RESUMEN

Excessive fructose consumption is associated with the incidence of obesity and systemic inflammation, resulting in increased oxidative damage and failure to the function of brain structures. Thus, we hypothesized that fructose consumption will significantly increase inflammation, oxidative damage, and mitochondrial dysfunction in the mouse brain and, consequently, memory damage. The effects of different fructose concentrations on inflammatory and biochemical parameters in the mouse brain were evaluated. Male Swiss mice were randomized into four groups: control, with exclusive water intake, 5%, 10%, and 20% fructose group. The 10% and 20% fructose groups showed an increase in epididymal fat, in addition to higher food consumption. Inflammatory markers were increased in epididymal fat and in some brain structures. In the evaluation of oxidative damage, it was possible to observe significant increases in the hypothalamus, prefrontal cortex, and hippocampus. In the epididymal fat and in the prefrontal cortex, there was a decrease in the activity of the mitochondrial respiratory chain complexes and an increase in the striatum. Furthermore, short memory was impaired in the 10% and 20% groups but not long memory. In conclusion, excess fructose consumption can cause fat accumulation, inflammation, oxidative damage, and mitochondrial dysfunction, which can damage brain structures and consequently memory.

Asunto(s)

Fructosa , Obesidad , Ratones , Masculino , Animales , Fructosa/efectos adversos , Estrés Oxidativo , Inflamación , Encéfalo

RESUMEN

OBJECTIVES: Doxorubicin is a highly effective chemotherapeutic agent for treating several types of cancer; however, it can induce cardiotoxicity. We evaluated the influence of Pera and Moro orange juices on cardiac remodeling induced by acute administration of doxorubicin in rats. METHODS: We allocated 120 male Wistar rats into six groups: control (C), Pera orange juice (PO), Moro orange juice (MO), doxorubicin (D), doxorubicin + Pera orange juice (DPO), and doxorubicin + Moro orange juice (DMO). Groups PO and DPO received Pera orange juice, MO and DMO received Moro orange juice, and C and D received water with maltodextrin (100 g/L) for 4 wk. Subsequently, groups D, DPO, and DMO received 20 mg/kg doxorubicin and C, PO, and MO received saline. Echocardiogram and euthanasia were performed 48 h after doxorubicin injection. Juice and animal-serum flavonoid identification and quantification were evaluated by liquid chromatography/electrospray ionization multistage mass spectrometry. Oxidative stress and myocardial metabolism were evaluated by spectrophotometry. RESULTS: Systolic and diastolic left ventricular dysfunction increased oxidative stress and pathologic changes in myocardial energy metabolism of rats treated with doxorubicin. Intake of both orange juices improved left ventricular function, decreased oxidative stress, and attenuated the myocardial energy metabolism changes. Moro orange juice had a more pronounced effect than Pera orange juice in glutathione peroxidase activity, citrate synthase, and ß-hydroxyacyl-CoA dehydrogenase activity. CONCLUSIONS: Pera and Moro orange juices attenuated cardiac remodeling induced by doxorubicin, improved myocardial energy metabolism, and attenuated oxidative stress. However, Moro orange juice was more effective than Pera orange juice in modifying energy metabolism.

Asunto(s)

Citrus sinensis , Disfunción Ventricular Izquierda , Animales , Cardiotoxicidad/etiología , Doxorrubicina/toxicidad , Metabolismo Energético , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Disfunción Ventricular Izquierda/inducido químicamente

RESUMEN

Studies have indicated that epilepsy, an important neurological disease, can generate oxidative stress and mitochondrial dysfunction, among other damages to the brain. In this context, the use of antioxidant compounds could provide neuroprotection and help to reduce the damage caused by epileptic seizures and thereby the use of anticonvulsant drugs. Rosmarinic acid (RA) is an ester of caffeic acid and 3,4-dihydroxyphenylactic acid that prevents cell damage caused by free radicals, acting as an antioxidant. It also presents anti-inflammatory, antimutagenic, and antiapoptotic properties. In this work, we used two models of acute seizure, 4-aminopyridine (4-AP) and picrotoxin (PTX)-induced seizures in mice, to investigate the anticonvulsant, antioxidant, and neuroprotective profile of RA. Diazepam and valproic acid, antiepileptic drugs already used in the treatment of epilepsy, were used as positive controls. Although RA could not prevent seizures in the models used in this study, neither enhance the latency time to first seizure at the tested doses, it exhibited an antioxidant and neuroprotective effect. RA (8 and 16 mg/kg) decreased reactive oxygen species production, superoxide dismutase activity, and DNA damage, measured in hippocampus, after seizures induced by PTX and 4-AP. Catalase activity was decreased by RA only after seizures induced by 4-AP. The activity of the mitochondrial complex II was increased by RA in hippocampus samples after both seizure models. The results obtained in this study suggest that RA is able to reduce cell damage generated by the 4-AP and PTX seizures and therefore could represent a potential candidate in reducing pathophysiological processes involved in epilepsy.

