Ornithine alpha-ketoglutarate limits muscle protein breakdown without stimulating tumor growth in rats bearing Yoshida ascites hepatoma.
The growth of the Yoshida ascites hepatoma AH130 (YAH) is associated with early wasting, depletion of intracellular amino acid pools, and a pronounced activation of protein degradation in skeletal muscle of the host animal. Ornithine alpha-ketoglutarate (OKG) is used in the treatment of hypercatabolic states, and it has been suggested that it may improve nitrogen balance through repletion of free amino acid pools and suppression of protein catabolism. In cancer, OKG might similarly improve host nutritional status or stimulate tumor growth if its metabolites are limiting for tumor growth. Enteral supplementation with OKG was investigated in Sprague-Dawley rats bearing YAH. Tumor-bearing rats were compared with ad libitum- and pair-fed controls. Rats received OKG (3.4 to 4.0 g/kg body weight/d) or an equal amount of nitrogen as glycine (n = 8 in each group) for 5 days. Tumor implantation decreased cumulative food intake (-40%), host weight (-6%), skeletal muscle weight, and free amino acid levels in muscle and plasma. Muscle protein balance was estimated in vitro; decreased protein synthesis (-30%) and increased proteolysis (+113%) were observed in epitrochlearis muscles (EPI) of YAH-bearing rats compared with control groups. OKG had no effect on the wet weight (10 +/- 1 g) and nitrogen content of the tumor, or on free amino acid levels in the tumor. In tumor-bearing rats, OKG improved muscle protein balance by reducing breakdown by 33% and overall amino acid release of incubated EPI by 46%.
Department of Animal Science, Faculty of Agriculture and Forestry, University of Alberta, Edmonton, Canada.
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D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D004435:Eating; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D009124:Muscle Proteins; C002118:ornithine alpha-ketoglutarate; D009952:Ornithine