title: The natural antioxidant otobaphenol delays the permeability transition of mitochondria and induces their aggregation.
abstract: The lignan otobaphenol, (8R,8'R,7R)-4'-hydroxy-5'-methoxy-3,4-methylenedioxy-2',7,8,8'-neolignan, extracted from Virola Aff. Pavonis leaves, completely inhibits at a concentration of 2.5 micro M the Fe(3+)-ascorbate-induced lipoperoxidation of rat liver mitochondria that was determined by oxygen consumption and accumulation of thiobarbituric acid-reactive species. At 25 micro M, it delays the mitochondrial permeability transition induced by tert-butyl hydroperoxide or Ca(2+), substantially inhibits the state 3 respiration, does not affect the state 4 respiration and the ADP/O ratio (with succinate), diminishes the rate of Ca(2+) uptake by mitochondria, and delays the ruthenium red-insensitive uncoupler-induced release of the loaded Ca(2+). Dose-dependent delaying of the calcium-induced swelling of mitochondria in the presence of otobaphenol nonlinearly correlates with its 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity. At 75 micro M and higher, this lignan causes mitochondrial aggregation and is able to aggregate itself, without mitochondria. The formed aggregates of otobaphenol do not cause an aggregation of subsequently added mitochondria. Thus, otobaphenol seems to be a promising target to prevent the oxidative stress death of cells.
authors.affiliation: School of Physics, Science Department, National University of Colombia, Medellin Branch, AA3840 Medellin, Colombia. vvasilie@perseus.unalmed.edu.co
authors.forename: Victor V
authors.initials: VV
authors.lastname: Lemeshko
authors.forename: Luis F
authors.initials: LF
authors.lastname: Lopez
authors.forename: Sigifredo
authors.initials: S
authors.lastname: Solano
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001713:Biphenyl Compounds; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D002463:Cell Membrane Permeability / Q000187:drug effects; D005290:Ferric Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009249:NADP / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010851:Picrates / Q000037:antagonists & inhibitors; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D013997:Time Factors; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D010636:Phenols; D010851:Picrates; D017392:Thiobarbituric Acid Reactive Substances; D002084:Butylated Hydroxytoluene; D009249:NADP; C061126:iron(III)-ascorbic acid complex; D020122:tert-Butylhydroperoxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D001205:Ascorbic Acid; D002118:Calcium