title: A strong protective action of guttiferone-A, a naturally occurring prenylated benzophenone, against iron-induced neuronal cell damage.
abstract: Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with several reported pharmacological actions. We have assessed the protective action of GA on iron-induced neuronal cell damage by employing the PC12 cell line and primary culture of rat cortical neurons (PCRCN). A strong protection by GA, assessed by the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carbox-anilide (XTT) assay, was revealed, with IC(50) values <1 µM. GA also inhibited Fe(3+)-ascorbate reduction, iron-induced oxidative degradation of 2-deoxiribose, and iron-induced lipid peroxidation in rat brain homogenate, as well as stimulated oxygen consumption by Fe(2+) autoxidation. Absorption spectra and cyclic voltammograms of GA-Fe(2+)/Fe(3+) complexes suggest the formation of a transient charge transfer complex between Fe(2+) and GA, accelerating Fe(2+) oxidation. The more stable Fe(3+) complex with GA would be unable to participate in Fenton-Haber Weiss-type reactions and the propagation phase of lipid peroxidation. The results show a potential of GA against neuronal diseases associated with iron-induced oxidative stress.
authors.affiliation: Laboratorio de Farmacología Molecular, Centro de Investigación y Desarrollo de Medicamentos, Ciudad Habana, Cuba.
authors.forename: Yanier Núñez
authors.initials: YN
authors.lastname: Figueredo
authors.forename: Laura
authors.initials: L
authors.lastname: García-Pupo
authors.forename: Osmany
authors.initials: O
authors.lastname: Cuesta Rubio
authors.forename: René
authors.initials: R
authors.lastname: Delgado Hernández
authors.forename: Zeki
authors.initials: Z
authors.lastname: Naal
authors.forename: Carlos
authors.initials: C
authors.lastname: Curti
authors.forename: Gilberto L
authors.initials: GL
authors.lastname: Pardo Andreu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001205:Ascorbic Acid / Q000737:chemistry / Q000633:toxicity; D001577:Benzophenones / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D003855:Deoxyribose / Q000378:metabolism; D004622:Embryo, Mammalian; D005290:Ferric Compounds / Q000737:chemistry / Q000633:toxicity; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D016877:Oxidants / Q000737:chemistry / Q000633:toxicity; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D001577:Benzophenones; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D018696:Neuroprotective Agents; D016877:Oxidants; C558133:guttiferone A; D008315:Malondialdehyde; D003855:Deoxyribose; C061126:iron(III)-ascorbic acid complex; D001205:Ascorbic Acid