COX-2 inhibition prevents insulin-dependent diabetes in low-dose streptozotocin-treated mice

Citation
T. Tabatabaie et al., COX-2 inhibition prevents insulin-dependent diabetes in low-dose streptozotocin-treated mice, BIOC BIOP R, 273(2), 2000, pp. 699-704
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006-291X → ACNP
Volume
273
Issue
2
Year of publication
2000
Pages
699 - 704
Database
ISI
SICI code
0006-291X(20000705)273:2<699:CIPIDI>2.0.ZU;2-2
Abstract
Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease believe d to be caused by an inflammatory process in the pancreas leading to select ive destruction of the beta cells. Inducible cyclooxygenase (COX-2) is expr essed under inflammatory conditions and its product prostaglandin E-2 (PGE( 2)) is an important inflammation mediator. We report here that administrati on of the selective COX-2 inhibitor NS-398 prevents the onset of diabetes i n mice brought on by multiple low-doses of streptozotocin (STZ). Histologic al observations indicated that STZ-mediated destruction of beta cells was p revented by NS-398 treatment. Delayed (day 3) administration of NS-398 was also protective in this model. No protective effect was observed when NS-39 8 was administered prior to a high, toxic dose of STZ. These results demons trate the critical importance of COX-2 activity in autoimmune destruction o f beta cells, and point to the fact that COX-2 inhibition can potentially d evelop into a preventive therapy against IDDM. (C) 2000 Academic Press.