Ascorbic acid supplementation attenuates schizophrenia-like symptoms in an animal model induced by ketamine.

Schizophrenia is a chronic neuropsychiatric disorder with a poorly understood pathophysiology. The theories about the disorder are mainly about dysregulation in one or more systems of neurotransmitters, and the progression triggers the presence of inflammatory markers indicates the possibility that the disorder is initially an inflammatory disease. The objective was to evaluate the ascorbic acid supplementation in an animal model of schizophrenia, on behavioral parameters, and cytokines involved in inflammation IL-1ß, IL-10. Wistar rats with 60 days of age were used which were supplemented with ascorbic acid at 0.1, 1, and 10 mg/kg or saline for 14 days via orogastric gavage. Subsequently, four groups were given ketamine (25 mg/kg) and four groups received intraperitoneal saline from the 9th-15th day of the experiment. After 30 min of the last administration of ketamine/saline, and behavioral test, rats were killed by guillotine decapitation and the brain structures were carefully dissected for biochemical analysis. Results showed that ascorbic acid supplementation prevented motor sensory loss but nor alter other parameters evaluated. We concluded that ascorbic acid may be used as a therapeutic adjuvant in schizophrenia and may help to improve the schizophrenic patient's life quality.

Evidence of hippocampal astrogliosis and antioxidant imbalance after L-tyrosine chronic administration in rats.

Tyrosinemia type II is a genetic disorder characterized by elevated blood levels of the amino acid tyrosine caused by the deficiency of tyrosine aminotransferase enzyme, resulting in neurologic and developmental difficulties in the patients. Although neurological sequelae are common in Tyrosinemia type II patients, the mechanisms involved are still poorly understood. The oxidative stress appears to be, at least in part, responsible for neurological complication in this inborn error metabolism. We observed that an acute injection of tyrosine in rats caused a massive oxidative stress in different brain structures. The glutathione system and superoxide dismutase enzyme are relevant antioxidant strategies of the cells and tissues, including in the brain. Other important point is the strong relation between oxidative damage and inflammatory events. Herein, we investigated the effects of chronic administration of tyrosine in the hippocampus of young rats, with emphasis in the activity of GSH related enzymes and superoxide dismutase enzyme, and the astrocytosis. We observed that rats exposed to high levels of tyrosine presented an increased content of tyrosine, which was associated with an increment in the activity of glutathione peroxidase and glutathione reductase as well as with a diminished activity of superoxide dismutase. This antioxidant imbalance was accompanied by enhanced glial fibrillary acidic protein immunoreactivity, a marker of astrocytes, in the brain area studied. In conclusion, hippocampus astrogliosis is also a characteristic of brain alteration in Tyrosinemia. In addition, the chronic exposition to high levels of tyrosine is associated with an alteration in the activity of fundamental antioxidant enzymes.

Effects of omega-3 fatty acids supplementation on inflammatory parameters after chronic administration of L-tyrosine.

Tyrosinemia type II is an autosomal recessive inborn error of metabolism caused by hepatic cytosolic tyrosine aminotransferase deficiency. Importantly, this disease is associated with neurological and developmental abnormalities in many patients. Considering that the mechanisms underlying neurological dysfunction in hypertyrosinemic patients are poorly understood, in the present work we investigated the levels of cytokines - tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6 and IL-10 - in cerebellum, hippocampus, striatum of young rats exposed to chronic administration of L-tyrosine. In addition, we also investigated the impact of the supplementation with Omega-3 fatty acids (n-3 PUFA) on the rodent model of Tyrosinemia. Notably, previous study demonstrated an association between L-tyrosine toxicity and n-3 PUFA deficiency. Our results showed a significant increase in the levels of pro- and anti-inflammatory cytokines in brain structures when animals were administered with L-tyrosine. Cerebral cortex and striatum seem to be more susceptible to the inflammation induced by tyrosine toxicity. Importantly, n-3 PUFA supplementation attenuated the alterations on cytokines levels induced by tyrosine exposure in brain regions of infant rats. In conclusion, the brain inflammation is also an important process related to tyrosine neurotoxicity observed in the experimental model of Tyrosinemia. Finally, n-3 PUFA supplementation could be considered as a potential neuroprotective adjunctive therapy for Tyrosinemias, especially type II.

