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Enhanced prostaglandin biosynthesis in human gingival fibroblasts isolated from patients treated with phenytoin
Author(s) -
Modéer T.,
Anduren I.,
Lerner U. H.
Publication year - 1992
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.1992.tb01005.x
Subject(s) - arachidonic acid , phenytoin , prostaglandin e , fibroblast , endocrinology , chemistry , medicine , prostaglandin , prostanoid , tumor necrosis factor alpha , prostaglandin e2 , interleukin , cyclooxygenase , phospholipase a2 , pharmacology , cytokine , enzyme , biochemistry , epilepsy , in vitro , psychiatry
Prostaglandin E 2 (PGE 2 ) formation was studied in human gingival fibroblasts derived from three epileptic patients before and after 9 months of phenytoin (PHT) therapy. Interleukin I (IL‐1α; 0.3‐6.0 ng/ml), (IL‐1β; 10–1000 pg/ml) and tumour necrosis factor (TNFα; 0.01–O.I μg/ml) dose‐dependently stimulated the formation of PGE: in 24 h cultures. In fibroblasts, derived after 9 months of PHT therapy. IL‐1α, IL‐1β and TNFα induced a significantly higher formation of PGE 2 compared to that in fibroblasts derived before PHT therapy. IL‐1β induced a significantly higher release also of 3 H‐arachidonic acid ( 3 H‐AA) from prelabelled PHT fibroblasts compared to that in prelabelled gingival fibroblasts isolated before the drug therapy. Addition of exogenous AA caused a spontaneous increase of PGE: formation in PHT fibroblasts compared to that in fibroblasts isolated before the PHT treatment. The results indicate that PHT medication results in an upregulation of prostanoid formation in gingival fibroblasts partly due to an increased phospholipase A; activity and partly due to an increased cyclooxygenase activity.