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Protective effect of L-carnitine on Phenylalanine-induced DNA damage

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Abstract

The pathogenesis and the progression of phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, have been associated with oxidative damage. Moreover, it has been increasingly postulated the antioxidant properties of L-Carnitine (LC). The aim of this study was to verify the effect of LC on Phe-induced DNA damage. The in vitro effect of different concentrations of LC (15, 30, 120 and 150 μM) on DNA damage-induced by high phenylalanine levels (1000 and 2500 μM) was examined in white blood cells from normal individuals using the comet assay. Urinary 8-hydroxydeoguanosine (8-OHdG) levels, a biomarker of oxidative DNA damage, and plasmatic sulfhydryl content were measured in eight patients with classical PKU, under therapy with protein restriction and supplemented with a special formula containing LC, and in controls individuals. Both in vitro tested Phe concentrations (1000 and 2500 μM) have resulted in DNA damage index significantly higher than control group. The in vitro co-treatment with Phe and LC reduced significantly DNA damage index when compared to Phe group. The urinary excretion of 8-OHdG and plasmatic sulfhydryl content presented similar levels in both groups analyzed (controls and treated PKU patients). In treated PKU patients, urinary 8-OHdG levels were positively correlated with blood Phe levels and negatively correlated with blood LC concentration and plasmatic sulfhydryl content. The present work yields experimental evidence that LC can reduce the in vitro DNA injury induced by high concentrations of phenylalanine, as well as, allow to hypothesize that LC protect against DNA damage in patients with PKU.

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Acknowledgments

We are indebted to all study participants (PKU patients and healthy volunteers) and their families for their fundamental collaboration. We gratefully acknowledge the Brazilian Foundation Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for financial support of our study (grant n.° 007481/2011-13). This study was also supported in part by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundo de Incentivo à Pesquisa e Eventos (FIPE/HCPA). The authors also thank the staff from Serviço de Genética Médica/Hospital de Clínicas de Porto Alegre.

Conflict of interest

The authors declare that there is no financial interests and/or no conflict of interest disclosure associated with this manuscript.

Ethical standards

All human studies presented in this paper have been approved by the appropriate ethics committees and have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. This included approval from the ethics in research committee of Hospital de Clínicas de Porto Alegre for data acquired at Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil (projects n.° 04 –080 and 14 –0180).

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Authors and Affiliations

  1. Serviço de Genética Médica, HCPA, Rua Ramiro Barcelos, 2350, CEP 90035-003, Porto Alegre, RS, Brazil

    Marion Deon, Sharon S. Landgraf, Jessica F. Lamberty, Moacir Wajner & Carmen R. Vargas

  2. Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, CEP 90610-000, Porto Alegre, RS, Brazil

    Marion Deon & Carmen R. Vargas

  3. Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, IFRJ, Rua Pereira de Almeida, 88, CEP 20260-100, Rio de Janeiro, RJ, Brazil

    Sharon S. Landgraf

  4. Laboratório de Genética Toxicológica, Universidade Federal de Ciências de Saúde de Porto Alegre, UFSPA, Rua Sarmento Leite, 245, CEP 90050170, Porto Alegre, RS, Brazil

    Dinara J. Moura & Jenifer Saffi

  5. Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003, Porto Alegre, RS, Brazil

    Moacir Wajner & Carmen R. Vargas

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  1. Marion Deon
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Correspondence to Marion Deon or Carmen R. Vargas.

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Deon, M., Landgraf, S.S., Lamberty, J.F. et al. Protective effect of L-carnitine on Phenylalanine-induced DNA damage. Metab Brain Dis 30, 925–933 (2015). https://doi.org/10.1007/s11011-015-9649-1

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