Mitochondria and the Brain: Bioenergetics and Beyond.

The view of mitochondria acting solely as a powerhouse of the cell is no longer accurate. Besides cell bioenergetics, primary targets of mitochondrial studies include their interplay with essential processes within the cell, including redox and calcium homeostasis, and apoptosis. Recent studies evidence the dynamic behavior of mitochondria, continuously moving, fusing, and dividing, and the interaction of these events with cellular degeneration and plasticity in neural cells. Our review summarizes novel data and technologies that are developed and applied to the identification and clarification of the mitochondrial role in neural plasticity using both cultured cells and in vivo approaches. The complete understanding and modulation of such mechanisms may represent a novel and promising therapeutic approach for treatment of diseases affecting central and peripheral nervous system.

Omega-3 fatty acid supplementation can prevent changes in mitochondrial energy metabolism and oxidative stress caused by chronic administration of L-tyrosine in the brain of rats.

Deficiency of hepatic enzyme tyrosine aminotransferase characterizes the innate error of autosomal recessive disease Tyrosinemia Type II. Patients may develop neurological and developmental difficulties due to high levels of the amino acid tyrosine in the body. Mechanisms underlying the neurological dysfunction in patients are poorly known. Importantly, Tyrosinemia patients have deficient Omega-3 fatty acids (n-3 PUFA). Here, we investigated the possible neuroprotective effect of the treatment with n-3 PUFA in the alterations caused by chronic administration of L-tyrosine on important parameters of energetic metabolism and oxidative stress in the hippocampus, striatum and cerebral cortex of developing rats. Chronic administration of L-tyrosine causes a decrease in the citrate synthase (CS) activity in the hippocampus and cerebral cortex, as well as in the succinate dehydrogenase (SDH) and isocitrate dehydrogenase (IDH) activities, and an increase in the α-ketoglutarate dehydrogenase activity in the hippocampus. Moreover, in the striatum, L-tyrosine administration caused a decrease in the activities of CS, SDH, creatine kinase, and complexes I, II-III and IV of the mitochondrial respiratory chain. We also observed that the high levels of L-tyrosine are related to oxidative stress in the brain. Notably, supplementation of n-3 PUFA prevented the majority of the modifications caused by the chronic administration of L-tyrosine in the cerebral enzyme activities, as well as ameliorated the oxidative stress in the brain regions of rats. These results indicate a possible neuroprotective and antioxidant role for n-3 PUFA and may represent a new therapeutic approach and potential adjuvant therapy to Tyrosinemia Type II individuals.

Fundamentals of CNS energy metabolism and alterations in lysosomal storage diseases.

The brain has a very high requirement for energy. Adult brain relies on glucose as an energy substrate, whereas developing brain can utilize alternative substrates as well as glucose for energy and for the biosynthesis of lipids and proteins required for brain development. Metabolism provides the energy required to support all cellular functions and brain development and building blocks for macromolecules. Lysosomes are organelles involved in breakdown of biological compounds including proteins and complex lipids in the body and brain. Recent studies suggest that lysosomal dysfunction can damage neurons and/or alter neurotransmitter homeostasis. Several studies also implicate mitochondrial dysfunction in the pathophysiology of brain damage in lysosomal storage diseases. This manuscript provides a brief review of energy metabolism and the key pathways involved in metabolism in brain. Roles of lysosomes related to metabolism and neurotransmission are discussed, and evidence for mitochondrial dysfunction in several lysosomal storage diseases is presented. This article is part of the Special Issue "Lysosomal Storage Disorders".

Effect of hypobaria and hyperoxia during sepsis on survival and energy metabolism.

