title: In vitro evaluation of the antioxidant activity and biomembrane interaction of the lazaroid U-74389G.
abstract: The aim of this paper was to clarify whether the interaction of the lazaroid U-74389G with phospholipid membranes might be relevant as to its antioxidant activity. Thus we evaluated the "in vitro" antioxidant activity of U-74389G in two experimental models: 1) bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical; 2) peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2-amidino-propane) hydrochloride, on mixed dipalmitoyl-phosphatidylcholine/linoleic acid unilamellar vesicles. Moreover, given that biophysical techniques may help in explaining the role of a drug in its interaction with the microenvironment of the model lipid membranes, we used a classical approach to investigate the U-74389G/model membrane interaction: the differential scanning calorimetry technique on dimyristoylphosphatidylcholine multilamellar and unilamellar vesicles and the Langmuir-Blodgett technique on dimyristoylphosphatidylcholine monolayers. The results evidenced the strong antioxidant activity of U-74389G (especially in a membranous system) and its capability to interact with and be transported across model membranes. Thus one can speculate that U-74389G can act as scavenger of chain-propagating lipid peroxyl radicals within the membranes and may be able to protect not only cell membranes, but also intracellular components against peroxidative attack. Furthermore, also if there is no certain proof that the effect on the lipid packing order may play a key role in its antioxidant activity, the fluidifying effect on phospholipid bilayers of U-74389G favourably complements its free radical scavenging characteristics.
authors.affiliation: Department of Pharmacology of Natural Substances & General Physiology, University of Rome La Sapienza, Italy. saija@pharma.unime.it
authors.forename: A
authors.initials: A
authors.lastname: Saija
authors.forename: A
authors.initials: A
authors.lastname: Tomaino
authors.forename: M L
authors.initials: ML
authors.lastname: Pellegrino
authors.forename: N
authors.initials: N
authors.lastname: Giuffrida
authors.forename: D
authors.initials: D
authors.lastname: Trombetta
authors.forename: F
authors.initials: F
authors.lastname: Castelli
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000578:Amidines / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D015764:Bepridil / Q000031:analogs & derivatives* / Q000378:metabolism; D001713:Biphenyl Compounds; D002152:Calorimetry, Differential Scanning; D003907:Dexamethasone / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism; D005609:Free Radicals; D066298:In Vitro Techniques; D019787:Linoleic Acid / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D010084:Oxidation-Reduction; D010851:Picrates; D011281:Pregnatrienes / Q000494:pharmacology*
chemical_list: D000578:Amidines; D000975:Antioxidants; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D008051:Lipid Bilayers; D010851:Picrates; D011281:Pregnatrienes; C074965:U 74389F; D015060:1,2-Dipalmitoylphosphatidylcholine; C046728:2,2'-azobis(2-amidinopropane); D015764:Bepridil; D003907:Dexamethasone; D019787:Linoleic Acid; C004931:1,1-diphenyl-2-picrylhydrazyl