PMID- 15509134 OWN - NLM STAT- MEDLINE DCOM- 20041130 LR - 20191109 IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 21 IP - 3 DP - 2004 May-Jun TI - In vitro and ex vivo antioxidant activities of labetalol on rabbit neutrophil respiratory burst. PG - 178-85 AB - 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. FAU - Kouoh, Ferdinand AU - Kouoh F AD - Laboratory of Pharmacology, Pharmacokinetic and Clinical Pharmacy, Faculty of Biological and Pharmaceutical Sciences, Lille Cedex, France. FAU - Gressier, Bernard AU - Gressier B FAU - Dine, Thierry AU - Dine T FAU - Luyckx, Michel AU - Luyckx M FAU - Brunet, Claude AU - Brunet C FAU - Ballester, Louis AU - Ballester L FAU - Cazin, Jean Claude AU - Cazin JC LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 11062-77-4 (Superoxides) RN - R5H8897N95 (Labetalol) MH - Animals MH - Cell Count MH - Cell Survival MH - Cells, Cultured MH - Disease Models, Animal MH - Humans MH - In Vitro Techniques MH - Infusions, Intravenous MH - Labetalol/*pharmacology MH - Neutrophil Activation MH - Neutrophils/*drug effects/physiology MH - Rabbits MH - Respiratory Burst/*drug effects MH - Sensitivity and Specificity MH - Statistics, Nonparametric MH - Superoxides/analysis/*metabolism EDAT- 2004/10/29 09:00 MHDA- 2004/12/16 09:00 CRDT- 2004/10/29 09:00 PHST- 2004/10/29 09:00 [pubmed] PHST- 2004/12/16 09:00 [medline] PHST- 2004/10/29 09:00 [entrez] AID - 343 [pii] AID - 10.1007/BF02850123 [doi] PST - ppublish SO - Adv Ther. 2004 May-Jun;21(3):178-85. doi: 10.1007/BF02850123.