Oxidative stress in patients with mucopolysaccharidosis type II before and during enzyme replacement therapy

• Published in: Molecular genetics and metabolism Vol. 103; no. 2; pp. 121 - 127
• Main Authors: Filippon, Letícia, Vanzin, Camila S., Biancini, Giovana B., Pereira, Izabela N., Manfredini, Vanusa, Sitta, Angela, Peralba, Maria do Carmo R., Schwartz, Ida V.D., Giugliani, Roberto, Vargas, Carmen R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2011
• Subjects: Antioxidants - metabolism; Catalase - metabolism; Child; Child, Preschool; Enzyme Replacement Therapy; Erythrocytes - enzymology; Humans; Iduronate Sulfatase - therapeutic use; Infant; Lysosomal storage diseases; Male; Malondialdehyde - blood; Mucopolysaccharidosis II - enzymology; Mucopolysaccharidosis II - therapy; Mucopolysaccharidosis type II; Oxidative Stress; Superoxide Dismutase - metabolism; Mucopolysaccharidosis type II; MPS; Oxidative stress; Enzyme replacement therapy; ERT; CAT; GAGs; TAS; SOD; Lysosomal storage diseases; MDA; LSD
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2011.02.016

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulfatase, responsible for the degradation of glycosaminoglycans dermatan and heparan sulfate. Once the generation of free radicals is involved in the pathogenesis of many diseases, including some inborn errors of metabolism, the aim of this study was to evaluate blood oxidative stress parameters in MPS II patients, before and during 6 months of enzyme replacement therapy. We found significantly increased levels of malondialdehyde and carbonyl groups in plasma as well as erythrocyte catalase activity in patients before treatment compared to the control group. Plasma sulfhydryl group content and total antioxidant status were significantly reduced before treatment, while superoxide dismutase enzyme was not altered at this time when compared to controls. During enzyme replacement therapy, there was a significant reduction in levels of malondialdehyde when compared to pretreatment. Sulfhydryl groups were significantly increased until three months of treatment in MPS II patients in comparison to pretreatment. There were no significant alterations in plasma total antioxidant status and carbonyl groups as well as in catalase and superoxide dismutase activities during treatment in relation to pretreatment. The results indicate that MPS II patients are subject to lipid and protein oxidative damage and present reduction in non-enzymatic antioxidants, suggesting a possible involvement of free radicals in the pathophysiology of this disease. Also, the results may suggest that enzyme replacement therapy seems to protect against lipid peroxidation and protein damage in these patients.