BACKGROUND: Injured warfighters air evacuated to tertiary medical care facilities are subjected to many stresses that may promote the development of sepsis. In this study, we tested the hypothesis that exposure to "in-flight" hypobaria and/or hyperoxia within 24 hours after onset of intra-abdominal infection in rats accelerates the development and/or severity of sepsis and neurologic injury in survivors. METHODS: Sprague-Dawley rats underwent cecal ligation/puncture (CLP) or sham procedures. Twenty-four hours later, rats were then placed in hypobaric chambers for 6 hours and assigned to normobaric conditions and maintained at either 21% or 100% O2, or under hypobaric conditions (pressure equivalent to an altitude of 8,000 ft) but maintained under either 28% or 100% O2. Two days after CLP or sham, blood samples were obtained for cytokine levels, and mitochondria were isolated from the brain and heart of a subset of animals for analysis of mitochondrial oxygen consumption. Animals were also evaluated for neuromotor impairment before and 15 days postsurgery. RESULTS: Among the 70 rats studied, 16.7% of CLP but none of the sham-treated rats died. All of the CLP but none of the sham rats had evidence of peritonitis at 2 days. Twenty percent (6 of 30) CLP rats undergoing hypobaria versus 12.5% (3 of 24) of CLP rats exposed to normobaria died (p = 0.715) while 12% (3 of 25) of CLP rats exposed to hyperoxia versus 20.7% (6 of 29) of CLP rats exposed to normoxia died (p = 0.48). The ratio of mitochondrial ATP-generating O2 consumption to resting respiration was higher in the CLP plus hypobaria under 100% compared with shams. The only difference in H2O2 production was observed in mitochondria from CLP rats exposed to hyperoxia under normobaric conditions. Composite neurologic scores obtained 15 days postinjury were lower than those at baseline for shams. CONCLUSION: We conclude that neither "in-flight" hyperoxia nor hypobaria exacerbate sepsis or neurologic injury.

Evaluation of plasma biomarkers of inflammation in patients with maple syrup urine disease.

Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder that affects branched-chain amino acid (BCAA) catabolism and is associated with acute and chronic brain dysfunction. Recent studies have shown that inflammation may be involved in the neuropathology of MSUD. However, these studies have mainly focused on single or small subsets of proteins or molecules. Here we performed a case-control study, including 12 treated-MSUD patients, in order to investigate the plasmatic biomarkers of inflammation, to help to establish a possible relationship between these biomarkers and the disease. Our results showed that MSUD patients in treatment with restricted protein diets have high levels of pro-inflammatory cytokines [IFN-γ, TNF-α, IL-1ß and IL-6] and cell adhesion molecules [sICAM-1 and sVCAM-1] compared to the control group. However, no significant alterations were found in the levels of IL-2, IL-4, IL-5, IL-7, IL-8, and IL-10 between healthy controls and MSUD patients. Moreover, we found a positive correlation between number of metabolic crisis and IL-1ß levels and sICAM-1 in MSUD patients. In conclusion, our findings in plasma of patients with MSUD suggest that inflammation may play an important role in the pathogenesis of MSUD, although this process is not directly associated with BCAA blood levels. Overall, data reported here are consistent with the working hypothesis that inflammation may be involved in the pathophysiological mechanism underlying the brain damage observed in MSUD patients.

Antioxidants Reverse the Changes in the Cholinergic System Caused by L-Tyrosine Administration in Rats.

Tyrosinemia type II is an inborn error of metabolism caused by a deficiency in the activity of the enzyme tyrosine aminotransferase, leading to tyrosine accumulation in the body. Although the mechanisms involved are still poorly understood, several studies have showed that higher levels of tyrosine are related to oxidative stress and therefore may affect the cholinergic system. Thus, the aim of this study was to investigate the effects of chronic administration of L-tyrosine on choline acetyltransferase activity (ChAT) and acetylcholinesterase (AChE) in the brain of rats. Moreover, we also examined the effects of one antioxidant treatment (N-acetylcysteine (NAC) + deferoxamine (DFX)) on cholinergic system. Our results showed that the chronic administration of L-tyrosine decreases the ChAT activity in the cerebral cortex, while the AChE activity was increased in the hippocampus, striatum, and cerebral cortex. Moreover, we found that the antioxidant treatment was able to prevent the decrease in the ChAT activity in the cerebral cortex. However, the increase in AChE activity induced by L-tyrosine was partially prevented the in the hippocampus and striatum, but not in the cerebral cortex. Our results also showed no differences in the aversive and spatial memory after chronic administration of L-tyrosine. In conclusion, the results of this study demonstrated an increase in AChE activity in the hippocampus, striatum, and cerebral cortex and an increase of ChAT in the cerebral cortex, without cognitive impairment. Furthermore, the alterations in the cholinergic system were partially prevented by the co-administration of NAC and DFX. Thus, the restored central cholinergic system by antioxidant treatment further supports the view that oxidative stress may be involved in the pathophysiology of tyrosinemia type II.

