Effects of systemic inhibition of prostaglandin production on protein metabolism in tumor-bearing rats.
Two rat tumors, Morris hepatoma 7777 (MH) and Yoshida ascites hepatoma AH130 (YAH) were compared, and the influence of systemic inhibition of prostaglandin (PG) synthesis on muscle protein metabolism was evaluated. Tumor-bearing rats were compared with ad libitum- and pair-fed controls. Rats were also treated with naproxen, an inhibitor of PG synthesis. Tumors caused progressive anorexia and weight loss and resulted in decreased weight and/or protein content of the soleus, extensor digitorum longus, and epitrochlearis muscles. The extent of this wasting varied with muscle and tumor type. Muscle wasting induced by the tumors appeared to result from increased protein degradation and/or decreased protein synthesis, as determined in isolated epitrochlearis muscle. In YAH, reduced feed intake did not appear to be responsible for muscle wasting; however, in MH, it accounted for a significant proportion of the muscle loss. YAH produced large amounts of PGE2. Treatment of rats with naproxen inhibited tumor PGE2 production and muscle protein loss in rats bearing YAH. Naproxen had no effect on muscle weight or protein degradation in rats bearing MH. These results would appear to implicate PGE2 in the development of cachexia in the laboratory rat.
Strelkov
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Department of Animal Science, University of Alberta, Edmonton, Canada.
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Baracos
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D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009288:Naproxen / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011448:Prostaglandin Antagonists; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D000596:Amino Acids; D009363:Neoplasm Proteins; D011448:Prostaglandin Antagonists; D011506:Proteins; D009288:Naproxen; D015232:Dinoprostone