Nutritional strategies cause memory damage and alter biochemical parameters without causing neuroinflammation.

Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48 h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.

Therapeutic effects of the gold nanoparticle on obesity-triggered neuroinflammation: a review.

Introduction: Obesity is considered a chronic non-communicable disease characterised by excess body fat. In recent years the prevalence of obesity has grown a lot. Individuals with obesity store the excess of nutrients consumed in the form of fat in adipose tissue, and generate an imbalance of this tissue, where there is the secretion of adipocytokines, which contributes to a peripheral and central inflammatory picture, reaching the central nervous system (CNS), generating neuroinflammation. There is still no effective and safe therapy for the treatment of obesity, many of the drugs marketed has serious side effects. Therefore, there is a search for therapies aimed mainly at reducing inflammation.Objective: In this work the possibility of using a new therapeutic option for obesity will be explored, using nanotechnology. Nanotechnology has gained prominence in recent years for being a promising technology for treatment and as a molecule-in-the-light in inflammatory diseases. Gold nanoparticles (GNP) stand out among nanomaterials because they demonstrate anti-inflammatory characteristics by various pathways, and have been widely used in the treatment of inflammatory diseases, including in the CNS, demonstrating excellent results.Result: Thus, the use of GNP for the treatment of obesity is promising due to the inflammatory state of obesity, thus acting as anti-inflammatory at the peripheral and central levels.

Neuroinflammation and neuroprogression produced by oxidative stress in euthymic bipolar patients with different onset disease times.

Bipolar disorder (BD) is associated with systemic toxicity, represented by changes in biomarkers associated with mood episodes, leading to neurological damage, which may reflect cognitive functions and functionality and the progression of the disease. We aimed to analyze the effect of four biomarkers, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and thiobarbituric acid reactive substances (TBA-RS), related to oxidative stress in BD and to correlate them with cognitive functions and functionality. We studied 50 bipolar types I/II patients in the euthymic phase, which was divided into two subgroups with 25 patients each (≤ 3 years and ≥ 10 years of diagnosis, from the first episode of mania) and 25 control patients. To analyze frontal cognitive functions and functionality, we used the Frontal Assessment Battery (FAB) and Functioning Assessment Short Test (FAST) tests, respectively. The scores of the FAST and FAB tests showed an increase and decrease respectively, in both bipolar groups, when compared to the control group, demonstrating impairment in cognitive functions and functionality since the disease onset. In addition, changes occurred in all six domains of the FAST test, and in four domains of the FAB test in bipolar patients when compared to the control group. Regarding oxidative stress biomarkers, we did not find changes in SOD and GSH-Px activities; however, a significant increase in CAT activity and lipid peroxidation was observed in both groups, although the patients were euthymic and medicated. These results allow us to raise the hypothesis that since the beginning of the disease, the euthymic bipolar patient has presented a level of oxidative stress, which gets worse with the evolution of the disease, promoting impairments in the frontal cognitive functions and functionality gradually.

Effects of Ethanolic Extract of Cynara cardunculus (Artichoke) Leaves on Neuroinflammatory and Neurochemical Parameters in a Diet-Induced Mice Obesity Model.

This study aimed to evaluate the effect of Cynara cardunculus leaf ethanol extract on inflammatory and oxidative stress parameters in the hypothalamus, prefrontal cortex, hippocampus, striatum, cerebral cortex and liver of high-fat diet-induced obese mice. Food intake, body weight, visceral fat weight, and liver weight were also evaluated. Male Swiss mice were divided into control (low-fat purified diet) and obese (high-fat purified diet) groups. After 6 weeks, mice were divided into control + saline, control + C. cardunculus leaf ethanol extract, obese + saline, obese + C. cardunculus leaf ethanol extract. Cynara cardunculus leaf ethanol extract (1600 mg/kg/day) or saline was administered orally for 4 weeks. Brain structures (hypothalamus, hippocampus, prefrontal cortex, striatum and cerebral cortex) and liver were removed. Treatment with C. cardunculus leaf ethanol extract did not affect body weight but did reduce visceral fat. Obesity can cause inflammation and oxidative stress and increase the activity of antioxidant enzymes in brain structures. Treatment with ethanolic extract of C. cardunculus leaves partially reversed the changes in inflammatory damage parameters and oxidative damage parameters and attenuated changes in the antioxidant defense. The C. cardunculus leaf ethanol extract benefited from the brains of obese animals by partially reversing the changes caused by the consumption of a high-fat diet and the consequent obesity. These results corroborate those of studies indicating that the C. cardunculus leaf ethanol extract can contribute to the treatment of obesity.

