Protection against nitrofurantoin-induced oxidative stress by coelenterazine analogues and their oxidation products in rat hepatocytes
Protection against nitrofurantoin-induced oxidative stress by coelenterazine analogues and their oxidation products in rat hepatocytes
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DOI：
10.1080/10715760100300251
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发表时间：
2001-01-01
影响因子：
3.3
通讯作者：
Rees, JF
中科院分区：
文献类型：
--
作者：
Dubuisson, MLN;De Wergifosse, B;Rees, JF
腔肠素（3，7-二氢-2-（对羟基苄基）-6-（对羟基苯基）-8-苄基咪唑并[1，2-a]吡嗪-3-酮）是许多海洋动物生物发光反应的底物，最近的研究表明，CLZn及其合成类似物CLZm，和它们共同的氧化产物腔肠素（CLM）在非细胞脂质过氧化系统以及在大鼠肝细胞中具有很强的抗氧化特性。丁基过氧化氢（t-BHP）。在这里，我们分析了CLZm和几个咪唑吡嗪酮（IMPZs）类似物的能力，以保护原代培养的大鼠肝细胞对呋喃妥因（NF）诱导的氧化应激。与参考抗氧化剂的保护能力的比较产生以下排序：CLZm > BHT > Trolox C（R）> prohucol > α-生育酚。CLZm与R-1中缺少苯酚基团的类似物的比较显示没有差异，尽管这种苯酚的存在赋予了对t-BHP的上级保护。CLM及其缺乏断链特性的甲氧基化类似物mCLM在预防NF引起的细胞损伤方面同样有效。mCLM和细胞色素P450（CYP 450）IAI抑制剂α-萘酚酮，类似地保护细胞免受NF诱导的死亡，也同样抑制甲基胆蒽诱导的肝细胞中的EROD活性。CLZm和CLM对EROD的抑制作用不太明显。我们认为，IMPZs对NF毒性的保护程度反映了细胞内产生的抗氧化特性解毒ROS和对NF生物还原中涉及的CYP 450亚型的抑制作用。
Coelenterazine (3,7-dihydro-2-(p-hydroxybenzyl)-6-(p -hydroxyphenyl)-8-benzylimidazolo [1,2-a]pyrazin-3-one) is a substrate for the bioluminescence reaction in many marine animals, Recent work showed that CLZn, its synthetic analogue CLZm, and their common oxidation product coelenteramine (CLM) have strong antioxidative properties in acellular lipid peroxidation systems as well as in rat hepatocytes subjected to tert-butyl hydroperoxide (t-BHP). Here, we analyzed the ability of CLZm and several imidazolopyrazinone (IMPZs) analogues to protect primary cultures of rat hepatocytes against a nitrofurantoin (NF)-induced oxidative stress. Comparison of protection capabilities with reference antioxidants yielded the following ranking: CLZm >>> BHT > Trolox C (R) > prohucol > alpha -tocopherol. The comparison of CLZm with analogues lacking the phenol group in R-1 revealed no differences although the presence of this phenol conferred superior protection against t-BHP. CLM, as well as its methoxylated analogue mCLM which lacks chain-breaking properties, were equally potent in preventing cellular damage caused by NF. mCLM and alpha -naphthoflavone, an inhibitor of cytochrome P450 (CYP450) IAI, similarly protected cells against NF-induced mortality and also equally inhibited EROD activity in methylcholanthrene-induced hepatocytes. The inhibition of EROD by CLZm and CLM was less pronounced. We suggest that the extent of protection conferred by IMPZs against NF-toxicity reflects both the occurrence of antioxidative properties detoxifying ROS produced within cells and inhibitory actions on CYP450 isoforms involved in the bioreduction of NF.