MODULATION OF GLUTATHIONE-PEROXIDASE ACTIVITY IN HUMAN VASCULAR ENDOTHELIAL-CELLS BY FATTY-ACIDS AND THE CYTOKINE INTERLEUKIN-1-BETA

Objectives of this study were (a) to assess the extent of oxidative st ress elicited in human endothelial cells by n - 3, n - 6 and n - 9 mon o- and polyunsaturated fatty acids and by interleukin-1 beta and (b) t o determine how such stress influenced glutathione peroxidase (GSHPx) activity, Fatty acids were co-incubated with human vascular endothelia l cells (HUVEC) for 24 h. Lipid peroxidation, monitored as conjugated diene (CD) formation, increased 3-4-fold with increasing eicosapentaen oic and docosahexaenoic acids; 2-3-fold with linoleic acid; decreased by 50% with arachidonic acid and was unchanged with oleic acid. Change s in glutathione peroxidase activity mirrored conjugated diene formati on in the HUVEC incubated with fatty acids. Interleukin-lp also increa sed glutathione peroxidase and conjugated diene formation; the latter increased enzyme activity dose-dependently suggesting a possible role for this oxidation product in the induction of glutathione peroxidase activity. The ability of fish oil fatty acids to induce antioxidant en zymes, particularly those of the glutathione redox system, may be an i mportant mechanism protecting cells and tissues against oxidative and inflammatory cytokine elicited damage.