Characterization of hydrophobic interaction and antioxidant properties of the phenothiazine nucleus in mitochondrial and model membranes.
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.
Borges
Marcelo B D
MB
Centro Interdisciplinar de Investigação Bioquímica-CIIB, Universidade de Mogi das Cruzes-UMC, SP, Brazil.
Dos Santos
Carolina G
CG
Yokomizo
César H
CH
Sood
Rohit
R
Vitovic
Pavol
P
Kinnunen
Paavo K J
PK
Rodrigues
Tiago
T
Nantes
Iseli L
IL
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
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