RESUMO
Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Usually diagnosed within the first month of birth, it is essential that the patient strictly follow the dietary restriction of natural protein intake. Otherwise, PKU impacts the development of the brain severely and may result in microcephaly, epilepsy, motor deficits, intellectual disability, and psychiatric and behavioral disorders. The neuropathology associated with PKU includes defects of myelination, insufficient synthesis of monoamine neurotransmitters, amino acid imbalance across the blood-brain barrier, and involves intermediary metabolic pathways supporting energy homeostasis and antioxidant defenses in the brain. Considering that the production of reactive oxygen species (ROS) is inherent to energy metabolism, we investigated the association of creatine+pyruvate (Cr + Pyr), both energy substrates with antioxidants properties, as a possible treatment to mitigate oxidative stress and phosphotransfer network impairment elicited in the brain of young Wistar rats by chemically-induced PKU. We induced PKU through the administration of α-methyl-L-phenylalanine and phenylalanine for 7 days, with and without Cr + Pyr supplementation, until postpartum day 14. The cotreatment with Cr + Pyr administered concurrently with PKU induction prevented ROS formation and part of the alterations observed in antioxidants defenses and phosphotransfer network enzymes in the cerebral cortex, hippocampus, and cerebellum. If such prevention also occurs in PKU patients, supplementing the phenylalanine-restricted diet with antioxidants and energetic substrates might be beneficial to these patients.
Assuntos
Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Creatina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fenilcetonúrias/metabolismo , Ácido Pirúvico/farmacologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Fenilalanina/análogos & derivados , Fenilcetonúrias/induzido quimicamente , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Evidences have suggested that the phosphoryl transfer network by the enzymatic activities of creatine kinase (CK), adenylate kinase (AK), pyruvate kinase (PK), and lactate dehydrogenase (LDH), shows new perspectives to understand some disturbances in the energy metabolism during bacterial infections. Thus, the aim of this study was to evaluate whether Staphylococcus aureus infection in mice could alter serum and cardiac activities of these enzymes and their association to disease pathophysiology. For that, we measured total leukocytes, lymphocytes and neutrophils (just 48â¯h of infection) that were lower in infected animals after 48 and 72â¯h in infected mice compared with negative control, while total protein and globulin plasma levels were higher after 72â¯h of infection. The serum CK activity was higher in infected animals 48 and 72â¯h post-infection compared to the control group, as well as observed for mitochondrial cardiac CK activity. The serum PK activity was higher in infected animals after 72â¯h of infection compared to the control group, and lower in the cardiac tissue. The cardiac AK activity was lower in infected animals 48â¯h and 72â¯h post-infection compared to the control group, while serum and cardiac LDH activities were higher. Based on these evidences, it is possible to conclude that the stimulation of CK activity exerts a key role as an attempt to maintain the bioenergetic homeostasis by the production of phosphocreatine to avoid a rapid fall on the concentrations of total adenosine triphosphate. In summary, the phosphoryl transfer network can be considered a pathway involved in the improvement on tissue and cellular energy homeostasis of S. aureus-infected mice.
