title: Oxidative stress and inflammation in mucopolysaccharidosis type IVA patients treated with enzyme replacement therapy.
abstract: Mucopolysaccharidosis type IVA (MPS IVA) is an inborn error of glycosaminoglycan (GAG) catabolism due to the deficient activity of N-acetylgalactosamine-6-sulfate sulfatase that leads to accumulation of the keratan sulfate and chondroitin 6-sulfate in body fluids and in lysosomes. The pathophysiology of this lysosomal storage disorder is not completely understood. The aim of this study was to investigate oxidative stress parameters, pro-inflammatory cytokine and GAG levels in MPS IVA patients. We analyzed urine and blood samples from patients under ERT (n=17) and healthy age-matched controls (n=10-15). Patients presented a reduction of antioxidant defense levels, assessed by a decrease in glutathione content and by an increase in superoxide dismutase activity in erythrocytes. Concerning lipid and protein damage, it was verified increased urine isoprostanes and di-tyrosine levels and decreased plasma sulfhydryl groups in MPS IVA patients compared to controls. MPS IVA patients showed higher DNA damage than control group and this damage had an oxidative origin in both pyrimidine and purine bases. Interleukin 6 was increased in patients and presented an inverse correlation with GSH levels, showing a possible link between inflammation and oxidative stress in MPS IVA disease. The data presented suggest that pro-inflammatory and pro-oxidant states occur in MPS IVA patients even under ERT. Taking these results into account, supplementation of antioxidants in combination with ERT can be a tentative therapeutic approach with the purpose of improving the patient's quality of life. To the best of our knowledge, this is the first study relating MPS IVA patients with oxidative stress.
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: donida.bruna@gmail.com.
authors.forename: Bruna
authors.initials: B
authors.lastname: Donida
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil; Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, 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 Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 Porto Alegre, RS, Brazil; Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: giovana.bb@gmail.com.
authors.forename: Giovana B
authors.initials: GB
authors.lastname: Biancini
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: Laboratório de Genética Toxicológica, Universidade Federal de Ciências de Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite, 245, CEP 90050-170 Porto Alegre, RS, Brazil. Electronic address: maninipaula@gmail.com.
authors.forename: Paula R
authors.initials: PR
authors.lastname: Manini
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Federal de Ciências de Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite, 245, CEP 90050-170 Porto Alegre, RS, Brazil. Electronic address: htdarosa@gmail.com.
authors.forename: Helen T
authors.initials: HT
authors.lastname: da Rosa
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Federal de Ciências de Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite, 245, CEP 90050-170 Porto Alegre, RS, Brazil. Electronic address: dinjamoura@gmail.com.
authors.forename: Dinara J
authors.initials: DJ
authors.lastname: Moura
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Federal de Ciências de Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite, 245, CEP 90050-170 Porto Alegre, RS, Brazil. Electronic address: jenifer.saffi@gmail.com.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Saffi
authors.affiliation: Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: bender.fernanda@gmail.com.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Bender
authors.affiliation: Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil. Electronic address: mburin@hcpa.ufrgs.br.
authors.forename: Maira G
authors.initials: MG
authors.lastname: Burin
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas-Fisiologia, Universidade Federal do Rio Grande do Sul, UFRGS, Instituto de Ciências Básicas e da Saúde, Rua Sarmento Leite, 500, CEP 90050-170 Porto Alegre, RS, Brazil. Electronic address: acoitinho@yahoo.com.br.
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Coitinho
authors.affiliation: Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, RS, Brazil; Departamento de Genética, e Programa de Pós-Graduação em Genética e Biologia Molecular, Instituto de Biociências, UFRGS, Av. Bento Gonçalves, 9500, CEP 90650-001 Porto Alegre, RS, Brazil. Electronic address: rgiugliani@hcpa.ufrgs.br.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, CEP 90610-000 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003 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 Regla
authors.initials: CR
authors.lastname: Vargas
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D001798:Blood Proteins / Q000032:analysis; D002648:Child; D002811:Chondroitinsulfatases / Q000627:therapeutic use*; D003404:Creatinine / Q000652:urine; D016207:Cytokines / Q000097:blood; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D056947:Enzyme Replacement Therapy / Q000379:methods*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D028421:Isoprostanes / Q000652:urine; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000097:blood; D013482:Superoxide Dismutase / Q000097:blood; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives / Q000652:urine; D055815:Young Adult
chemical_list: D001798:Blood Proteins; D016207:Cytokines; D006025:Glycosaminoglycans; D028421:Isoprostanes; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003404:Creatinine; C007543:dityrosine; D009195:Peroxidase; D013482:Superoxide Dismutase; D002811:Chondroitinsulfatases; C102295:GALNS protein, human; D003849:Deoxyguanosine; D005978:Glutathione
keywords: Glycosaminoglycan; Inflammation; Morquio A Syndrome; Mucopolysaccharidosis type IVA; Oxidative stress