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Effects of gamma-linolenic acid, flavonoids, and vitamins on cytotoxicity and lipid peroxidation.

Gamma linolenic acid (GLA), a polyunsaturated fatty acid, promoted lipid peroxidation in Raji lymphoma suspension cultures, in a dose (10 microM-100 microM) and time-dependent (4 h-48 h) manner. The increase in lipid peroxidation could be correlated to an increase in cytotoxicity. The plant flavonoids (quercetin, luteolin, butein, rutin) and the fat-soluble components (retinol, retinoic acid, alpha-tocopherol) by themselves did not affect lipid peroxidation in Raji cells. Quercetin, luteolin, retinol, and alpha-tocopherol were able to inhibit cell proliferation significantly. Although GLA only decreased the cytotoxicity of retinol-treated cells, the latter compound was able to block the prooxidative action of GLA by scavenging the free radicals induced by it. Quercetin at 50 and 100 microM exerted equipotent superoxide anion scavenging effects, but at the higher concentration it had no effect on lipid peroxidation. Although the bioactive test compounds are well known natural antioxidants, interestingly, our data showed that their potent cytotoxic actions do not involve free radicals or lipid peroxidation reactions.