Role of antioxidant treatment on DNA and lipid damage in the brain of rats subjected to a chemically induced chronic model of tyrosinemia type II.

Tyrosine levels are abnormally elevated in tissues and body fluids of patients with inborn errors of tyrosine metabolism. Tyrosinemia type II, which is caused by tyrosine aminotransferase deficiency, provokes eyes, skin, and central nervous system disturbances in affected patients. However, the mechanisms of brain damage are still poorly known. Considering that studies have demonstrated that oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia, in the present study we investigated the effects of antioxidant treatment (NAC and DFX) on DNA damage and oxidative stress markers induced by chronic administration of L-tyrosine in cerebral cortex, hippocampus, and striatum of rats. The results showed elevated levels of DNA migration, and thus DNA damage, after chronic administration of L-tyrosine in all the analyzed brain areas, and that the antioxidant treatment was able to prevent DNA damage in cerebral cortex and hippocampus. However, the co-administration of NAC plus DFX did not prevent the DNA damage in the striatum. Moreover, we found a significant increase in thiobarbituric acid-reactive substances (TBA-RS) and DCFH oxidation in cerebral cortex, as well as an increase in nitrate/nitrite levels in the hippocampus and striatum. Additionally, the antioxidant treatment was able to prevent the increase in TBA-RS levels and in nitrate/nitrite levels, but not the DCFH oxidation. In conclusion, our findings suggest that reactive oxygen and nitrogen species and oxidative stress can play a role in DNA damage in this disorder. Moreover, NAC/DFX supplementation to tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the current treatment of this disease.

Acute and long-term effects of intracerebroventricular administration of α-ketoisocaproic acid on oxidative stress parameters and cognitive and noncognitive behaviors.

Maple Syrup Urine Disease (MSUD) is biochemically characterized by elevated levels of leucine, isoleucine and valine, as well as their corresponding transaminated branched-chain α-keto acids in tissue and biological fluids. Neurological symptoms and cerebral abnormalities, whose mechanisms are still unknown, are typical of this metabolic disorder. In the present study, we evaluated the early effects (1 h after injection) and long-term effects (15 days after injection) of a single intracerebroventricular administration of α-ketoisocaproic acid (KIC) on oxidative stress parameters and cognitive and noncognitive behaviors. Our results showed that KIC induced early and long-term effects; we found an increase in TBARS levels, protein carbonyl content and DNA damage in the hippocampus, striatum and cerebral cortex both one hour and 15 days after KIC administration. Moreover, SOD activity increased in the hippocampus and striatum one hour after injection, whereas after 15 days, SOD activity decreased only in the striatum. On the other hand, KIC significantly decreased CAT activity in the striatum one hour after injection, but 15 days after KIC administration, we found a decrease in CAT activity in the hippocampus and striatum. Finally, we showed that long-term cognitive deficits follow the oxidative damage; KIC induced impaired habituation memory and long-term memory impairment. From the biochemical and behavioral findings, it we presume that KIC provokes oxidative damage, and the persistence of brain oxidative stress is associated with long-term memory impairment and prepulse inhibition.

Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II.

Tyrosinemia type II is an inborn error of metabolism caused by a mutation in a gene encoding the enzyme tyrosine aminotransferase leading to an accumulation of tyrosine in the body, and is associated with neurologic and development difficulties in numerous patients. Because the accumulation of tyrosine promotes oxidative stress and DNA damage, the main aim of this study was to investigate the possible antioxidant and neuroprotective effects of omega-3 treatment in a chemically-induced model of Tyrosinemia type II in hippocampus, striatum and cerebral cortex of rats. Our results showed chronic administration of L-tyrosine increased the frequency and the index of DNA damage, as well as the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the hippocampus, striatum and cerebral cortex. Moreover, omega-3 fatty acid treatment totally prevented increased DNA damage in the striatum and hippocampus, and partially prevented in the cerebral cortex, whereas the increase in 8-OHdG levels was totally prevented by omega-3 fatty acid treatment in hippocampus, striatum and cerebral cortex. In conclusion, the present study demonstrated that the main accumulating metabolite in Tyrosinemia type II induce DNA damage in hippocampus, striatum and cerebral cortex, possibly mediated by free radical production, and the supplementation with omega-3 fatty acids was able to prevent this damage, suggesting that could be involved in the prevention of oxidative damage to DNA in this disease. Thus, omega-3 fatty acids supplementation to Tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the curren t treatment of this disease.

