title: Co-administration of creatine plus pyruvate prevents the effects of phenylalanine administration to female rats during pregnancy and lactation on enzymes activity of energy metabolism in cerebral cortex and hippocampus of the offspring.
abstract: Phenylketonuria (PKU) is the most frequent inborn error of metabolism. It is caused by deficiency in the activity of phenylalanine hydroxylase, leading to accumulation of phenylalanine and its metabolites. Untreated maternal PKU or hyperphenylalaninemia may result in nonphenylketonuric offspring with low birth weight and neonatal sequelae, especially microcephaly and intellectual disability. The mechanisms underlying the neuropathology of brain injury in maternal PKU syndrome 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 phenylalanine administration to female Wistar rats during pregnancy and lactation on some enzymes involved in the phosphoryltransfer network in the brain cortex and hippocampus of the offspring at 21 days of age. Phenylalanine administration provoked diminution of body, brain cortex an hippocampus weight and decrease of adenylate kinase, mitochondrial and cytosolic creatine kinase activities. Co-administration of creatine plus pyruvate was effective in the prevention of those alterations provoked by phenylalanine, suggesting that altered energy metabolism may be important in the pathophysiology of maternal PKU. If these alterations also occur in maternal PKU, it is possible that pyruvate and creatine supplementation to the phenylalanine-restricted diet might be beneficial to phenylketonuric mothers.
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Vanessa Trindade
authors.initials: VT
authors.lastname: Bortoluzzi
authors.forename: Itiane Diehl
authors.initials: ID
authors.lastname: de Franceschi
authors.forename: Elenara
authors.initials: E
authors.lastname: Rieger
authors.forename: Clóvis Milton Duval
authors.initials: CM
authors.lastname: Wannmacher
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003401:Creatine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007774:Lactation / Q000187:drug effects* / Q000378:metabolism; D010649:Phenylalanine / Q000633:toxicity*; D011247:Pregnancy; D019289:Pyruvic Acid / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010649:Phenylalanine; D019289:Pyruvic Acid; D003401:Creatine