Lipoic acid prevents oxidative stress in vitro and in vivo by an acute hyperphenylalaninemia chemically-induced in rat brain

Moraes, Tarsila Barros; Zanin, Fernanda Rech; Rosa, Andréa; Oliveira, Amanda de; Coelho, Juliana G.; Petrillo, Felipe; Wajner, Moaçir; Dutra-Filho, Carlos Severo

doi:10.1016/j.jns.2010.01.016

Cited by 39 publications

(16 citation statements)

References 41 publications

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“…The authors also found that the major metabolites of Phe catabolism, phenylpyruvate, phenyllactate, and phenylacetate also increased lipid peroxidation in cerebral cortex (Fernandes et al 2010) and that the lipid oxidative damage induced by Phe was totally prevented by the free radical scavengers alpha-tocopherol and melatonin, implying a Phe-elicited production of peroxyl and hydroxyl radicals. Another study showed that the antioxidant lipoic acid prevented the reduced activity of the antioxidant enzymes CAT, SOD and GSHPx, as well as increased the levels of antioxidant defenses provoked in vitro and in vivo by an acute chemically induced model of hyperphenylalaninemia in rat brain (Moraes et al 2010).…”

Section: Oxidative Stress In Pku: Insights From Animal Studiesmentioning

confidence: 99%

Oxidative Stress in Phenylketonuria: What is the Evidence?

et al. 2011

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Phenylketonuria (PKU) is an inborn error of amino acid metabolism caused by severe deficiency of phenylalanine hydroxylase activity, leading to the accumulation of phenylalanine and its metabolites in blood and tissues of affected patients. Phenylketonuric patients present as the major clinical feature mental retardation, whose pathomechanisms are poorly understood. In recent years, mounting evidence has emerged indicating that oxidative stress is possibly involved in the pathology of PKU. This article addresses some of the recent developments obtained from animal studies and from phenylketonuric patients indicating that oxidative stress may represent an important element in the pathophysiology of PKU. Several studies have shown that enzymatic and non-enzymatic antioxidant defenses are decreased in plasma and erythrocytes of PKU patients, which may be due to an increased free radical generation or secondary to the deprivation of micronutrients which are essential for these defenses. Indeed, markers of lipid, protein, and DNA oxidative damage have been reported in PKU patients, implying that reactive species production is increased in this disorder. A considerable set of data from in vitro and in vivo animal studies have shown that phenylalanine and/or its metabolites elicit reactive species in brain rodent. These findings point to a disruption of pro-oxidant/antioxidant balance in PKU. Considering that the brain is particularly vulnerable to oxidative attack, it is presumed that the administration of appropriate antioxidants as adjuvant agents, in addition to the usual treatment based on restricted diets or supplementation of tetrahydrobiopterin, may represent another step in the prevention of the neurological damage in PKU.

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Section: Oxidative Stress In Pku: Insights From Animal Studiesmentioning

confidence: 99%

Oxidative Stress in Phenylketonuria: What is the Evidence?

et al. 2011

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“…Conversely, GPx activity levels express a tight negative connection with the serum Phe level, which suggests that Phe per Se inhibits GPx activity [25]. Glutathione, an important component of antioxidant defense system, was also reported to be diminished in erythrocytes for PKU patients [16].…”

Section: Introductionmentioning

confidence: 99%

Prooxidant-antioxidant balance in patients with phenylketonuria and its correlation to biochemical and hematological parameters

Tavana

Amini

Hakhamaneshi

et al. 2016

Journal of Pediatric Endocrinology and Metabolism

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“…In this scenario, high Phe concentrations also increases sulfhydryl oxidation, TBA-RS and MDA levels, and 2',7'-dichlorofluorescein (DCFH) oxidation, indicating protein and lipid oxidative damage and increased production of reactive species of oxygen, respectively [38][39][40][41][42][43]. Most of these findings were prevented by supplementation with lipoic acid, melatonin, alpha-tocopherol and/or ascorbic acid, which are potent and well-known antioxidants [22].…”

Section: Oxidative Stressmentioning

confidence: 99%

Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations

Schuck¹,

Malgarin²,

Cararo³

et al. 2015

Aging and disease

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Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by the deficiency of phenylalanine hydroxylase. This deficiency leads to the accumulation of Phe and its metabolites in tissues and body fluids of PKU patients. The main signs and symptoms are found in the brain but the pathophysiology of this disease is not well understood. In this context, metabolic alterations such as oxidative stress, mitochondrial dysfunction, and impaired protein and neurotransmitters synthesis have been described both in animal models and patients. This review aims to discuss the main metabolic disturbances reported in PKU and relate them with the pathophysiology of this disease. The elucidation of the pathophysiology of brain damage found in PKU patients will help to develop better therapeutic strategies to improve quality of life of patients affected by this condition.

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Lipoic acid prevents oxidative stress in vitro and in vivo by an acute hyperphenylalaninemia chemically-induced in rat brain

Cited by 39 publications

References 41 publications

Oxidative Stress in Phenylketonuria: What is the Evidence?

Oxidative Stress in Phenylketonuria: What is the Evidence?

Prooxidant-antioxidant balance in patients with phenylketonuria and its correlation to biochemical and hematological parameters

Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations

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