Megestrol acetate treatment influences tissue amino acid uptake and incorporation during cancer cachexia
2012
Toledo, Míriam | Marmonti, Enrica | Massa, David | Mola, Marina | López-Soriano, Francisco J. | Busquets, Silvia | Argilés, Josep M.
BACKGROUND & AIMS: Cachexia is a multi-organic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation, being often associated with anorexia. The aim of the present investigation was to study the effects of megestrol acetate (MA) on the rate of leucine incorporation into muscle tissue and on the uptake of AIB (a non-metabolizable analogue of alanine) in both skeletal muscle and liver tissue. METHODS: The effects of MA (100 mg/kg) were tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma). Tissue amino acid uptake was assessed by means of the alanine analogue α-amino-³H-isobutyrate (AIB). ¹⁴C-leucine oxidation and tissue protein incorporation were also determined. RESULTS: Administration of MA to tumour-bearing rats resulted in an important reversal of the muscle wasting process, as reflected by individual muscle weights. Treatment with the progestogen resulted in an increased AIB uptake together with an increased leucine incorporation in skeletal muscle. MA treatment significantly decreased AIB uptake by the liver. CONCLUSIONS: MA treatment results in both a significant increased uptake of neutral amino acids (AIB) by skeletal muscle and a significant incorporation of the branched-chain amino acid leucine into muscle protein, indicating a clear anabolic action of the drug on muscle tissue.
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