Neurological Damage in MSUD The Role of Oxidative

Authors: Angela Sitta Graziela S Ribas Caroline P Mescka Alethéa G Barschak Moacir Wajner Carmen R Vargas

Publish Date: 2013/11/13

Volume: 34, Issue: 2, Pages: 157-165

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Abstract

Maple syrup urine disease MSUD is a metabolic disease caused by a deficiency in the branchedchain αketo acid dehydrogenase complex leading to the accumulation of branchedchain keto acids and their corresponding branchedchain amino acids BCAA in patients Treatment involves proteinrestricted diet and the supplementation with a specific formula containing essential amino acids except BCAA and micronutrients in order to avoid the appearance of neurological symptoms Although the accumulation of toxic metabolites is associated to appearance of symptoms the mechanisms underlying the brain damage in MSUD remain unclear and new evidence has emerged indicating that oxidative stress contributes to this damage In this context this review addresses some of the recent findings obtained from cells lines animal studies and from patients indicating that oxidative stress is an important determinant of the pathophysiology of MSUD Recent works have shown that the metabolites accumulated in the disease induce morphological alterations in C6 glioma cells through nitrogen reactive species generation In addition several works demonstrated that the levels of important antioxidants decrease in animal models and also in MSUD patients what have been attributed to proteinrestricted diets Also markers of lipid protein and DNA oxidative damage have been reported in MSUD probably secondary to the high production of free radicals Considering these findings it is wellestablished that oxidative stress contributes to brain damage in MSUD and this review offers new perspectives for the prevention of the neurological damage in MSUD which may include the use of appropriate antioxidants as a novel adjuvant therapy for patients

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