Rats with a glucocorticoid-induced catabolic state show symptoms of oxidative stress and spleen atrophy: The effects of age and recovery

In this study we wanted to determine whether changes in antioxidant profile could follow the catabolic effects of glucocorticoids. We also wanted to compare resistance to glucocorticoid overload in young and old rats. To address these questions, whole body catabolism was induced by the administration of dexamethasone (Dex) at either 2 mg/kg bodyweight/day to young (6 weeks old) or 0.5 mg/kg bodyweight/day to old (94 weeks old) rats. Bodyweight loss of pair-fed rats not given Dex was only 2% in the young rats and 8% in the old rats, whereas in Dex-treated rats the decrease in bodyweight was 22% in the young rats and 13% in the old rats after 5 days of treatment. Spleen weight decreased by 65% in the young rats and by 52% in the old rats. Additionally, in the young rats there was a 46% reduction in glutathione (GSH) in erythrocytes as well as a 36% reduction in GSH/tissue wet weight in the soleus muscle. The corresponding figures for the old rats were 35 and 26%, respectively. Taken together, these results suggest that Dex directly and/or indirectly impaired the antioxidant reactions. This was further confirmed by a significant (50%) decline in Cu–Zn superoxide dismutase (SOD-1) activity in erythrocytes isolated from the young rats treated with Dex but not the old rats as they showed a significant elevation in SOD-1 activity (by 101%). Thiobarbituric acid reactant substances were significantly higher in both young and old rats. Activity of blood plasma creatine kinase increased by 73% in the young rats and by 307% in the old rats treated with Dex. Although both the young and the old rats could recover from oxidative stress, the old rats in contrast to the young rats remained catabolic until the end of the experiment. In conclusion, we suggest that old rats are more vulnerable to the catabolic action of Dex, whereas young rats are more susceptible to the oxidative stress induced by Dex.