title: Comparative study on determination of antioxidant and membrane activities of propofol and its related compounds.
abstract: Certain anesthetics have been suggested to protect against the pathological states associated with oxidative stress. We compared the antioxidant and membrane activities of propofol (2,6-diisopropylphenol) and its related compounds to address the structure-activity relationship especially in a lipid membrane phase. They were studied for the effects on 1,1-diphenyl-2-picrylhydrazyl radicals, nitro blue tetrazolium reduction by superoxide anions and membrane lipid peroxidation by peroxynitrite, and also for the induced changes in membrane fluidity of liposomes. 2-Isopropylphenols scavenged free radicals with the potency being propofol>2,5-diisopropylphenol>2-isopropylphenol>2,4-diisopropylphenol, but not 3- and 4-isopropylphenols and 1,3- and 1,4-diisopropylbenzenes. The tested compounds showed no significant superoxide dismutase-like effects. Propofol inhibited membrane lipid peroxidation more intensively than 2,5-diisopropylphenol, 2,4-diisopropylphenol and 2-isopropylphenol. Despite structurally resembling antioxidant alpha-tocopherol, 2,6-dimethylphenol was less potent than propofol. Propofol produced 50% inhibition of the lipid peroxidation in unsaturated phosphatidylcholine liposomal membranes and cell-mimetic membranes at 4.0 and 10.1 microM, respectively. Propofol and 2-alkylphenolic compounds interacted with membranes to increase their fluidity with the potency correlating with lipid peroxidation inhibiting activity. The 2-isopropylphenol structure is a requisite for both lipid peroxidation inhibition and membrane fluidity modification. The structure-specific membrane interactivity appears to be one of possible antioxidant mechanisms for propofol.
authors.affiliation: Department of Dental Basic Education, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan. hiro@dent.asahi-u.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueno
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Matsuura
authors.forename: Maki
authors.initials: M
authors.lastname: Mizogami
mesh_terms: D018686:Anesthetics, Intravenous / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects*; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D015742:Propofol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D018686:Anesthetics, Intravenous; D000975:Antioxidants; D002839:Chromans; D008081:Liposomes; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D015742:Propofol