Day/night differences in stress-induced gastric lesions in rats with an intact pineal gland or after pinealectomy.
The formation of acute gastric lesions depends upon the balance between the aggressive factors promoting mucosal damage and the natural defense mechanisms. Previous studies have shown that melatonin inhibits gastric acid secretion, enhances the release of gastrin, augments gastric blood flow (GBF), increases the cyclooxygenase-2 (COX-2)-prostaglandin (PG) system and scavenges free radicals, resulting in the prevention of stress-induced gastric lesions. Besides the pineal gland, melatonin is also generated in large amounts in the gastrointestinal tract and due to its antioxidant and anti-inflammatory properties; this indole might serve as local protective endogen preventing the development of acute gastric damage. The results of the present study indicate that stress-induced gastric lesions show circadian variations with an increase in the day time and a decline at night. These changes are inversely related to plasma melatonin levels. Following pinealectomy, stress-induced gastric mucosal lesions were more pronounced both during the day and at night, and were accompanied by markedly reduced plasma melatonin levels with a pronounced reduction in mucosal generation of prostaglandin E(2) (PGE(2)), GBF and increased free radical formation and by small rise in plasma melatonin during the dark phase. We conclude that stress-induced gastric ulcerations exhibit a circadian variation with an increase in the day and attenuation at night and that these fluctuations of gastric stress ulcerogenesis occur also after pinealectomy, depending upon the interaction of COX-PG and free radicals, probably mediated by the changes in local gastric melatonin.
Konturek
Stanisław J
SJ
Department of Clinical Physiology, Jagiellonian University Medical College, Cracow, Poland. mpkontur@cyf-kr.edu.pl
Brzozowski
Tomasz
T
Konturek
Piotr C
PC
Zwirska-Korczala
Krystyna
K
Reiter
Russel J
RJ
D000818:Animals; D002940:Circadian Rhythm; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000097:blood; D005609:Free Radicals / Q000378:metabolism; D005755:Gastrins / Q000096:biosynthesis; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D010870:Pineal Gland / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013276:Stomach Ulcer / Q000097:blood* / Q000209:etiology / Q000473:pathology; D013312:Stress, Physiological / Q000097:blood* / Q000150:complications / Q000473:pathology
D005609:Free Radicals; D005755:Gastrins; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D008550:Melatonin; D015232:Dinoprostone