In vitro and ex vivo antioxidant activities of labetalol on rabbit neutrophil respiratory burst

• Published in: Advances in therapy 2004-05, Vol.21 (3), p.178-185
• Main Authors: Kouoh, Ferdinand, Gressier, Bernard, Dine, Thierry, Luyckx, Michel, Brunet, Claude, Ballester, Louis, Cazin, Jean Claude
• Format: Article
• Language: English
• Subjects: Animals; Cell Count; Cell Survival; Cells, Cultured; Disease Models, Animal; Health technology assessment; Humans; In Vitro Techniques; Infusions, Intravenous; Labetalol - pharmacology; Neutrophil Activation; Neutrophils - drug effects; Neutrophils - physiology; Rabbits; Respiratory Burst - drug effects; Sensitivity and Specificity; Statistics, Nonparametric; Superoxides - analysis; Superoxides - metabolism
• ISSN: 0741-238X; 1865-8652
• DOI: 10.1007/BF02850123

The beta-adrenoreceptor blocker labetalol has demonstrated important antioxidant properties in vitro that inhibit superoxide anion production during normal leukocyte oxidative metabolism. This study investigated the in vitro and ex vivo effects of labetalol on respiratory burst in rabbit neutrophils. The production of superoxide anions was examined in activated purified rabbit neutrophils after intravenous administration of labetalol (4.0 mg/kg of body weight). At a concentration up to 200 mg/L, labetalol did not demonstrate any cytotoxic effects on neutrophils, as determined by enzyme lactate dehydrogenase activity. In the cell-free system, labetalol demonstrated no significant activity, but in formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated rabbit neutrophils, labetalol demonstrated concentration-dependent antioxidant activity. The in vitro 50% inhibitory concentration (IC50) with the fMLP stimulus was 16.5+/-0.21 mg/L in the rabbit neutrophils and 13.2+/-0.16 mg/L in the human neutrophils. In the fMLP-stimulated rabbit polymorphonuclear leukocytes, labetalol demonstrated its peak inhibitory activity (47%) 3 hours after administration. The mechanism by which labetalol acts in the treatment of hypertension may occur from an interaction in the signaling pathway of protein kinase C activation. The antioxidant properties demonstrated in this mechanism contribute to the drug's antihypertensive action and thus, may reduce the risk of injuries inflicted by reactive oxygen species involved in the pathogenesis of hypertension.