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.

Determination of in Vitro Antioxidant and Radical Scavenging Activities of Propofol

“…These patients usually suffer from the pathologic effects of oxidative stress, predominantly caused an imbalance between the generation of reactive oxygen species (ROS) and antioxidant defence system. 2) ROS are formed and degraded by all aerobic organisms. ROS can readily react with most biomolecules including protein lipids and lipoproteins and DNA.…”

Does vitamin C prevent the effects of high dose dexmedetomidine on rat erythrocyte deformability?

“…The effects of anesthetic agents on microcirculation are specifi c and dose dependent. The mechanisms that cause this interaction may be associated with oxidative disorders that occur during or after various anesthetic procedures (18)(19)(20).…”

Antioxidant Activity Analysis by Liposomal Membrane System and Application to Anesthetics

“…These comparative results almost agree with previous studies. 25,26 In peroxynitrite-induced lipid peroxidation, the relative antioxidant potency was lidocaine > bupivacaine > ropivacaine >> mepivacaine and prilocaine in amide-type drugs and tetracaine > benzocaine > procaine in ester-type drugs. Tetracaine was reported to inhibit the lipid peroxidation of mouse heart homogenates at 0.25 mM, while lidocaine showed no prominent effect.…”

“…Although previous screenings suggested that certain anesthetics may be potent antioxidants, 26,28,29 only limited information is available regarding their comparative effects, and the employed analytical methods vary according to studies. Therefore, the proposed method was applied to various anesthetics for comparing their antioxidant activities on the same methodological basis (Fig.…”