Biomolecules damage and redox status abnormalities in Fabry patients before and during enzyme replacement therapy

Biancini, Giovana Brondani; Jacques, Carlos Eduardo Diaz; Hammerschmidt, Tatiane Grazieli; Souza, Heryk Motta de; Donida, Bruna; Deon, Marion; Vairo, Filippo Pinto e; Lourenço, Charles Marques; Giugliani, Roberto; Vargas, Carmen Regla

doi:10.1016/j.cca.2016.07.016

Cited by 32 publications

(30 citation statements)

References 47 publications

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“…However, it is not known the exact extent of these antibodies; probably the inflammatory and oxidative chain reactions generated by the immune system are responsible for the increased protein damage. As well as Morquio A patients, Fabry patients without treatment presented high levels of GSH and no protein damage, while treated Fabry patients presented decreased GSH levels [4]. Probably, the high levels of GSH found in untreated patients can be masking the measurement of sulfhydryl content, once one third of sulfhydryl groups were represented by GSH.…”

Section: Discussionmentioning

confidence: 96%

Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels

Donida

Marchetti

Jacques

et al. 2017

Molecular Genetics and Metabolism Reports

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Morquio A disease (Mucopolysaccharidosis type IVA, MPS IVA) is one of the 11 mucopolysaccharidoses (MPSs), a heterogeneous group of inherited lysosomal storage disorders (LSDs) caused by deficiency in enzymes need to degrade glycosaminoglycans (GAGs). Morquio A is characterized by a decrease in N-acetylgalactosamine-6-sulfatase activity and subsequent accumulation of keratan sulfate and chondroitin 6-sulfate in cells and body fluids. As the pathophysiology of this LSD is not completely understood and considering the previous results of our group concerning oxidative stress in Morquio A patients receiving enzyme replacement therapy (ERT), the aim of this study was to investigate oxidative stress parameters in Morquio A patients at diagnosis. It was studied 15 untreated Morquio A patients, compared with healthy individuals. The affected individuals presented higher lipid peroxidation, assessed by urinary 15-F2t-isoprostane levels and no protein damage, determined by sulfhydryl groups in plasma and di-tyrosine levels in urine. Furthermore, Morquio A patients showed DNA oxidative damage in both pyrimidines and purines bases, being the DNA damage positively correlated with lipid peroxidation. In relation to antioxidant defenses, affected patients presented higher levels of reduced glutathione (GSH) and increased activity of glutathione peroxidase (GPx), while superoxide dismutase (SOD) and glutathione reductase (GR) activities were similar to controls. Our findings indicate that Morquio A patients present at diagnosis redox imbalance and oxidative damage to lipids and DNA, reinforcing the idea about the importance of antioxidant therapy as adjuvant to ERT, in this disorder.

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Section: Discussionmentioning

confidence: 96%

Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels

Donida

Marchetti

Jacques

et al. 2017

Molecular Genetics and Metabolism Reports

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“…There are few studies in literature evaluating oxidative stress in FD (Shen et al 2008a, Biancini et al 2016 and no work evaluating ETC activity in this disease. In this sense, our work aims to analyze, in vitro, the effect of the main metabolite accumulated in FD, GB3, on ETC protein complexes, production of reactive species, lipoperoxidation and antioxidant enzymes CAT and SOD.…”

Section: Discussionmentioning

confidence: 99%

In vitro effect of globotriaosylceramide on electron transport chain complexes and redox parameters

Alvariz

Moreira

Cury

et al. 2019

An. Acad. Bras. Ciênc.

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Fabry disease (FD) is an X-linked inherited disease and occurs due to mutations in GLA gene that encodes the α-galactosidase enzyme. Consequently, there is an accumulation of enzyme substrates, namely globotriaosylceramide (GB3). FD is a multisystemic disease, caused by storage of GB3 in vascular endothelia, with significant renal, cardiac and vascular involvement. The aim of this work was to evaluate the in vitro effect of GB3 on electron transport chain complexes (ETC) and redox parameters. Biochemical biomarkers were determined in homogenates of cerebral cortex, kidneys and liver of Wistar rats in the presence or absence of GB3 at concentrations of 3, 6, 9 and 12 mg/L. We found that GB3 caused an increase of ETC complexes II and IV activities, increased production of reactive species and decreased superoxide dismutase enzyme activity in homogenates of cerebral cortex. As well also increased production of reactive species and superoxide dismutase activity in kidney homogenates. The results obtained in our work suggest that GB3 interferes in ETC complexes II and IV activities, however, the magnitude of this increase seems to be too low to present a physiologically importance. However, the imbalance in cellular redox state indicating that these alterations may be involved in the pathophysiology of FD, mainly in renal and cerebral manifestations.

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“…The pathological processes in FD are associated with increased oxidative, nitrosative, and carbonyl stress as evidenced by excessive production of reactive oxygen species (ROS) [ 11 – 13 ]; increased plasma and urinary carbonylated proteins [ 14 ]; and nitrotyrosine in plasma, cardiac, and vascular tissues [ 15 – 17 ], resulting in DNA oxidative damage in the cells and tissues [ 12 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…Bilirubin has been reported to be a strong negative predictor/biomarker of oxidative stress-mediated diseases such as atherosclerosis [ 21 ]. On the other hand, decreased systemic antioxidant defense mechanisms have been reported in patients with FD [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Bilirubin Levels and Promoter Variations in HMOX1 and UGT1A1 Genes in Patients with Fabry Disease

Jirásková

Bortolussi

Dostálová

et al. 2017

Oxidative Medicine and Cellular Longevity

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The aim of our study was to assess the possible relationships among heme oxygenase (HMOX), bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variations, serum bilirubin levels, and Fabry disease (FD). The study included 56 patients with FD (M : F ratio = 0.65) and 185 healthy individuals. Complete standard laboratory and clinical work-up was performed on all subjects, together with the determination of total peroxyl radical-scavenging capacity. The (GT)n and (TA)n dinucleotide variations in the HMOX1 and UGT1A1 gene promoters, respectively, were determined by DNA fragment analysis. Compared to controls, patients with FD had substantially lower serum bilirubin levels (12.0 versus 8.85 μmol/L, p = 0.003) and also total antioxidant capacity (p < 0.05), which showed a close positive relationship with serum bilirubin levels (p = 0.067) and the use of enzyme replacement therapy (p = 0.036). There was no association between HMOX1 gene promoter polymorphism and manifestation of FD. However, the presence of the TA7 allele UGT1A1 gene promoter, responsible for higher systemic bilirubin levels, was associated with a twofold lower risk of manifestation of FD (OR = 0.51, 95% CI = 0.27–0.97, p = 0.038). Markedly lower serum bilirubin levels in FD patients seem to be due to bilirubin consumption during increased oxidative stress, although UGT1A1 promoter gene polymorphism may modify the manifestation of FD as well.

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Biomolecules damage and redox status abnormalities in Fabry patients before and during enzyme replacement therapy

Cited by 32 publications

References 47 publications

Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels

Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels

In vitro effect of globotriaosylceramide on electron transport chain complexes and redox parameters

Serum Bilirubin Levels and Promoter Variations in HMOX1 and UGT1A1 Genes in Patients with Fabry Disease

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