Oxidative and nitrative stress and pro-inflammatory cytokines in Mucopolysaccharidosis type II patients: effect of long-term enzyme replacement therapy and relation with glycosaminoglycan accumulation
| Autor: | Carolina Fischinger Moura de Souza, Caroline Paula Mescka, Carlos Eduardo Diaz Jacques, Maira Graeff Burin, Bruna Donida, Roberto Giugliani, Daiane Rodrigues, Carmen Regla Vargas, Fernanda Hendges de Bitencourt, Desirèe Padilha Marchetti |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Adolescent Glutathione reductase Interleukin-1beta Iduronate Sulfatase medicine.disease_cause Superoxide dismutase Lipid peroxidation 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Internal medicine medicine Humans Enzyme Replacement Therapy Mucopolysaccharidosis type II Child Molecular Biology Glycosaminoglycans Mucopolysaccharidosis II chemistry.chemical_classification biology Tumor Necrosis Factor-alpha Glutathione peroxidase nutritional and metabolic diseases Enzyme replacement therapy Glutathione Oxidative Stress 030104 developmental biology Endocrinology chemistry Biochemistry Nitrosative Stress Case-Control Studies biology.protein Molecular Medicine Cytokines 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Biochimica et biophysica acta. 1862(9) |
| ISSN: | 0006-3002 |
| Popis: | Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by a deficient activity of iduronate-2-sulfatase, leading to abnormal accumulation of glycosaminoglycans (GAG). The main treatment for MPS II is enzyme replacement therapy (ERT). Previous studies described potential benefits of six months of ERT against oxidative stress in patients. Thus, the aim of this study was to investigate oxidative, nitrative and inflammatory biomarkers in MPS II patients submitted to long term ERT. It were analyzed urine and blood samples from patients on ERT (mean time: 5.2years) and healthy controls. Patients presented increased levels of lipid peroxidation, assessed by urinary 15-F2t-isoprostane and plasmatic thiobarbituric acid-reactive substances. Concerning to protein damage, urinary di-tyrosine (di-Tyr) was increased in patients; however, sulfhydryl and carbonyl groups in plasma were not altered. It were also verified increased levels of urinary nitrate+nitrite and plasmatic nitric oxide (NO) in MPS II patients. Pro-inflammatory cytokines IL-1β and TNF-α were increased in treated patients. GAG levels were correlated to di-Tyr and nitrate+nitrite. Furthermore, IL-1β was positively correlated with TNF-α and NO. Contrastingly, we did not observed alterations in erythrocyte superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, in reduced glutathione content and in the plasmatic antioxidant capacity. Although some parameters were still altered in MPS II patients, these results may suggest a protective role of long-term ERT against oxidative stress, especially upon oxidative damage to protein and enzymatic and non-enzymatic defenses. Moreover, the redox imbalance observed in treated patients seems to be GAG- and pro-inflammatory cytokine-related. |
| Databáze: | OpenAIRE |
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