Increased risk of developing schizophrenia in animals exposed to cigarette smoke during the gestational period.

Cigarette smoking during the prenatal period has been investigated as a causative factor of obstetric abnormalities, which lead to cognitive and behavioural changes associated with schizophrenia. The aim of this study was to investigate behaviour and AChE activity in brain structures in adult rats exposed to cigarette smoke during the prenatal period. Pregnant rats were divided into non-PCSE (non-prenatal cigarette smoke exposure) and PCSE (prenatal cigarette smoke exposure) groups. On post-natal day 60, the rats received saline or ketamine for 7days and were subjected to behavioural tasks. In the locomotor activity task, the non-PCSE+ketamine and PCSE+ketamine groups exhibited increased locomotor activity compared with the saline group. In the social interaction task, the non-PCSE+ketamine and PCSE+ketamine groups exhibited an increased latency compared with the control groups. However, the PCSE+ketamine group exhibited a decreased latency compared with the non-PCSE+ketamine group, which indicates that the cigarette exposure appeared to decrease, the social deficits generated by ketamine. In the inhibitory avoidance task, the non-PCSE+ketamine, PCSE, and PCSE+ketamine groups exhibited impairments in working memory, short-term memory, and long-term memory. In the pre-pulse inhibition (PPI) test, cigarette smoke associated with ketamine resulted in impaired PPI in 3 pre-pulse (PP) intensity groups compared with the control groups. In the biochemical analysis, the AChE activity in brain structures increased in the ketamine groups; however, the PCSE+ketamine group exhibited an exacerbated effect in all brain structures. The present study indicates that exposure to cigarette smoke during the prenatal period may affect behaviour and cerebral cholinergic structures during adulthood.

Apoptotic signaling pathways induced by acute administration of branched-chain amino acids in an animal model of maple syrup urine disease.

Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of the branched-chain α-keto acid dehydrogenase complex activity. This blockage leads to accumulation of the branched-chain amino acids leucine, isoleucine and valine, as well as their corresponding α-keto acids and α-hydroxy acids. The affected patients present severe neurological symptoms, such as coma and seizures, as well as edema and cerebral atrophy. Considering that the mechanisms of the neurological symptoms presented by MSUD patients are still poorly understood, in this study, protein levels of apoptotic factors are measured, such as Bcl-2, Bcl-xL, Bax, caspase-3 and -8 in hippocampus and cerebral cortex of rats submitted to acute administration of branched-chain amino acids during their development. The results in this study demonstrated that BCAA acute exposure during the early postnatal period did not significantly change Bcl-2, Bcl-xL, Bax and caspase-8 protein levels. However, the Bax/Bcl-2 ratio and procaspase-3 protein levels were decreased in hippocampus. On the other hand, acute administration of BCAA in 30-day-old rats increase in Bax/Bcl-2 ratio followed by an increased caspase-3 activity in cerebral cortex, whereas BCAA induces apoptosis in hippocampus through activation and cleavage of caspase-3 and -8 without changing the Bax/Bcl-2 ratio. In conclusion, the results suggest that apoptosis could be of pivotal importance in the developmental neurotoxic effects of BCAA. In addition, the current studies also suggest that multiple mechanisms may be involved in BCAA-induced apoptosis in the cerebral cortex and hippocampus.

Antioxidants reverse the changes in energy metabolism of rat brain after chronic administration of L.-tyrosine.

