1. 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
- Author
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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, and Desirèe Padilha Marchetti
- Subjects
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 - Abstract
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.
- Published
- 2016