1. The toxic effects of nonsteroidal anti-inflammatory drugs for the lower gastrointestinal tract share certain features with inflammatory processes, suggesting that the release of @entity32 cytokines such as @entity1505 may damage the intestine. 2. @entity35 received a s.c. injection of @entity3352 . Then, jejunum-ileum was taken up for the quantification of ulcerations, production of @entity1505 , @entity2648 and @entity1421 ex vivo and activity of @entity460 -independent NO synthase and myeloperoxydase. Activation of NO metabolism and myeloperoxydase were measured as potential effectors of @entity1505 . 3. Jejunum-ileum from @entity35 having received @entity3352 (10 mg kg(-1)) produced @entity1505 ex vivo. Cytokine production was associated with the onset of macroscopic ulcerations of the small intestine, and preceded @entity3542 production and tissue activity of @entity1589 . 4. Similar intestinal ulcerations and upregulation of @entity1505 were obtained with @entity8726 (30 mg kg(-1)), chemically unrelated to @entity3352 . 5. @entity1505 production was proportional to the @entity3352 dose (from 3-20 mg kg(-1)) and correlated with the surface area of ulcerations and @entity3542 production, 24 h after @entity3352 administration. 6. Pretreatment of @entity35 with @entity1926 , a type-IV phosphodiesterase inhibitor which inhibits @entity1505 synthesis, substantially reduced jejunum-ileum ulcerations, @entity1505 and @entity3542 production and tissue enzyme activities. 7. These findings provide evidence that @entity1505 is increased in @entity3352 -induced intestinal ulcerations and support suggestions that @entity1505 is involved at an early stage of nonsteroidal anti-inflammatory @entity137 for the small intestine.

Increase in tumor necrosis factor-alpha production linked to the XXXX of @entity3352 for the @entity35 small intestine.

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity137 :: ('MESH:D064420', 'Disease') :: ['drug toxicity'] @entity1926 :: ('MESH:D012368', 'Chemical') :: ['RO 20-1724'] @entity1421 :: ('MESH:D015232', 'Chemical') :: ['PGE2'] @entity3542 :: ('CHEBI:16301', 'Chemical') :: ['nitrite'] @entity1505 :: ('24835(Tax:10116)', 'Gene') :: ['TNF-alpha'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity35 :: ('10116', 'Species') :: ['Rats', 'rats'] @entity3352 :: ('MESH:D007213', 'Chemical') :: ['indomethacin'] @entity2648 :: ('MESH:D009573', 'Chemical') :: ['nitrites'] @entity1589 :: ('303413(Tax:10116)', 'Gene') :: ['myeloperoxidase'] @entity8726 :: ('MESH:D005480', 'Chemical') :: ['flurbiprofen']
@entity137 :: (MESH:D064420,Disease) :: ['toxicity']
