[en] BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
GENERAL SIGNIFICANCE: 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Nyssen, Pauline ; Université de Liège - ULiège > Complex and Entangled Systems from Atoms to Materials (CESAM)
Maho, Anthony ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie inorganique structurale et Chimie des matériaux inorganiques (LCIS-GreenMAT)
Malempré, Romain ; Université de Liège - ULiège > Département des sciences de la vie > Enzymologie et repliement des protéines
Matagne, André ; Université de Liège - ULiège > Département des sciences de la vie > Centre d'ingénierie des protéines
Mouithys-Mickalad, Ange ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Hoebeke, Maryse ; Université de Liège - ULiège > Complex and Entangled Systems from Atoms to Materials (CESAM)
Language :
English
Title :
Propofol inhibits the myeloperoxidase activity by acting as substrate through a redox process.
Access to the computating facilities of the PTCI platform of UNamur is deeply acknowledged. The purchased of myeloperoxidase was supported by the group CESAM (Uli?ge).This work was supported by grants from the University of Li?ge (Uli?ge).Access to the computating facilities of the PTCI platform of UNamur is deeply acknowledged. The purchased of myeloperoxidase was supported by the group CESAM (Uliège).This work was supported by grants from the University of Liège (Uliège).
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