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Leucine-rich diet supplementation modulates foetal muscle protein metabolism impaired by Walker-256 tumour

Abstract

Cancer-cachexia induces a variety of metabolic disorders on protein turnover and is more pronounced when associated with pregnancy. Tumour-bearing pregnant rats have impaired protein balance, which decreases protein synthesis and increases muscle breakdown. Knowing that branched- chain amino acids, especially leucine, stimulate protein synthesis, in this study, we investigated the effect of a leucine-rich diet on protein metabolism in the foetal gastrocnemius muscles of tumour-bearing pregnant rats. Foetuses of pregnant rats with or without Walker 256 tumours were obtained from six groups. During the 20 days of the experiment, the pregnant groups were fed with a control diet (C - control rats; W - tumour-bearing rats; Cp - rats pair-fed the same normoprotein-diet as the W group) or with a leucine- rich diet (L - leucine rats; LW - leucine tumour-bearing rats; and Lp - rats pair- fed the same leucine-rich diet as the LW group). After sacrifice, foetal gastrocnemius muscle samples were resected, and the protein synthesis and degradation and tissue chymotrypsin-like, cathepsin and calpain enzyme activities were assayed. The muscle oxidative enzymes (catalase, glutathione- S-transferase and superoxide dismutase), alkaline phosphatase enzyme activities and lipid peroxidation (malondialdehyde) were also determined. Results: Tumour growth led to foetal-weight reduction that was associated with decreased serum protein, albumin and glucose levels and low haematocrit in the foetuses of the W group, whereas in WL foetuses, these changes were less pronounced. Muscle protein synthesis (measured by L-[3 H]-phenylalanine incorporation) was reduced in the W foetuses but was recovered in the LW 3 group. Protein breakdown (as assessed by tyrosine release) was enhanced in the L and W groups, but chymotrypsin-like activity increased in only group W and tended to increase in the LW foetuses. The activity of cathepsin H was significantly higher in the W foetuses, but the proteolytic, calcium-dependent pathway showed similar enzyme activity. In parallel, an intense oxidative stress process was observed only in the W foetuses. These data suggested that the proteasome and lysosome proteolytic pathways and oxidative stress likely participate in the process of foetal muscle catabolism of Walker's tumour-bearing pregnant rats. In contrast, LW foetuses had similar values as the control groups, suggesting that this group was protected by leucine-diet supplementation. (AU)

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