Asunto(s)

Anticonvulsivantes/farmacología , Cinamatos/farmacología , Depsidos/farmacología , Complejo II de Transporte de Electrones/metabolismo , Mitocondrias/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Convulsiones/tratamiento farmacológico , 4-Aminopiridina/farmacología , Animales , Antioxidantes/metabolismo , Conducta Animal/efectos de los fármacos , Daño del ADN , Modelos Animales de Enfermedad , Complejo II de Transporte de Electrones/genética , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ratones , Mitocondrias/metabolismo , Estrés Oxidativo/genética , Picrotoxina/farmacología , Convulsiones/metabolismo , Ácido Rosmarínico

RESUMEN

New molecular hybrids were synthesized by combining tetrahydroquinoline (THQ) and isoxazole (ISX) scaffolds, in search for chemical structures with improved pharmacological properties. Our tetrahydroquinoline (THQ) and isoxazole (ISX) hybrids differ in the X and Y substituents: FM53 (X = H; Y= H), FM49 (X = CH3; Y= OCH3), FM50 (X = Cl; Y= H) and FM48 (X = Cl; Y= OCH3). Aiming at exploring their bioactivity in liver cancer cells, in this paper we report the effect of four THQ-ISX hybrids on viability, respiration and oxidative stress in Hep-G2 human hepatoma cells. In addition, we measured the alterations induced by these compounds on oxygen uptake and respiratory chain enzymes in isolated mitochondria. Cell viability assay indicated that these THQ-ISX hybrids displayed antiproliferative activity on Hep-G2 cells. Among these, FM50 (IC50 = 5.2 ±â€¯1.9 µM) and FM53 (IC50 = 6.8 ±â€¯0.7 µM) had the highest cytotoxicity. These four hybrids also inhibited the Hep-G2 cells respiration in the uncoupled state, with FM50 decreasing all respiratory states (basal, leak, uncoupled). While only FM49 and FM53 altered the Hep-G2 cells redox function. In terms of mitochondrial bioenergetics, THQ-ISX hybrids decreased the oxygen consumption in state 3 (via complex I and II), and also inhibited NADH oxidase and NADH cytochrome c reductase enzyme activities. In these experiments, the structural homologues FM50 and FM53 had a remarkable inhibitory effect (~50%) with respect to FM49 and FM48. These results show that THQ-ISX hybrids are promising compounds for hepatoma cancer treatment and that the phenyl substituent (Y= H) in the ISX scaffold intensifies both, the cytotoxicity in Hep-G2 cells and, inhibition of electron transport through complex I of the mitochondrial respiratory chain.

Asunto(s)

Metabolismo Energético/efectos de los fármacos , Isoxazoles/química , Mitocondrias Hepáticas/metabolismo , Quinolinas/química , Animales , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Supervivencia Celular/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Complejos Multienzimáticos/metabolismo , NADH NADPH Oxidorreductasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar

