[Suppression of hypotalamic-pituitary-adrenocortical system as a reason of aggravation of indomethacin-induced gastric ulcerogenic effect by cortisol treatment with pharmacological dose].
In the present study, we verified the hypothesis that an aggravated effect of glucocorticoid therapy on indomethacin-induced gastric erosion formation could be due to a deficiency of glucocorticoid production caused by suppression of the hypothalamic-pituitary-adrenocortical system (HPAS). Gastric erosions were induced by indomethacin (25 mg/kg, sc) in rats after 24 h fasting. The effects of cortisol pharmacological dose on indomethacin-induced gastric erosions and plasma corticosterone levels were investigated 1 and 4 weeks after cortisol pretreatment. Indomethacin caused a plasma corticosterone rise that was almost fully prevented in cortisol-pretreated rats 1 week after the pretreatment. Indomethacin-induced gastric erosions were significantly aggravated 1 week after cortisol pretreatment, and an acute corticosterone replacement mimicking indomethacin-induced corticosterone rise prevented this aggravation. 4 weeks after cortisol pretreatment, both corticosterone and gastric responses to indomethacin were restored. The results suggest that suppression HPAS function seems to be a reason of an aggravated effect of glucocorticoid therapy on indomethacin-induced gastric erosions.
Morozova
O Iu
OIu
Bagaeva
T R
TR
Filaretova
L P
LP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D006854:Hydrocortisone / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000473:pathology; D007213:Indomethacin / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000097:blood* / Q000139:chemically induced* / Q000473:pathology; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003345:Corticosterone; D006854:Hydrocortisone; D007213:Indomethacin