly et al., 2000). In contrast, we have previously shown that procysteine restored muscle GSH levels in rats fed alcohol for 6 weeks while reducing oxidant stress and mRNA expression of 2 catabolic factors, atrogin‐1 and TGFβ 1 (Otis et al., 2007)—each occurring despite the absence of clinical alcoholic myopathy (e.g., atrophy).…”

Alcohol Exposure and Mechanisms of Tissue Injury and Repair

“…For example, providing alcoholics dietary supplements of zinc, an essential cofactor for superoxide dismutase and glutathione peroxidase, did not alleviate symptoms of alcoholic myopathy (Ferna´ndez-Sola`et al, 1998). Further, a-tocopherol supplementation had little effect on the rates of protein synthesis or the total protein content in skeletal muscle (Koll et al, 2003). Moreover, precursors of the nonvitamin antioxidant glutathione have been used to rectify alcohol-induced derangements to lung and skeletal muscle tissue (Otis and Guidot, 2009;Otis et al, 2007;Velasquez et al, 2002).…”

Molecular and Cellular Events in Alcohol‐Induced Muscle Disease

“…(2004). Intervention studies with chronic alpha‐tocopherol and zinc supplementation in rats do not ameliorate either chronic or acute alcohol‐induced muscle changes (Durán‐Castellón et al., 2005; Koll et al., 2003; Reilly et al., 2000b) and in some instances may be damaging in the dosage regimens used (see Koll et al., 2003). The exception appears to be studies with uncoupling protein 3 (UCP3) mRNA, which is reduced in alcohol exposure but ameliorated with alpha‐tocopherol supplementation (Baffy et al., 2006a,b).…”

“…Oxidative alteration of structural proteins may also alter protein degradation (Basoah et al., 2005). Decreased protein synthesis is a well‐described feature in alcoholic myopathy (Hunter et al., 2003; Lang et al., 2001; Preedy et al., 2001); however, available data do not support an unequivocal role of oxidative stress in its pathogenesis (Koll et al., 2003).…”