Aruoma O I, Smith C, Cecchini R, Evans P J, Halliwell B
Department of Biochemistry, University of London, King's College, U.K.
Biochem Pharmacol. 1991 Jul 25;42(4):735-43. doi: 10.1016/0006-2952(91)90030-9.
It has been proposed that beta-blockers and agents affecting Ca2+ metabolism might exert cardioprotective actions because of their ability to act as antioxidants in vivo. The feasibility of this proposal was tested by examining the reaction of a series of such compounds with various oxygen-derived species. None of the compounds tested was sufficiently reactive with superoxide radical, hydrogen peroxide or hypochlorous acid for scavenging of these species to be feasible in vivo at the drug concentrations present in patients given the usual therapeutic doses. All the drugs tested were powerful scavengers of hydroxyl radical except for flunarizine, which stimulated iron ion-dependent hydroxyl radical generation from hydrogen peroxide. However, none of the drugs significantly inhibited production of hydroxyl radicals in this system. Propranolol, verapamil and flunarizine had significant inhibitory effects on the peroxidation of rat liver microsomes in the presence of iron ions and ascorbic acid. All three compounds exerted weaker inhibitory effects on peroxidation of arachidonic acid caused by a mixture of myoglobin and H2O2: pindolol stimulated peroxidation in this system. It is concluded that the ability of beta-blockers and "Ca(2+)-blockers" to inhibit lipid peroxidation varies with the lipid substrate used and the mechanism by which peroxidation is induced. We conclude that suggestions that beta-blockers and "Ca(2+)-blockers" exert antioxidant effects in vivo are not well founded, although there is a possibility that verapamil and propranolol might have some inhibitory effects against peroxidation if they accumulate in membranes to a sufficiently-high concentration in vivo. We could not confirm the reported ability of propranolol to inhibit the enzyme xanthine oxidase.
有人提出，β受体阻滞剂和影响Ca2+代谢的药物可能具有心脏保护作用，因为它们在体内具有抗氧化能力。通过检测一系列此类化合物与各种氧衍生物种的反应，对这一观点的可行性进行了测试。在所测试的化合物中，没有一种与超氧自由基、过氧化氢或次氯酸的反应活性足以在给予常规治疗剂量的患者体内存在的药物浓度下清除这些物种。除氟桂利嗪外，所有测试药物都是羟基自由基的强清除剂，氟桂利嗪会刺激过氧化氢产生铁离子依赖性羟基自由基。然而，在该系统中，没有一种药物能显著抑制羟基自由基的产生。在铁离子和抗坏血酸存在的情况下，普萘洛尔、维拉帕米和氟桂利嗪对大鼠肝微粒体的过氧化有显著抑制作用。这三种化合物对由肌红蛋白和H2O2混合物引起的花生四烯酸过氧化的抑制作用较弱：吲哚洛尔在该系统中会刺激过氧化。结论是，β受体阻滞剂和“钙阻滞剂”抑制脂质过氧化的能力因所用脂质底物和过氧化诱导机制而异。我们得出结论，关于β受体阻滞剂和“钙阻滞剂”在体内发挥抗氧化作用的观点缺乏充分依据，尽管维拉帕米和普萘洛尔有可能在体内在膜中积累到足够高的浓度时对过氧化有一些抑制作用。我们无法证实普萘洛尔抑制黄嘌呤氧化酶的报道能力。