RESUMEN

Crude oil (CO) is a super mixture of chemical compounds whose toxic effects are reported in fish species according to international guidelines. In the current study a proteomic analysis of oxidized proteins (ox) was performed on the brain and liver of Nile tilapia exposed to WAF obtained from relevant environmental loads (0.01, 0.1 and 1.0 g/L) of Maya CO. Results have shown that oxidation of specific proteins was a newly discovered organ-dependent process able to disrupt key functions in Nile tilapia. In control fish, enzymes involved on aerobic metabolism (liver aldehyde dehydrogenase and brain dihydrofolate reductase) and liver tryptophan--tRNA ligase were oxidized. In WAF-treated liver specimens, fructose-bisphosphate aldolase (FBA), ß-galactosidase (ß-GAL) and dipeptidyl peptidase 9 (DPP-9) were detected in oxidized form. oxDPP-9 could be favorable by reducing the risk associated with altered glucose metabolism, the opposite effects elicited by oxFBA and oxß-GAL. oxTrypsin showed a clear adverse effect by reducing probably the hepatocyte capacity to achieve proteolysis of oxidized proteins as well as for performing the proper digestive function. Additionally, enzyme implicated in purine metabolism adenosine (deaminase) was oxidized. Cerebral enzymes of mitochondrial respiratory chain complex (COX IV, COX5B), of glycosphingolipid biosynthesis (ß-N-acetylhexosaminidase), involved in catecholamines degradation (catechol O-methyltransferase), and microtubule cytoskeleton (stathmin) were oxidized in WAF-treated specimens. This response suggests, in the brain, an adverse scenario for the mitochondrial respiration process and for ATP provision as for ischemia/reoxygenation challenges. Proteomic analysis of oxidized proteins is a promising tool for monitoring environmental quality influenced by hydrocarbons dissolved in water.

Asunto(s)

Encéfalo/efectos de los fármacos , Cíclidos , Hígado/efectos de los fármacos , Petróleo/toxicidad , Proteoma , Contaminantes Químicos del Agua/toxicidad , Animales , Encéfalo/metabolismo , Catalasa/metabolismo , Catecolaminas/metabolismo , Monitoreo del Ambiente , Glutatión Peroxidasa/metabolismo , Glicoesfingolípidos/metabolismo , Peroxidación de Lípido , Hígado/metabolismo , Microtúbulos/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteolisis , Especies Reactivas de Oxígeno/metabolismo , Estatmina/metabolismo , Superóxido Dismutasa/metabolismo

RESUMEN

Electron leakage from dysfunctional respiratory chain and consequent superoxide formation leads to mitochondrial and cell injury during ischemia and reperfusion (IR). In this work we evaluate if the supramolecular assembly of the respiratory complexes into supercomplexes (SCs) is associated with preserved energy efficiency and diminished oxidative stress in post-ischemic hearts treated with the antioxidant N-acetylcysteine (NAC) and the cardioprotective maneuver of Postconditioning (PostC). Hemodynamic variables, infarct size, oxidative stress markers, oxygen consumption and the activity/stability of SCs were compared between groups. We found that mitochondrial oxygen consumption and the activity of respiratory complexes are preserved in mitochondria from reperfused hearts treated with both NAC and PostC. Both treatments contribute to recover the activity of individual complexes. NAC reduced oxidative stress and maintained SCs assemblies containing Complex I, Complex III, Complex IV and the adapter protein SCAFI more effectively than PostC. On the other hand, the activities of CI, CIII and CIV associated to SCs assemblies were preserved by this maneuver, suggesting that the activation of other cardioprotective mechanisms besides oxidative stress contention might participate in maintaining the activity of the mitochondrial respiratory complexes in such superstructures. We conclude that both the monomeric and the SCs assembly of the respiratory chain contribute to the in vivo functionality of the mitochondria. However, although the ROS-induced damage and the consequent increased production of ROS affect the assembly of SCs, other levels of regulation as those induced by PostC, might participate in maintaining the activity of the respiratory complexes in such superstructures.

Asunto(s)

Acetilcisteína/farmacología , Antioxidantes/farmacología , Cardiotónicos/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Daño por Reperfusión Miocárdica/prevención & control , Animales , Transporte de Electrón/efectos de los fármacos , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismo , Complejo III de Transporte de Electrones/genética , Complejo III de Transporte de Electrones/metabolismo , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Regulación de la Expresión Génica , Poscondicionamiento Isquémico/métodos , Mitocondrias Cardíacas/enzimología , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/enzimología , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/patología , Miocardio/enzimología , Miocardio/patología , Fosforilación Oxidativa/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Ratas , Ratas Wistar

