title: DNA damage in leukocytes from pretreatment mucopolysaccharidosis type II patients; protective effect of enzyme replacement therapy.
abstract: Mucopolysaccharidosis type II (MPS II) is an X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues and organs. Enzyme replacement therapy reduces the storage of these substances in the lysosomes. Oxidative stress is related to the pathophysiology of many disorders, including inborn errors of metabolism. Oxidative damage to protein and lipid has been described in MPS types I and III. The aim of this study was to analyze DNA damage, as determined by the alkaline comet assay using silver staining, in peripheral leukocytes from MPS II patients before treatment and during the first six months of enzyme replacement therapy. We also correlated DNA damage with lipid and protein oxidative damages, analyzed by plasma malondialdehyde levels and carbonyl group content, respectively. We found a significant increase in lipid and protein damage in MPS II patients before treatment when compared to controls. Also, our results showed greater DNA damage in terms of damage index (DI) in pretreatment MPS II patients (DI=18.0 ± 2.4) when compared to controls (DI=66.0 ± 2.0). Enzyme replacement therapy led to a significant decrease in levels of malondialdehyde and DNA damage when compared to pretreatment, but did not reach control values. Significant positive correlations between DNA damage and malondialdehyde levels, as well as carbonyl group content, were observed. Our findings indicate that MPS II patients are subject to DNA damage and that enzyme replacement therapy is able to protect against this process.
authors.affiliation: Bioquímica, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos 2700, Porto Alegre, Brazil.
authors.forename: Letícia
authors.initials: L
authors.lastname: Filippon
authors.forename: Carlos A Y
authors.initials: CA
authors.lastname: Wayhs
authors.forename: Diana M
authors.initials: DM
authors.lastname: Atik
authors.forename: Vanusa
authors.initials: V
authors.lastname: Manfredini
authors.forename: Silvani
authors.initials: S
authors.lastname: Herber
authors.forename: Clarissa G
authors.initials: CG
authors.lastname: Carvalho
authors.forename: Ida V D
authors.initials: IV
authors.lastname: Schwartz
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Vargas
mesh_terms: D002648:Child; D002675:Child, Preschool; D004249:DNA Damage; D056947:Enzyme Replacement Therapy; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D016532:Mucopolysaccharidosis II / Q000188:drug therapy / Q000235:genetics*; D050050:Protein Carbonylation / Q000187:drug effects
chemical_list: D008315:Malondialdehyde