Subject(s)
Glycosaminoglycans/urine , Iduronate Sulfatase/therapeutic use , Mucopolysaccharidosis II/urine , Biomarkers/urine , Case-Control Studies , Child , Child, Preschool , Enzyme Replacement Therapy , Humans , Infant , Mucopolysaccharidosis II/diagnosis , Mucopolysaccharidosis II/drug therapy , Oxidative StressABSTRACT
Mucopolysaccharidosis IVA is a lysosomal storage disorder leading to an increase in glycosaminoglycans storage. Genistein is an isoflavone capable to inhibit glycosaminoglycans production. The objective of this study was to analyze the in vitro effect of different concentrations of genistein on DNA injury in mucopolysaccharidosis IVA patients. The lower concentration tested (10 µM) showed a significant increase on DNA injury in vitro, although higher concentrations (30 µM and 50 µM) showed higher DNA damage.
Subject(s)
Genistein/pharmacology , Leukocytes, Mononuclear/drug effects , Mucopolysaccharidosis IV/pathology , Adolescent , Adult , Cells, Cultured , Child , Comet Assay , DNA Fragmentation/drug effects , Dose-Response Relationship, Drug , Female , Humans , Leukocytes, Mononuclear/pathology , MaleABSTRACT
It is well established that the involvement of reactive species in the pathophysiology of several neurological diseases, including phenylketonuria (PKU), a metabolic genetic disorder biochemically characterized by elevated levels of phenylalanine (Phe). In previous studies, we verified that PKU patients (treated with a protein-restricted diet supplemented with a special formula not containing L-carnitine and selenium) presented high lipid and protein oxidative damage as well as a reduction of antioxidants when compared to the healthy individuals. Our goal in the present study was to evaluate the effect of Phe-restricted diet supplemented with L-carnitine and selenium, two well-known antioxidant compounds, on oxidative damage in PKU patients. We investigated various oxidative stress parameters in blood of 18 treated PKU patients before and after 6 months of supplementation with a special formula containing L-carnitine and selenium. It was verified that treatment with L-carnitine and selenium was capable of reverting the lipid peroxidation, measured by thiobarbituric acid-reactive species, and the protein oxidative damage, measured by sulfhydryl oxidation, to the levels of controls. Additionally, the reduced activity of glutathione peroxidase was normalized by the antioxidant supplementation. It was also verified a significant inverse correlation between lipid peroxidation and L-carnitine blood levels as well as a significant positive correlation between glutathione peroxidase activity and blood selenium concentration. In conclusion, our results suggest that supplementation of L-carnitine and selenium is important for PKU patients since it could help to correct the oxidative stress process which possibly contributes, at least in part, to the neurological symptoms found in phenylketonuric patients.
