title: Effects of chronic treatment with sodium tetrachloroaurate(III) in mice and membrane models.
abstract: Gold is a nonessential element with a variety of applications in medicine. A few gold(I) compounds are used in the clinics for treatment of rheumatoid arthritis and of discoid lupus. Some novel gold(III) compounds are under evaluation as anticancer agents. It is known that gold compounds generally produce toxic effects on the kidneys and characteristic lesions in the brain. However, information concerning the neurotoxicity of gold derivatives in humans as well as in experimental toxicology is rather scarce. For this reason we tried to shed some further light on this aspect of gold neurotoxicity by chronic treatment of mice with sodium tetrachloroaurate(III) in order to observe possible biophysical and morphological alterations that may occur in the brain. Chronic gold treatment resulted in a markedly decreased expression of metallothioneins and of glial fibrillary acidic protein in astrocytes of different brain areas. To examine its effects on cell membranes, interactions of sodium tetrachloroaurate(III) with molecular models were also evaluated. The models consisted in bilayers built-up of classes of phospholipids located in the outer and inner monolayers of biological membranes. Structural perturbation of cell membrane models was observed only at concentrations 10(5) times higher than those detected in the brains of animals after three months' treatment. These results show that toxic effects on animal brain upon treatment with sodium tetrachloroaurate develop with difficulty and may be observed only at high doses.
authors.affiliation: Faculty of Chemical Sciences, University of Concepcion, Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Suwalsky
authors.forename: Pamela
authors.initials: P
authors.lastname: Zambenedetti
authors.forename: Emilio
authors.initials: E
authors.lastname: Carpené
authors.forename: Meryem
authors.initials: M
authors.lastname: Ibnlkayat
authors.forename: Werner
authors.initials: W
authors.lastname: Wittkowski
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.forename: Paolo
authors.initials: P
authors.lastname: Zatta
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000187:drug effects; D017612:Gold Compounds / Q000378:metabolism* / Q000494:pharmacology*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010743:Phospholipids / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D002712:Chlorides; D005904:Glial Fibrillary Acidic Protein; D017612:Gold Compounds; D008565:Membrane Proteins; D010743:Phospholipids; C024568:gold tetrachloride, acid; D012964:Sodium