Relative and combined effects of propylthiouracil, ethanol and protein deficiency on muscle

A hypermetabolic state with increased oxygen consumption has been described in alcoholic hepatitis, playing a major role in ethanol-induced liver damage. Based on its ability to decrease oxygen consumption, propylthiouracil (PTU) has been proposed as a therapeutic agent in this context. On the other hand, several muscle changes have been described in hypothyroidism, including both atrophy and hypertrophy of muscle fibres. The aim of this experimental study was to analyse the effects of PTU on the alcohol-induced changes in muscle fibre size and proportion, also taking into account the presence or absence of protein deficiency. The study was performed on 64 male Wistar rats divided into eight groups, fed with: (1) Lieber-DeCarli control diet: (2) an isocaloric 36% ethanol-containing diet: (3) an isocaloric 2% protein-containing diet: (4) an isocaloric 36% ethanol 2% protein-containing diet, without and with PTU, respectively. Right gastrocnemius muscle was removed 2 months later and histochemical and morphometric studies were performed. Type IIb fibre atrophy was observed both in the alcoholic and protein-deficient animals, but not in the PTU-treated animals. The combination of protein deficiency and ethanol led to a more marked type IIb atrophy, with PTU reversing this effect. Malnutrition led to a decrease in type I fibre diameter: ethanol and PTU caused an increase in its size and PTU reversed the effect of protein deficiency. Proportion of type IIb fibres decreased in the three experimental groups without PTU with respect to the control, especially in the alcoholic protein-deficient animals. PTU-treated animals, especially those fed a low-protein diet, showed a more marked reduction in type IIb fibre proportion than that presented by the groups without PTU. However, an increase in type I fibre proportion was observed in the PTU-treated animals, especially marked in those fed a low-protein diet. Thus, PTU seems to ameliorate ethanol-induced changes on type IIb muscle fibres.