Comparative study on determination of antioxidant and membrane activities of propofol and its related compounds.
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.
Tsuchiya
Hironori
H
Department of Dental Basic Education, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan. hiro@dent.asahi-u.ac.jp
Ueno
Takahiro
T
Tanaka
Toshiyuki
T
Matsuura
Nobuyasu
N
Mizogami
Maki
M
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
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