Propofol versus midazolam regarding their antioxidant activities

Propofol and midazolam are commonly used as sedatives for critically ill pa tients. These patients usually suffer from the pathologic effects of oxidat ive 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 importa nce. We investigated the activities of these two sedatives against hydrophi lic or lipophilic peroxyl radicals in a homogeneous solution and in the pre sence of erythrocyte membranes. A chemical analysis of the homogeneous solu tion revealed that propofol efficiently scavenged hydrophilic peroxyl radic als (50% inhibitory concentration [IC50] = 1.3 x 10(-4) M), whereas midazol am efficiently scavenged lipophilic radicals (IC50 = 1.5 x 10(-5) M). Furth er, in membrane systems, propofol inhibited the oxidative damage induced by either hydrophilic or lipophilic radicals (IC50 = 1.5 x 10-5 M for hydroph ilic radicals and IC50 = 3.0 x 10(-4) M for lipophilic radicals), whereas m idazolam did very little. In previous studies, we demonstrated that antioxi dant activity is highly affected by the location and properties of the reac tion site. The discrepancy in antioxidant activity between a homogeneous co ndition and in the presence of membranes can be well explained by this conc ept, and again emphasizes the importance of membranes in determining antiox idant activity. To further understand the biologic significance of these an tioxidant 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 acety lcholine-induced relaxation after submaximal contraction with phenylephrine . Propofol pretreatment greatly attenuated the impairment in comparison wit h midazolam, which agrees with the concept of antioxidant activity in the p resence of membranes. The results of the present study suggest that propofo l has a greater potential to reduce oxidative stress than midazolam.