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.
This study was designed to determine the protective effect of melatonin treatment against oxidative damage in rat brain induced by hyperhomocysteinemia (Hhcy). Oral administration of methionine and its degradation product, homocysteine (hcy), causes mild to moderate Hhcy. The major end-point of oxidative damage measured in this report was lipid peroxidation (LPO). The levels of malondialdehyde (MDA) were assayed as index of lipid peroxidation. The increase in lipid peroxidation was inhibited by melatonin. Rats were divided into seven groups: one was used as control and each remaining group was supplemented with methionine dissolved and added to the drinking water daily for 4 weeks (0.5, 1, 1.5, 2, 3 g /kg BW). Additional groups of rats were given both melatonin (30 mg/kg BW) and methionine in drinking water daily. At the conclusion of the study, MDA levels were significantly increased in the brains of methionine-treated rats compared with control rats, whereas melatonin prevented the increases in MDA levels. Plasma hcy levels in animals treated with melatonin were significantly lower than those of controls. Melatonin lowered plasma hcy levels and could potentially be beneficial in prevention of neurodegeneration caused by mild hyperhomocysteinemia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.