The effect of trinitrobenzene sulfonic acid (TNB) on colonocyte arachidonic acid metabolism.
In previous studies we found that luminal perfusion of the isolated left colon of the rabbit with the hapten, trinitrobenzene, resulted in the production of an acute inflammatory process associated with alterations in eicosanoid metabolism. As the colitis was attenuated by cyclooxygenase inhibitors it is possible that the inflammation was mediated by arachidonic acid metabolites. In the present study it was intended to evaluate the effect of trinitrobenzene on eicosanoid metabolism in transformed human colonic cells by exposing Caco-2++ cells to various doses of trinitrobenzene. Cell injury was evaluated by measuring lactate dehydrogenase levels and cyclooxygenase and lipoxygenase activity was evaluated by measuring prostanoid and leukotriene production. In separate experiments resting and trinitrobenzene stimulated cells were treated with indomethacin and dexamethasone. Trinitrobenzene produced increased prostaglandin E2 and 6-keto prostaglandin F1alpha++ and increased lactate dehydrogenase levels. Leukotriene B4 was significantly increased compared to control values at the highest TNB concentration administered. Indomethacin inhibited the lactate dehydrogenase and prostanoid changes, suggesting that the inflammatory changes produced were mediated by the prostanoids. Dexamethasone administered for 1 hr prior to trinitrobenzene decreased the 6-keto prostaglandin F1alpha but did not alter trinitrobenzene produced changes in lactate dehydrogenase concentrations. Exposure of Caco-2 cells to dexamethasone for 24 hr decreased the trinitrobenzene produced lactate dehydrogenase and eicosanoid changes. The results suggest that trinitrobenzene produces an acute injury to Caco-2 cells that may be mediated by the cyclooxygenase enzymes.
Stratton
M D
MD
Department of Surgery, Surgical Research Institute, Saint Louis University Scool of Medicine, St.Louis, Missouri 63110-0250, USA.
Sexe
R
R
Peterson
B
B
Kaminski
D L
DL
Li
A P
AP
Longo
W E
WE
D016718:Arachidonic Acid / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007975:Leukotriene B4; D016718:Arachidonic Acid; D014302:Trinitrobenzenesulfonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin