Maple syrup urine disease (MSUD) is a
metabolic disease caused by a deficiency in the branched-chain α-keto
acid dehydrogenase complex, leading to the accumulation of branched-chain
keto acids and their corresponding
branched-chain amino acids (BCAA) in patients. Treatment involves
protein-restricted 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
protein-restricted 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 well-established 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.