Deon, Marion

Jardim, Laura Bannach

Rockenbach, Francieli Juliana

Vargas, Carmen Regla

English

Lume 5.8

ISSN 0102-6593 caderno de farmácia Órgão Oficial da Faculdade de Farmácia da Universidade Federal do Rio Grande do Sul volume 26, Suplemento, 201 O INVESTIGAÇÃO DE ALVOS TERAPÊUTICOS E BIOMARCADORES lnvestigation of therapeutic targets and biomarkers ------------------------------------161 X-LINKED ADRENOLEUKODYSTROPHY: ROLE OF PROINFLAMMATORY CYTOKINES, ANTIOXIDANTS ANO HEMATOPOIETIC CELL TRANSPLANTATION ON SOME PARAMETERS OF OXIDA TIVE STRESS. Rockenbach. F. J. a.b.d; Jardim, L.B. d; Oeon, M. d; Vargas, C. R. a,b.c,d aPrograma de Pós Graduação em Ciências Farmacêuticas UFRGS, Porto Alegre, RS, Brazil; bDepartamento de Análises, Faculdade de Farmácia, UFRGS, Porto Alegre, RS, Brazil; c Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, RS, BraziF dServiço de Genética Médica, HCPA, Porto Alegre, RS, Brazil; Mestranda - Início: 2010/1 lntroduction: X-linked adrenoleukodystrophy (X-ALO) is an inherited disorder of peroxisomal metabolism, characterized by deficient 13-oxidation of saturated very long chain fatty acids (VLCFA). Patients affected present a progressiva brain and peripheral demyelination and adrenal cortex insufficiency, associated with accumulation of the VLCFA in tissues and biological fluids. X-ALO is characterized by heterogeneous clinicai phenotypes, including adrenomyeloneuropathy (AMN) and cerebral childhood (CCER). Treatment options for X-ALO have been used in an attempt to achieve the main goals: stabilizing the adrenal insufficiency, decrease the concentration of VLCFA in plasma and demyelination in the brain. The hematopoietic stem cell transplantation is currently the most effective method for the therapy of CCER when detected in early stages of the disease and is the only method that improves cerebral demyelination. lt has been demonstrated that several parameters of oxidative stress are altered in plasma, erythrocytes and fibroblasts of X-ALO patients, suggesting that it may explain at least part of the neurological impairment of these patients. Neurological damage in X-ALO seems to be mediated by activation of astrocytes and induction of pro-inflammatory cytokines such as tumor necrosis factor -TNFa- and interleukins- IL 113 and IL6. Evidences of the function of antioxidants, such as N-acetylcysteine (NAC), can open an additional therapeutic approach to the currently employed. Objective: This research aim to evaluate the role of pro-inflammatory cytokines and of hematopoietic stem cell transplantation on various parameters of oxidative stress in patients with X-linked adrenoleukodystrophy as well as to investigate the in vitro effect of NAC on ONA damage in leukocytes from individuais with X-ALO. Materiais and Methods: The subjects will be recruited in Medicai Genetic Service of Clinicai Hospital from Porto Alegre. Heparinized blood will be collected at the time diagnosis, before and after hematopoietic cell transplantation for X-ALO patients and contrais matched for age and sex. lt will be determined the malondialdehyde (MOA), total antioxidant reactivity (T AR), total antioxidant status (TAS), carbonyl group and sulfhydryl assay and quantified the cytokines (TNF-a, IL 113 and IL6) in plasma. Quantification of cytokines will be performed by an immunoenzymatic method using a kit multiplex "Human Cytokine/Chemokine Multiplex lmmunoassay", Millipore. The enzyme activities (superoxide dismutase, catalase and glutathione peroxidase) and glutathione (GSH) concentration will be measured in erythrocytes. Comet assay will be performed in leukocytes from whole blood treated with NAC. The data will be analyzed by T'Student test or ANOVA or by Mann Whitney and Wilcoxon. The correlation between parameters of oxidative stress, plasma leveis of VLCFA and the concentrations of pro-inflammatory cytokines will be done by Pearson test. The correlation between oxidative damage to ONA and the other parameters mentioned above will be performed by Spearman's test. The research will be submitted to_ Ethical Comitte from Porto Alegre Clinicai Hospital. Acknowldgements: This work is supported in part by grants from Capes, FAPERGS, CNPq and FIPE/HCPA- Brazil. 

X-linked adrenoleukosdystrophy : role of proinflammatory cytokines, antioxidants and hematopoietic cell transplantation on some parameters of oxidative stress

https://lume.ufrgs.br/bitstream/10183/267766/1/000858066.pdf

X-linked adrenoleukosdystrophy : role of proinflammatory cytokines, antioxidants and hematopoietic cell transplantation on some parameters of oxidative stress

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Lume 5.8