Energy metabolism and behavioral parameters in female mice subjected to obesity and offspring deprivation stress.

This study aimed to evaluate the behavioral and energy metabolism parameters in female mice subjected to obesity and offspring deprivation (OD) stress. Eighty female Swiss mice, 40 days old, were weighed and divided into two groups: Control group (control diet, n = 40) and Obese group (high-fat diet, n = 40), for induction of the animal model of obesity, the protocol was based on the consumption of a high-fat diet and lasted 8 weeks. Subsequently, the females were subjected to pregnancy, after the birth of the offspring, were divided again into the following groups (n = 20): Control non-deprived (ND), Control + OD, Obese ND, and Obese + OD, for induction of the stress protocol by OD. After the offspring were 21 days old, weaning was performed and the dams were subjected to behavioral tests. The animals were humanely sacrificed, the brain was removed, and brain structures were isolated to assess energy metabolism. Both obesity and OD led to anhedonia in the dams. It was shown that the structures most affected by obesity and OD are the hypothalamus and hippocampus, as evidenced by the mitochondrial dysfunction found in these structures. When analyzing the groups separately, it was observed that OD led to more pronounced mitochondrial damage; however, the association of obesity with OD, as well as obesity alone, also generated damage. Thus, it is concluded that obesity and OD lead to anhedonia in animals and to mitochondrial dysfunction in the hypothalamus and hippocampus, which may lead to losses in feeding control and cognition of the dams.

Manual Therapy Reduces Pain Behavior and Oxidative Stress in a Murine Model of Complex Regional Pain Syndrome Type I.

Complex regional pain syndrome type I (CRPS-I) is a chronic painful condition. We investigated whether manual therapy (MT), in a chronic post-ischemia pain (CPIP) model, is capable of reducing pain behavior and oxidative stress. Male Swiss mice were subjected to ischemia-reperfusion (IR) to mimic CRPS-I. Animals received ankle joint mobilization 48h after the IR procedure, and response to mechanical stimuli was evaluated. For biochemical analyses, mitochondrial function as well as oxidative stress thiobarbituric acid reactive substances (TBARS), protein carbonyls, antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) levels were determined. IR induced mechanical hyperalgesia which was subsequently reduced by acute MT treatment. The concentrations of oxidative stress parameters were increased following IR with MT treatment preventing these increases in malondialdehyde (MDA) and carbonyls protein. IR diminished the levels of SOD and CAT activity and MT treatment prevented this decrease in CAT but not in SOD activity. IR also diminished mitochondrial complex activity, and MT treatment was ineffective in preventing this decrease. In conclusion, repeated sessions of MT resulted in antihyperalgesic effects mediated, at least partially, through the prevention of an increase of MDA and protein carbonyls levels and an improvement in the antioxidant defense system.

Temporal changes of oxidative stress markers in Escherichia coli K1-induced experimental meningitis in a neonatal rat model.

Despite advances in antimicrobial therapy and advanced critical care neonatal bacterial meningitis has a mortality rate of over 10% and induces neurological sequelae in 20-50% of cases. Escherichia coli K1 (E. coli K1) is the most common gram-negative organism causing neonatal meningitis and is the second most common cause behind group B streptococcus. We previously reported that an E. coli K1 experimental meningitis infection in neonatal rats resulted in habituation and aversive memory impairment and a significant increase in cytokine levels in adulthood. In this present study, we investigated the oxidative stress profile including malondialdehyde (MDA) levels, carbonyl protein formation, myeloperoxidase activity (MPO) activity, superoxide dismutase (SOD) activity and catalase (CAT) activity 6, 12, 24, 48, 72 and 96h after E. coli K1 experimental meningitis infection. In addition, sulfhydryl groups, nitrite and nitrate levels and activity of the mitochondrial respiratory chain enzymes were also measured in the frontal cortex and hippocampus of neonatal rats. The results from this study demonstrated a significant increase in MDA, protein carbonyls and MPO activity and a simultaneous decrease in SOD activity in the hippocampus of the neonatal meningitis survivors but the same was not observed in frontal cortex. In addition, we also observed a significant increase in complex IV activity in the hippocampus and frontal cortex of meningitis survivor rats. Thus, the results from this study reaffirmed the possible role of oxidative stress, nitric oxide and its related compounds in the complex pathophysiology of E. coli K1-induced bacterial meningitis.

