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

• Published in: Molecular biology reports 2019-12, Vol.46 (6), p.5897-5908
• Main Authors: Mezzomo, Nathana Jamille, Becker Borin, Diego, Ianiski, Francine, Dotto Fontana, Barbara, Diehl de Franceschi, Itiane, Bolzan, Juliane, Garcez, Renata, Grings, Mateus, Parmeggiani, Belisa, da Silva Fernandes, Liana, de Almeida Vaucher, Rodrigo, Leipnitz, Guilhian, Duval Wannmacher, Clovis Milton, Cielo Rech, Virginia
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Animals; Biomedical and Life Sciences; Body weight; Brain - metabolism; Cerebral cortex; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Creatine; Creatine - metabolism; Creatine - physiology; Creatine kinase; Creatine Kinase - metabolism; Electron transport; Energy balance; Energy Metabolism; Female; Hippocampus - metabolism; Histology; Homeostasis; Hydroxylase; Life Sciences; Liposomes; Liposomes - metabolism; Male; Metabolic disorders; Metabolites; Mitochondria; Morphology; Nanoparticles; Nanoparticles - therapeutic use; Neurotoxicity; Original Article; Oxidation-Reduction; Oxidative stress; Oxidative Stress - drug effects; Phenylalanine; Phenylalanine - metabolism; Phenylalanine 4-monooxygenase; Phenylketonuria; Phenylketonurias - metabolism; Pyruvate kinase; Pyruvic acid; Rats; Rats, Wistar
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-019-05023-y

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