Creatine supplementation attenuates corticosteroid-induced muscle wasting and impairment of exercise performance in rats

Abstract

The objective of the present study was to investigate whether creatine (Cr) could attenuate the deleterious effects of high doses of dexamethasone (Dexa) on body mass, exercise performance, and respiratory variables of rodents. Forty-four Wistar rats performed incremental maximal exercise tests. They were then assigned to four groups: G1: subcutaneous (s.c.) and intraperitoneal (i.p.) saline; G2: s.c. saline and i.p. Cr (250 mg x kg(-1) x day(-1)); G3: s.c. Dexa (7.5 mg x kg(-1) x day(-1)) and i.p. saline; G4: s.c. Dexa and i.p. Cr. New exercise tests and analysis of the respiratory pattern under resting conditions and after stimulation with doxapram (2 mg/kg i.p.) were performed after 18 days. Post- minus pretreatment differences were compared between groups. G3 and G4 showed a significant impairment in body mass gain compared with G1 and G2 (P < 0.05) (G1: 65.3 +/- 26.1, G2: 93.1 +/- 27.4, G3: -18.4 +/- 20.1, G4: 9.8 +/- 23.1 kg x 10(-3)). Similar results were observed for maximal oxygen consumption (G1: 9.5 +/- 8.5, G2: 25.8 +/- 14.5, G3: -25.5 +/- 6.0, G4: -4.8 +/- 9.5 ml x kg(-1) x min(-1)) and test duration (G1: 43.0 +/- 45.0, G2: 72.0 +/- 59.5, G3: -165.0 +/- 60.6, G4: -48.0 +/- 48.5 s). Simultaneous use of Cr significantly attenuated the Dexa-induced impairment of the last two variables. Cr attenuated Dexa-induced gastrocnemius and diaphragm muscle weight losses and the atrophy of gastrocnemius type IIb fibers. Cr supplementation had only small effects on Dexa-induced respiratory changes. These results suggest that Cr may play a role in the prophylaxis or treatment of steroid-induced myopathy.

Exercise training prevents hyperinsulinemia, muscular glycogen loss and muscle atrophy induced by dexamethasone treatment

“…This attenuation may be a direct consequence of the improvement of insulin signal transduction through the phosphatidylinositol-3-kinase/ Akt-1 pathway, IRS-1 and IRS-2 activity and GLUT-4 expression discussed earlier. (Tanner et al 2002;Luciano et al 2002) It has been suggested that DEX treatment decreases body weight in a dose-dependent manner (De Vries et al 2002;Komamura et al 2003;Ahtikoski et al 2004;Rhee et al 2004;Coderre et al 2007;Kaasik et al 2007;Menezes et al 2007;Rafacho et al 2008). In the present study, both DEX-treated groups had signiWcantly reduced body weight.…”

“…Body weight loss is usually followed by muscle atrophy and skeletal muscle protein loss, including collagen IV, which may aVect muscle contraction (De Vries et al 2002;Komamura et al 2003;Ahtikoski et al 2004;Lumbers et al 2005;Gilson et al 2007;Kaasik et al 2007;Menezes et al 2007). This present study demonstrated that sedentary animals had a 33.5% reduction on TA muscle weight after DEX treatment.…”

“…In addition, it has been observed that a dose-dependent reduction of body weight occurs in animals treated with glucocorticoids (De Vries et al 2002;Komamura et al 2003;Ahtikoski et al 2004;Rhee et al 2004;Coderre et al 2007;Kaasik et al 2007;Menezes et al 2007). This weight loss is usually followed by muscle atrophy and a reduction of several muscle proteins, contributing to impaired muscle function (De Vries et al 2002;Komamura et al 2003;Ahtikoski et al 2004;Lumbers et al 2005;Gilson et al 2007;Kaasik et al 2007;Menezes et al 2007).…”

“…It has been shown that exercise may act through alternate pathways in order to improve peripheral insulin sensitivity. Further, an increase in glucose uptake seems to occur in an insulin-independent manner (Ryder et al 2001;Jessen et al 2003;Menezes et al 2007). However, the intracellular mechanisms mediating GLUT-4 translocation to the plasma membrane by exercise are not fully understood.…”

Mechanisms of glucocorticoid-induced myopathy

“…Dietary supplementation with creatine monohydrate has been shown to attenuate the muscle weight loss and the atrophy of gastrocnemius type IIb fibers caused by glucocorticoids (Roy et al 2002, Menezes et al 2007). Furthermore, this protective effect was associated with an attenuation of the impairment of daily spontaneous running of animals receiving glucocorticoids (Campos et al 2006).…”