Mitochondrial dysfunction in bipolar disorder: Evidence, pathophysiology and translational implications.

Bipolar disorder (BD) is a chronic psychiatric illness characterized by severe and biphasic changes in mood. Several pathophysiological mechanisms have been hypothesized to underpin the neurobiology of BD, including the presence of mitochondrial dysfunction. A confluence of evidence points to an underlying dysfunction of mitochondria, including decreases in mitochondrial respiration, high-energy phosphates and pH; changes in mitochondrial morphology; increases in mitochondrial DNA polymorphisms; and downregulation of nuclear mRNA molecules and proteins involved in mitochondrial respiration. Mitochondria play a pivotal role in neuronal cell survival or death as regulators of both energy metabolism and cell survival and death pathways. Thus, in this review, we discuss the genetic and physiological components of mitochondria and the evidence for mitochondrial abnormalities in BD. The final part of this review discusses mitochondria as a potential target of therapeutic interventions in BD.

Effects of Mood Stabilizers on Brain Energy Metabolism in Mice Submitted to an Animal Model of Mania Induced by Paradoxical Sleep Deprivation.

There is a body of evidence suggesting that mitochondrial dysfunction is involved in bipolar disorder (BD) pathogenesis. Studies suggest that abnormalities in circadian cycles are involved in the pathophysiology of affective disorders; paradoxical sleep deprivation (PSD) induces hyperlocomotion in mice. Thus, the present study aims to investigate the effects of lithium (Li) and valproate (VPA) in an animal model of mania induced by PSD for 96 h. PSD increased exploratory activity, and mood stabilizers prevented PSD-induced behavioral effects. PSD also induced a significant decrease in the activity of complex II-III in hippocampus and striatum; complex IV activity was decreased in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex. Additionally, VPA administration was able to prevent PSD-induced inhibition of complex II-III and IV activities in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex, whereas Li administration prevented PSD-induced inhibition only in prefrontal cortex and hippocampus. Regarding the enzymes of Krebs cycle, only citrate synthase activity was increased by PSD in prefrontal cortex. We also found a similar effect in creatine kinase, an important enzyme that acts in the buffering of ATP levels in brain; its activity was increased in prefrontal cortex, hippocampus and cerebral cortex. These results are consistent with the connection of mitochondrial dysfunction and hyperactivity in BD and suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.

Fluvoxamine alters the activity of energy metabolism enzymes in the brain

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. .

ω-3 and major depression: a review.

BACKGROUND: The World Health Organization estimates that major depression affects about 350 million people all over the world and reports this disorder as the major contributor to the global burden of diseases. Despite the well-defined symptomatology, major depression is a heterogeneous psychiatric disorder whose pathophysiology is not clearly established. Although several treatments are available, most depressed patients do not achieve the complete remission of symptoms. Factors linked to the persistence of the disorder have been investigated, particularly those related to the way of life. Moreover, it has been suggested that nutritional aspects may influence its development. Among them, a diet rich in ω-3 has been associated with a reduced risk of major depression, although its deficiency is associated with depressive disorders. METHODS: This review provides a general view about evidences of the use of ω-3 in major depression cases. RESULTS: Several studies have demonstrated beneficial effects of ω-3 in the prevention and treatment of major depression. However, not all the results have shown significant statistical benefits. CONCLUSIONS: More studies are necessary to clarify detailed mechanisms of the antidepressant effects of ω-3 and may explain the source of contradictions in results published until the moment.

Evaluation of Na+, K+-ATPase activity in the brain of young rats after acute administration of fenproporex

Objectives: Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of young rats. Methods: Young male Wistar rats received a single injection of fenproporex (6.25, 12.5, or 25 mg/kg intraperitoneally) or polysorbate 80 (control group). Two hours after the last injection, the rats were killed by decapitation and the brain was removed for evaluation of Na+, K+-ATPase activity. Results: Fenproporex decreased Na+, K+-ATPase activity in the striatum of young rats at doses of 6.25, 12.5, and 25 mg/kg and increased enzyme activity in the hypothalamus at the same doses. Na+, K+-ATPase activity was not affected in the hippocampus or prefrontal cortex. Conclusion: Fenproporex administration decreased Na+, K+-ATPase activity in the striatum even in low doses. However, in the hypothalamus, Na+, K+-ATPase activity was increased. Changes in this enzyme might be the result of the effects of fenproporex on neuronal excitability. .