Treatment with isolated gold nanoparticles reverses brain damage caused by obesity.

In this study, we performed two experiments. In the first experiment, the objective was to link gold nanoparticles (GNPs) with sodium diclofenac and/or soy lecithin and to determine their concentration in tissues and their toxicity using hepatic and renal analyzes in mice to evaluate their safety as therapeutic agents in the subsequent treatment of obesity. In the second experiment, we evaluated the effect of GNPs on inflammatory and biochemical parameters in obese mice. In the first experiment, we synthesized and characterized 18 nm GNPs that were administered intraperitoneally in isolation or in association with sodium diclofenac and/or soy lecithin in mice once daily for 1 or 14 days. Twenty-four hours after the single or final administration, the animals were euthanized, following which the tissues were removed for evaluating the concentration of GNPs, and serum samples were collected for hepatic and renal analysis. Hepatic damage was evaluated based on the levels of alanine aminotransferase (ALT), whereas renal damage was evaluated based on creatinine levels. A higher concentration of GNPs was detected in the tissues upon administration for 14 days, and there were no signs of hepatic or renal damage. In the second experiment, the mice were used as animal models of obesity and were fed a high-fat diet (obese group) and control diet (control group). After eight weeks of high-fat diet administration, the mice were treated with saline or with GNPs (average size of 18 nm) at a concentration of 70 mg/L (70 mg/kg) once a day, for 14 days, for 10 weeks. Body weight and food intake were measured frequently. After the experiment ended, the animals were euthanized, serum samples were collected for glucose and lipid profile analysis, the mesenteric fat content was weighed, and the brains were removed for inflammatory and biochemical analysis. In obese mice, although GNP administration did not reduce body and mesenteric fat weight, it reduced food intake. The glucose levels were reversed upon administration of GNPs, whereas the lipid profile was not altered in any of the groups. GNPs exerted a beneficial effect on inflammation and oxidative stress parameters, without reverting mitochondrial dysfunction. Our results indicate that the intraperitoneal administration of GNPs for 14 days results in a significant GNP concentration in adipose tissues, which could be an interesting finding for the treatment of inflammation associated with obesity. Based on the efficacy of GNPs in reducing dietary intake, inflammation, and oxidative stress, they can be considered potential alternative agents for the treatment of obesity.

Effects of photobiomodulation on mitochondria of brain, muscle, and C6 astroglioma cells.

The purpose of this study was to investigate the effect of different doses of photobiomodulation (PBM) on mitochondrial respiratory complexes and oxidative cellular energy metabolic enzymes in the mitochondria of brain, muscle, and C6 glioma cells after different time intervals. C6 cells were irradiated with an AlGaInP laser at 10, 30, and 60 J/cm2 for 20, 60, and 120 s, respectively. After irradiation, the cells were maintained in serum-free Dulbecco's Modified Eagle's medium for 24 h, and biochemical measurements were made subsequently. Mitochondrial suspensions from adult rat skeletal muscles/brains were irradiated with an AlGaInP laser at the abovementioned doses. In one group, the reaction was stopped 5 min after irradiation and in the other 60 min after irradiation. Both the C6 cells that received the doses of 10 and 30 J/cm² showed increased complex I activity; the cells that were irradiated at 30 J/cm2 showed increased hexokinase activity. Five minutes after the introduction of PBM of the muscle mitochondria (at 30 and 60 J/cm2), the activity of complex I increased, while the activity of complex IV increased only at 60 J/cm2. One hour after the laser session, complex II activity increased in the cells treated with 10 and 60 J/cm²; however, complex IV activity showed an increase in all PBM groups. In brain mitochondria, 5 min after irradiation only the activity of complex IV increased in all PBM groups. One hour after the laser session, complex II activity increased at 60 J/cm2, and complex IV activity increased for all PBM groups when compared to controls. PBM could increase the activity of respiratory chain complexes in an apparently dose- and time-dependent manner.

Diet-induced obesity causes hypothalamic neurochemistry alterations in Swiss mice.

The aim of this study was to assess inflammatory parameters, oxidative stress and energy metabolism in the hypothalamus of diet-induced obese mice. Male Swiss mice were divided into two study groups: control group and obese group. The animals in the control group were fed a diet with adequate amounts of macronutrients (normal-lipid diet), whereas the animals in the obese group were fed a high-fat diet to induce obesity. Obesity induction lasted 10 weeks, at the end of this period the disease model was validated in animals. The animals in the obese group had higher calorie consumption, higher body weight and higher weight of mesenteric fat compared to control group. Obesity showed an increase in levels of interleukin 1ß and decreased levels of interleukin 10 in the hypothalamus. Furthermore, increased lipid peroxidation and protein carbonylation, and decreased level of glutathione in the hypothalamus of obese animals. However, there was no statistically significant difference in the activity of antioxidant enzymes, superoxide dismutase and catalase. The obese group had lower activity of complex I, II and IV of the mitochondrial respiratory chain, as well as lower activity of creatine kinase in the hypothalamus as compared to the control group. Thus, the results from this study showed changes in inflammatory markers, and dysregulation of metabolic enzymes in the pathophysiology of obesity.

