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Melatonin ameliorates oxidative stress and DNA damage of rats subjected to a chemically induced chronic model of Maple Syrup Urine Disease.
Metab Brain Dis. 2020 08; 35(6):905-914.MB

Abstract

Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of branched α-ketoacid dehydrogenase complex (BCKDC) activity. Branched-chain amino acids (BCAA) accumulation is, at least in part, responsible for neurological disturbances characteristic of this metabolic disorder. Experimental studies demonstrated that high levels of BCAA induce brain oxidative stress. Considering that many antioxidants are obtained from the diet, the dietary restriction in MSUD patients probably produce deficiency of vitamins and micronutrients involved in antioxidant defenses. Supplementation with synthetic melatonin has been used to prevention and treatment of pathological conditions, including brain diseases. In this study, we aimed at investigating the potential neuroprotective effect of melatonin treatment in a MSUD experimental model. Infant rats (7 day old) received twice daily subcutaneous injections of a BCAA pool (0.21472 g/kg, 190 mmol/L leucine, 59 mmol/L isoleucine and 69 mmol/L valine in saline solution (15.8 µL/g per weight/injection) or saline alone, and supplemented with melatonin (10 mg/kg, intraperitoneal) for 21 days. Oxidative stress parameters, i.e. antioxidant enzyme activity, reactive species production and damage to lipids and proteins, were assessed in the cerebral cortex, hippocampus and striatum at twenty-eight days of age. In addition, the damage to blood cell DNA was evaluated. The chronic administration of BCAA pool in infant rats induced significant oxidative stress (p < 0.05) - such as oxidation of lipids and proteins, imbalance in antioxidant enzymes activities - damages in DNA (p < 0.05) and in brain structures (cerebral cortex, hippocampus and striatum). Notably, melatonin supplementation was able to ameliorate the oxidative (p < 0.05) and antioxidant (p < 0.05) parameters in the brain and blood of the rat model of MSUD. Our results show that melatonin could be a promising therapeutic agent for MSUD.

Authors+Show Affiliations

Laboratório de Neurologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806-000, Brazil.Laboratório de Neurologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806-000, Brazil.Laboratório de Neurologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806-000, Brazil.Laboratório de Neurologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806-000, Brazil.Laboratório de Neurologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806-000, Brazil.Laboratório de Biomedicina Translacional, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806-000, Brazil.Programa de Pós-graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90035-000, Brazil.Laboratório de Biomedicina Translacional, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806-000, Brazil.Laboratório de Neurologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806-000, Brazil. emiliostreck@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32297169

Citation

Wessler, Leticia B., et al. "Melatonin Ameliorates Oxidative Stress and DNA Damage of Rats Subjected to a Chemically Induced Chronic Model of Maple Syrup Urine Disease." Metabolic Brain Disease, vol. 35, no. 6, 2020, pp. 905-914.
Wessler LB, Ise K, Lemos IC, et al. Melatonin ameliorates oxidative stress and DNA damage of rats subjected to a chemically induced chronic model of Maple Syrup Urine Disease. Metab Brain Dis. 2020;35(6):905-914.
Wessler, L. B., Ise, K., Lemos, I. C., Rezende, V. L., Duarte, M. B., Damiani, A. P., de Oliveira, J., de Andrade, V. M., & Streck, E. L. (2020). Melatonin ameliorates oxidative stress and DNA damage of rats subjected to a chemically induced chronic model of Maple Syrup Urine Disease. Metabolic Brain Disease, 35(6), 905-914. https://doi.org/10.1007/s11011-020-00572-9
Wessler LB, et al. Melatonin Ameliorates Oxidative Stress and DNA Damage of Rats Subjected to a Chemically Induced Chronic Model of Maple Syrup Urine Disease. Metab Brain Dis. 2020;35(6):905-914. PubMed PMID: 32297169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melatonin ameliorates oxidative stress and DNA damage of rats subjected to a chemically induced chronic model of Maple Syrup Urine Disease. AU - Wessler,Leticia B, AU - Ise,Kely, AU - Lemos,Isabela C, AU - Rezende,Victoria L, AU - Duarte,Mariane B, AU - Damiani,Adriani P, AU - de Oliveira,Jade, AU - de Andrade,Vanessa M, AU - Streck,Emilio L, Y1 - 2020/04/15/ PY - 2019/09/13/received PY - 2020/03/26/accepted PY - 2020/4/17/pubmed PY - 2021/7/30/medline PY - 2020/4/17/entrez KW - Maple Syrup Urine Disease KW - Melatonin KW - Oxidative stress SP - 905 EP - 914 JF - Metabolic brain disease JO - Metab Brain Dis VL - 35 IS - 6 N2 - Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of branched α-ketoacid dehydrogenase complex (BCKDC) activity. Branched-chain amino acids (BCAA) accumulation is, at least in part, responsible for neurological disturbances characteristic of this metabolic disorder. Experimental studies demonstrated that high levels of BCAA induce brain oxidative stress. Considering that many antioxidants are obtained from the diet, the dietary restriction in MSUD patients probably produce deficiency of vitamins and micronutrients involved in antioxidant defenses. Supplementation with synthetic melatonin has been used to prevention and treatment of pathological conditions, including brain diseases. In this study, we aimed at investigating the potential neuroprotective effect of melatonin treatment in a MSUD experimental model. Infant rats (7 day old) received twice daily subcutaneous injections of a BCAA pool (0.21472 g/kg, 190 mmol/L leucine, 59 mmol/L isoleucine and 69 mmol/L valine in saline solution (15.8 µL/g per weight/injection) or saline alone, and supplemented with melatonin (10 mg/kg, intraperitoneal) for 21 days. Oxidative stress parameters, i.e. antioxidant enzyme activity, reactive species production and damage to lipids and proteins, were assessed in the cerebral cortex, hippocampus and striatum at twenty-eight days of age. In addition, the damage to blood cell DNA was evaluated. The chronic administration of BCAA pool in infant rats induced significant oxidative stress (p < 0.05) - such as oxidation of lipids and proteins, imbalance in antioxidant enzymes activities - damages in DNA (p < 0.05) and in brain structures (cerebral cortex, hippocampus and striatum). Notably, melatonin supplementation was able to ameliorate the oxidative (p < 0.05) and antioxidant (p < 0.05) parameters in the brain and blood of the rat model of MSUD. Our results show that melatonin could be a promising therapeutic agent for MSUD. SN - 1573-7365 UR - https://www.unboundmedicine.com/medline/citation/32297169/Melatonin_ameliorates_oxidative_stress_and_DNA_damage_of_rats_subjected_to_a_chemically_induced_chronic_model_of_Maple_Syrup_Urine_Disease_ L2 - https://doi.org/10.1007/s11011-020-00572-9 DB - PRIME DP - Unbound Medicine ER -