Abstract
Glucorcorticoids are well known for its therapeutic anti-inflammatory effects when used acutely and in low doses. However, it is already known that chronic and/or acute high doses promote several side effects, such as skeletal muscle atrophy. Furthermore, experimental models in order to induce glucocorticoid-induced skeletal muscle atrophy with high doses fail, according to the mode and dose of administration, in promoting a significant atrophic response with low death tool. PURPOSE: To evaluate the magnitude of two experimental models of acute glucocorticoid-induced skeletal muscle atrophy based on different modes of administration. METHODS: The study was conducted in accordance with the National Institute of Health Guidelines. Adult male Wistar rats (400g) were randomly divided into a dexamethasone-treated via intraperitoneal injection (IP; n=6) and via drinking water (DW; n=6). Both groups received 5 mg/kg-1 of DEXA per day during 7 days. Control group was pair-fed (PF; n=6) to dexamethasone-treated groups. Blood samples were collected for measuring plasma glucose levels. Soleus, plantaris and EDL muscles were used for protein content measurement. Statistical analyses consisted of a one-way ANOVA with Tukeys post hoc testing. RESULTS: IP, DW, and PF groups showed a 23%, 25% and 4% decrease in body weight, respectively. Soleus muscle mass and total protein content showed no statistical difference among groups. Plantaris muscle mass and total protein content were significantly decreased in DW compared with IP and PF (274±27 vs. 337±32 vs. 405±27mg, p<0.05; 8.6±1.4 vs. 9.8±1.0 vs. 11.1±2.3μg/μl, p<0.05). The same result pattern was observed for EDL muscle for DW, IP, and PF (160±17 vs. 184±23 vs. 206±15mg, p<0.05; 5.9±0.5 vs. 7.3±0.6 vs. 9.6±0.8μg/μl, p<0.05). Blood glucose level was significantly increased in DEXA-treated groups but did not differ between them (140±11 in DW and 139±66 in IP vs. 93±9mg/dl in PF, p<0.05). CONCLUSION: Acute high dose DEXA treatment promoted significant atrophy of type IIb (EDL) and IIa (plantaris) muscles and did no affect type I muscle (soleus). Oral DEXA-treatment (DW) promoted greater muscle atrophy compared with IP. Both DEXA-treatments promoted a diabetogenic effect without difference between them. Supported by FAPESP (Grants no08/51070-1 and 09/02896-6).
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