Different effects of corticosteroid-induced muscle wasting compared with undernutrition on rat diaphragm energy metabolism

Abstract

An important adverse effect of corticosteroid treatment is respiratory muscle weakness with diaphragm muscle wasting, but little is known about the underlying pathophysiological processes involved. In order to differentiate between the effects of nutrition depletion and corticosteroids on diaphragm muscle metabolism, a study was performed to investigate the effects of triamcinolone (TR) for 2 weeks and of chronic undernutrition in a pair-weight (PW) group on the structure and energy metabolism of the diaphragm in male Wistar rats compared with a free-fed (FF) group. Diaphragm mass was reduced in TR and PW rats to a similar degree, but the extent of type-IIx/b atrophy was more pronounced in TR rats than in PW rats. No myopathic features were observed after either treatment. ATP in absolute terms as well as the ATP/ADP ratio, total adenine nucleotides, the phosphocreatine (PCr) level and the ratio between PCr and creatine (PCr/Cr) were decreased in the diaphragm of both TR and PW rats. In contrast to the PW group, the total Cr pool was reduced and pyruvate and lactate levels were elevated in the diaphragm of the TR group compared with the FF group. In conclusion, the results of this study indicate that severe undernutrition causes a decrease in muscle energy status resulting in a new metabolic equilibrium, while chronic low-dose TR treatment (0.25 mg/kg per day i.m.) causes a decrease in muscle energy status together with a mismatch between glycolysis and oxidative metabolism.