Mitochondrial damage induced by fetal hyperphenylalaninemia in the rat brain and liver: its prevention by melatonin, Vitamin E, and Vitamin C.
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.
Martínez-Cruz
Francisco
F
Department of Medical Biochemistry and Molecular Biology, University of Seville, School of Medicine, Virgen del Rocío Hospital, Avda. Sánchez Pizjuán 4, Spain.
Osuna
Carmen
C
Guerrero
Juan M
JM
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001205:Ascorbic Acid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000627:therapeutic use*; D028361:Mitochondrial Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D010627:Phenethylamines; D010649:Phenylalanine / Q000378:metabolism; D010661:Phenylketonurias / Q000139:chemically induced / Q000150:complications; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014801:Vitamin A / Q000627:therapeutic use*
D000447:Aldehydes; D010627:Phenethylamines; D014801:Vitamin A; C024320:4-chlorophenethylamine; D010649:Phenylalanine; D008315:Malondialdehyde; D008550:Melatonin; C027576:4-hydroxy-2-nonenal; D001205:Ascorbic Acid