4-hydroxy-2-nonenal and Phenylketonurias

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