The metabolic changes caused by dexamethasone in the adjuvant-induced arthritic rat.
The action of orally administered dexamethasone (0.2 mg kg(-1) day(-1)) on metabolic parameters of adjuvant-induced arthritic rats was investigated. The body weight gain and the progression of the disease were also monitored. Dexamethasone was very effective in suppressing the Freund's adjuvant-induced paw edema and the appearance of secondary lesions. In contrast, the body weight loss of dexamethasone-treated arthritic rats was more accentuated than that of untreated arthritic or normal rats treated with dexamethasone, indicating additive harmful effects. The perfused livers from dexamethasone-treated arthritic rats presented high content of glycogen in both fed and fasted conditions, as indicated by the higher rates of glucose release in the absence of exogenous substrate. The metabolization of exogenous L: -alanine was increased in livers from dexamethasone-treated arthritic rats in comparison with untreated arthritic rats, but there was a diversion of carbon flux from glucose to L: -lactate and pyruvate. Plasmatic levels of insulin and glucose were significantly higher in arthritic rats following dexamethasone administration. Most of these changes were also found in livers from normal rats treated with dexamethasone. The observed changes in L: -alanine metabolism and glycogen synthesis indicate that insulin was the dominant hormone in the regulation of the liver glucose metabolism even in the fasting condition. The prevalence of the metabolic effects of dexamethasone over those ones induced by the arthritis disease suggests that dexamethasone administration was able to suppress the mechanisms implicated in the development of the arthritis-induced hepatic metabolic changes. It seems thus plausible to assume that those factors responsible for the inflammatory responses in the paws and for the secondary lesions may be also implicated in the liver metabolic changes, but not in the body weight loss of arthritic rats.
Caparroz-Assef
Silvana M
SM
Laboratory of Liver Metabolism, Department of Biochemistry, University of Maringá, 87020900 Maringá, Brazil.
Bersani-Amado
Ciomar A
CA
Kelmer-Bracht
Ana M
AM
Bracht
Adelar
A
Ishii-Iwamoto
Emy L
EL
D000409:Alanine / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005215:Fasting; D005247:Feeding Behavior / Q000187:drug effects; D005620:Freund's Adjuvant; D006003:Glycogen / Q000378:metabolism; D007249:Inflammation; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D014508:Urea / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D000641:Ammonia; D003907:Dexamethasone; D014508:Urea; D006003:Glycogen; D005620:Freund's Adjuvant; D000409:Alanine; D010100:Oxygen