Corticosterone at physiological dose accelerates the healing of experimental gastric erosions in rats

Abstract

The data of literature about the action of glucocorticoids on the gastric ulcer/erosion healing mainly concern the effects of lasting glucocorticoid therapy or single injection of glucocorticoids at pharmacological doses. These data clearly indicate that glucocorticoids delay the natural healing of experimental gastric injury. However, the role of endogenous glucocorticoids in the gastric mucosal healing processes remained unknown for a long time. In our previous studies we tested this question and the results obtained argue the contribution of endogenous glucocorticoids to the healing of injured gastric mucosa. In the present study we verified whether natural exogenous glucocorticoids (such as corticosterone in rodents) injected at physiological doses similar to endogenous ones may contribute to the healing of gastric erosions accelerating the healing process. For this, in experiments in male SD rats we studied the effects of corticosterone injected at physiological dose 4 mg/kg or dexamethasone injected at the dose 1 mg/kg on the healing of injured gastric mucosa. The glucocorticoid receptor antagonist RU‐38486 (20 mg/kg) was injected to one half of each group 2 h before the glucocorticoid administration. Glucocorticoid or RU‐38486 vehicle (propylene glycol) was injected as a control. Indomethacin (IM) at the dose 35 mg/kg and 3.5 h gastric ischemia‐reperfusion (IR, 30 min occlusion of celiac artery followed by 3 h of reperfusion) were used as ulcerogenic stimuli in preliminary fasted rats. To estimate IM‐ or IR‐induced gastric erosion formation (erosion area) two groups of rats were sacrificed in 4 h after IM injection or 3.5 h after IR. Corticosterone or dexamethasone as well as their vehicle were injected 4 h after IM administration or 3.5 h after IR (0 time point of healing) to other groups to estimate their effects on the healing of injured gastric mucosa in 6 h and 24 h after the hormonal or vehicle administration. IM‐ and IR‐induced erosions healed with time. In control (vehicle treated rats) an average area of erosions in 6 h time point did not differ from that in 0 time point. At the same time an average area of erosions in 24 h time point was significantly lower than that in 0 time point (healing). Corticosterone but not dexamethasone injection accelerated the healing: in corticosterone treated rats significant decrease in an average area of erosions was already observed in 6 h time point. The preliminary glucocorticoid receptor antagonist RU‐38486 injection prevented accelerating effect of corticosterone on the healing process. The findings suggest that natural glucocorticoid corticosterone injected at physiological dose may accelerate the healing of experimental gastric erosions in rats.Support or Funding InformationThe study was supported by grant of Russian Science Foundation (RSF) N 19‐15‐00430.