Reaction targets of antioxidants in azo-initiator or lipid hydroperoxide induced lipid peroxidation
Reaction targets of antioxidants in azo-initiator or lipid hydroperoxide induced lipid peroxidation
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DOI：
10.1080/10715762.2020.1761020
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发表时间：
2020-04
影响因子：
3.3
通讯作者：
Kota Saito;Y. Matsuoka;Ken‐ichi Yamada
中科院分区：
文献类型：
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作者：
Kota Saito;Y. Matsuoka;Ken‐ichi Yamada
摘要脂质过氧化（LPO）参与了多种氧化性疾病的发病机制，抗氧化剂的治疗方法也已被提出。LPO被认为是通过一系列复杂的多步反应进行的，这表明每种抗氧化剂的活性可能不同，并取决于反应分子。因此，在这项研究中，我们评估了几种抗氧化剂对由偶氮引发剂2，2 '-偶氮二（2-脒基丙烷）二盐酸盐（AAPH）或脂质过氧化氢，氢过氧十八碳二烯酸（HpODE）/氯化血红素诱导的花生四烯酸（AA）过氧化的抑制机制。依达拉奉，ferrostatin-1，克里思和trolox有效地抑制AAPH诱导的LPO中产生的丙二醛（MDA）和几种氧化的AA，因为它们对脂质过氧自由基的清除能力。相比之下，ebselen和ferrostatin-1在HpODE/氯化血红素诱导的过氧化反应中表现出较强的抗氧化活性。在此条件下，依布硒啉和ferrostatin-1被认为可以将HpODE及其衍生的烷氧基自由基还原为相应的脂质醇。总之，我们发现，每种抗氧化剂具有不同的抗氧化活性，阻止LPO的进展。我们希望这些发现将有助于设计新的治疗策略，使用适当的抗氧化剂针对氧化应激疾病发展的每一步。
Abstract Lipid peroxidation (LPO) is reported to be involved in the pathogenesis of several oxidative diseases, and several therapeutic approaches using antioxidants have been proposed. LPO is thought to progress via a complicated series of multistep reactions suggesting that the activity of each antioxidant may be different, and depends on the reacting molecules. Hence, in this study, we evaluated the inhibitory mechanisms of several antioxidants toward arachidonic acid (AA) peroxidation induced by the azo initiator 2,2’-azobis(2-amidinopropane) dihydrochloride (AAPH) or a lipid hydroperoxide, hydroperoxyoctadecadienoic acid (HpODE)/hemin. Edaravone, ferrostatin-1, TEMPO and trolox effectively inhibited the production of malondialdehyde (MDA) and several oxidised AAs generated in the AAPH-induced LPO because of their scavenging ability toward lipid peroxyl radicals. In contrast, ebselen and ferrostatin-1 showed strong antioxidative activity in the HpODE/hemin-induced peroxidation. Under this condition, ebselen and ferrostatin-1 were thought to reduce HpODE and its derived alkoxyl radicals to the corresponding lipid alcohols. In conclusion, we found that each antioxidant had different antioxidative activities that prevented the progression of LPO. We expect that these findings will contribute to the design of novel therapeutic strategies using an appropriate antioxidant targeted to each step of the development of oxidative stress diseases.