Worsening effect of partial sleep deprivation on indomethacin-induced gastric mucosal damage.
The present study was to investigate the roles of cyclooxygenase-1 and -2 (COX-1 and COX-2) and prostaglandin (PG) on gastric mucosal integrity of partially sleep deprived (PSD) rats. A slowly moving drum was used to induce PSD. The PG levels in the gastric mucosa of PSD rats, with or without indomethacin or rofecoxib treatment, were determined. Exogenous prostaglandin E (PGE) analog, misoprostol, was administered to PSD rats to investigate the modulating effect of PG in indomethacin-induced gastric damage. It was observed that COX-1 mRNA and protein were up-regulated in the gastric mucosa of PSD rats. Selective COX-2 inhibition by rofecoxib failed to decrease mucosal PGE2 levels nor to affect mucosal integrity in both PSD and sleep undisturbed rats. However, indomethacin, a COX-1 preferential non-selective COX inhibitor, significantly reduced mucosal PGE2 content and produced more severe mucosal damage in PSD rats than in the controls. The deleterious effect of indomethacin on gastric mucosal integrity of PSD rats was significantly attenuated with the administration of misoprostol. These results suggest that PSD enhances COX-1 biosynthesis of gastroprotective PGE2 as an adaptive response of the stomach to stress. The administration of non-selective COX inhibitors to subjects with chronic sleep deprivation may induce more gastric damages.
Guo
Jin Sheng
JS
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
Chau
Fung Ling
FL
Cho
Chi Hin
CH
Koo
Marcel Wing Leung
MW
D000818:Animals; D001483:Base Sequence; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D017931:DNA Primers; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000293:injuries / Q000378:metabolism; D007213:Indomethacin / Q000009:adverse effects*; D007783:Lactones / Q000494:pharmacology; D008297:Male; D016595:Misoprostol / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012892:Sleep Deprivation; D013450:Sulfones / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D007783:Lactones; D011453:Prostaglandins; D012333:RNA, Messenger; D013450:Sulfones; D016595:Misoprostol; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007213:Indomethacin