ascorbic-acid and Phenylketonurias

Topics: Adult; Amino Acid Metabolism, Inborn Errors; Ascorbic Acid; Child; Diet; Female; Humans; Infant; Infant, Newborn; Male; Mass Screening; Phenylalanine; Phenylalanine Hydroxylase; Phenylketonurias; Time Factors

Topics: Ascorbic Acid; Birth Weight; Black People; Clinical Trials as Topic; Dietary Proteins; Humans; Infant, Newborn; Infant, Premature; Injections, Intramuscular; Phenylalanine; Phenylketonurias; Time Factors; Tyrosine

Topics: Ascorbic Acid; Folic Acid; Humans; Magnetic Resonance Imaging; Phenylketonurias; Siderosis

Abnormal oxidative stress was observed in hyperphenylalaninemia and other inborn errors of intermediary metabolism, owing to the accumulation of toxic metabolites, free radical production and increased LPO products. In our model of maternal hyperphenylalaninemia, pregnant rats were injected with 300 mg/kg BW l-phenylalanine (PHE) and 50 mg/kg BW p-chlorophenylalanine (PCPA) dissolved in saline. In this research study, we measured LPO-by-products, i.e., malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) and we demonstrated that maternal hyperphenylalaninemia increased both markers of oxidative stress in the brain and liver mitochondria of the pups. We also demonstrated that administration of melatonin, Vitamin E, and Vitamin C, in this order of potency, prevented the oxidative damage to the mitochondria, especially in the brain. We therefore conclude that maternal hyperphenylalaninemia induces a clear state of oxidative stress that is somehow directly involved in brain and liver impairment, which can be prevented by melatonin, Vitamin E, and Vitamin C.

Topics: Aldehydes; Animals; Animals, Newborn; Ascorbic Acid; Disease Models, Animal; Drug Interactions; Female; Male; Malondialdehyde; Melatonin; Mitochondrial Diseases; Phenethylamines; Phenylalanine; Phenylketonurias; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Time Factors; Vitamin A

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of the phenylalanine hydroxylation system and is characterized by a block in the conversion of phenylalanine (PHE) to tyrosine. We examined the effects of maternal hyperphenylalaninemia on the morphological and biochemical development of pup rat brain and cerebellum. In our model of PKU we evaluated a number of markers of oxidative stress such as Ehrlich adducts formation, lipid peroxidation, as well as the levels of reduced and oxidized glutathione, and the activities of the enzymes glutathione peroxidase and glutathione reductase. We also studied the expression of heme-oxigenase-1 and mitogen-activated protein kinase 1/2 (MAPK 1/2) as additional markers of oxidative stress. We demonstrate that PKU strongly increased most of the oxidative stress markers studied and induced significant morphological damage. We also showed that daily administration of melatonin (20 mg/kg BW), vitamin E (30 mg/kg BW), and vitamin C (30 mg/kg BW) until delivery prevented the oxidative biomolecular damage in the rat brain and cerebellum. Although no significant differences were observed among the antioxidants studied, it should be noted that the doses of melatonin were less than those for vitamins E and C. We conclude that PKU induces a clear state of oxidative stress that is somehow involved in the brain and body damage occurring in this inborn error. Moreover, melatonin and other antioxidants are capable of preventing completely the damage induced by PKU.

Topics: Animals; Animals, Newborn; Antioxidants; Ascorbic Acid; Brain; Cerebellum; Disease Models, Animal; Female; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Humans; Lipid Peroxidation; Melatonin; Nervous System Malformations; Neurons; Oxidative Stress; Phenylalanine; Phenylketonurias; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Vitamin E

Topics: Animals; Ascorbic Acid; Biopterins; Child, Preschool; Humans; Hydroxocobalamin; In Vitro Techniques; Infant; Leucovorin; Male; NADH, NADPH Oxidoreductases; Phenylketonurias; Rats; Tetrahydrofolates

A deficiency of hepatic dihydropteridine reductase (DHPR) activity was found in a neurologically impaired infant with mild hyperphenylalaninemia and normal levels of hepatic phenylalanine hydroxylase. DHPR is required for the regeneration of tetrahydrobiopterin, an essential cofactor in aromatic amino acid hydroxylation, a necessary step in the biosynthesis of the neurotransmitters, dopamine and serotonin. Evidence for decreased synthesis of these transmitters in this patient was provided by the finding of reduced levels of homovanillic acid and 5-hydroxyindole acetic acid, metabolites of dopamine and serotonin, respectively, in the cerebrospinal fluid and urine. Treatment with dopamine and serotonin precursors, L-3,4 dihydroxyphenylalanine and 5-hydroxytryptophan, respectively, was associated with improvement in temperament and motor tone and less frequent seizures. However, there was no improvement in gross motor function or language development.

Topics: 5-Hydroxytryptophan; Ascorbic Acid; Consanguinity; Dopamine; Humans; Infant; Levodopa; Liver; Male; NADH, NADPH Oxidoreductases; Nervous System Diseases; Phenylalanine; Phenylalanine Hydroxylase; Phenylketonurias; Serotonin

Topics: Administration, Oral; Ascorbic Acid; Chromatography, Gas; Female; Hippurates; Humans; Male; Mandelic Acids; Phenylacetates; Phenylalanine; Phenylketonurias; Phenylpyruvic Acids; Stimulation, Chemical

Topics: Ascorbic Acid; Butyrates; Chemistry, Clinical; Chromatography, Thin Layer; Cystinosis; Glyoxylates; Humans; Hydrazines; Keto Acids; Ketoglutaric Acids; Levulinic Acids; Methods; Oxaloacetates; Phenylketonurias; Phenylpyruvic Acids; Pyruvates

Topics: Anemia; Anemia, Sickle Cell; Ascorbic Acid; Counseling; Eugenics; Galactosemias; Genetics, Medical; Humans; Immunity; Malaria; Metabolism, Inborn Errors; Phenylketonurias; Preventive Medicine

Topics: 5-Hydroxytryptophan; Adrenal Glands; Ascorbic Acid; Blood; Brain; Brain Chemistry; Carboxy-Lyases; Cholinesterases; Corticosterone; Dopamine; Glutamates; Liver; Metabolism; Mixed Function Oxygenases; Norepinephrine; Phenylalanine; Phenylketonurias; Rats; Research; Serotonin; Transaminases; Tryptophan; Tyrosine

Topics: Amino Acid Metabolism, Inborn Errors; Ascorbic Acid; Blood; Brain; Carboxy-Lyases; Guinea Pigs; Metabolic Diseases; Monoamine Oxidase; Pharmacology; Phenylalanine; Phenylketonurias; Research; Serotonin; Toxicology; Tyrosine

Topics: Animals; Ascorbic Acid; Guinea Pigs; Metabolism; Phenylketonurias; Phenylpyruvic Acids; Rats; Research; Tyrosine