RESUMEN
Maple Syrup Urine Disease is an inborn error of metabolism caused by severe deficiency in the activity of branched-chain α-keto acid dehydrogenase complex. Neurological disorder is common in patients with maple syrup urine disease. Although leucine is considered the main toxic metabolite, the mechanisms underlying the neuropathology of brain injury are poorly understood. In the present study, we evaluated the possible preventive effect of the co-administration of creatine plus pyruvate on the effects elicited by leucine administration to female Wistar rats during pregnancy and lactation on some oxidative stress parameters as well as the activities of some enzymes involved in the phosphoryltransfer network in the brain cortex and hippocampus of the offspring at 21 days of age. Leucine administration induced oxidative stress and altered the activities of pyruvate kinase, adenylate kinase, mitochondrial and cytosolic creatine kinase. Co-administration of creatine plus pyruvate was partially effective in the prevention of some alterations provoked by leucine administration on the oxidative stress but not in the enzymes of phosphoryltransfer network. These results suggest that non-treated maternal hyperleucinemia may be toxic to the brain of the offspring.
Asunto(s)
Corteza Cerebral/metabolismo , Hipocampo/metabolismo , Leucina/farmacología , Enfermedad de la Orina de Jarabe de Arce/fisiopatología , Fosfotransferasas/metabolismo , Efectos Tardíos de la Exposición Prenatal , Animales , Antioxidantes/metabolismo , Corteza Cerebral/efectos de los fármacos , Creatina/farmacología , Femenino , Hipocampo/efectos de los fármacos , Lactancia/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Embarazo , Ácido Pirúvico/farmacología , Ratas , Ratas WistarRESUMEN
Histidinemia is an inborn error of metabolism of amino acids caused by deficiency of histidase activity in liver and skin with consequent accumulation of histidine in plasma and tissues. Histidinemia is an autosomal recessive trait usually considered harmless to patients and their offspring, but some patients and children born from histidinemic mothers have mild neurologic alterations. Considering that histidinemia is one of the most frequently identified metabolic conditions, in the present study we investigated the effect of L-histidine load to female rats during pregnancy and lactation on some parameters of phosphoryltransfer network in cerebral cortex and hippocampus of the offspring. Pyruvate kinase, cytosolic and mitochondrial creatine kinase activities decreased in cerebral cortex and in hippocampus of rats at 21 days of age and this pattern remained in the cerebral cortex and in hippocampus at 60 days of age. Moreover, adenylate kinase activity was reduced in the cerebral cortex and in hippocampus of the offspring at 21 days of age, whereas the activity was increased in the two tissues at 60 days of age. These results suggest that administration of L-histidine to female rats in the course of pregnancy and lactation could impair energy homeostasis in the cerebral cortex and hippocampus of the offspring. Considering that histidinemia is usually a benign condition and little attention has been given to maternal histidinemia, it seems important to perform more studies in the children born from histidinemic mothers.
Asunto(s)
Corteza Cerebral/metabolismo , Hipocampo/metabolismo , Histidina/farmacología , Lactancia/efectos de los fármacos , Preñez/efectos de los fármacos , Adenilato Quinasa/metabolismo , Animales , Corteza Cerebral/efectos de los fármacos , Creatina Quinasa/metabolismo , Metabolismo Energético/efectos de los fármacos , Femenino , Hipocampo/efectos de los fármacos , Histidina/sangre , Masculino , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/biosíntesis , Embarazo , Piruvato Quinasa/metabolismo , Ratas , Ratas WistarRESUMEN
Histidinemia is an inherited metabolic disorder biochemically characterized by high concentrations of histidine in biological fluids. Usually affected patients are asymptomatic although some individuals have mental retardation and speech disorders. Considering the high prevalence of histidinemia and the scarce information on the effects of maternal histidinemia on their progeny, we investigated various parameters of oxidative stress in brain cortex and hippocampus of the offspring from female rats that received histidine (0.5 mg/g of body weight) in the course of pregnancy and lactation. At 21 days of age we found a significant increase of thiobarbituric acid reactive substances (TBARS), 2',7'-dihydrodichlorofluorescein oxidation, superoxide dismutase (SOD) activity, catalase (CAT) activity, total sulfhydryls and glutathione (GSH) content in cerebral cortex and hippocampus. We also verified that at 60 days of age, GSH, SOD and total sulfhydryls returned to normal levels in brain cortex, while the other parameters decreased in the same structure. In the hippocampus, at 60 days of age GSH returned to normal levels, CAT persisted elevated and the other parameters decreased. These results indicate that histidine administration to female rats can induce oxidative stress in the brain from the offspring, which partially recovers 40 days after breastfeeding stopped.