Dose-dependent scavenging activity of the ultra-short-acting β1-blocker landiolol against specific free radicals

Abstract

Landiolol, a highly cardioselective ultra-short-acting β1-blocker, prevents perioperative atrial fibrillation associated with systemic inflammation and oxidative stress. We evaluated the direct scavenging activity of landiolol against multiple free radical species. Nine free radical species (hydroxyl, superoxide anion, ascorbyl, tert-butyl peroxyl, tert-butoxyl, singlet oxygen, 2,2-diphenyl-1-picrylhydrazyl, nitric oxide, and tyrosyl radicals) were directly quantified using an X-band ESR spectrometer with the spin-trapping method. IC50 and reaction rate constants were estimated from the dose-response curve for each free radical. Landiolol scavenged six of the free radical species examined: hydroxyl radical (IC50 = 0.76 mM, klandiolol = 1.4 × 1010 M−1 s−1, p<0.001), superoxide anion (58 mM, 2.1 M−1 s−1, p = 0.044), tert-butoxyl radical (4.3 mM, klandiolol/kCYPMPO = 0.77, p<0.001), ascorbyl free radical (0.31 mM, p<0.001), singlet oxygen (0.69 mM, klandiolol/k4-OH TEMP = 2.9, p<0.001), and nitric oxide (15 mM, 1.7 × 10 M−1 s−1, p<0.001). This study is the first to report that landiolol dose-dependently scavenges multiple free radical species with different reaction rate constants. These results indicate the potential clinical application of landiolol as an antioxidative and anti-inflammatory agent in addition to its present clinical use as an anti-arrhythmic agent.