Fluvoxamine alters the activity of energy metabolism enzymes in the brain.

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.

Omega-3 fatty acids alter behavioral and oxidative stress parameters in animals subjected to fenproporex administration.

Studies have consistently reported the participation of oxidative stress in bipolar disorder (BD). Evidences indicate that omega-3 (ω3) fatty acids play several important roles in brain development and functioning. Moreover, preclinical and clinical evidence suggests roles for ω3 fatty acids in BD. Considering these evidences, the present study aimed to investigate the effects of ω3 fatty acids on locomotor behavior and oxidative stress parameters (TBARS and protein carbonyl content) in brain of rats subjected to an animal model of mania induced by fenproporex. The fenproporex treatment increased locomotor behavior in saline-treated rats under reversion and prevention model, and ω3 fatty acids prevented fenproporex-related hyperactivity. Moreover, fenproporex increased protein carbonyls in the prefrontal cortex and cerebral cortex, and the administration of ω3 fatty acids reversed this effect. Lipid peroxidation products also are increased in prefrontal cortex, striatum, hippocampus and cerebral after fenproporex administration, but ω3 fatty acids reversed this damage only in the hippocampus. On the other hand, in the prevention model, fenproporex increased carbonyl content only in the cerebral cortex, and administration of ω3 fatty acids prevented this damage. Additionally, the administration of fenproporex resulted in a marked increased of TBARS in the prefrontal cortex, hippocampus, striatum and cerebral cortex, and prevent this damage in the prefrontal cortex, hippocampus and striatum. In conclusion, we are able to demonstrate that fenproporex-induced hyperlocomotion and damage through oxidative stress were prevented by ω3 fatty acids. Thus, the ω3 fatty acids may be important adjuvant therapy of bipolar disorder.

Fenproporex increases locomotor activity and alters energy metabolism, and mood stabilizers reverse these changes: a proposal for a new animal model of mania.

Fenproporex (Fen) is converted in vivo into amphetamine, which is used to induce mania-like behaviors in animals. In the present study, we intend to present a new animal model of mania. In order to prove through face, construct, and predictive validities, we evaluated behavioral parameters (locomotor activity, stereotypy activity, and fecal boli amount) and brain energy metabolism (enzymes citrate synthase; malate dehydrogenase; succinate dehydrogenase; complexes I, II, II-III, and IV of the mitochondrial respiratory chain; and creatine kinase) in rats submitted to acute and chronic administration of fenproporex, treated with lithium (Li) and valproate (VPA). The administration of Fen increased locomotor activity and decreased the activity of Krebs cycle enzymes, mitochondrial respiratory chain complexes, and creatine kinase, in most brain structures evaluated. In addition, treatment with mood stabilizers prevented and reversed this effect. Our results are consistent with the literature that demonstrates behavioral changes and mitochondrial dysfunction caused by psychostimulants. These findings suggest that chronic administration of Fen may be a potential animal model of mania.

Evaluation of Na+, K+-ATPase activity in the brain of young rats after acute administration of fenproporex.

OBJECTIVES: Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of young rats. METHODS: Young male Wistar rats received a single injection of fenproporex (6.25, 12.5, or 25 mg/kg intraperitoneally) or polysorbate 80 (control group). Two hours after the last injection, the rats were killed by decapitation and the brain was removed for evaluation of Na+, K+-ATPase activity. RESULTS: Fenproporex decreased Na+, K+-ATPase activity in the striatum of young rats at doses of 6.25, 12.5, and 25 mg/kg and increased enzyme activity in the hypothalamus at the same doses. Na+, K+-ATPase activity was not affected in the hippocampus or prefrontal cortex. CONCLUSION: Fenproporex administration decreased Na+, K+-ATPase activity in the striatum even in low doses. However, in the hypothalamus, Na+, K+-ATPase activity was increased. Changes in this enzyme might be the result of the effects of fenproporex on neuronal excitability.

