Health Technology Research Center, National Institute of Advanced Industrial Science & Technology, Osaka 563-8577, Japan.
Free Radic Biol Med. 2010 May 15;48(10):1358-65. doi: 10.1016/j.freeradbiomed.2010.02.018. Epub 2010 Feb 19.
Free radical-mediated lipid peroxidation has been implicated in the pathogenesis of various diseases. Lipid peroxidation products are cytotoxic and they modify proteins and DNA bases, leading eventually to degenerative disorders. Various synthetic antioxidants have been developed and assessed for their capacity to inhibit lipid peroxidation and oxidative stress induced by free radicals. In this study, the capacity of novel 6-amino-2,4,5-trimethyl-3-pyridinols for scavenging peroxyl radicals, inhibiting plasma lipid peroxidation in vitro, and preventing cytotoxicity induced by glutamate, 6-hydroxydopamine, 1-methyl-4-phenylpyridium (MPP(+) ), and hydroperoxyoctadecadienoic acid was assessed. It was found that they exerted higher reactivity toward peroxyl radicals and more potent activity for inhibiting the above oxidative stress than alpha-tocopherol, the most potent natural antioxidant, except against the cytotoxicity induced by MPP(+). These results suggest that the novel 6-amino-3-pyridinols may be potent antioxidants against oxidative stress.
自由基介导的脂质过氧化作用与多种疾病的发病机制有关。脂质过氧化产物具有细胞毒性，可修饰蛋白质和 DNA 碱基，最终导致退行性疾病。已经开发了各种合成抗氧化剂，并评估了它们抑制自由基诱导的脂质过氧化和氧化应激的能力。在这项研究中，评估了新型 6-氨基-2,4,5-三甲基-3-吡啶醇清除过氧自由基、体外抑制血浆脂质过氧化以及预防谷氨酸、6-羟多巴胺、1-甲基-4-苯基吡啶（MPP(+)）和过氧氧代十八碳二烯酸诱导的细胞毒性的能力。结果发现，与 α-生育酚（最有效的天然抗氧化剂）相比，它们对过氧自由基的反应性更高，抑制上述氧化应激的活性更强，除了对 MPP(+)诱导的细胞毒性外。这些结果表明，新型 6-氨基-3-吡啶醇可能是有效的抗氧化剂，可对抗氧化应激。
