Hiramoto Kazuyuki, Yasuhara Yoshinobu, Sako Ken-ichi, Aoki Kazuhiro, Kikugawa Kiyomi
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.
Biol Pharm Bull. 2003 Aug;26(8):1129-34. doi: 10.1248/bpb.26.1129.
The results of the present study have shown that unoxidized linoleic acid (LA) and low density lipoprotein (LDL) suppressed free radical-induced supercoiled plasmid DNA strand breaks. Unoxidized LA suppressed DNA strand breaks induced by free radicals generated from hydrogen peroxide/Fe(II) ion, 2'-azobis(2-amidinopropane)hydrochloride (AAPH), and 4-(hydroxymethyl)benzene diazonium salt. Thiobarbituric acid reactive substances (TBARS) of LA were increased on treatment with the radical generators. The intensities of the electron spin resonance (ESR) signals of the spin adducts of the radicals were reduced by unoxidized LA. Although LA hydroperoxide caused DNA strand breaks as has already been shown, its strand breaking activity was observed only at the higher concentrations. Unoxidized LDL inhibited ascorbic acid/Cu(II) ion-, ascorbic acid/Fe(II) ion-, peroxynitrite- and AAPH-induced DNA strand breaks. The TBARS of LDL were increased by treatment with the agents. LDL oxidized with Cu(II) ion did not cause DNA strand breaks. The results indicate that the potency of the free radicals to cause DNA strand breaks was attenuated by the fatty acid and the lipoprotein through lipid peroxidation.
本研究结果表明,未氧化的亚油酸(LA)和低密度脂蛋白(LDL)可抑制自由基诱导的超螺旋质粒DNA链断裂。未氧化的LA可抑制由过氧化氢/亚铁离子、2'-偶氮二(2-脒基丙烷)盐酸盐(AAPH)和4-(羟甲基)苯重氮盐产生的自由基诱导的DNA链断裂。用自由基发生器处理后,LA的硫代巴比妥酸反应性物质(TBARS)增加。未氧化的LA可降低自由基自旋加合物的电子自旋共振(ESR)信号强度。尽管如已表明的那样,氢过氧化亚油酸会导致DNA链断裂,但其链断裂活性仅在较高浓度下才会观察到。未氧化的LDL可抑制抗坏血酸/铜离子、抗坏血酸/亚铁离子、过氧亚硝酸盐和AAPH诱导的DNA链断裂。用这些试剂处理后,LDL的TBARS增加。用铜离子氧化的LDL不会导致DNA链断裂。结果表明,脂肪酸和脂蛋白通过脂质过氧化作用减弱了自由基导致DNA链断裂的能力。