title: Role of circadian rhythm and endogenous melatonin in pathogenesis of acute gastric bleeding erosions induced by stress.
abstract: Stress that appears as a consequence of burns, surgical trauma and life threatening conditions is a serious clinical entity, can result in acute gastric mucosal lesions. Such stress lesions can develop in response to the imbalance between the aggressive factors promoting mucosal damage and the gastric mucosal defense mechanisms including predominantly gastric blood flow (GBF), biosynthesis of gastroprotective prostaglandins (PG) and enhanced mucus/bicarbonate secretion. Melatonin, a major hormone of pineal gland, whose activity is also abundant in the gastrointestinal tract, was shown to inhibit gastric acid secretion, augment GBF and scavenge free radicals, resulting in the attenuation of stress-induced gastric lesions. Melatonin is released during the night but little is known about the effect of circadian rhythm and day/night alterations in melatonin secretion on the formation of stress-induced gastric lesions. Using rats with intact pineal glands and those with removed pineal glands (pinealectomy) exposed to water immersion and restraint stress (WRS) at both, day and night hours, we studied the effect of light and nocturnal melatonin on the formation of these lesions, and accompanying changes in GBF and plasma melatonin levels. It was found that the gastric mucosa exposed to WRS of various time duration's lasting 1.5, 3 and 6 h, time-dependently increased the number of gastric lesions and this effect was accompanied by the time-dependent fall in the GBF and an increase in the plasma and luminal melatonin levels. Pinealectomy augmented WRS-induced lesions at each time intervals of WRS and produced a marked fall in the GBF and plasma and luminal melatonin levels at each time interval of WRS tested. WRS lesions were significantly reduced at night hours and showed circadian variations in plasma levels melatonin with significantly higher plasma melatonin levels at night than in the day and with a greater magnitude of damage induced in the daily hours than at night hours. WRS-induced gastric mucosal lesions were markedly enhanced in pinealectomized rats, both at day and night, and this was accompanied by a significant fall in plasma melatonin levels Stress that appears as a consequence of burns, surgical trauma and life threatening conditions is a serious clinical entity, can result in acute gastric mucosal lesions. Such stress lesions can develop in response to the imbalance between the aggressive factors promoting mucosal damage and the gastric mucosal defense mechanisms including predominantly gastric blood flow (GBF), biosynthesis of gastroprotective prostaglandins (PG) and enhanced mucus/bicarbonate secretion. Melatonin, a major hormone of pineal gland, whose activity is also abundant in the gastrointestinal tract, was shown to inhibit gastric acid secretion, augment GBF and scavenge free radicals, resulting in the attenuation of stress-induced gastric lesions. Melatonin is released during the night but little is known about the effect of circadian rhythm and day/night alterations in melatonin secretion on the formation of stress-induced gastric lesions. Using rats with intact pineal glands and those with removed pineal glands (pinealectomy) exposed to water immersion and restraint stress (WRS) at both, day and night hours, we studied the effect of light and nocturnal melatonin on the formation of these lesions, and accompanying changes in GBF and plasma melatonin levels. It was found that the gastric mucosa exposed to WRS of various time duration's lasting 1.5, 3 and 6 h, time-dependently increased the number of gastric lesions and this effect was accompanied by the time-dependent fall in the GBF and an increase in the plasma and luminal melatonin levels. Pinealectomy augmented WRS-induced lesions at each time intervals of WRS and produced a marked fall in the GBF and plasma and luminal melatonin levels at each time interval of WRS tested. WRS lesions were significantly reduced at night hours and showed circadian variations in plasma levels melatonin with significantly higher plasma melatonin levels at night than in the day and with a greater magnitude of damage induced in the daily hours than at night hours. WRS-induced gastric mucosal lesions were markedly enhanced in pinealectomized rats, both at day and night, and this was accompanied by a significant fall in plasma melatonin levels with a pronounced reduction in mucosal generation of PGE(2) and GBF and by a small increase in plasma melatonin levels during the dark phase. We conclude that 1) stress-induced gastric bleeding erosions exhibit circadian rhythm with an increase in the day and attenuation at night and that these fluctuations in the formation of stress-induced gastric damage may depend upon the melatonin synthesis 2) the progressive increase in plasma melatonin in pinealectomized animals exposed to various time intervals of WRS suggests that extra-pineal melatonin possibly that derived from gastrointestinal tract, play an important role in the gastric mucosal defense against stress-induced gastric damage.
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, Cracow, Poland. mpbrzozo@cyf-kr.edu.pl
authors.forename: T
authors.initials: T
authors.lastname: Brzozowski
authors.forename: K
authors.initials: K
authors.lastname: Zwirska-Korczala
authors.forename: P C
authors.initials: PC
authors.lastname: Konturek
authors.forename: S J
authors.initials: SJ
authors.lastname: Konturek
authors.forename: Z
authors.initials: Z
authors.lastname: Sliwowski
authors.forename: M
authors.initials: M
authors.lastname: Pawlik
authors.forename: S
authors.initials: S
authors.lastname: Kwiecien
authors.forename: D
authors.initials: D
authors.lastname: Drozdowicz
authors.forename: M
authors.initials: M
authors.lastname: Mazurkiewicz-Janik
authors.forename: W
authors.initials: W
authors.lastname: Bielanski
authors.forename: W W
authors.initials: WW
authors.lastname: Pawlik
mesh_terms: D000208:Acute Disease; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology; D010438:Peptic Ulcer Hemorrhage / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D010870:Pineal Gland / Q000503:physiopathology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D008550:Melatonin