Dual action of glucocorticoid hormones on the gastric mucosa: how the gastroprotective action can be transformed to the ulcerogenic one

Abstract

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.

Clinical, clinicopathologic, and gastrointestinal changes from aspirin, prednisone, or combination treatment in healthy research dogs: A double‐blind randomized trial

“…Peroxidase is rich in the parietal cell and also plays a role in the control of acid secretion . Inactivation of peroxidase leads to increased free radical damage, decreased synthesis of prostaglandin, hyperacidity, and altered vascular permeability, ultimately resulting in GI ulceration …”

“…Both sustained glucocorticoid and low‐dose aspirin treatment are associated with gastrointestinal (GI) bleeding in people . The use of other nonsteroidal medications in combination with prednisolone also causes GI bleeding in dogs .…”

Anti-inflammatory glucocorticoid drugs: reflections after 60 years

“…Previous treatment of rats with a single dose of dexamethasone (1-12 h) induces gastric resistance to the ulcerogenic effects of indomethacin. However, extending the pre-treatment interval (1-7 days still with a single dose) increases the susceptibility to gastric damage by indomethacin (Filaretova et al 2009). • Either stimulating, or inhibiting, MIF production with increasing concentrations (10 -12 -10 -7 M) dexamethasone ).…”

Activation of the Hypothalamic-Pituitary-Adrenocortical Axis as a Gastroprotective Component of Stress Response

“…Although there is a long-standing debate over whether glucocorticoid therapy by itself leads to peptic ulcer disease in human (Luo et al, 2009;Olsen et al, 2010), it is established that administration of glucocorticoids to experimental animals can result in an acute gastric erosion (Bandyopadhyay et al, 1999, as cited in Filaretova et al, 2009bBlack, 1988, as cited in Filaretova et al, 1998Takeuchi et al, 2008). In the same time, in some cases administration of glucocorticoids to animals can attenuate gastric erosion (Derelanko & Long 1982;Filaretova et al, 2009b;McCafferty et al, 1995). It is also known that basal glucocorticoid production contribute to the maintenance of the gastric mucosal integrity (Takeuchi et al, 1989).…”

“…It means that control of glucose regulation and its correction in case of need may be considered as useful approach minimizing ulcerogenic side effect of glucocorticoid therapy. In conclusion, the data obtained so far suggest that short-lasting maintenance of blood glucose levels may be responsible for the gastroprotective action of glucocorticoids, while www.intechopen.com glucocorticoid-induced long-lasting maintenance of blood glucose levels accompanied with the signs of their catabolic effect and glucocorticoid-induced corticosterone deficiency may be responsible, at least partly, for the transformation of gastroprotective action of glucocorticoids to their proulcerogenic effect (Filaretova et al 2009a(Filaretova et al , 2009b. Further investigation of detailed mechanisms underlying proulcerogenic glucocorticoid action is the task of our future studies.…”