From gastroprotective to proulcerogenic action of glucocorticoids on the gastric mucosa.
Glucocorticoids may have dual action on the gastric mucosa: physiological gastroprotective and pathological proulcerogenic one. In the present study we investigated how gastroprotective action of glucocorticoids can be transformed to proulcerogenic effect. Dose- and time-dependent effects of single injection of dexamethasone on cold-restraint-induced gastric erosions, corticosterone and blood glucose levels, somatic parameters were investigated in fasted rats. Dexamethasone at a dose of 1 mg/kg decreased the gastric erosion area and maintained blood glucose level in fasted rats in the case of its injection 1 h before the stress. A dose of 1 mg/kg has been selected for the time-dependent study. The results demonstrate that single injection of dexamethasone at a dose of 1 mg/kg may attenuate or aggravate cold-restraint-induced gastric erosions depending on the time of the injection before the stress. Gastroprotective action of dexamethasone was observed in the case of its injection 1 and 12 h before cold-restraint. The further increase in the time interval caused transformation of gastroprotective action of dexamethasone to proulcerogenic effect. Both short-term and long-term dexamethasone action resulted in maintenance of blood glucose level in fasted rats. The results suggest that glucocorticoid-induced long-lasting maintenance of blood glucose levels accompanied with the signs of their catabolic effect and dexamethasone-induced corticosterone deficiency may be responsible, at least partly, for the transformation of gastroprotective action of glucocorticoids to their proulcerogenic effect.
Filaretova
L
L
Laboratory of Experimental Endocrinology, Pavlov Institute of Physiology, St. Petersburg, Russia. filaretovalp@yandex.ru
Morozova
O
O
Bagaeva
T
T
Podvigina
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003080:Cold Temperature / Q000009:adverse effects; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012720:Severity of Illness Index; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013276:Stomach Ulcer / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D000897:Anti-Ulcer Agents; D001786:Blood Glucose; D003907:Dexamethasone; D003345:Corticosterone