エイコサペンタエン酸(EPA)並びにその自動酸化生成物のマウス致死並びにヘモグロビン酸化作用について

Hemoglobin (Hb) oxidation and mouse lethal toxicity of eicosapentaenoic acid (EPA) and its oxidized products by continuous aeration of EPA at 37°C for a week were investigated. To clarify the effects of oxidized EPA (EPA-Ox), they were separated into two fractions (Fr. 1 : oxidized EPA ; Fr. 2 ; unoxidized EPA) by thin-layer chromatography, and their effects were studied. By monitoring the substances in Fr. 1 by spectrophotometry at 230 nm and 280 nm they were separated by high performance liquid chromatography, and many hydrophobic substances were detected. The activity of Hb oxidation was 7.4 times higher in oxidized EPA (Fr. 1) than original EPA (Fr. 2). And the activity of EPA without 0.2% α-tocopherol was also 6.6 times that with the antioxidant. By intraperitoneal injection, mice were killed much earlier by oxidized EPA (EPA-Ox and Fr. 1) than by EPA. LD50 observed 24 h after injection of the above samples using 4 mice in each group, were 9.0 mg for EPA-Ox, 7.4 mg for Fr. 2, 7.3 mg for EPA and 4.2 mg for Fr. 1, and Fr. 1 was more toxic than others. The mouse lethal activity was not inhibited by the further addition of α-tocopherol up to 8.2%. In conclusion, it is suggested that radical oxygens occurred by heme iron-catalyzed autoxidation of EPA are concerned to this Hb oxidation. For the effect of mouse lethal toxicity by EPA, however, it is considered that the mechanism inducing the mouse death is different from that inducing the Hb oxidation, because the toxicity was not inhibited by the addition of α-tocopherol at higher doses.