A longitudinal study of antioxidant status in phenylketonuric patients

Artuch, Rafael; Colomé, Catrina; Sierra, Cristina; Brandi, Nuria; Lambruschini, Nilo; Campistol, Jaume; Ugarte, M. D.; Vilaseca, M. A.

doi:10.1016/j.clinbiochem.2003.10.017

Cited by 58 publications

(47 citation statements)

References 24 publications

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“…Numerous studies have provided experimental evidence demonstrating oxidative stress in human PKU patients and animal models (Artuch et al, 2001(Artuch et al, ,2004Colome et al, 2003;Ercal et al, 2002;Martinez-Cruz et al, 2002;Sierra et al, 1998;Sirtori et al, 2005). Our laboratory previously demonstrated increased inducible nitric oxide synthase production by infiltrative cd11b macrophage cells in the mesencephalon and hypothalamus of PKU mice (Embury et al, 2005), providing further evidence of oxidative processes occurring in these regions.…”

Section: Discussionmentioning

confidence: 86%

“…Ercal et al (2002) provided experimental evidence of oxidative damage in Pah enu2 mice that included increased concentration of the lipid peroxidation by-product malon-dialdehyde in brain tissue, decreased glutathione/glutathione disulfide also in brain and increased catalase and glucose-6-phosphate dehydrogenase in erythrocytes of these animals. Other studies indicating the role of oxidative stress in PKU include human studies by Artuch et al (2001Artuch et al ( , 2004; Colome et al (2003);and Sierra et al (1998). Sirtori et al (2005) demonstrated the involvement of oxidative stress in human PKU patients through increased levels of thiobarbituric acid reactive species (indicative of lipid peroxidation) and decreased total antioxidant reactivity, suggestive of deficient capacity to handle increases in reactive species.…”

Section: Discussionmentioning

confidence: 99%

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PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pahenu2 mice

et al. 2007

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Phenylketonuria (PKU) is a common genetic disorder in humans that arises from deficient activity of phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine. There is a resultant hyperphenylalanemia with subsequent impairment in cognitive abilities, executive functions and motor coordination. The neuropathogenesis of the disease has not been completely elucidated, however, oxidative stress is considered to be a key feature of the disease process. Hyperphenylalanemia also adversely affects monoaminergic metabolism in the brain. For this reason we chose to evaluate the nigrostriatum of Pah enu2 mice, to determine if alterations of monoamine metabolism resulted in morphologic nigrostriatal pathology. Furthermore, we believe that recent developments in adeno-associated virus (AAV)-based vectors have greatly increased the potential for long-term gene therapy and may be a viable alternative to dietary treatment for this metabolic disorder. In this study we identified neurodegenerative changes with regenerative responses in the nigrostriatum of Pah enu2 mice that are consistent with oxidative injury and occurred as early as 4 weeks of age. These neuropathologic changes were reversed following portal vein delivery of a recombinant adeno-associated virus-mouse phenylalanine hydroxylase-woodchuck hepatitis virus post-transcriptional response element (rAAV-mPAH-WPRE) vector to Pah enu2 mice and corresponded to rapid reduction of serum Phe levels.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pahenu2 mice

et al. 2007

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“…Evita-se, ainda, a manipulação inadequada e problemas na aquisição/compra da substância utilizada como complemento, sendo possível evitar, também, erros nos cálculos da dose a ser utilizada. O aumento dos parâmetros bioquímicos relacionados ao selênio reforça a necessidade de complementação contínua do mineral, justificada pela existência de correlação positiva entre as concentrações de selênio no soro e as dosagens de GPX nos eritrócitos 22 .…”

Section: Discussionunclassified

“…Como relatado na literatura 16,22,23 , não foram encontradas manifestações clínicas da deficiência de selênio em nossos pacientes. Portanto, a deficiência de selênio nessa população também é apenas bioquímica.…”

Section: Discussionunclassified

Selenium intake and nutritional status of children with phenylketonuria in Minas Gerais, Brazil

Alves¹,

Starling²,

Kanufre³

et al. 2012

J Pediatr (Rio J)