Evaluation of the protective effect of Ilex paraguariensis and Camellia sinensis extracts on the prevention of oxidative damage caused by ultraviolet radiation.

We evaluated the effects green and mate teas on oxidative and DNA damages in rats exposed to ultraviolet radiation. Were utilized 70 adult male Wistar rats that received daily oral or topic green or mate tea treatment during exposed to radiation by seven days. After, animals were killed by decapitation. Thiobarbituric acid-reactive species levels, protein oxidative damage were evaluated in skin and DNA damage in blood. Our results show that the rats exposed to ultraviolet radiation presented DNA damage in blood and increased protein carbonylation and lipid peroxidation in skin. Oral and topic treatment with green tea and mate tea prevented lipid peroxidation, both treatments with mate tea also prevented DNA damage. However, only topic treatment with green tea and mate tea prevented increases in protein carbonylation. Our findings contribute to elucidate the beneficial effects of green tea and mate tea, here in demonstrated by the antioxidant and antigenotoxic properties presented by these teas.

Mitochondrial respiratory chain and creatine kinase activities following trauma brain injury in brain of mice preconditioned with N-methyl-D-aspartate.

Traumatic brain injury (TBI) induces glutamatergic excitotoxicity through N-methyl-D-aspartate (NMDA) receptors, affecting the integrity of the mitochondrial membrane. Studies have pointed to mitochondria as the master organelle in the preconditioning-triggered endogenous neuroprotective response. The present study is aimed at understanding energy metabolism in the brains of mice after preconditioning with NMDA and TBI. For this purpose, male albino CF-1 mice were pre-treated with NMDA (75 mg/kg) and subjected to brain trauma. Mitochondrial respiratory chain and creatine kinase activities were assessed at 6 or 24 h after trauma. The mice preconditioned and subjected to TBI exhibited augmented activities of complexes II and IV in the cerebral cortex and/or cerebellum. Creatine kinase activity was also augmented in the cerebral cortex after 24 h. We suggest that even though NMDA preconditioning and TBI have similar effects on enzyme activities, each manage their response via opposite mechanisms because the protective effects of preconditioning are unambiguous. In conclusion, NMDA preconditioning induces protection via an increase of enzymes in the mitochondria.

Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage.

Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats.

Energy metabolism, leptin, and biochemical parameters are altered in rats subjected to the chronic administration of olanzapine.

OBJECTIVES: Olanzapine, an atypical antipsychotic drug with affinities for dopamine, serotonin, and histamine binding sites appears to be associated with substantial weight gain and metabolic alterations. The aim of this study was to evaluate weight gain and metabolic alterations in rats treated with olanzapine on a hypercaloric diet. METHODS: We used 40 rats divided into 4 groups: Group 1, standard food and water conditions (control); Group 2, standard diet plus olanzapine; Group 3, cafeteria diet (hypercaloric); and Group 4, olanzapine plus cafeteria diet. Olanzapine was administered by gavage at a dose of 3 mg/kg for 9 weeks. RESULTS There were no significant changes in the cholesterol levels in any group. Glucose levels increased in Group 3 by the fourth week. Triglyceride levels were altered in group 2 toward the end of the experiment. Leptin levels decreased in Groups 2 and 4. Complex II activity in the muscles and liver was altered in Group 2 (muscle), and Groups 2, 3, and 4 (liver). Complex IV activity was altered only in the liver in Group 2, without significant alterations within the muscles. CONCLUSION: These results suggest that olanzapine is correlated with weight gain and the risks associated with obesity.

