In vitro effect of antipsychotics on brain energy metabolism parameters in the brain of rats

2013 ◽  
Vol 25 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Giselli Scaini ◽  
Natália Rochi ◽  
Meline O. S. Morais ◽  
Débora D. Maggi ◽  
Bruna T. De-Nês ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Respiratory Chain ◽  
Antipsychotic Drugs ◽  
Reaction Medium ◽  
Respiratory Chain Complexes ◽  
Posterior Cortex ◽  
Chain Complexes ◽  
Vitro Effect ◽  
The Brain

ObjectiveTypical and atypical antipsychotic drugs have been shown to have different clinical, biochemical and behavioural profiles. It is well described that impairment of metabolism, especially in the mitochondria, leads to oxidative stress and neuronal death and has been implicated in the pathogenesis of a number of diseases in the brain. In this context, we investigated the in vitro effect of antipsychotic drugs on energy metabolism parameters in the brain of rats.MethodsClozapine (0.1, 0.5 and 1.0 mg/ml), olanzapine (0.1, 0.5 and 1.0 mg/ml) and aripiprazole (0.05, 0.15 and 0.3 mg/ml) were suspended in buffer and added to the reaction medium containing rat tissue homogenates and the respiratory chain complexes, succinate dehydrogenase and creatine kinase (CK) activities were evaluated.ResultsOur results showed that olanzapine and aripriprazole increased the activities of respiratory chain complexes. On the other hand, complex IV activity was inhibited by clozapine, olanzapine and aripriprazole. CK activity was increased by clozapine at 0.5 and 1.0 mg/ml in prefrontal cortex, cerebellum, striatum, hippocampus and posterior cortex of rats. Moreover, olanzapine and aripiprazole did not affect CK activity.ConclusionIn this context, if the hypothesis that metabolism impairment is involved in the pathophysiology of neuropsychiatric disorders is correct and these results also occur in vivo, we suggest that olanzapine may reverse a possible diminution of metabolism.

Effects of maintenance electroshock on mitochondrial respiratory chain and creatine kinase activities in the rat brain

2012 ◽  
Vol 24 (5) ◽  
pp. 275-285
Author(s):  
Gislaine Z. Réus ◽  
Roberto B. Stringari ◽  
Gislaine T. Rezin ◽  
Daiana P. Pezente ◽  
Giselli Scaini ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Energy Metabolism ◽  
Rat Brain ◽  
Respiratory Chain ◽  
Brain Area ◽  
Mitochondrial Respiratory Chain ◽  
Respiratory Chain Complexes ◽  
Chain Complexes ◽  
Male Wistar Rats ◽  
Mitochondrial Respiratory

Réus GZ, Stringari RB, Rezin GT, Pezente DP, Scaini G, Maggi DD, De-Nês BT, Streck EL, Quevedo J, Feier G. Effects of maintenance electroshock on mitochondrial respiratory chain and creatine kinase activities in the rat brain.Objective: Electroconvulsive therapy is used efficacious treatment for a variety of complicated psychiatric disorders and evidences have indicated that energy metabolism impairment may be involved in pathophysiology and treatment of mood disorders. This work was performed to determine creatine kinase and mitochondrial respiratory chain activities at different times after the maintenance electroconvulsive shock (ECS).Methods: Male Wistar rats received a protocol mimicking therapeutic of maintenance or simulated ECS (sham) and were subsequently sacrificed immediately after, 48 h and 7 days after the last maintenance ECS. We measured creatine kinase and mitochondrial respiratory chain activities in the prefrontal cortex, hippocampus, cortex, cerebellum and striatum.Results: Our results showed that maintenance ECS alter respiratory chain complexes and creatine kinase activities in the rat brain, but these effects were related to brain area and time after the ECS, in which the animal were killed.Conclusion: Finally, these findings further support the hypothesis that alteration on the energy metabolism could be involved in the therapeutic or adverse effects of ECS.

