Biomedical Spectroscopy Laboratory, Department of Physics, CESAM, University of Liège, Building B5a, Quartier Agora, Allée du 6 Août, 19, Sart-Tilman, 4000 Liège, Belgium.
Greenmat, Department of Chemistry, CESAM, University of Liège, Building B6c, Quartier Agora, Allée du 6 Août, 19, Sart-Tilman, 4000 Liège, Belgium.
Biochim Biophys Acta Gen Subj. 2022 May;1866(5):130100. doi: 10.1016/j.bbagen.2022.130100. Epub 2022 Feb 10.
Propofol (2,6-diisopropylphenol) is frequently used as intravenous anesthetic agent, especially in its injectable form (Diprivan), to initiate and maintain sedative state during surgery or in intensive care units. Numerous studies have reported the antioxidant and anti-inflammatory effect of propofol. The oxidant enzyme myeloperoxidase (MPO), released from activated neutrophils, plays a key role in host defense. An increase of the circulating MPO concentration has been observed in patients admitted in intensive care unit and presenting a systemic inflammatory response related to septic shock or trauma.
This study investigates the immunomodulatory action of propofol and Diprivan as inhibitor of the oxidant activity of MPO. The understanding of the redox action mechanism of propofol and Diprivan on the myeloperoxidase chlorination and peroxidase activities has been refined using the combination of fluorescence and absorption spectroscopies with docking and cyclic voltammetry.
Propofol acts as a reversible MPO inhibitor. The molecule interacts as a reducing substrate in the peroxidase cycle and promotes the accumulation of compound II. At acidic pH (5.5), propofol and Diprivan do not inhibit the chlorination activity, but their action increases at physiological pH (7.4). The main inhibitory action of Diprivan could be attributed to its HOCl scavenging property.
Propofol can act as a reversible MPO inhibitor at clinical concentrations. This property could, in addition to other previously proven anti-inflammatory actions, induce an immunomodulatory action, beneficial during clinical use, particularly in the treatment of systemic inflammation response syndrome.
丙泊酚（2,6-二异丙基苯酚）常作为静脉麻醉剂使用，尤其以其注射剂型（得普利麻）用于手术或重症监护病房中镇静状态的诱导和维持。许多研究已经报道了丙泊酚的抗氧化和抗炎作用。氧化酶髓过氧化物酶（MPO）从活化的中性粒细胞中释放，在宿主防御中发挥关键作用。在入住重症监护病房并出现与感染性休克或创伤相关的全身炎症反应的患者中，观察到循环 MPO 浓度增加。
本研究探讨了丙泊酚和得普利麻作为 MPO 氧化活性抑制剂的免疫调节作用。使用荧光和吸收光谱学与对接和循环伏安法相结合，对丙泊酚和得普利麻对髓过氧化物酶氯化和过氧化物酶活性的氧化还原作用机制进行了深入研究。
丙泊酚作为一种可逆的 MPO 抑制剂。该分子在过氧化物酶循环中作为还原底物相互作用，并促进化合物 II 的积累。在酸性 pH 值（5.5）下，丙泊酚和得普利麻不抑制氯化活性，但在生理 pH 值（7.4）下其作用增强。得普利麻的主要抑制作用可能归因于其对 HOCl 的清除作用。
丙泊酚可以在临床浓度下作为一种可逆的 MPO 抑制剂。除了其他已证明的抗炎作用外，这种特性可能会诱导一种免疫调节作用，在临床应用中有益，特别是在治疗全身炎症反应综合征时。
