Role of Glucocorticoids in Gastroprotection Induced by Capsaicin

Abstract

The pivotal role of capsaicin‐sensitive peptidergic sensory fibers in maintaining of gastric mucosal integrity against injurious interventions has been well established in rats and then in human. Clinical finding suggests that capsaicin‐induced gastric mucosal protection against the injurious effects of ethanol or indomethacin is due to the acute stimulatory effect of the compound. It was concluded that patients taking non‐steroidal anti‐inflammatory drugs (NSAID) regularly can decrease the incidence and severity of gastric ulceration, if they have moderate spicy foods. Opposite effect has been observed in rats desensitized by capsaicin. Functional blockade of gastric sensory nerve endings elicited by systemic capsaicin application was resulted in impaired mucosal protection against various ulcerogenic agents. Our previous findings suggest a pivotal compensatory role of glucocorticoids in maintenance of gastric mucosal integrity in rats desensitized by capsaicin. In this study, we tested if glucocorticoids can participate in capsaicin‐caused gastroprotection during NSAID‐caused gastropathy accompanied by prostaglandin deficiency in rats. Gastric injury was induced by indomethacin (IM). A single IM administration (35 mg/kg, sc) into fasting (24 h) rats caused the formation of gastric erosions 4 h after injection. The effects of small doses (0.1, 0.5, 1.0, 2.0, 3.0, 5.0, 10.0 mg/kg, sc) of capsaicin on the blood corticosterone and glucose levels and IM‐induced gastric injury were tested. A single capsaicin administration was performed one hour before IM administration. To test the participation of corticosterone in the gastroprotective effect of capsaicin, the pretreatment by the inhibitor of glucocorticoid synthesis, metyrapone (30 mg/kg, i.p., 30 min before capsaicin) was used. We found that the pretreatment with capsaicin (0.5–10.0 mg/kg, sc) reduced dose dependently the area of IM‐induced erosions. This protection was accompanied by a gradual increase in blood corticosterone and glucose levels. Metyrapone injected shortly before capsaicin administration (1.0 mg/kg) caused a fast inhibition of capsaicin‐induced corticosterone response and reversed the protective effect of capsaicin on the gastric mucosa against the IM‐produced injury. The present study confirms evidence for the powerful gastroprotective potency of capsaicin during NSAID‐caused gastropathy. The findings obtained demonstrate that capsaicin administration resulted in an increase in plasma corticosterone levels which in turn plays a pivotal role in maintaining of gastric mucosal integrity against injurious intervention of IM.Support or Funding InformationThe study was supported by grants of RSF N 19‐15‐00430 (NSAID‐caused gastropathy with prostaglandin deficiency) and RFBR N 19‐015‐00514a (capsaicin‐induced gastroprotection)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.