The impact of obesity on neurodegenerative diseases.

Neurodegenerative diseases are a growing health concern. The increasing incidences of these disorders have a great impact on the patients' quality of life. Although the mechanisms of neurodegenerative diseases are still far from being clarified, several studies look for new discoveries about their pathophysiology and prevention. Furthermore, evidence has shown a strong correlation between obesity and the development of Alzheimer's disease (AD) and Parkinson's disease (PD). Metabolic changes caused by overweight are related to damage to the central nervous system (CNS), which can lead to neural death, either by apoptosis or cell necrosis, as well as alter the synaptic plasticity of the neuron. This review aims to show the association between neurodegenerative diseases, focusing on AD and PD, and metabolic alterations.

Safety protocol for the gold nanoparticles administration in rats.

Gold nanoparticles (GNPs) have antioxidant and anti-inflammatory effects. However, toxicity is still a concern; therefore, it is critical to study both the therapeutic and toxic properties of GNPs. In this study, we evaluated the effects of the intraperitoneal administration of GNPs (20nm, at a concentration of 2.5mg/L for 21days) every 24 or 48h on oxidative stress, antioxidant status, and electron chain transport (ETC) in the brain. Liver histology and blood marker analyses were conducted to establish a time routine of GNP administration. The concentrations of GNP in the brain and liver were similar. Hepatic and serum levels of cholesterol, triglycerides, and transaminases were not altered after the administration of GNP every 24 or 48h. The superoxide and nitric oxide levels were unchanged after administration of GNP. Dichlorodihydrofluorescein (DCFH) levels decreased after the administration of GNP every 48h compared with that in the saline group. Sulfhydryl and carbonyl levels, as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione (GSH) activities were not altered in the brain after administration of GNP in the two time periods studied. The GNP 48h group showed increased brain ETC activity. Compared to that in the saline group, the GNP 24h group showed marked parenchyma changes with cell necrosis and leukocyte infiltration. We therefore suggest that a concentration of 2.5mg/L of GNP administered every 48h has potential therapeutic benefits without toxicity.

Single dose and repeated administrations of liraglutide alter energy metabolism in the brains of young and adult rats.

Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue that was recently approved to treat obesity in some countries. Considering that liraglutide effects on brain energy metabolism are little known, we evaluated the effects of liraglutide on the energy metabolism. Animals received a single or daily injection of saline or liraglutide during 7 days (25, 50, 100, or 300 µg/kg i.p.). Twenty-four hours after the single or last injection, the rats were euthanized and the hypothalamus, prefrontal cortex, cerebellum, hippocampus, striatum, and posterior cortex were isolated. Our results demonstrated that a single dose of liraglutide in young rats increased the activity of complexes and inhibited creatine kinase activity. Repeated administrations of liraglutide in young rats reduced the activity of complexes and activated creatine kinase activity. In adult rats, a single dose of liraglutide reduced the activity of complex I and creatine kinase and increased the activity of complexes II and IV. Repeated administrations of liraglutide in adult rats increased the activity of complexes I and IV and reduced the activity of complex II and creatine kinase. We concluded that liraglutide may interfere in energy metabolism, because analysis of different times of administrations, concentrations, and level of brain development leads to divergent results.

Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

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.

Effects of acute administration of mazindol on brain energy metabolism in adult mice.

OBJECTIVES: Mazindol is a sympathomimetic amine, widely used as an anorectic agent in the treatment of obesity. This drug causes psychostimulant effects because of its pharmacological profile similar to amphetamine, acting like a monoamine reuptake inhibitor. However, the mechanisms underlying the action of mazindol are still not clearly understood. METHODS: Swiss mice received a single acute administration of mazindol (0.25, 1.25 and 2.5 mg/kg, ip) or saline. After 2 h, the animals were killed by decapitation; the brain was removed and used for the evaluation of activities of mitochondrial respiratory chain complexes, Krebs cycle enzymes and creatine kinase. RESULTS: Acute administration of mazindol decreased complex I activity only in the hippocampus. Complex IV activity was increased in the cerebellum (2.5 mg/kg) and cerebral cortex (0.25 mg/kg). Citrate synthase activity was increased in the cerebellum (1.25 mg/kg) and cerebral cortex (1.25 mg/kg), and creatine kinase activity was increased in the cerebellum (1.25 mg/kg). CONCLUSION: We suggest that the inhibition of complex I in the hippocampus only and activation of complex IV, citrate synthase and creatine kinase occurs because of a stimulus effect of mazindol in the central nervous system, which causes a direct impairment on energy metabolism.

