Suppression of human T-cell growth in vitro by cis-unsaturated fatty acids: relationship to free radicals and lipid peroxidation.

Cis-unsaturated fatty acids such as dihomogamma-linolenic acid (DGLA), arachidonic acid (AA) and eicosapentaenoic acid (EPA), which form precursors to 1, 2 and 3 series prostaglandins (PGs), have been shown to suppress human T-cell growth in vitro by a prostaglandin E (PGE)-independent mechanism. In an earlier study, we showed that these fatty acids can induce free radical generation in human neutrophils and tumor cells. Here we show that cis-unsaturated fatty acids augment free radical generation and lipid peroxidation in human T-cells. The growth suppressive action of cis-unsaturated fatty acids on human T-cells could be blocked by anti-oxidant, vitamin E and the superoxide anion quencher superoxide dismutase. These results suggest that c-UFAs-induced cell growth suppression is a free radical dependent process.

Oxy-radicals, lipid peroxides and essential fatty acids in patients with glomerular disorders.

It is now believed that free radicals and eicosanoids participate in the pathogenesis of immune mediated mesangial cell injury and renal tissue damage including glomerulonephritis. But relatively little information is available about the role of essential fatty acids, (EFAs), the precursors of eicosanoids, in renal diseases. We studied the levels of superoxide anion, hydrogen peroxide, lipid peroxides and the concentrations of various metabolites of EFAs in the plasma phospholipid fraction of patients with glomerular disorders. A significant increase in the production of superoxide anion and hydrogen peroxide both by unstimulated and phorbol-myristate acetate (PMA)-stimulated leukocytes, increase in the plasma lipid peroxide levels and a marked reduction in the levels of arachidonic acid (AA) and eicosapentaenoic acid, the precursors of 2 and 3 series prostaglandins (PGs) respectively, were observed in these patients. Since eicosapentaenoic acid and prostacyclin, which is derived from AA, are believed to be of benefit in the prevention of progression of renal disease, and as free radicals can cause renal dysfunction, our results suggest that free radicals and the metabolites of EFAs play a significant role in the pathogenesis of glomerular disorders.

Free radical generation, lipid peroxidation and essential fatty acids in patients with septicemia.

Infections due to gram-negative bacteria and other organisms can lead to septicemia and shock in some patients. Endotoxins, which cause these pathophysiological events, stimulate macrophages to elaborate tumor necrosis factor and other lymphokines. These lymphokines can augment free radical generation by polymorphonuclear leukocytes, macrophages and other cells, which may ultimately produce respiratory distress syndrome, multiorgan failure and irreversible shock seen in septicemia. This is supported by our results presented here that there is indeed an increase in free radical generation and lipid peroxidation in patients with septicemia. In addition, analysis of plasma lipid profile in these patients showed that gamma-linolenic, dihomogamma-linolenic and arachidonic acids of n-6 series and alpha-linolenic and eicosapentaenoic acids of the n-3 series are decreased in their plasma phospholipid fraction. These results suggest that free radicals, lipid peroxides, and alteration in essential fatty acid metabolism may have a role in the pathogenesis of septicemia.

Free radical generation, lipid peroxidation and essential fatty acids in uncontrolled essential hypertension.

Vascular endothelium produces prostacyclin (PG12) and endothelium-derived vascular relaxing factor (EDRF), which are potent vasodilators and hence, may have a role in the regulation of blood pressure. Both PG12 and EDRF are readily degraded by free radicals, especially superoxide anion. Hence, we studied free radical generation and lipid peroxidation in patients with uncontrolled essential hypertension. It was observed that superoxide anion and hydrogen peroxide production by polymorphonuclear leukocytes (PMN) and the levels of lipid peroxides (measured by thiobarbituric acid assay) were higher in uncontrolled hypertensives compared to controls. Both free radical generation and the levels of lipid peroxides reverted to normal values when assayed after the control of hypertension. The calcium antagonist, verapamil, and beta-1 blocker, metoprolol, at the doses used inhibited free radical generation by phorbolmyristate acetate-stimulated PMNs. On the other hand, angiotensin II augmented free radical generation in normal PMN. In addition, it was also observed that both linoleic acid and arachidonic acid levels are low in the plasma of patients with hypertension compared to controls. These results suggest that increase in free radical generation by PMN and alterations in the plasma concentrations of essential fatty acids are closely associated with uncontrolled hypertension.