Propofol metabolites and derivatives inhibit the oxidant activities of neutrophils and myeloperoxidase.

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 inhibits the myeloperoxidase activity by acting as substrate through a redox process.

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.

Photochemical properties and activity of water-soluble polymer/c(60) nanohybrids for photodynamic therapy.

Water-soluble star-like poly(vinyl alcohol)/C(60) and poly{[poly(ethylene glycol) acrylate]-co-(vinyl acetate)}/C(60) nanohybrids are prepared by grafting macroradicals onto C(60) and are assessed as photosensitizers for photodynamic therapy. The photophysical and biological properties of both nanohybrids highlight key characteristics influencing their overall efficiency. The macromolecular structure (linear/graft) and nature (presence/absence of hydroxyl groups) of the polymeric arms respectively impact the photodynamic activity and the stealthiness of the nanohybrids.

Optimizing photodynamic therapy by liposomal formulation of the photosensitizer pyropheophorbide-a methyl ester: in vitro and ex vivo comparative biophysical investigations in a colon carcinoma cell line.

Photodynamic therapy (PDT), induced by a photosensitizer (PS) encapsulated in a nanostructure, has emerged as an appropriate treatment to cure a multitude of oncological and non-oncological diseases. Pyropheophorbide-a methyl ester (PPME) is a second-generation PS tested in PDT, and is a potential candidate for future clinical applications. The present study, carried out in a human colon carcinoma cell line (HCT-116), evaluates the improvement resulting from a liposomal formulation of PPME versus free-PPME.

Does propofol alter membrane fluidity at clinically relevant concentrations? An ESR spin label study.

General anesthetics have been shown to perturb the membrane properties of excitable tissues. Due to their lipid solubility, anesthetics dissolve in every membrane, penetrate into organelles and interact with numerous cellular structures in multiple ways. Several studies indicate that anesthetics alter membrane fluidity and decrease the phase-transition temperature.

Physical and chemical properties of pyropheophorbide-a methyl ester in ethanol, phosphate buffer and aqueous dispersion of small unilamellar dimyristoyl-L-alpha-phosphatidylcholine vesicles.

The aggregation process of pyropheophorbide-a methyl ester (PPME), a second-generation photosensitizer, was investigated in various solvents. Absorption and fluorescence spectra showed that the photosensitizer was under a monomeric form in ethanol as well as in dimyristoyl-L-alpha-phosphatidylcholine liposomes while it was strongly aggregated in phosphate buffer. A quantitative determination of reactive oxygen species production by PPME in these solvents has been undertaken by electron spin resonance associated with spin trapping technique and absorption spectroscopy.

Synoviocytes, not chondrocytes, release free radicals after cycles of anoxia/re-oxygenation.

By oxymetry and electron paramagnetic resonance (EPR), we investigated the effects of repeated anoxia/re-oxygenation (A/R) periods on the respiration and production of free radicals by synoviocytes (rabbit HIG-82 cell line and primary equine synoviocytes) and equine articular chondrocytes. Three periods of 20 min anoxia followed by re-oxygenation were applied to 10(7)cells; O(2) consumption was measured before anoxia and after each re-oxygenation. After the last A/R, cellular free radical formation was investigated by EPR spectroscopy with spin trapping technique (n=3 for each cell line).

Quantification of lipid bilayer effective microviscosity and fluidity effect induced by propofol.

Electron spin resonance (ESR) spectroscopy with nitroxide spin probes was used as a method to probe the liposome microenvironments. The effective microviscosities have been determined from the calibration of the ESR spectra of the probes in solvent mixtures of known viscosities. In the first time, by measuring ESR order parameter (S) and correlation time (tau(c)) of stearic spin probes, we have been able to quantify the value of effective microviscosity at different depths inside the liposome membrane.

Effects of COX-2 inhibitors on ROS produced by Chlamydia pneumoniae-primed human promonocytic cells (THP-1).

Chronic inflammation through foam cells and macrophages is important in atherosclerosis development, and can be considered as therapeutic targets. Cyclooxygenase and NADPH-oxidase were expressed within atherosclerotic lesions. Reactive oxygen species produced by NADPH oxidase were found to trigger the cyclooxygenase-2 expression.

In vitro evaluation of glutathione peroxidase (GPx)-like activity and antioxidant properties of some Ebselen analogues.

Four analogues of Ebselen were synthesized and their glutathione peroxidase activity and antioxidant property evaluated and compared to Ebselen. Among the studied compounds, only diselenide [3] exhibited both glutathione peroxidase activity and radical-scavenging capability. Compounds [3] and [4] showed a strong inhibitory effect (53% and 43%, respectively) on the lipid peroxidation of linoleic acid compared to Ebselen and selenide derivatives ([1] and [2]) which were less active (28%, 26% and 18% inhibition, respectively).

Investigation of singlet oxygen reactivity towards propofol.

The reaction between the anaesthetic agent 2,6-diisopropylphenol (propofol, PPF) and singlet oxygen (1O2) has been investigated in aqueous solution by means of HPLC, GC, absorption spectroscopy and laser flash photolysis with infrared luminescence detection. The rate constants for the physical and chemical quenching of 1O2 by PPF (kPPF) are found to be 2.66 x 10(5) M(-1) s(-1) and approximately 3.

Determination of the singlet oxygen quantum yield of bacteriochlorin a: a comparative study in phosphate buffer and aqueous dispersion of dimiristoyl-L-alpha-phosphatidylcholine liposomes.

The production of singlet oxygen (1O2) by bacteriochlorin a (BCA) was studied in phosphate buffer and in dimyristoyl-L-alpha-phosphatidylcholine (DMPC) unilamellar liposomes. The comparative method used to measure 1O2 production was a quantitative analysis of photooxidation reactions leading to the loss of absorbance of the water-soluble specific probe: anthracene-9,10-dipropionic acid. Rose Bengal, whose 1O2 quantum yield (phi(RB)) is well known in alcohols and phosphate buffer, was used as the standard for the quantification of the BCA singlet oxygen production.

Effect of aggregation on bacteriochlorin a triplet-state formation: a laser flash photolysis study.

Bacteriochlorin a (BCA) is a potential photosensitizer for photodynamic therapy of cancer. It has been shown previously that the photoefficiency of the dye is mainly dependent on singlet oxygen (1O2) generation. Nanosecond laser flash photolysis was used to produce and to investigate the excited triplet state of the dye in methanol, phosphate buffer and dimiristoyl-L-alpha-phosphatidylcholine (DMPC) liposomes.