Inibição da atividade da citrato sintase cerebral em um modelo animal de sepse / Inhibition of brain citrate synthase activity in an animal model of sepsis

OBJETIVO: Um amplo corpo de evidência oriundo de estudos experimentais indica que a sepse se associa com um aumento da produção de espécies de oxigênio reativo, depleção de antioxidantes, e acúmulo de marcadores de estresse oxidativo. Além disto, a disfunção mitocondrial foi implicada na patogênese da síndrome de disfunção de múltiplos órgãos. A citrato sintase é uma enzima que se localiza no interior das células, na matriz mitocondrial, sendo uma etapa importante do ciclo de Krebs; esta enzima foi utilizada como um marcador enzimático quantitativo da presença de mitocôndrias intactas. Assim, investigamos a atividade da citrato sintase no cérebro de ratos submetidos ao modelo sepse com de ligadura e punção do ceco. MÉTODOS: Em diferentes horários (3, 6, 12, 24 e 48 horas) após cirurgia de ligadura e punção do ceco, seis ratos foram sacrificados por decapitação, sendo seus cérebros removidos e dissecados o hipocampo, estriato, cerebelo, córtex cerebral e córtex pré-frontal, e utilizados para determinação da atividade de citrato sintase. RESULTADOS: Verificamos que a atividade de citrato sintase no córtex pré-frontal estava inibida após 12, 24 e 48 horas da ligadura e punção do ceco. No córtex cerebral, esta atividade estava inibida após 3, 12, 24 e 48 horas da ligadura e punção do ceco. Por outro lado a citrato sintase não foi afetada no hipocampo, estriato e cerebelo até 48 horas após a ligadura e punção do ceco. CONCLUSÃO: Considerando-se que é bem descrito o comprometimento da energia decorrente da disfunção mitocondrial na sepse, e que o estresse oxidativo desempenha um papel essencial no desenvolvimento da sepse, acreditamos que o comprometimento da energia pode também estar evolvido nestes processos. Se a inibição da citrato sintase também ocorre em um modelo de sepse, é tentador especular que a redução do metabolismo cerebral pode provavelmente estar relacionada com a fisiopatologia desta doença.

OBJECTIVE: An extensive body of evidence from experimental studies indicates that sepsis is associated with increased reactive oxygen species production, depletion of antioxidants, and accumulation of markers of oxidative stress. Moreover, mitochondrial dysfunction has been implicated in the pathogenesis of multiple organ dysfunction syndrome (MODS). Citrate synthase is an enzyme localized in the mitochondrial matrix and an important component of the Krebs cycle; consequently, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase activity in the brains of rats submitted to a cecal ligation puncture model of sepsis. METHODS: At several times points (3, 6, 12, 24 and 48 hours) after the cecal ligation puncture operation, six rats were killed by decapitation. Their brains were removed, and the hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex were dissected and used to determine citrate synthase activity. RESULTS: We found that citrate synthase activity in the prefrontal cortex was inhibited 12, 24 and 48 hours after cecal ligation puncture. In the cerebral cortex, citrate synthase activity was inhibited 3, 12, 24 and 48 hours after cecal ligation puncture. Citrate synthase was not affected in the hippocampus, striatum or cerebellum up to 48 hours after cecal ligation puncture. CONCLUSION: Considering that energy impairment due to mitochondrial dysfunction in sepsis has been well described and that oxidative stress plays a crucial role in sepsis development, we believe that energy impairment may also be involved in these processes. If citrate synthase inhibition also occurs in a sepsis model, it is tempting to speculate that a reduction in brain metabolism may be related to the pathophysiology of this disease.

Inhibition of brain citrate synthase activity in an animal model of sepsis. / Inibição da atividade da citrato sintase cerebral em um modelo animal de sepse.

