Dual action of glucocorticoid hormones on the gastric mucosa: how the gastroprotective action can be transformed to the ulcerogenic one.
Glucocorticoid hormones have dual action on the stomach: gastroprotective and ulcerogenic one. The present study was designed to investigate how physiological gastroprotective action of glucocorticoids can be transformed to pathological ulcerogenic effect. Dose- and time-dependent effects of single injection of dexamethasone on indomethacin-induced gastric erosions, corticosterone and blood glucose levels, somatic parameters were investigated in rats. Dexamethasone at the doses of 0.1, 1, 10 mg/kg decreased the gastric erosion area dose dependently in the case of its injection 1 h before indomethacin administration. Gastroprotective action of dexamethasone (at a dose of 1 mg/kg) was also observed in the case of its injection 6 and 12 h before indomethacin. However, the further increase in the time interval caused transformation of gastroprotective action of dexamethasone to ulcerogenic one. Accordingly to the data obtained short-term maintenance of blood glucose level provides the gastroprotective action of dexamethasone, while dexamethasone-induced long-lasting maintenance of blood glucose level accompanied with the signs of catabolic effects may be responsible at least partly for its ulcerogenic effect.
Filaretova
L
L
Laboratory of Experimental Endocrinology, Pavlov Institute of Physiology, nab. Makarova 6, St. Petersburg 199034, Russia. filaretova@pavlov.infran.ru
Podvigina
T
T
Bagaeva
T
T
Morozova
O
O
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001786:Blood Glucose / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D005938:Glucocorticoids; D003907:Dexamethasone; D003345:Corticosterone; D007213:Indomethacin