Energy metabolism, leptin, and biochemical parameters are altered in rats subjected to the chronic administration of olanzapine / Metabolismo calórico, leptina e parâmetros bioquímicos se alteram em ratos submetidos à administração crônica de olanzapina

OBJECTIVES: Olanzapine, an atypical antipsychotic drug with affinities for dopamine, serotonin, and histamine binding sites appears to be associated with substantial weight gain and metabolic alterations. The aim of this study was to evaluate weight gain and metabolic alterations in rats treated with olanzapine on a hypercaloric diet. METHODS: We used 40 rats divided into 4 groups: Group 1, standard food and water conditions (control); Group 2, standard diet plus olanzapine; Group 3, cafeteria diet (hypercaloric); and Group 4, olanzapine plus cafeteria diet. Olanzapine was administered by gavage at a dose of 3 mg/kg for 9 weeks. RESULTS There were no significant changes in the cholesterol levels in any group. Glucose levels increased in Group 3 by the fourth week. Triglyceride levels were altered in group 2 toward the end of the experiment. Leptin levels decreased in Groups 2 and 4. Complex II activity in the muscles and liver was altered in Group 2 (muscle), and Groups 2, 3, and 4 (liver). Complex IV activity was altered only in the liver in Group 2, without significant alterations within the muscles. CONCLUSION: These results suggest that olanzapine is correlated with weight gain and the risks associated with obesity.

OBJETIVOS: A olanzapina, uma droga antipsicótica atípica com afinidade por locais de ligação de dopamina, serotonina e histamina, parece se associar a um ganho de peso e a alterações metabólicas consideráveis. O objetivo desse estudo foi avaliar o ganho de peso e as alterações metabólicas em ratos tratados com olanzapina numa dieta hipercalórica. MÉTODOS: Usamos 40 ratos divididos em 4 grupos: Grupo 1, condições padrão de alimento e água (controle); Grupo 2, dieta padrão mais olanzapina; Grupo 3, dieta hipercalórica; e Grupo 4, olanzapina mais dieta hipercalórica. Olanzapina foi administrada por gavagem a uma dose de 3 mg/kg por 9 semanas. RESULTADOS: Não houve alterações significativas nos níveis de colesterol em qualquer um dos grupos. Os níveis de glicose aumentaram no Grupo 3 por volta da quarta semana. Os níveis de triglicerídeos estavam alterados no Grupo 2 ao final do experimento. Os níveis de leptina diminuíram nos Grupos 2 e 4. A atividade do complexo II nos músculos e no fígado se alterou no Grupo 2 (músculos) e nos Grupos 2, 3 e 4 (fígado). A atividade do complexo IV se alterou apenas no fígado no Grupo 2, sem alterações significativas nos músculos. CONCLUSÃO: Esses resultados sugerem que olanzapina se correlaciona ao ganho de peso e aos riscos associados à obesidade.

Alterations in muscular oxidative metabolism parameters in incremental treadmill exercise test in untrained rats.

The present study investigates the effects of incremental exercise test on muscular oxidative metabolism. Thirty-six 2-month-old male Wistar rats were distributed in seven groups that performed exercise at different levels: first level (control), second level (0.6 km/h), third level (0.6 and 0.8 km/h), fourth level (0.6, 0.8 and 1.0 km/h), fifth level (0.6, 0.8, 1.0 and 1.2 km/h), sixth level (0.6, 0.8, 1.0, 1.2 and 1.4 km/h), and seventh level (0.6, 0.8, 1.0, 1.2, 1.4 and 1.6 km/h). At the end of the exercise challenge, level of blood lactate (BL), glycogen content (MG), creatine kinase (CK), complexes (CI, CII, CIII, CIV), oxidative damage, succinate dehydrogenase (SDH), cytochrome c oxidase as well as antioxidant enzymes (SOD and CAT) expression were measured. The speed of 1.0 km/h increased BL level, while 1.2 km/h decreased MG and increased serum CK. Increased SDH expression was observed after intensity levels 6 and 7, and cytochrome c oxidase expression increased after levels 5, 6 and 7, in comparison with lower intensity levels, ETC enzyme activities increased when exercise was applied at intensities of 0.8 km/h (CI), 1.0 km/h (CII and CIII), and 1.2 km/h (CIV). The increase in SOD expression did not occur as observed for superoxide production, except for rats that underwent exercise at level 7, but CAT expression increased significantly in all levels, starting from level 3. Our results show interesting alterations in the muscular metabolism parameters, and suggest a differential response of muscle oxidative metabolism when intense exercise is applied at different speeds.