Antioxidant protection of propofol and its recycling in erythrocyte membranes.
alpha-Tocopherol is a potent antioxidant that effectively protects biological membranes against oxidative injury through coordination with ascorbic acid. Because propofol has a phenolic structure similar to that of alpha-tocopherol, this intravenous anesthetic may also have similar antioxidant activity. To test this hypothesis, the effect of propofol on oxidative injury of human erythrocytes was examined. Propofol inhibited oxidative hemolysis and cis-parinaric acid oxidation in erythrocyte membranes (ED(50) = 6 microM). Although ascorbic acid alone has no appreciable effect, the protective effect of propofol was enhanced by ascorbic acid. An electron spin resonance (ESR) study showed that propofol-derived radicals (g = 2.005) were continuously generated during the oxidation of erythrocyte membranes by an ascorbic acid-inhibitable mechanism. These and other results suggest that propofol interacts with ascorbic acid, thereby exhibiting potent antioxidant activity in and around membranes as does alpha-tocopherol. Kinetic analysis revealed that propofol increased the membrane fluidity of erythrocytes, thereby increasing their resistance to physical and hemodynamic stress. Further, a greater preservation of red blood cell counts was seen after surgery with propofol compared with conventional sevoflurane anesthesia. Thus, propofol may protect erythrocytes against both oxidative and physical stress, indicating its potential as an efficient and safe antioxidant.
Tsuchiya
Masahiko
M
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, Abenoku, Osaka, Japan. oxymasa@ea.mbn.or.jp
Asada
Akira
A
Kasahara
Emiko
E
Sato
Eisuke F
EF
Shindo
Mitsuo
M
Inoue
Masayasu
M
D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004578:Electron Spin Resonance Spectroscopy; D004906:Erythrocyte Count; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D005609:Free Radicals / Q000009:adverse effects / Q000032:analysis; D005743:Gastrectomy / Q000009:adverse effects*; D006461:Hemolysis / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D008875:Middle Aged; D009996:Osmotic Fragility / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D015742:Propofol / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D013314:Stress, Mechanical; D024502:alpha-Tocopherol / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D016166:Free Radical Scavengers; D005609:Free Radicals; C027149:cis-parinaric acid methyl ester; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D015742:Propofol