Urinary biomarkers of oxidative damage in maple syrup urine disease : the l-carnitine role

Maple Syrup Urine Disease (MSUD) is a disorder of branched-chain amino acids (BCAA). The defect in the branched-chain α-keto acid dehydrogenase complex activity lead to an accumulation of these compounds and their corresponding α-keto-acids and α-hydroxy-acids. Studies have shown that oxidative stress may be involved in neuropathology of MSUD. L-carnitine (L-car) have an important role as antioxidant through reducing and scavenging free radicals formation and by enhancing the activity of antioxidant enzymes. Our study evaluated the oxidative stress parameters, dityrosine, isoprostanes and antioxidant capacity, in urine of MSUD patients on proteinrestricted diet supplemented or not with L-car capsules at a dose of 50 mg kg-1 day-1. We also determined the BCAAs, α-keto acids and α-hydroxy levels in urine and quantified the free L-car levels. Firstly, we found a deficiency of carnitine in patients before the L-car supplementation. Significant increases of di-tyrosine and isoprostanes, as well as reduced antioxidant capacity were observed in urine of MSUD patients before the treatment with L-car. The L-car supplementation was able to reduce the di-tyrosine and isoprostanes levels, as well as to increase the antioxidant capacity. We also quantified the BCAAs and metabolites in urine from these patients, detecting a significantly increase of leucine, isoleucine, α-ketoisocaproic acid, α- hydroxyisocaproate and α-hydroxy-B-methylvalerate after 2 months of treatment, compared to control group. In conclusion, our results suggest that L-car may have additional beneficial effects in the treatment of MSUD, not only by preventing oxidative damage, but also by increasing the excretion of MSUD metabolites, reducing the toxic effects caused by their accumulation