RESUMEN

Postoperative cognitive dysfunction (POCD) is defined by cognitive impairment determined by neuropsychological tests from before to after surgery. Several mechanisms have been proposed in this bidirectional communication between the immune system and the brain after surgery. We aimed at understanding the mechanisms underlying POCD elderly rats in an experimental tibial fracture model. Elderly male Wistar rats were subjected to tibial fracture (TF) model. Control (sham) and fracture (TF) groups were followed to determine nitrite/nitrate concentration; oxidative damage to lipids and proteins; the activity of antioxidant enzymes (superoxide dismutase-SOD and catalase-CAT), mitochondrial respiratory chain enzymes, and creatine kinase (CK); and BDNF levels in the hippocampus and prefrontal cortex (at 24 h and at seven days) and cognitive function through habituation to the open field task and novel object recognition task (only at seven days). TF group presented increased concentration of nitrite/nitrate, hippocampal lipid peroxidation at seven days, protein oxidative damage in the prefrontal cortex and hippocampus at 24 h, decreased antioxidant activity in both structures on the first postoperative day and compromised function of the mitochondrial respiratory chain complexes as well as the CK enzyme. In addition, the levels of BDNF were reduced and memory function was impaired in the TF group. In conclusion, elderly rats submitted to an experimental model of tibial fracture displayed memory impairment accompanied by an increase in oxidative stress, mitochondrial dysfunction and reduced neurotrophin level.

Asunto(s)

Disfunción Cognitiva/fisiopatología , Mitocondrias/fisiología , Estrés Oxidativo/fisiología , Factores de Edad , Animales , Antioxidantes/metabolismo , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cognición/fisiología , Trastornos del Conocimiento/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Peroxidación de Lípido , Masculino , Trastornos de la Memoria/metabolismo , Complicaciones Posoperatorias/fisiopatología , Corteza Prefrontal/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo

RESUMEN

ß-Alanine occurs naturally in the human central nervous system and performs different functions. It can act as either a neurotransmitter or a neuromodulator, depletion of taurine levels and competitive antagonist of γ-aminobutyric acid (GABA). The ß-amino acid accumulation exerts an important biological function as delay in brain development, oxidative stress and disturbances in energy metabolism, characterized as an inborn error of metabolism classified as ß-alaninemia. We evaluated the effects of the chronic administration of ß-alanine on some parameters of oxidative stress and enzymes of energy metabolism in cerebral cortex and cerebellum of 21-day-old Wistar rats. The animals received peritoneal injections of ß-alanine (300 mg/kg of body weight), and the controls received the same volume (10 µl/g of body weight) of saline solution (NaCl 0.9%), twice a day at 12-h interval, from the 7th to the 21st postpartum day. We observed that ß-amino acid was able to increase the levels of reactive oxygen species (ROS) in the two tissues; however, only in cerebral cortex total content of sulfhydryl was increased. ROS are possibly acting on antioxidant enzymes glutathione peroxidase (GPx) (cerebral cortex and cerebellum) and superoxide dismutase (SOD) (cerebellum) inhibiting their activities. We also evaluated the activities of enzymes of the phosphoryl transfer network, where we observed an increase in hexokinase and cytosolic creatine kinase (Cy-CK) activities; however, it decreased glyceraldehyde 3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) activities, in both tissues. Besides, the ß-alanine administration increased the activities of complex II, complex IV and succinate dehydrogenase (SDH). Those results suggest that the chronic administration of ß-alanine causes cellular oxidative damage, significantly changing the energy metabolism.

Asunto(s)

Cerebelo/patología , Corteza Cerebral/patología , Metabolismo Energético/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , beta-Alanina/toxicidad , Animales , Proteínas del Complejo de Cadena de Transporte de Electrón/metabolismo , Ratas Wistar , beta-Alanina/administración & dosificación

RESUMEN

The present study investigated stress oxidative parameters and activities of enzymes of the energy metabolism in various brain structures. Rats were subjected to acute and long-term administration of gold nanoparticles (GNPs) with mean diameters of 10nm and 30nm. Adult (60days old) male Wistar rats received a single intraperitoneal injection (acute administration; 70µg·kg-1) or repeated injections once daily for 28days (long-term administration; 70µg·kg-1) of saline solution or GNPs (10nm or 30nm). Twenty-four hours after administration of the final dose, the animals were killed and the cerebral structures were isolated for enzyme analysis. In this study, we observed that the thiobarbituric acid-reactive species and carbonyl protein levels were decreased after acute administration of GNPs, whereas the superoxide dismutase activity was increased after acute and long-term of GNPs. The catalase activity was affected by the administration of GNPs. Furthermore, we have not found change in the citrate synthase activity. The succinate dehydrogenase, malate dehydrogenase, complexes I, II, II-III and IV, and creatine kinase activities were altered. These results indicate that inhibition energy metabolism can be caused by oxidative stress.

