title: Biomolecules damage and redox status abnormalities in Fabry patients before and during enzyme replacement therapy.
abstract: Fabry disease (FD) is caused by deficient activity of the lysosomal enzyme α-galactosidase A. Its substrates, mainly globotriaosylceramide (Gb3), accumulate and seem to induce other pathophysiological findings of FD. Once enzyme replacement therapy (ERT) is not completely efficient on preventing disease progress in FD patients, elucidating the underlying mechanisms in FD pathophysiology is essential to the development of additional therapeutic strategies. We investigated 58 Fabry patients (23 male and 35 female) subdivided into two groups (at diagnosis and during long-term ERT) and compared them to healthy individuals. Fabry patients at diagnosis presented altered glutathione (GSH) metabolism (higher GSH levels, lower glutathione peroxidase - GPx - and normal glutathione reductase - GR - activities), higher lipid peroxidation levels (thiobarbituric acid reactive species - TBARS - and malondialdehyde - MDA), nitric oxide (NO(.)) equivalents and urinary Gb3. Fabry patients on ERT presented GSH metabolism similar to controls, although lipid peroxidation and urinary levels of NO(.) equivalents remained higher whereas Gb3 levels were lower than at diagnosis but still higher than controls. These data demonstrated that redox impairment occurs in Fabry patients before and after ERT, probably as a consequence of Gb3 accumulation, providing targets to future therapy approaches using antioxidants in combination with ERT in FD.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas:Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil. Electronic address: giovana.bb@gmail.com.
authors.forename: Giovana Brondani
authors.initials: GB
authors.lastname: Biancini
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Jacques
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Tatiane
authors.initials: T
authors.lastname: Hammerschmidt
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Heryk Motta
authors.initials: HM
authors.lastname: de Souza
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas:Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Donida
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Marion
authors.initials: M
authors.lastname: Deon
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Filippo Pinto
authors.initials: FP
authors.lastname: Vairo
authors.affiliation: Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Charles Marques
authors.initials: CM
authors.lastname: Lourenço
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas:Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil; Departamento de Genética, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas:Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address: crvargas@hcpa.edu.br.
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
mesh_terms: D000328:Adult; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000201:enzymology / Q000378:metabolism* / Q000628:therapy*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D055815:Young Adult
chemical_list: D005979:Glutathione Peroxidase; D005980:Glutathione Reductase
keywords: Antioxidant defenses; Fabry disease; Globotriaosylceramide; Lysosomal diseases; Oxidative stress; Reactive species