Antioxidative properties of natural coelenterazine and synthetic methyl coelenterazine in rat hepatocytes subjected to tert-butyl hydroperoxide-induced oxidative stress
Antioxidative properties of natural coelenterazine and synthetic methyl coelenterazine in rat hepatocytes subjected to tert-butyl hydroperoxide-induced oxidative stress
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DOI：
10.1016/s0006-2952(00)00359-2
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发表时间：
2000-08-15
影响因子：
5.8
通讯作者：
Rees, JF
中科院分区：
文献类型：
--
作者：
Dubuisson, MLN;de Wergifosse, B;Rees, JF
Coelenterazine （CLZn; 3,7-二氢-2-（对羟基苯基）-6-（对羟基苯基）-8-benzylimidazolo[1,2-a]pyrazin-3-one）是许多海洋动物生物发光反应的底物，具有较高的抗氧化性能。本研究研究了氯化锌在氧化过氧化叔丁基（t-BHP）大鼠肝细胞原代培养物中的抗氧化性能。在2.5 × 10(-4) M t-BHP作用6小时的大鼠肝细胞中，微摩尔浓度的CLZn提高了存活率，降低了脂质过氧化。然而，CLZn的强毒性限制了保护程度(IC（50) = 6.9 x 10(-5) M）。t-BHP的存在增加了CLZn的细胞毒性。甲基coelenterazine （CLZm, 3,7-二氢-2-甲基-6-（对羟基苯基）-8 benzylimidazolo[1,2-a] pyrazin-3-one）是CLZn的合成类似物，即使在非常低的浓度（3 × 10(-6) M）下也表现出优异的抗氧化性能，并且在其大部分有效浓度范围内无毒。CLZm被证明比参照抗氧化剂如Trolox C(R)， α -生育酚，BHT和probucol更有效。与细胞和培养基相关的硫代巴比妥反应性物质（TBARS）的测定表明，10(-5)M CLZm对t- bhp诱导的脂质过氧化具有完全的保护作用。该胶肠嗪类似物可作为研究咪唑吡嗪类药物在哺乳动物肝细胞内作用机制的模型化合物。生物化学药学60；4:471 - 478, 2000。(C) 2000 Elsevier Science Inc.；
Coelenterazine (CLZn; 3,7-dihydro-2-(p-hydroxybenzyl)-6-(p-hydroxyphenyl)-8-benzylimidazolo[1,2-a]pyrazin-3-one), the substrate for bioluminescence reactions in many marine animals, is endowed with high antioxidant: properties. This work investigated the antioxidative properties of CLZn in primary cultures of rat hepatocytes subjected to the oxidant tert-butyl hydroperoxide (t-BHP). Micromolar concentrations of CLZn increased survival and decreased lipid peroxidation in rat hepatocytes subjected for 6 hr to 2.5 x 10(-4) M t-BHP. However, the extent of protection was limited by a strong toxicity of CLZn (IC(50) = 6.9 x 10(-5) M). The presence of t-BHP increased the cellular toxicity of CLZn. Methyl coelenterazine (CLZm, 3,7-dihydro-2-methyl-6-(p-hydroxyphenyl)-8 benzylimidazolo[1,2-a] pyrazin-3-one), a synthetic analogue of CLZn, demonstrated excellent antioxidant properties, even at very low (3 x 10(-6) M) concentrations and was not toxic throughout most of its effective concentration range. CLZm proved far more effective than reference antioxidants such as Trolox C(R), alpha-tocopherol, BHT, and probucol. The assay of thiobarbituric reactive substances (TBARS) associated with cells and in the culture medium indicated that 10(-5) M CLZm provided a total protection against t-BHP-induced lipid peroxidation. This coelenterazine analogue could be used as a model compound for investigating the action mechanism of imidazolopyrazinones in mammalian hepatocytes. BIOCHEM PHARMACOL 60;4:471-478, 2000. (C) 2000 Elsevier Science Inc.