title: Characterization of hydrophobic interaction and antioxidant properties of the phenothiazine nucleus in mitochondrial and model membranes.
abstract: The antioxidant properties of the phenothiazine nucleus (PHT) associated with mitochondrial membranes and liposomes were investigated. PHT exhibited hydrophobic interaction with lipid bilayers, as shown by the quenching of excited states of 1-palmitoyl-2[10-pyran-1-yl)]-decanoyl-sn-glycero-3-phophocholine (PPDPC) incorporated in phosphatidylcholine/phosphatidylethanolamine/cardiolipin liposomes, observed even in high ionic strength; and by the spectral changes of PHT following the addition of mitochondrial membranes. Inserted into bilayers, 5 microM PHT was able to protect lipids and cytochrome c against pro-oxidant agents and exhibited spectral changes suggestive of oxidative modifications promoted by the trapping of the reactive species. In this regard, PHT exhibited the ability to scavenge DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical. PHT was also able to protect rat liver mitochondria against peroxide- and iron-induced oxidative damage and consequent swelling. At the concentration range in which the antioxidant properties were observed, PHT did not cause alterations in the membrane structure and function. This study contributes to the comprehension of the correlation structure and function of phenothiazines and antioxidant properties.
authors.affiliation: Centro Interdisciplinar de Investigação Bioquímica-CIIB, Universidade de Mogi das Cruzes-UMC, SP, Brazil.
authors.forename: Marcelo B D
authors.initials: MB
authors.lastname: Borges
authors.forename: Carolina G
authors.initials: CG
authors.lastname: Dos Santos
authors.forename: César H
authors.initials: CH
authors.lastname: Yokomizo
authors.forename: Rohit
authors.initials: R
authors.lastname: Sood
authors.forename: Pavol
authors.initials: P
authors.lastname: Vitovic
authors.forename: Paavo K J
authors.initials: PK
authors.lastname: Kinnunen
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.forename: Iseli L
authors.initials: IL
authors.lastname: Nantes
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004247:DNA / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism / Q000494:pharmacology; D008567:Membranes, Artificial; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D010640:Phenothiazines / Q000737:chemistry / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats
chemical_list: D000975:Antioxidants; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D008567:Membranes, Artificial; D010640:Phenothiazines; D010713:Phosphatidylcholines; D011506:Proteins; C021248:1-palmitoyl-2-pyrenedecanoylphosphatidylcholine; D004247:DNA; C031637:phenothiazine