In vivo rates of skeletal muscle protein synthesis in rats are decreased by acute ethanol treatment but are not ameliorated by supplemental alpha-tocopherol.
Some studies have shown that reductions in tissue protein synthesis, under a variety of cytotoxic conditions, are ameliorated by alpha-tocopherol (ATC) supplementation. We have also shown evidence of increased oxidative stress and reduced protein synthesis rates in alcohol-exposed muscle. Serum levels of ATC fall and rates of muscle protein synthesis are reduced in patients with alcoholic myopathy. We therefore tested the hypothesis that treatment with ATC could ameliorate the ethanol-induced changes in muscle protein synthesis, a contributory event in the pathogenesis of alcoholic muscle disease. Studies were carried out on gastrocnemius (Type II fiber-predominant and usually considered representative of the musculature as a whole), soleus (Type I fiber-predominant) and plantaris (Type II fiber-predominant) muscles. For comparative purposes, we also investigated the liver. Young male Wistar rats (90 g body weight) were injected intraperitoneally (i.p.) daily with ATC (30 mg/kg body weight) in Intralipid fat emulsion (0.1 mL/100 g body, i.p.) for 5 d. Controls were similarly injected with the Intralipid vehicle alone. After ATC supplementation, rats were given ethanol (75 mmol/kg body weight, i.p., 2.5 h) or saline (0.15 mol/L NaCl, i. p.). Fractional rates of tissue protein synthesis (i.e., the percentage of the tissue protein pool renewed each day, k(s), %/d) and RNA activities [i.e., the amount of protein synthesis each day per unit RNA, k(RNA), mg protein/d/mg RNA)] were then measured. Supplementation increased ATC concentrations in plasma, gastrocnemius and liver. There was no effect of ATC supplementation alone on k(s) in any of the tissues. ATC supplementation in the absence of alcohol increased k(RNA) in the plantaris muscle. In nonsupplemented groups, acute ethanol treatment reduced skeletal muscle (soleus, plantaris and gastrocnemius) k(s). Hepatic k(s) was not altered by ethanol, although ATC concentrations in this tissue increased due to ethanol. However, none of the changes in muscle k(s) or k(RNA) due to ethanol were significantly affected by ATC supplementation. In conclusion, ATC supplementation does not appear beneficial in ameliorating acute alcohol toxicity in skeletal muscle as defined by reductions in protein synthesis.
Reilly
M E
ME
Departments of. Nutrition and Dietetics and. Clinical Biochemistry, King's College, London, UK.
Patel
V B
VB
Peters
T J
TJ
Preedy
V R
VR
D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000493:pharmacokinetics / Q000494:pharmacology*
D009124:Muscle Proteins; D014810:Vitamin E; D000431:Ethanol