Brain energy metabolism is increased by chronic administration of bupropion

2012 ◽  
Vol 24 (2) ◽  
pp. 115-121 ◽  
Author(s):  
Gabriela K. Ferreira ◽  
Gislaine T. Rezin ◽  
Mariane R. Cardoso ◽  
Cinara L. Gonçalves ◽  
Lislaine S. Borges ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Malate Dehydrogenase ◽  
Respiratory Chain ◽  
Citrate Synthase ◽  
Chronic Administration ◽  
Mitochondrial Respiratory Chain ◽  
Brain Energy Metabolism ◽  
Respiratory Chain Complexes ◽  
Chain Complexes ◽  
Brain Energy

Objectives: Based on the hypothesis that energy impairment may be involved in the pathophysiology of depression, we evaluated the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase (SDH), mitochondrial respiratory chain complexes I, II, II-III, IV and creatine kinase (CK) in the brain of rats submitted to chronic administration of bupropion.Methods: Animals received daily administration of bupropion dissolved in saline (10 mg/kg, intraperitoneal) at 1.0 ml/kg body weight. The rats received injections once a day for 14 days; control rats received an equivalent volume of saline. Twelve hours after the last administration, the rats were killed by decapitation and brain was rapidly removed and kept on an ice plate. The activities of the enzymes were measured in different brain areas.Results: We observed that the activities of citrate synthase and malate dehydrogenase, mithocondrial respiratory chain complexes I, II-III and IV and CK were not altered after chronic administration of bupropion. However, SDH activity was increased in the prefrontal cortex and cerebellum. In the hippocampus, cerebellum and striatum the activity of complex II was increased after chronic administration of bupropion.Conclusions: Our results demonstrated that bupropion increased some enzymes of brain energy metabolism. These findings are in accordance with other studies which showed that some antidepressants may improve energy metabolism. The present results reinforce the hypothesis that antidepressants modulate brain energy metabolism.

scholarly journals The Novel Arylamidine T-2307 Selectively Disrupts Yeast Mitochondrial Function by Inhibiting Respiratory Chain Complexes

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Kohei Yamashita ◽  
Taiga Miyazaki ◽  
Yoshiko Fukuda ◽  
Junichi Mitsuyama ◽  
Tomomi Saijo ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Mitochondrial Function ◽  
Yeast Cells ◽  
Dependent Manner ◽  
The Novel ◽  
Respiratory Chain Complexes ◽  
Content Type ◽  
Chain Complexes

ABSTRACT The novel arylamidine T-2307 exhibits broad-spectrum in vitro and in vivo antifungal activities against clinically significant pathogens. Previous studies have shown that T-2307 accumulates in yeast cells via a specific polyamine transporter and disrupts yeast mitochondrial membrane potential. Further, it has little effect on rat liver mitochondrial function. The mechanism by which T-2307 disrupts yeast mitochondrial function is poorly understood, and its elucidation may provide important information for developing novel antifungal agents. This study aimed to determine how T-2307 promotes yeast mitochondrial dysfunction and to investigate the selectivity of this mechanism between fungi and mammals. T-2307 inhibited the respiration of yeast whole cells and isolated yeast mitochondria in a dose-dependent manner. The similarity of the effects of T-2307 and respiratory chain inhibitors on mitochondrial respiration prompted us to investigate the effect of T-2307 on mitochondrial respiratory chain complexes. T-2307 particularly inhibited respiratory chain complexes III and IV not only in Saccharomyces cerevisiae but also in Candida albicans, indicating that T-2307 acts against pathogenic fungi in a manner similar to that of yeast. Conversely, T-2307 showed little effect on bovine respiratory chain complexes. Additionally, we demonstrated that the inhibition of respiratory chain complexes by T-2307 resulted in a decrease in the intracellular ATP levels in yeast cells. These results indicate that inhibition of respiratory chain complexes III and IV is a key factor for selective disruption of yeast mitochondrial function and antifungal activity.

