Excess of Glucocorticoids Impairs Whole-Body Antioxidant Status in Young Rats. Relation to the Effect of Dexamethasone in Soleus Muscle and Spleen

Abstract

The action of glucocorticoids in high doses is catabolic, but not much is known about the accompanying effects on antioxidative capacity of the entire body. Animals were treated (or not) with dexamethasone (Dex) 2 mg/kg b.w. d-1 during 5 consecutive days followed by recovery, during which an additional group received 3-hydroxy-3-methylbutyrate (40 mg/kg b.w.). Animals were killed after treatment with Dex, and after 5 days of the recovery period. Dexamethasone treatment decreased appetite almost twofold (from 20 g/day to 10 g/day, P < 0.001). Feed restriction, however, seemed to have only minor impact on the effects observed since body weight loss of pair-fed rats after the 5th day of treatment was only 2% and Dex-treated rats decrease in body weight was 22% (P < 0.05). In turn, wet weight of the soleus muscle (expressed per body weight) did not significantly decrease after Dex treatment, suggesting relative resistance of oxidative type muscles to the catabolic action of dexamethasone. Spleen wet weight expressed per body weight dropped by 65% (P<0.001). Additionally, there was a 46% reduction (P<0.001) of blood glutathione (GSH/Hb), and 36% (P < 0.001) of muscle glutathione (GSH/tissue wet weight). This suggests that dexamethasone directly and/or indirectly impaired antioxidant reactions. This was further confirmed by a significant (49%) decline of SOD-1 activity in erythrocytes isolated from the group treated with dexamethasone. Another index of lipid peroxidation (TBARS) was also significantly increased. Activity of blood plasma CK increased by 73% (P<0.001) in Dex-treated rats, indicating moderate injury of muscle tissue. In conclusion, young growing rats were sensitive to the dosage of dexamethasone, but in contrast to lymphoid tissue, could easily compensate the outcomes of impaired antioxidative defence within 5 days of recovery.

Dexamethasone-mediated regulation of death and differentiation of muscle cells. Is hydrogen peroxide involved in the process?

“…In a series of in vitro experiments these authors have shown that dexamethasone represses the activity of genes encoding antioxidant enzymes leading to impaired viability and apoptotic cell death [5,9]. Our own in vivo study performed on rats corroborates the working hypothesis that high doses of glucocorticoids are involved in the suppression of antioxidant defense systems and lead to growth retardation and muscle cachexia [34]. Muscle cells proliferate in growth-promoting conditions while becoming post-mitotic and fusing into multinucleated myotubes when deprived of serum mitogens.…”

Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet

“…Intrauterine oxidative stress could be attributed to exposure to excess maternal glucocorticoids (21,30) and to nutrient restriction, which can, in itself, induce oxidative stress in the pregnant dam with placental and potentially fetal repercussions (13). In addition, elevated glucocorticoids can increase the susceptibility to oxidative stress, especially in young animals, in part through impairment of antioxidant status (1,11,56,57). Therefore, the combination of increased production of ROS by ANG II and decreased antioxidant capacity (through nutrient restriction and exposure to excess glucocorticoids) can increase the susceptibility of the "programmed" fetus to oxidative stress at birth when tissue PO 2 increases dramatically.…”

“…In this condition, the excessive production of superoxide anions, which participate in vascular dysfunction and remodeling seems secondary to the increased activation of the NADPH oxidase by ANG II (46). Considering the early role of the RAS in programmed HT (68), the impaired antioxidant defenses associated with fetal malnutrition (28,45) and the fact that glucocorticoids have been shown to enhance susceptibility to oxidant stress (1,56), especially in younger subjects (11,57), one can postulate that infants born after intrauterine deprivation or who are relatively immature are at risk of sustaining early oxidative stress, which could lead to altered cardiovascular development and long-term consequences.…”

Evaluation of the relationship between milk glutathione peroxidase activity, milk composition and various parameters of subclinical mastitis under seasonal variations

“…High levels of glucocorticoids have been reported to decrease blood glutathione and erythrocyte superoxide dismutase activity in rats (ORZECHOWSKI et al, 2000) and goats (ALILA JOHANSSON et al, 2003). BHAT et al (2008) reported that the high temperature and humidity of summer increase neuroendocrine stress and lipid peroxidation, which contribute to reduced erythrocyte antioxidant response in rats.…”