Assuntos
Endocardite/metabolismo , Metabolismo Energético/fisiologia , Mitocôndrias Cardíacas/metabolismo , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/fisiopatologia , Staphylococcus aureus/metabolismo , Trifosfato de Adenosina/metabolismo , Adenilato Quinase/sangue , Adenilato Quinase/metabolismo , Animais , Creatina Quinase/sangue , Creatina Quinase/metabolismo , Creatina Quinase Mitocondrial/metabolismo , Modelos Animais de Doenças , Endocardite/microbiologia , Coração/microbiologia , Coração/fisiologia , Homeostase , Leucócitos , Fígado/microbiologia , Fígado/patologia , Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos , Fosfocreatina/metabolismo , Piruvato Quinase/sangue , Piruvato Quinase/metabolismo , Baço/microbiologia , Baço/patologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/enzimologiaRESUMO
Aflatoxin B1 (AFB1) is an environmental toxicant and neurotoxic compound that induces the production of free radicals, causing oxidative stress. Creatine kinase (CK) is a central controller of energy metabolism in tissues with a large and fluctuating energy demand, and it is highly susceptible to inactivation by free radicals and oxidative damage. Thus, the aim of this study was to evaluate whether a diet for freshwater silver catfish (Rhamdia quelen) containing AFB1 inhibits cerebral CK activity, as well as the involvement of the oxidative stress on this inhibition. Brain CK activity was lower on days 14 and 21 post-feeding in animals that received AFB1-contaminated diet compared to the control group (basal diet), similarly to the brain sodium-potassium pump (Na+, K+-ATPase) activity. On the other hand, lipid peroxidation and protein carbonylation levels were higher on days 14 and 21 post-feeding in animals fed with AFB1-contaminated feed compared to the control group, while the antioxidant capacity against peroxyl radicals and thiol content was lower. Based on these evidences, the data demonstrated that diet containing AFB1 severely affects CK activity, an essential enzyme that plays an important role in brain energy homeostasis. Also, the impairment of energetic homeostasis linked with the use and generation of ATP via inhibition of CK activity elicited an inhibition of enzymes ATP-dependent, such as Na+, K+-ATPase. Moreover, the inhibition of brain CK activity appears to be mediated by the oxidation of lipids, proteins, and thiol group, as well as by a reduction in the antioxidant capacity.
Assuntos
Aflatoxina B1/toxicidade , Ração Animal/análise , Peixes-Gato/fisiologia , Cérebro/enzimologia , Creatina Quinase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Creatina Quinase/antagonistas & inibidores , Dieta/veterinária , Contaminação de Alimentos , Venenos/toxicidadeRESUMO
Cytosolic and mitochondrial creatine kinases (CK), through the creatine kinase-phosphocreatine (CK/PCr) system, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. However, the effects of bacterial infections on the kidney remain poorly understood and are limited only to histopathological analyses. Thus, the aim of this study was to investigate the involvement of cytosolic and mitochondrial CK activities in renal energetic homeostasis in silver catfish experimentally infected with Aeromonas caviae. Cytosolic CK activity decreased in infected animals, while mitochondrial CK activity increased compared to uninfected animals. Moreover, the activity of the sodium-potassium pump (Na+, K+-ATPase) decreased in infected animals compared to uninfected animals. Based on this evidence, it can be concluded that the inhibition of cytosolic CK activity by A. caviae causes an impairment on renal energy homeostasis through the depletion of adenosine triphosphate (ATP) levels. This contributes to the inhibition of Na+, K+-ATPase activity, although the mitochondrial CK activity acted in an attempt to restore the cytosolic ATP levels through a feedback mechanism. In summary, A. caviae infection causes a severe energetic imbalance in infected silver catfish, which may contribute to disease pathogenesis.
Assuntos
Aeromonas caviae/patogenicidade , Peixes-Gato/microbiologia , Creatina Quinase Mitocondrial/metabolismo , Citosol/metabolismo , Metabolismo Energético/fisiologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Rim/metabolismo , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Brasil , Creatina Quinase/metabolismo , Citosol/enzimologia , Modelos Animais de Doenças , Doenças dos Peixes/patologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Homeostase , Rim/microbiologia , Rim/patologia , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Fosfocreatina/metabolismo , Fosforilação , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
The aim of this study was to investigate the activities of important enzymes involved in the phosphoryl transfer network (adenylate kinase and creatine kinase (CK)), lactate dehydrogenase (LDH), respiratory chain complexes and biomarkers of cardiac function in rat experimentally infected by Trypanosoma evansi. Rat heart samples were evaluated at 5 and 15 days post-infection (PI). At 5 day PI, there was an increase in LDH and CK activities, and a decrease in respiratory chain complexes II, IV and succinate dehydrogenase activities. In addition, on day 15 PI, a decrease in the respiratory chain complex IV activity was observed. Biomarkers of cardiac function were higher in infected animals on days 5 and 15 PI. Considering the importance of the energy metabolism for heart function, it is possible that the changes in the enzymatic activities involved in the cardiac phosphotransfer network and the decrease in respiratory chain might be involved partially in the role of biomarkers of cardiac function of T. evansi-infected rats.