Excess of glucocorticoids impairs whole-body antioxidant status in young rats. relation to the effect of dexamethasone in soleus muscle and spleen.
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.
Orzechowski
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Department of Physiology, Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Warsaw Agricultural University, Poland. orzechowski@alpha.sggw.waw.pl
Ostaszewski
P
P
Brodnicka
A
A
Wilczak
J
J
Jank
M
M
Balasińska
B
B
Grzelkowska
K
K
Ploszaj
T
T
Olczak
J
J
Mrówczyńska
A
A
D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014631:Valerates / Q000494:pharmacology
D000975:Antioxidants; D005938:Glucocorticoids; D017392:Thiobarbituric Acid Reactive Substances; D014631:Valerates; C004961:beta-hydroxyisovaleric acid; D003907:Dexamethasone; D005978:Glutathione