Minocycline Protects Against Oxidative Stress in a Model of Maple Syrup Urine Disease

Branched-chain amino acids (BCAA) leucine, isoleucine, and valine are metabolized by complex branched-chain ketoacids dehydrogenase (BCKDH). In Maple Syrup Urine Disease (MSUD), the BCKDH complex has its activity blocked by a genetic mutation, compromising the BCAA metabolism and leading to the accumulation of these BCAA, related to neurological damage in this disease. Thus, minocycline is a broad-spectrum antibiotic, bacteriostatic, and studies have shown benefits in neurodegenerative disease progression, like reduction of oxidative stress, inflammation, and downregulation of molecular pathways, such as apoptosis. Therefore, we make the hypothesis that the minocycline can ameliorate oxidative stress in the MSUD model. For this, we used 7-day-old male rats, who were treated with BCAA (leucine 393.42 mg/kg, isoleucine 121.66 mg/kg and valine 126.4 mg/kg) or saline solution (0,9%) subcutaneously, water, or minocycline (50 mg/kg) via gavage. Our results show that the MSUD group presents an increase in DCFH oxidation and TBARS levels, as well as a decrease in sulfhydryl content, related to oxidative species production, lipid and protein damage, and minocycline treatment rescues this damage found. In antioxidant activity, we found an increase in SOD activity also, a decrease in CAT in all groups studied compared to the control group. So, our results present positive effects of minocycline in MSUD, showing a potential use in this disease; moreover, more studies are necessary to understand the role of this molecule in this disease.