Sodium ascorbate (ASC) and ascorbic acid phosphate (ASC-P) differently modulate glucocorticoid-dependent metabolic effects in growing rats

well known that dexamethasone treatment in certain doses induces oxidative stress, insulin resistance, diabetes, and muscle cachexia. This survey was carried out to investigate the effect of ascorbate derivatives on dexamethasone-induced metabolic disturbances. Experiment was performed on 6 weeks old male rats. Oral dose of sodium ascorbate (600 mg/kg b.w., ASC) or ascorbic acid phosphate (785 mg/kg b.w., ASC-P) was given separately (BID) or as co-treatment with dexamethasone phosphate (daily dose of 2 mg/kg b.w., DEX). Rats were randomly divided into control and experimental groups and the effect of 5-day treatment without (CTRL) or with ASC, ASC-P, DEX, or DEX combined with ASC or with ASC-P (Treatment) was compared with respect to indices of animal growth, somatic indices and results of glucose tolerance test. The effects of 5-day treatment and 5-day recovery period (when none of the experimental factors was used) were compared. Administration of DEX caused significant decline of serum ascorbate and dehydroascorbate (-87%, P 0.05). In contrast, spleen SI dropped significantly upon DEX treatment (-57%). After 5-day recovery period DEX-altered SI-s did not return to control values (P<0.05). Neither ASC nor ASC-P affected SI-s nor they could reverse DEX-induced changes in SI-s except ASC-P which confined the rise of renal SI (P<0.05). ASC in contrast to ASC-P even augmented DEX-dependent hepatomegaly (P<0.05). Interestingly, both ascorbate derivatives efficiently inhibited DEX-induced muscle cachexia at least with respect to gastrocnemius muscle (P<0.05). Summing up, these results suggest differences between the fast and slow effects evoked by ascorbate in the experimental model of growth retardation and muscle cachexia induced by DEX and accompanied by glucocorticoid-dependent diabetes.