title: Antioxidant activity of different dihydropyridines.
abstract: Lacidipine, a dihydropyridine-based calcium antagonist (DHP), has already been demonstrated to possess antioxidant activity and to reduce the intracellular production of reactive oxygen species (ROS). To verify if this effect is a peculiarity of this molecule, or belongs to other DHPs, the activity of lacidipine was compared with those of amlodipine, lercanidipine, nimodipine, and nifedipine. The DHPs were incorporated in bovine aortic endothelial cells (BAECs). Cu(2+)-oxidized LDL (ox-LDL, 5 microM) was incubated with BAECs for 5 min. 2',7'-Dichlorofluorescein (DCF) as expression of intracellular ROS production was measured by flow cytometry. Ox-LDL induced a strong increase in intracellular ROS formation (p<0.001) that was significantly reduced only with lacidipine and lercanidipine (p from <0.05 to <0.01); the effect of lacidipine, however, resulted in being much more evident than lercanidipine (p<0.01); amlodipine, nimodopine, and nifedipine had no effect on ROS formation. The lowest IC50s, i.e. the concentrations determining the 50% reduction of ROS, were obtained with lacidipine (p<0.01). The inhibitory effect of lacidipine on ox-LDL-induced ROS production in endothelial cells is a peculiarity of this molecule through its antioxidant activity.
authors.affiliation: Dipartimento di Scienze Biomediche Chirurgiche, c/o Medicina Interna D-Ospedale Policlinico, Università di Verona, Verona 37134 Italy. comina@medicinnad.univr.it
authors.forename: Luciano
authors.initials: L
authors.lastname: Cominacini
authors.forename: Anna
authors.initials: A
authors.lastname: Fratta Pasini
authors.forename: Ulisse
authors.initials: U
authors.lastname: Garbin
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Pastorino
authors.forename: Anna
authors.initials: A
authors.lastname: Davoli
authors.forename: Cristina
authors.initials: C
authors.lastname: Nava
authors.forename: Mario
authors.initials: M
authors.lastname: Campagnola
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossato
authors.forename: V
authors.initials: V
authors.lastname: Lo Cascio
mesh_terms: D017311:Amlodipine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D015394:Molecular Structure; D009543:Nifedipine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009553:Nimodipine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004095:Dihydropyridines; D005452:Fluoresceins; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D017311:Amlodipine; C060285:lacidipine; C037631:2',7'-dichlorofluorescein; D009553:Nimodipine; D009543:Nifedipine; C060343:lercanidipine