Inflammatory process and oxidative/nitrative stress: in vivo study in mucopolysaccharidosis type IV A patients under long-term enzyme replacement therapy

被引:0
作者
Delgado, Camila Aguilar [1 ,3 ]
Hammerschmidt, Tatiane [2 ,3 ]
Faverzini, Jessica Lamberty [2 ,3 ]
Lopes, Franciele [2 ,3 ]
Giugliani, Roberto [3 ]
Baldo, Guilherme [3 ]
Vargas, Carmen Regla [1 ,2 ,3 ]
机构
[1] Univ Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Programa Posgrad Ciencias Biol Bioquim, R Ramiro Barcelos 2600, BR- 9003503 Porto Alegre, RS, Brazil
[2] Univ Fed Rio Grande do Sul, Fac Farm, Programa Posgrad Ciencias Farmaceut, Av Ipiranga 27522, BR-90610000 Porto Alegre, RS, Brazil
[3] HCPA, Serv Genet Med, R Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil
关键词
Mucopolysaccharidosis type IV A; Oxidative stress; Inflammation; HO-1; Nrf2 andNf-k; SYRUP-URINE-DISEASE; OXIDATIVE STRESS; ELOSULFASE ALPHA; INBORN-ERRORS; II PATIENTS; DNA-DAMAGE; MORQUIO; PATHWAY; LEUKOCYTES; RESPONSES;
D O I
10.1016/j.abb.2023.109541
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mucopolysaccharidosis type IV A (MPS IVA) is an inborn error of the metabolism (IEM) caused by a deficiency of the enzyme N-acetylgalactosamine 6-sulfate sulfatase (GALNS). Since 2014, enzyme replacement therapy (ERT) is the recommended treatment for these patients. It is known that the inflammatory response is closely related to antioxidant defenses and oxidative stress, and literature shows involvement of oxidative stress in the patho-genesis of IEM. The aim of this study is to investigate the mechanisms of oxidative/nitrative stress and inflammation in patients with MPS IVA under long-term ERT. In the present work we investigate parameters of oxidative/nitrative stress in plasma and urine of MPS IVA patients under long-term ERT and controls, such as plasmatic nitrate/nitrite levels using the LDH Method, urinary di-tyrosine levels by fluorometric method, plas-matic content of sulfhydryl groups, urinary oxidized guanine species by ELISA kit and the plasmatic total antioxidant status. We next evaluated the plasmatic pro and anti-inflammatory cytokines concentration (IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-alpha) and the expression of factors and enzymes Nrf-2, NF-kappa beta and HO-1, main mediators between inflammation and oxidative stress. In concern to the oxidative/nitrative stress parameters, there was no significant difference between the groups MPS IVA patients under long-term ERT and controls, showing that there is no overproducing of RNS, no protein damage, no DNA/RNA oxidative damage and no modification in the non-enzymatic antioxidant capacity of a tissue to prevent the damage associated to free radical processes in these patients. It was also verified no significant difference between the MPS IVA patients under long-term ERT and controls groups regarding the production of proinflammatory cytokines. About anti-inflammatory cytokines, IL 10 was shown to be elevated in MPS IVA patients under long-term ERT in com-parison to the control group. We next evaluated the genic expression of Nrf-2, NF-kappa beta and HO-1and there was no significant difference between the MPS IVA patients under long-term ERT and control groups. In conclusion, MPS IVA patients under long term ERT are not in an inflammatory state and there is no alteration in genic expression in the genes analyzed which are involved in oxidative stress and inflammatory pathways. It is,however, important to consider that absence of imbalance of antioxidant defenses in MPS IVA patients under long term ERT is so far preliminary it is supported by methodologies that are not highly sensitive nor very accurate. Further experiments in future using state-of-the-art methodologies will corroborate these findings. Nevertheless, our results demonstrated the protective effect of the treatment in relation to the parameters studied and the importance of starting treatment in the early stages of the disease.
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页数:8
相关论文
共 51 条
[1]   The crucial roles of inflammatory mediators in inflammation: A review [J].
Abdulkhaleq, L. A. ;
Assi, M. A. ;
Abdullah, Rasedee ;
Zamri-Saad, M. ;
Taufiq-Yap, Y. H. ;
Hezmee, M. N. M. .
VETERINARY WORLD, 2018, 11 (05) :627-635
[2]   Changes in thiol content and expression of glutathione redox system genes in the hippocampus and cerebellum in Alzheimer's disease [J].
Aksenov, MY ;
Markesbery, WR .
NEUROSCIENCE LETTERS, 2001, 302 (2-3) :141-145
[3]   Home treatment with Elaprase® and Naglazyme® is safe in patients with mucopolysaccharidoses types II and VI, respectively [J].
Bagewadi, S. ;
Roberts, J. ;
Mercer, J. ;
Jones, S. ;
Stephenson, J. ;
Wraith, J. E. .
JOURNAL OF INHERITED METABOLIC DISEASE, 2008, 31 (06) :733-737
[4]   Erythrocyte glutathione peroxidase activity and plasma selenium concentration are reduced in maple syrup urine disease patients during treatment [J].
Barschak, Alethea G. ;
Sitta, Angela ;
Deon, Marion ;
Barden, Amanda T. ;
Schmitt, Graziela O. ;
Dutra-Filho, Carlos S. ;
Wajner, Moacir ;
Vargas, Carmen R. .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 2007, 25 (05) :335-338
[5]  
Blanco M.L., 2003, MINI-REV MED CHEM, V12, P341
[6]  
Chaves AG., 2003, Rev Bras Otorrinolaringol, V69, P267
[7]   Selective screening of 10,000 high-risk Brazilian patients for the detection of inborn errors of metabolism [J].
Coelho, JC ;
Wajner, M ;
Burin, MG ;
Vargas, CR ;
Giugliani, R .
EUROPEAN JOURNAL OF PEDIATRICS, 1997, 156 (08) :650-654
[8]   Enzyme replacement therapy for mucopolysaccharidoses: Opinions of patients and families [J].
Coman, David J. ;
Hayes, Ian M. ;
Collins, Veronica ;
Sahhar, Margaret ;
Wraith, J. Ed ;
Delatycki, Martin B. .
JOURNAL OF PEDIATRICS, 2008, 152 (05) :723-727
[9]  
Copple IM, 2012, ADV PHARMACOL, V63, P43, DOI 10.1016/B978-0-12-398339-8.00002-1
[10]  
Delgado C.A., ARCH BIOCHEM BIOPHYS