Tyrosinemia type II is a rare autosomal recessive disease caused by deficiency of hepatic tyrosine aminotransferase and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that high concentrations of tyrosine provoke mitochondrial dysfunction and oxidative stress, in the present study we investigated the in vivo influence of antioxidants (N-acetylcysteine, NAC; and deferoxamine, DFX) administration on the inhibitory effects on parameters of energy metabolism in cerebral cortex, hippocampus and striatum of rats, provoked by chronic administration of L.-tyrosine. Our results showed that chronic administration of L.-tyrosine results in a marked decrease in the activity of citrate synthase in all the analyzed structures and succinate dehydrogenase activities in hippocampus and striatum, and that antioxidants administration can prevent this inhibition in hippocampus and striatum. Moreover, chronic administration of L.-tyrosine inhibited the activity of complex I, II-III and IV in the striatum, which can be prevented by antioxidant treatment. However, the co-administration of NAC plus DFX could not prevent the inhibition of creatine kinase activity in the striatum. In conclusion, the present study demonstrates that the administration of antioxidants NAC and DFX attenuates the L.-tyrosine effects on enzymes of the Krebs cycle and the mitochondrial respiratory chain, suggesting that impairment of energy metabolism can be involved with oxidative stress. These results also indicate a possible neuroprotective role for NAC and DFX as a potential adjuvant therapy to the patients with Tyrosinemia type II.

Effect of folic acid on oxidative stress and behavioral changes in the animal model of schizophrenia induced by ketamine.

Recent studies have shown benefits for the supplementation of folic acid in schizophrenic patients. The aim of this study was to evaluate the effects of folic acid addition on adult rats, over a period of 7 or 14 days. It also sets out to verify any potential protective action using an animal model of schizophrenia induced by ketamine, in behavioral and biochemical parameters. This study used two protocols (acute and chronic) for the administration of ketamine at a dose of 25 mg/kg (i.p.). The folic acid was given by oral route in doses of 5, 10 and 50 mg/kg, once daily, for 7 and/or 14 days in order to compare the protective effects of folic acid. Thirty minutes after the last administration of ketamine, the locomotor and social interaction activities were evaluated, and immediately the brain structure were removed for biochemical analysis. In this study, ketamine was administered in a single dose or in doses over the course of 7 days increasing the animal's locomotion. This study showed that the administration of folic acid over 7 days was unable to prevent hyper locomotion. In contrast, folic acid (10 and 50 mg/kg) administrated over a period of 14 days, was able to partially prevent the hyper locomotion. Our data indicates that both acute and chronic administrations of ketamine increased the time to first contact between the animals, while the increased latency for social contact was completely prevented by folic acid (5, 10 and 50 mg/kg). Chronic and acute administrations of ketamine also increased lipid peroxidation and protein carbonylation in brain. Folic acid (10 and 50 mg/kg) supplements showed protective effects on the oxidative damage found in the different brain structures evaluated. All together, the results indicate that nutritional supplementation with folic acid provides promising results in an animal model of schizophrenia induced by ketamine.

Evidence of oxidative stress in brain and liver of young rats submitted to experimental galactosemia.

Galactosemia is a disorder of galactose metabolism, leading to the accumulation of this carbohydrate. Galactosemic patients present brain and liver damage. For evaluated oxidative stress, 30-day-old males Wistar rats were divided into two groups: galactose group, that received a single injection of this carbohydrate (5 µmol/g), and control group, that received saline 0.9 % in the same conditions. One, twelve or twenty-four hours after the administration, animals were euthanized and cerebral cortex, cerebellum, and liver were isolated. After one hour, it was found a significant increase in TBA-RS levels, nitrate and nitrite and protein carbonyl contents in cerebral cortex, as well as protein carbonyl content in the cerebellum and in hepatic level of TBA-RS, and a significant decrease in nitrate and nitrite contents in cerebellum. TBA-RS levels were also found increased in all studied tissues, as well as nitrate and nitrite contents in cerebral cortex and cerebellum, that also present increased protein carbonyl content and impairments in the activity of antioxidant enzymes of rats euthanized at twelve hours. Finally, animals euthanized after twenty-four hours present an increase of TBA-RS levels in studied tissues, as well as the protein carbonyl content in cerebellum and liver. These animals also present an increased nitrate and nitrite content and impairment of antioxidant enzymes activities. Taken together, our data suggest that acute galactose administration impairs redox homeostasis in brain and liver of rats.