|
Oxidative stress analysis in patients with mucopolysaccharidosis type I undergoing enzyme replacement therapy
Pereira VG1, Abreu PA1, Micheletti C1, Secches TAVA1, Martins AM1, D'Almeida V2
Departments of Pediatrics1 and Health Sciences2 – UNIFESP - SP
Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by a deficiency of a-L-iduronidase (IDUA), involved in the degradation of glycosaminoglycans (GAGs). Undegraded or partially degraded GAGs accumulate in the lysosomes, leading to cell, tissue and organ dysfunction. Oxidative stress has been thought to be involved in the pathogenesis of several inborn errors of metabolism, in which excessive free radicals production may be due to the accumulation of toxic metabolites in the cell. Enzyme replacement therapy (ERT) with a recombinant human IDUA, laronidase, has been shown to improve some clinical aspects and reduce the GAGs accumulation in patients.
The aim of this study was to evaluate some oxidative stress markers in MPS I patients before starting ERT and during 6 months of treatment. Levels of total glutathione (tGSH) and thiobarbituric acid reactive substances (TBARS) were evaluated by colorimetric methods, and superoxide dismutase (SOD) and catalase (CAT) activities were analyzed by spectrophotometry in 11 patients before starting ERT, and 1, 3 and 6 months during the treatment.
A significant increase in CAT activity was demonstrated after 1 month of ERT when compared to baseline data (p=0.014), and this increase was maintained after 3 and 6 months of treatment (p<0.01 for both periods). A decrease of SOD activity was demonstrated in the third month of ERT when compared to baseline data (p=0.025) and 1 month (p=0.023), but after 6 months of treatment there was no difference between periods. TBARS levels were above reference values at baseline and they did not differ during ERT. tGSH values were inside the normal range and there was no alterations with the treatment.
Untreated MPS I patients present a state of oxidative stress, and this could not be totally reverted by ERT. However, we demonstrated that ERT could induce the activation of an antioxidant mechanism by increasing CAT activity right after 1 month of treatment and it was maintained during the whole period. Financial support: CNPq, FAPESP, AFIP e Genzyme do Brasil
|