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Glucocorticoids Are Involved in the Gastroprotective Effect of Forced Treadmill Running on Indomethacin–induced Gastric Injury in Rats
Author(s) -
Filaretova Ludmila,
Komkova Olga,
Yarushkitalia
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.00322
Subject(s) - corticosterone , medicine , glucocorticoid , metyrapone , treadmill , endocrinology , pharmacology , anesthesia , hormone
Non‐steroidal anti‐inflammatory drugs (NSAIDs) are widely used to reduce pain and inflammation. However, additional to analgesic and anti‐inflammatory effects, NSAIDs have adverse effects on the gastrointestinal tract due to inhibiting synthesis of prostaglandins that play a key role in the gastrointestinal protection. Previously we have shown that glucocorticoids exert compensatory gastroprotective action under circumstances of prostaglandin deficiency. We have also demonstrated that forced treadmill running is a natural stressor activating the hypothalamic‐pituitary‐adrenocortical (HPA) axis and moreover stressor that has a gastroprotective effect against ulcerogenic action of indomethacin (IM). Here we verify the hypothesis that glucocorticoids released during forced treadmill running are involved in its gastroprotective influence against ulcerogenic action of IM. The contribution of glucocorticoids to the gastroprotective effect of forced treadmill running was studied by using the inhibitor of glucocorticoid synthesis metyrapone. On a day of experiment preliminary fasted (24 h) rats were subjected forced running in treadmill (15 m/min at a 0 incline) for 30 min, then, they were given back in their cages and kept at room temperature for 1 h before the IM administration. Control animals were kept in their cages, but they were also given IM as ulcerogenic stimulus. Metyrapone (30 mg/kg, ip) or its vehicle was administered 30 min before the onset of treadmill session in running as well as control rats. IM‐induced gastric erosions were examined 4 h after IM administration. Plasma corticosterone levels as well as somatic pain sensitivity (tail flick test) were also measured before and after IM administration. A single treadmill running session by itself caused an elevation of plasma corticosterone levels suggesting the HPA axis activation and development of stress‐induced analgesia. Pretreatment with metyrapone eliminated corticosterone rise induced by treadmill running. A single treadmill running session 1 h before IM injection attenuated IM‐induced gastric erosions. Pretreatment with metyrapone not only prevented the gastroprotective effect of treadmill running but also aggravated the ulcerogenic action of IM. The data suggest that glucocorticoids released under forced treadmill running are involved in its gastroprotective effect against the ulcerogenic action of IM. Thus, forced treadmill running can increase the resilience of gastric mucosa to ulcerogenic action of IM through the mechanisms associated with glucocorticoids.