Creatine nanoliposome reverts the HPA-induced damage in complex II–III activity of the rats’ cerebral cortex

  • Nathana Jamille MezzomoEmail author
  • Diego Becker Borin
  • Francine Ianiski
  • Barbara Dotto Fontana
  • Itiane Diehl de Franceschi
  • Juliane Bolzan
  • Renata Garcez
  • Mateus Grings
  • Belisa Parmeggiani
  • Liana da Silva Fernandes
  • Rodrigo de Almeida Vaucher
  • Guilhian Leipnitz
  • Clovis Milton Duval Wannmacher
  • Virginia Cielo RechEmail author
Original Article


Phenylketonuria (PKU) is a metabolic disorder accumulating phenylalanine (Phe) and its metabolites in plasma and tissues of the patients. Regardless of the mechanisms, which Phe causes brain impairment, are poorly understood, energy deficit may have linked to the neurotoxicity in PKU. It is widely recognized that creatine is involved in maintaining of cerebral energy homeostasis. Because of this, in a previous work, we incorporated it into liposomes and this increased the concentration of creatine in the cerebral cortex. Here, we examined the effect of creatine nanoliposomes on parameters of oxidative stress, enzymes of phosphoryl transfer network, and activities of the mitochondrial respiratory chain complexes (RCC) in the cerebral cortex of young rats chemically induced hyperphenylalaninemia (HPA). HPA was induced with l-phenylalanine (5.2 µmol/g body weight; twice a day; s.c.), and phenylalanine hydroxylase inhibitor, α-methylphenylalanine (2.4 µmol/g body weight; once a day; i.p.), from the 7th to the 19th day of life. HPA reduced the activities of pyruvate kinase, creatine kinase, and complex II + III of RCC in the cerebral cortex. Creatine nanoliposomes prevented the inhibition of the activities of the complexes II + III, caused by HPA, and changes oxidative profile in the cerebral cortex. Considering the importance of the mitochondrial respiratory chain for brain energy production, our results suggesting that these nanoparticles protect against neurotoxicity caused by HPA, and can be viable candidates for treating patients HPA.

Graphic abstract


Hyperphenylalaninemia Phenylketonuria Neurotoxicity Brain energy metabolism Nanoparticle Respiratory chain complexes 



We would like to thank the Franciscan University (UFN) for the support and facilities and the financial support and fellowships from Coordination for the Improvement of Higher Education Personnel (CAPES—Finance Code 001), National Council for Scientific and Technological Development (CNPq), and Foundation for Research Support of the State of Rio Grande do Sul (Fapergs).

Compliance with ethical standards

Conflict of interest

The authors declare that no conflict of interest exists.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Nathana Jamille Mezzomo
    • 1
    Email author
  • Diego Becker Borin
    • 1
  • Francine Ianiski
    • 1
  • Barbara Dotto Fontana
    • 1
  • Itiane Diehl de Franceschi
    • 2
  • Juliane Bolzan
    • 1
  • Renata Garcez
    • 1
  • Mateus Grings
    • 2
  • Belisa Parmeggiani
    • 2
  • Liana da Silva Fernandes
    • 1
  • Rodrigo de Almeida Vaucher
    • 1
  • Guilhian Leipnitz
    • 2
  • Clovis Milton Duval Wannmacher
    • 2
  • Virginia Cielo Rech
    • 1
    Email author
  1. 1.Graduate Program in NanoscienceFranciscan University, UFNSanta MariaBrazil
  2. 2.Graduate Program in Biological Sciences: Toxicological Biochemistry, Institute of Basic Health SciencesFederal University of Rio Grande do Sul, UFRGSPorto AlegreBrazil

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