Asunto(s)

Nanopartículas del Metal , Animales , Encéfalo , Metabolismo Energético , Oro , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar

RESUMEN

Abstract Currently, there is a paucity of available treatment strategies for oxidative phosphorylation disorders. Coenzyme Q10 (CoQ10) and related synthetic quinones are the only agents to date that have proven to be beneficial in the treatment of these heterogeneous disorders. The therapeutic efficacy of CoQ10 is not restricted to patients with an underlying CoQ10 deficiency and is thought to result from its ability to restore electron flow in the mitochondrial respiratory chain (MRC) as well as to increase the cellular antioxidant capacity. At present, however, there is no consensus on the appropriate dosage or therapeutic plasma level of CoQ10, and this information will be required before CoQ10 can be utilized effectively in the treatment of mitochondrial disease. The following review will outline our current knowledge on the use of CoQ10 in the treatment of MRC disorders and primary CoQ10 deficiencies.

RESUMEN

This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

Asunto(s)

Metabolismo Energético/efectos de los fármacos , Oro/toxicidad , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Ciclo del Ácido Cítrico/efectos de los fármacos , Sistemas de Liberación de Medicamentos/efectos adversos , Oro/administración & dosificación , Oro/análisis , Oro/química , Inyecciones Intraperitoneales , Riñón/química , Riñón/enzimología , Riñón/metabolismo , Hígado/química , Hígado/enzimología , Hígado/metabolismo , Masculino , Nanopartículas del Metal/administración & dosificación , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Mitocondrias/metabolismo , Miocardio/química , Miocardio/enzimología , Miocardio/metabolismo , Tamaño de la Partícula , Carbonilación Proteica/efectos de los fármacos , Ratas Wistar , Distribución Tisular , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subaguda , Toxicocinética

RESUMEN

Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent. .

Asunto(s)

Animales , Masculino , Encéfalo/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Fluvoxamina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Antidepresivos/administración & dosificación , Encéfalo/enzimología , Ciclo del Ácido Cítrico/efectos de los fármacos , Creatina Quinasa/efectos de los fármacos , Trastorno Depresivo/tratamiento farmacológico , Transporte de Electrón/efectos de los fármacos , Malato Deshidrogenasa/efectos de los fármacos , Ratas Wistar

RESUMEN

Objective: To investigate the effects of cannabidiol (CBD) on mitochondrial complex and creatine kinase (CK) activity in the rat brain using spectrophotometry. Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60 mg/kg) in an acute (single dose) or chronic (once daily for 14 consecutive days) regimen. The activities of mitochondrial complexes and CK were measured in the hippocampus, striatum, and prefrontal cortex. Results: Both acute and chronic injection of CBD increased the activity of the mitochondrial complexes (I, II, II-III, and IV) and CK in the rat brain. Conclusions: Considering that metabolism impairment is certainly involved in the pathophysiology of mood disorders, the modulation of energy metabolism (e.g., by increased mitochondrial complex and CK activity) by CBD could be an important mechanism implicated in the action of CBD. .

Asunto(s)

Animales , Masculino , Ratas , Encéfalo/efectos de los fármacos , Cannabidiol/administración & dosificación , Creatina Quinasa/metabolismo , Mitocondrias/efectos de los fármacos , Encéfalo/metabolismo , Mitocondrias/metabolismo , Ratas Wistar

RESUMEN

NDUFV1 mutations have been related to encephalopathic phenotypes due to mitochondrial energy metabolism disturbances. In this study, we report two siblings affected by a diffuse leukodystrophy, who carry the NDUFV1 c.1156C>T (p.Arg386Cys) missense mutation and a novel 42-bp deletion. Bioinformatic and molecular analysis indicated that this deletion lead to the synthesis of mRNA molecules carrying a premature stop codon, which might be degraded by the nonsense-mediated decay system. Our results add information on the molecular basis and the phenotypic features of mitochondrial disease caused by NDUFV1 mutations.

Asunto(s)

Heterocigoto , Enfermedades Mitocondriales/genética , Mutación Missense , NADH Deshidrogenasa/genética , Secuencia de Aminoácidos , Preescolar , Complejo I de Transporte de Electrón , Metabolismo Energético , Humanos , Imagen por Resonancia Magnética , Masculino , Datos de Secuencia Molecular , NADH Deshidrogenasa/química