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Objective: To evaluate selenium dietary intake and nutritional status of patients with phenylketonuria. Methods:The study prospectively evaluated 54 children with phenylketonuria, from 4 to10 years old. The study was performed before and after the use of a selenium-supplemented amino acid mixture. The second phase of the study was performed after, at least, 90 days of use of the supplementation. Selenium nutritional status was assessed through the analysis of biochemical parameters: serum free thyroxin and selenium and glutathione peroxidase in erythrocytes. Selenium dietary intake was evaluated by the administration of the Food Frequency Questionnaire.Results: Mean age of the children was of 7.0±1.8 years, and 35.2% were female. Mean time of supplementation of selenium, on special formula, was 122.2±25.1 days. The selenium-supplemented amino acid mixture represented 72.9% of the daily supply of the mineral. Upon supplementation, mean concentrations of serum selenium and glutathione peroxidase in erythrocytes increased significantly (p < 0.05). The average daily intake of selenium increased significantly (p < 0.001), reaching the levels recommended by the Dietary Reference Intakes. The concentration of free thyroxin, in serum, presented significant reduction (p < 0.001) in all patients during the second phase of the study, and returned to normal limits in those who had changed levels. Conclusion:Selenium supplementation through protein replacement is effective to improve and adapt the nutritional status of selenium in patients with phenylketonuria.J Pediatr (Rio J). 2012;88(5):396-400: Phenylketonuria, selenium, glutathione peroxidase, thyroid hormones. ResumoObjetivo: Avaliar a ingestão alimentar e o estado nutricional em selênio em pacientes com fenilcetonúria. Métodos:Foram avaliados prospectivamente 54 crianças com fenilcetonúria, entre 4 e 10 anos de idade. O estudo foi realizado antes e após o uso de mistura de aminoácidos complementada com selênio. A segunda fase do estudo foi realizada com, no mínimo, 90 dias de utilização da mistura complementada. O estado nutricional em selênio foi avaliado por meio da análise de parâmetros bioquímicos: dosagens séricas de selênio e tiroxina livre e dosagem de glutationa peroxidase no eritrócito. A ingestão alimentar de selênio foi avaliada por aplicação de Questionário de Frequência Alimentar Quantitativo.Resultados: A idade média das crianças foi de 7,0±1,8 anos, e 35,2% eram do sexo feminino. O tempo médio de complementação de selênio, em fórmula especial, foi de 122,2±25,1 dias. A mistura de aminoácidos complementada com o mineral representou 72,9% da oferta diária de selênio. Após a complementação, as concentrações médias de selênio sérico e de glutationa peroxidase no eritrócito apresentaram aumento significativo (p < 0,05). A ingestão média diária de selênio aumentou significativamente (p < 0,001), alcançando o recomendado pela Ingestão Dietética de Referência. A concentração de tiroxina livre, no soro, apresentou redução significativa (p < 0,001) em tod...

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“…In PKU, accumulation of Phe and/or its metabolites may lead to a disturbance of redox homeostasis (Artuch et al 2004;Mazzola et al 2013). Some studies showed an increase of lipoperoxidation markers (Sanayama et al 2011) and DNA damages (Sitta et al 2009), or a reduction of various antioxidant compounds, especially selenium, coenzyme Q10, or antioxidant system of glutathione (Menzel et al 1983;Sitta et al 2006;Sanayama et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria

et al. 2017

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Background: Several studies have highlighted disturbance of redox homeostasis in patients with phenylketonuria (PKU) which may be associated with neurological disorders observed in patients, especially during adulthood when phenylalanine restrictive diets are not maintained. The aim of this study was to assess the antioxidant profile in a cohort of PKU patients in comparison to the controls and to evaluate its relation to biochemical parameters especially phenylalaninemia. Methods:We measured RNA expression of 22 antioxidant genes and reactive oxygen species (ROS) levels in white blood cells of 10 PKU patients and 10 age-and gendermatched controls. We also assessed plasma amino acids, vitamins, oligo-elements, and urinary organic acids concentrations. Then we evaluated the relationship between redox status and biochemical parameters. Results: In addition to expected biochemical disturbances, we highlighted a significant global decrease of antioxidant genes expression in PKU patients in comparison to the controls. This global decrease of antioxidant genes expression, including various isoforms of peroxiredoxins, glutaredoxins, glutathione peroxidases, and superoxide dismutases, was significantly correlated to hyperphenylalaninemia. Conclusion: This study is the first to evaluate the expression of 22 antioxidant genes in white blood cells regarding biochemical parameters in PKU. These findings highlight the association of hyperphenylalaninemia with antioxidant genes expression. New experiments to specify the role of oxidative stress in PKU pathogenesis may be useful in suggesting new recommendations in PKU management and new therapeutic trials based on antioxidant defenses.

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A longitudinal study of antioxidant status in phenylketonuric patients

Cited by 58 publications

References 24 publications

PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pahenu2 mice

PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pahenu2 mice

Selenium intake and nutritional status of children with phenylketonuria in Minas Gerais, Brazil

Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria

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