PDF(Pubmed)
Abstract：
Bilirubin (BR), a product of heme catabolism, plays a critical role in biological systems. Although increased levels of BR result in hyperbilirubinemia or jaundice, there is increasing evidence that lower concentrations substantially decrease the risk of oxidative stress-mediated diseases due to antioxidant functions of BR. We studied the radical-trapping ability of BR in two model systems, micellar and liposomal, at a broad pH range. At pH < 6.0, BR behaves as a retardant; however, at pH ≥ 6.0, BR becomes strong radical trapping antioxidant, with rate constants for reaction with lipidperoxyl radicals (kinh) within the range from 1.2 × 104 M-1 s-1 to 3.5 × 104 M-1 s-1, and in liposomal system, the activity of BR is comparable to α-tocopherol. This transition is likely facilitated by the ionization of carboxyl groups, leading to a conformational shift in BR and improved solubility/localization at the water/lipid interface. This is the first experimental evidence of the role of pH on the antioxidant activity of bilirubin, and the observed pH-dependent radical-trapping ability of BR holds practical significance, particularly in jaundice treatment where light therapy targets the skin\'s weakly acidic surface. Minor adjustments toward neutral or alkaline pH can enhance radical-trapping action of BR, thereby mitigating oxidative stress induced with blue or violet light exposure.
摘要：
胆红素(BR),血红素分解代谢的产物，在生物系统中起着至关重要的作用。尽管BR水平升高会导致高胆红素血症或黄疸，有越来越多的证据表明，较低的浓度显著降低了由BR的抗氧化功能引起的氧化应激介导的疾病的风险。我们在两个模型系统中研究了BR的自由基捕获能力，胶束和脂质体，在较宽的pH范围内。在pH<6.0时，BR表现为阻滞剂；然而，在pH≥6.0时，BR成为强自由基捕获抗氧化剂，与脂质过氧自由基（kinh）反应的速率常数在1.2×104M-1s-1至3.5×104M-1s-1的范围内，并且在脂质体系统中，BR的活性与α-生育酚相当。羧基的电离可能会促进这种转变，导致BR中的构象移位和改善水/脂质界面处的溶解度/定位。这是pH值对胆红素抗氧化活性作用的第一个实验证据，观察到的BR的pH依赖性自由基捕获能力具有实际意义，特别是在黄疸治疗中，光疗的目标是皮肤的弱酸性表面。对中性或碱性pH的微小调整可以增强BR的自由基捕获作用，从而减轻蓝光或紫光暴露引起的氧化应激。