scholarly journals Evaluation of theIn VivoandIn VitroEffects of Fructose on Respiratory Chain Complexes in Tissues of Young Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ernesto António Macongonde ◽  
Thais Ceresér Vilela ◽  
Giselli Scaini ◽  
Cinara Ludvig Gonçalves ◽  
Bruna Klippel Ferreira ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cerebral Cortex ◽  
Respiratory Chain ◽  
Biological Fluids ◽  
Control Group ◽  
Respiratory Chain Complexes ◽  
Mitochondrial Energy Metabolism ◽  
Chain Complexes ◽  
Aldolase B

Hereditary fructose intolerance (HFI) is an autosomal-recessive disorder characterized by fructose and fructose-1-phosphate accumulation in tissues and biological fluids of patients. This disease results from a deficiency of aldolase B, which metabolizes fructose in the liver, kidney, and small intestine. We here investigated the effect of acute fructose administration on the activities of mitochondrial respiratory chain complexes, succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) in cerebral cortex, liver, kidney, and skeletal muscle of male 30-day-old Wistar rats. The rats received subcutaneous injection of sodium chloride (0.9%; control group) or fructose solution (5 μmol/g; treated group). One hour later, the animals were euthanized and the cerebral cortex, liver, kidney, and skeletal muscle were isolated and homogenized for the investigations. Acute fructose administration increased complex I-III activity in liver. On the other hand, decreased complexes II and II-III activities in skeletal muscle and MDH in kidney were found. Interestingly, none of these parameters were affectedin vitro. Our present data indicate that fructose administration elicits impairment of mitochondrial energy metabolism, which may contribute to the pathogenesis of the HFI patients.

scholarly journals In Vitro Mitochondrial Toxicity of Metacavir, a New Nucleoside Reverse Transcriptase Inhibitor for Treatment of Hepatitis B Virus

2010 ◽  
Vol 54 (11) ◽  
pp. 4887-4892 ◽  
Author(s):  
Pinghu Zhang ◽  
Luyong Zhang ◽  
Zhenzhou Jiang ◽  
Tao Wang ◽  
Hongkui Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Respiratory Chain ◽  
Enzyme Activities ◽  
Mitochondrial Toxicity ◽  
Respiratory Chain Complexes ◽  
Chain Complexes ◽  
B Virus

ABSTRACT Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Metacavir (PNA) is a novel synthetic nucleoside analog for oral administration with potent and specific antiviral activity against hepatitis B virus (HBV). We assessed the potential for mitochondrial toxicity of PNA in long-term cultures of HepG2 hepatoma cells by measuring mitochondrial function (through lactate secretion), levels of mitochondrial DNA (mtDNA), and the activities of respiratory-chain complexes I to IV. Exposure of HepG2 cells to PNA at concentrations up to 50 μM for 15 days resulted in no deleterious effect on cell proliferation, levels of lactate or mtDNA, or enzyme activities of respiratory-chain complexes I to IV. In contrast, dideoxycytosine at 10 μM and zidovudine at 50 μM have significant effects on cell proliferation, levels of lactate and mtDNA, and enzyme activities of respiratory-chain complexes I to IV. However, PNA at a supratherapeutic concentration of 250 μM could result in significant alterations in the levels of mtDNA and the activities of respiratory-chain complex enzymes, revealing evidence of the potential mitochondrial toxicity of PNA. In summary, these in vitro results indicate that the potential for PNA to interfere with mitochondrial functions is low.

Enzymatic activities linked to cardiac energy metabolism of Trypanosoma evansi-infected rats and their possible functional correlations to disease pathogenesis

Parasitology ◽  
2015 ◽  
Vol 142 (9) ◽  
pp. 1163-1170 ◽  
Author(s):  
MATHEUS D. BALDISSERA ◽  
VIRGINIA C. RECH ◽  
MATEUS GRINGS ◽  
LUCAS T. GRESSLER ◽  
RODRIGO A. VAUCHER ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cardiac Function ◽  
Respiratory Chain ◽  
Heart Function ◽  
Chain Complex ◽  
Trypanosoma Evansi ◽  
Enzymatic Activities ◽  
Phosphoryl Transfer ◽  
Respiratory Chain Complexes ◽  
Chain Complexes

SUMMARYThe 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.

Sign in / Sign up

Export Citation Format

Share Document