In previous studies, propofol has shown immunomodulatory abilities on various in vitro models. As this anesthetic molecule is extensively used in intensive care units, its anti-inflammatory properties present a great interest for the treatment of inflammatory disorders like the systemic inflammatory response syndrome. In addition to its inhibition abilities on important neutrophils mechanisms (chemotaxis, reactive oxygen species (ROS) production, Neutrophil Extracellular Traps (NETs) formation, …), our group has shown that propofol is also a reversible inhibitor of the oxidant myeloperoxidase (MPO) activity. Propofol being subject to rapid metabolism, its derivatives could contribute to its anti-inflammatory action. First, propofol-β-glucuronide (PPFG), 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3′,5′-tetraisopropyl-(4,4′)-diphenoquinone (PPFDQ) were compared on their superoxide (O₂^.-) scavenging properties and more importantly on their inhibitory action on the O₂^.- release by activated neutrophils using EPR spectroscopy and chemiluminescence assays. PPFQ and PPFDQ are potent superoxide scavengers and also inhibit the release of ROS by neutrophils. An Enzyme-Linked Immunosorbent Assay (ELISA) has also highlighted the ability of both molecules to significantly decrease the MPO degranulation process of neutrophils. Fluorescence enzymatic assays helped to investigate the action of the propofol derivatives on the peroxidase and chlorination activities of MPO. In addition, using SIEFED (Specific Immunological Extraction Followed by Enzyme Detection) assays and docking, we demonstrated the concentration-dependent inhibitory action of PPFQ and its ability to bind to the enzyme active site while PPFG presented a much weaker inhibitory action. Overall, the oxidation derivatives and metabolites PPFQ and PPFDQ can, at physiological concentrations, perpetuate the immunomodulatory action of propofol by acting on the oxidant response of PMN and MPO.

在之前的研究中，丙泊酚已在各种体外模型中显示出免疫调节能力。由于这种麻醉剂分子广泛用于重症监护病房，因此其抗炎特性对于治疗炎症性疾病（如全身炎症反应综合征）具有很大的意义。除了对重要的中性粒细胞机制（趋化性、活性氧 (ROS) 产生、中性粒细胞胞外陷阱 (NETs) 形成等）具有抑制能力外，我们小组还表明，丙泊酚还是氧化剂髓过氧化物酶 (MPO) 的可逆抑制剂活动。丙泊酚代谢迅速，其衍生物可能有助于其抗炎作用。一、丙泊酚-β-葡糖苷酸（PPFG），2,6-diisopropyl-1,4- p-苯醌 (PPFQ) 和 3,5,3',5'-四异丙基-(4,4')-联苯醌 (PPFDQ) 的超氧化物 (O ₂ ^.- ) 清除性能，更重要的是它们的抑制作用O ₂ ^.-使用 EPR 光谱和化学发光测定法由活化的中性粒细胞释放。PPFQ 和 PPFDQ 是有效的超氧化物清除剂，还抑制中性粒细胞释放 ROS。酶联免疫吸附试验 (ELISA) 也强调了这两种分子显着降低中性粒细胞 MPO 脱粒过程的能力。荧光酶法有助于研究丙泊酚衍生物对 MPO 过氧化物酶和氯化活性的作用。此外，使用 SIEFED（酶检测后特异性免疫提取）测定和对接，我们证明了 PPFQ 的浓度依赖性抑制作用及其与酶活性位点结合的能力，而 PPFG 的抑制作用要弱得多。总的来说，氧化衍生物和代谢物 PPFQ 和 PPFDQ 可以，