Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

Abstract

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

Oxidative stress and its role in insulin resistance in polycystic ovary syndrome

“…Findings from recent decades show that dysfunction of the endothelial cell by inflammatory and oxidative stress can be associated with the pathogenesis of diabetes for development of premature atherosclerosis. Therefore, antioxidants can be effective role in suppressing of the inflammatory cytokines secration in the human coronary artery endothelial cells (22).…”

Development and Therapeutic Potential of Selenazo Compounds

“…Endothelial dysfunction in uremia may be induced by accumulation of ROS, and deficient levels of glutathione peroxidase-3 (GPx3) may cause the development of kidney disease-induced cardiac risk. Thus, the potentiation of the antioxidant pathways by using GPx mimetic EBS can be an effective strategy to reduce the cardiovascular risk. , Recently, Haas et al have reported that EBS can reduce the levels of proinflamatory cytokines secretion such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) in cells maintained in different high dextrose concentrations acting as human coronary artery endothelial protector.…”