title: Protective effect of antioxidants on DNA damage in leukocytes from X-linked adrenoleukodystrophy patients.
abstract: Toxic metabolites accumulation and oxidative stress have been associated to the pathophysiology of X-linked adrenoleukodystrophy (X-ALD), an inborn error of peroxisome metabolism. Parameters of oxidative damage to proteins and lipids in X-ALD patients were already described in literature; however, DNA injuries were not studied yet. Considering that, the aims were to investigate DNA damage by comet assay in heterozygotes and symptomatic X-ALD patients, to look for associations between DNA damage and lipid peroxidation as measured by urinary 15-F2t-isoprostane; and to evaluate the in vitro effect of N-acetyl-l-cysteine (NAC), trolox (TRO) and rosuvastatin (RSV) on DNA damage in leukocytes from symptomatic patients. Symptomatic patients presented higher DNA damage levels than those found in heterozygotes and controls; heterozygotes and controls showed similar results. In order to investigate the in vitro antioxidant effect on DNA damage, whole blood cells from symptomatic patients were incubated with NAC (1 and 2.5mM), TRO (25 and 75 μM) and RSV (0.5, 2 and 5 μM) before DNA damage analysis. NAC, TRO and RSV, at all tested concentrations, were all capable to reduce DNA damage in symptomatic X-ALD patients until control levels. Finally, DNA damage correlated with urinary isoprostanes and plasmatic levels of TBA-RS and DCFH-DA, allowing to hypothesize that DNA damage might be induced by lipid peroxidation in symptomatic patients. The present work yields experimental evidence that NAC, TRO and RSV reduce the in vitro DNA injury in symptomatic X-ALD patients, what may suggest that the administration of these antioxidants might be considered as an adjuvant therapy for X-ALD.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: desireepmarchetti@gmail.com.
authors.forename: Desirèe P
authors.initials: DP
authors.lastname: Marchetti
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil. Electronic address: donida.bruna@gmail.com.
authors.forename: Bruna
authors.initials: B
authors.lastname: Donida
authors.affiliation: Universidade Federal de Ciências de Saúde de Porto Alegre, UFSPA, Rua Sarmento Leite, 245, CEP 90050170 Porto Alegre, RS, Brazil. Electronic address: htdarosa@gmail.com.
authors.forename: Helen T
authors.initials: HT
authors.lastname: da Rosa
authors.affiliation: Universidade Federal de Ciências de Saúde de Porto Alegre, UFSPA, Rua Sarmento Leite, 245, CEP 90050170 Porto Alegre, RS, Brazil. Electronic address: maninipaula@gmail.com.
authors.forename: Paula R
authors.initials: PR
authors.lastname: Manini
authors.affiliation: Universidade Federal de Ciências de Saúde de Porto Alegre, UFSPA, Rua Sarmento Leite, 245, CEP 90050170 Porto Alegre, RS, Brazil. Electronic address: dinjamoura@gmail.com.
authors.forename: Dinara J
authors.initials: DJ
authors.lastname: Moura
authors.affiliation: Universidade Federal de Ciências de Saúde de Porto Alegre, UFSPA, Rua Sarmento Leite, 245, CEP 90050170 Porto Alegre, RS, Brazil. Electronic address: jenifer.saffi@gmail.com.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Saffi
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil; Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: marion_deon@yahoo.com.br.
authors.forename: Marion
authors.initials: M
authors.lastname: Deon
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: carolmescka@yahoo.com.br.
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Mescka
authors.affiliation: Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: dcoelho@hcpa.ufrgs.br.
authors.forename: Daniella M
authors.initials: DM
authors.lastname: Coelho
authors.affiliation: Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Médicas, UFRGS, Rua Ramiro Barcelos, 2400, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: ljardim@hcpa.ufrgs.br.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Jardim
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil; Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: crvargas@hcpa.ufrgs.br.
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Vargas
mesh_terms: D000326:Adrenoleukodystrophy / Q000097:blood*; D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005227:Fatty Acids; D017392:Thiobarbituric Acid Reactive Substances
keywords: DNA damage; N-Acetyl-l-cysteine; Rosuvastatin; Trolox; X-linked adrenoleukodystrophy