title: Propofol versus midazolam regarding their antioxidant activities.
abstract: Propofol and midazolam are commonly used as sedatives for critically ill patients. These patients usually suffer from the pathologic effects of oxidative stress, predominantly caused by an imbalance between the generation of reactive oxygen species and the antioxidant defense system. Therefore, the antioxidant activities of propofol and midazolam may be of clinical importance. We investigated the activities of these two sedatives against hydrophilic or lipophilic peroxyl radicals in a homogeneous solution and in the presence of erythrocyte membranes. A chemical analysis of the homogeneous solution revealed that propofol efficiently scavenged hydrophilic peroxyl radicals (50% inhibitory concentration [IC50] = 1.3 x 10(-4) M), whereas midazolam efficiently scavenged lipophilic radicals (IC50 = 1.5 x 10(-5) M). Further, in membrane systems, propofol inhibited the oxidative damage induced by either hydrophilic or lipophilic radicals (IC50 = 1.5 x 10(-5) M for hydrophilic radicals and IC50 = 3.0 x 10(-4) M for lipophilic radicals), whereas midazolam did very little. In previous studies, we demonstrated that antioxidant activity is highly affected by the location and properties of the reaction site. The discrepancy in antioxidant activity between a homogeneous condition and in the presence of membranes can be well explained by this concept, and again emphasizes the importance of membranes in determining antioxidant activity. To further understand the biologic significance of these antioxidant properties, the effect of the two agents on endothelium-dependent relaxation was studied. Application of oxidative stress to aortic rings by treating them with peroxyl radicals led to a significant blockade of acetylcholine-induced relaxation after submaximal contraction with phenylephrine. Propofol pretreatment greatly attenuated the impairment in comparison with midazolam, which agrees with the concept of antioxidant activity in the presence of membranes. The results of the present study suggest that propofol has a greater potential to reduce oxidative stress than midazolam.
authors.affiliation: Department of Biochemistry, and Department of Anesthesiology and Intensive Care Medicine, Osaka City University Medical School, Abenoku, Osaka, Japan. oxymasa@ea.mbn.or.jp
authors.forename: M
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: A
authors.initials: A
authors.lastname: Asada
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Ueda
authors.forename: E F
authors.initials: EF
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Shindo
authors.forename: M
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008874:Midazolam / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010799:Phycoerythrin / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D010799:Phycoerythrin; D008874:Midazolam; D015742:Propofol