OBJECTIVE: An extensive body of evidence from experimental studies indicates that sepsis is associated with increased reactive oxygen species production, depletion of antioxidants, and accumulation of markers of oxidative stress. Moreover, mitochondrial dysfunction has been implicated in the pathogenesis of multiple organ dysfunction syndrome (MODS). Citrate synthase is an enzyme localized in the mitochondrial matrix and an important component of the Krebs cycle; consequently, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase activity in the brains of rats submitted to a cecal ligation puncture model of sepsis. METHODS: At several times points (3, 6, 12, 24 and 48 hours) after the cecal ligation puncture operation, six rats were killed by decapitation. Their brains were removed, and the hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex were dissected and used to determine citrate synthase activity. RESULTS: We found that citrate synthase activity in the prefrontal cortex was inhibited 12, 24 and 48 hours after cecal ligation puncture. In the cerebral cortex, citrate synthase activity was inhibited 3, 12, 24 and 48 hours after cecal ligation puncture. Citrate synthase was not affected in the hippocampus, striatum or cerebellum up to 48 hours after cecal ligation puncture. CONCLUSION: Considering that energy impairment due to mitochondrial dysfunction in sepsis has been well described and that oxidative stress plays a crucial role in sepsis development, we believe that energy impairment may also be involved in these processes. If citrate synthase inhibition also occurs in a sepsis model, it is tempting to speculate that a reduction in brain metabolism may be related to the pathophysiology of this disease.

Mecanismos básicos da encefalopatia urêmica: [revisão] / Mechanisms underlying uremic encephalopathy: [review]

Em pacientes com insuficiência renal, a encefalopatia é um problema comum que pode ser provocado pela uremia, deficiência de tiamina, diálise, rejeição de transplante, hipertensão, desequilíbrios hidroeletrolíticos e toxicidades medicamentosas. Em geral a encefalopatia se apresenta como um complexo de sintomas que progride de uma leve obnubilação sensitiva até delírio e coma. Esta revisão discute questões importantes com relação aos mecanismos de base da fisiopatologia da encefalopatia urêmica. A fisiopatologia da encefalopatia urêmica é até hoje incerta, mas postula-se o envolvimento de diversos fatores; trata-se de um processo complexo e provavelmente multifatorial. Distúrbios hormonais, estresse oxidativo, acúmulo de metabólitos, desequilíbrio entre os neurotransmissores excitatórios e inibitórios, e distúrbio do metabolismo intermediário foram identificados como fatores contribuintes. A despeito do progresso continuado na terapêutica, a maior parte das complicações neurológicas da uremia, como a encefalopatia urêmica, não respondem plenamente à diálise e muitas delas são desencadeadas ou agravadas pela diálise ou transplante renal. Por outro lado, estudos prévios demonstraram que a terapia antioxidante pode ser utilizada como terapia coadjuvante para o tratamento destas complicações neurológicas.

In patients with renal failure, encephalopathy is a common problem that may be caused by uremia, thiamine deficiency, dialysis, transplant rejection, hypertension, fluid and electrolyte disturbances or drug toxicity. In general, encephalopathy presents with a symptom complex progressing from mild sensorial clouding to delirium and coma. This review discusses important issues regarding the mechanisms underlying the pathophysiology of uremic encephalopathy. The pathophysiology of uremic encephalopathy up to now is uncertain, but several factors have been postulated to be involved; it is a complex and probably multifactorial process. Hormonal disturbances, oxidative stress, accumulation of metabolites, imbalance in excitatory and inhibitory neurotransmitters, and disturbance of the intermediary metabolism have been identified as contributing factors. Despite continuous therapeutic progress, most neurological complications of uremia, like uremic encephalopathy, fail to fully respond to dialysis and many are elicited or aggravated by dialysis or renal transplantation. On the other hand, previous studies showed that antioxidant therapy could be used as an adjuvant therapy for the treatment of these neurological complications.

Mechanisms underlying uremic encephalopathy. / Mecanismos básicos da encefalopatia urêmica.

In patients with renal failure, encephalopathy is a common problem that may be caused by uremia, thiamine deficiency, dialysis, transplant rejection, hypertension, fluid and electrolyte disturbances or drug toxicity. In general, encephalopathy presents with a symptom complex progressing from mild sensorial clouding to delirium and coma. This review discusses important issues regarding the mechanisms underlying the pathophysiology of uremic encephalopathy. The pathophysiology of uremic encephalopathy up to now is uncertain, but several factors have been postulated to be involved; it is a complex and probably multifactorial process. Hormonal disturbances, oxidative stress, accumulation of metabolites, imbalance in excitatory and inhibitory neurotransmitters, and disturbance of the intermediary metabolism have been identified as contributing factors. Despite continuous therapeutic progress, most neurological complications of uremia, like uremic encephalopathy, fail to fully respond to dialysis and many are elicited or aggravated by dialysis or renal transplantation. On the other hand, previous studies showed that antioxidant therapy could be used as an adjuvant therapy for the treatment of these neurological complications.