Direct Antioxidant Properties of Bilirubin and Biliverdin. Is there a Role for Biliverdin Reductase?
Direct Antioxidant Properties of Bilirubin and Biliverdin. Is there a Role for Biliverdin Reductase?
复制标题
DOI：
10.3389/fphar.2012.00030
复制
发表时间：
2012
影响因子：
5.6
通讯作者：
Daiber A
中科院分区：
文献类型：
--
作者：
Jansen T;Daiber A
活性氧（ROS）和信号转导事件参与内皮功能障碍的发病机制，并代表了血管调节的主要贡献。分子信号高度依赖于ROS。但根据ROS产生的量，它可能具有毒性或保护作用。尽管在大型临床试验中有大量的负面结果（例如，HOPE，HOPE-TOO），抗氧化分子和试剂是影响活性氧和氮物质的产生和消除之间的关键平衡的重要参与者。然而，慢性全身抗氧化治疗缺乏临床疗效，可能是通过干扰重要的生理氧化还原信号通路。因此，它可能是一个更有前途的尝试，诱导内在的抗氧化剂途径，以增加抗氧化剂，而不是全身性的，但在氧化应激和并发症的地方。其中，血红素加氧酶（HO）已被证明通过其降解血红素和产生一氧化碳和胆绿素/胆红素的能力对于在广泛的疾病状态中减弱ROS的总体产生是重要的。与目前的审查，我们想强调HO系统的重要的抗氧化作用，特别是讨论的贡献，胆绿素，胆红素，胆绿素还原酶（BVR），这些有益的效果。据报道，BVR赋予抗氧化剂氧化还原放大循环，通过该循环，低生理胆红素浓度通过BVR从氧化胆红素中回收胆绿素，将氧化剂的汇连接到NADPH池，从而赋予有效的抗氧化剂保护。到目前为止，这种抗氧化剂氧化还原循环的存在和作用仍在争论中，我们提出并讨论了利弊以及我们自己对这个话题的研究结果。
Reactive oxygen species (ROS) and signaling events are involved in the pathogenesis of endothelial dysfunction and represent a major contribution to vascular regulation. Molecular signaling is highly dependent on ROS. But depending on the amount of ROS production it might have toxic or protective effects. Despite a large number of negative outcomes in large clinical trials (e.g., HOPE, HOPE-TOO), antioxidant molecules and agents are important players to influence the critical balance between production and elimination of reactive oxygen and nitrogen species. However, chronic systemic antioxidant therapy lacks clinical efficacy, probably by interfering with important physiological redox signaling pathways. Therefore, it may be a much more promising attempt to induce intrinsic antioxidant pathways in order to increase the antioxidants not systemically but at the place of oxidative stress and complications. Among others, heme oxygenase (HO) has been shown to be important for attenuating the overall production of ROS in a broad range of disease states through its ability to degrade heme and to produce carbon monoxide and biliverdin/bilirubin. With the present review we would like to highlight the important antioxidant role of the HO system and especially discuss the contribution of the biliverdin, bilirubin, and biliverdin reductase (BVR) to these beneficial effects. The BVR was reported to confer an antioxidant redox amplification cycle by which low, physiological bilirubin concentrations confer potent antioxidant protection via recycling of biliverdin from oxidized bilirubin by the BVR, linking this sink for oxidants to the NADPH pool. To date the existence and role of this antioxidant redox cycle is still under debate and we present and discuss the pros and cons as well as our own findings on this topic.
登录
查看更多内容
影响因子：
15.9
作者：
Bassenge, E;Fink, N;Fink, B
通讯作者：
Fink, B
影响因子：
2.8
作者：
Daiber, A;Mülsch, A;Münzel, T
通讯作者：
Münzel, T
影响因子：
4.3
作者：
Daiber, Andreas
通讯作者：
Daiber, Andreas
影响因子：
4.8
作者：
Ahmad, Z;Salim, M;Maines, MD
通讯作者：
Maines, MD
影响因子：
4.7
作者：
Barone, Eugenio;Mancuso, Cesare;Butterfield, D. Allan
通讯作者：
Butterfield, D. Allan