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Abstract Background The non-signalling chemokine receptors, including receptors DARC, D6 and CCX-CKR, have recently been shown to be involved in chemokine clearance and activity regulation. The human chemokine receptor CRAM (also known as HCR or CCRL2) is the most recently identified member of this atypical group. CRAM is expressed on B cells in a maturation-stage dependent manner and absent on T cells. We have recently shown that it competitively binds CCL19. CCL19 and its signalling receptor CCR7 are critical components involved in cell recruitment to secondary lymphoid organs and in maturation. B cell Chronic Lymphocytic Leukemia (B-CLL) is a low-grade lymphoma characterized by proliferative centres (or pseudofollicles). Proliferative centres develop due to abnormal cellular localisation and they are involved in the development of malignant cells. CCR7 is highly expressed on B cells from CLL patients and mediates migration towards its ligands CCL19 and CCL21, while CRAM expression and potential interferences with CCR7 are yet to be characterized. Results In this study, we show that B cells from patients with B-CLL present highly variable degrees of CRAM expression in contrast to more consistently high levels of CCR7. We investigated the hypothesis that, similar to the atypical receptor DARC, CRAM can modulate chemokine availability and/or efficacy, resulting in the regulation of cellular activation. We found that a high level of CRAM expression was detrimental to efficient chemotaxis with CCL19. MAP-kinase phosphorylation and intracellular calcium release induced by CCL19 were also altered by CRAM expression. In addition, we demonstrate that CRAM-induced regulation of CCL19 signalling is maintained over time. Conclusions We postulate that CRAM is a factor involved in the fine tuning/control of CCR7/CCL19 mediated responses. This regulation could be critical to the pivotal role of CCL19 induced formation of proliferation centres supporting the T/B cells encounter as well as disease progression in B-CLL.

Abstract Background Cryopreservation of peripheral blood mononuclear cells has been used to preserve and standardize immunologic measurements for multicenter studies, however, effects of cryopreservation on cytokine responses are incompletely understood. In designing immunologic studies for a new multicenter birth cohort study of childhood asthma, we performed a series of experiments to determine the effects of two different methods of cryopreservation on the cytokine responses of cord and peripheral blood mononuclear cells. Results Paired samples of PBMC were processed freshly, or after cryopreservation in a Nalgene container (NC) or a controlled-rate freezer (CRF). Although there were some differences between the methods, cryopreservation inhibited PHA-induced IL-10 secretion and Der f 1-induced IL-2 secretion, and augmented PHA-induced IL-2 secretion and spontaneous secretion of TNF-α. In separate experiments, NC cryopreservation inhibited secretion of several cytokines (IL-13, IL-10, IFN-γ, TNF-α) by PHA-stimulated cord blood mononuclear cells. With the exception of PHA-induced IL-13, results from fresh and cryopreserved cord blood samples were not significantly correlated. Finally, in reproducibility studies involving processing of identical cell samples in up to 4 separate laboratories, variances in cytokine responses of fresh cells stimulated at separate sites did not exceed those in cryopreserved cells stimulated at a central site. Conclusion Collectively, these studies indicate that cryopreservation can affect mononuclear cell cytokine response profiles, and that IL-10 secretion and antigen-induced responses may be especially vulnerable. These studies also demonstrate that mononuclear cell responses can be standardized for performance in a small number of laboratories for multicenter studies, and underscore the importance of measuring reproducibility and of testing whether cryopreservation techniques alter specific immunologic outcomes.

Purpose: The aim of the present study was to investigate the effect of cerebral palsy and dental caries on dental plaque index, salivary parameters and oxidative stress in children and adolescents., Methods: Seventy children and adolescents aged 2-20 years were divided into four groups: neurotypical controls-inactive caries (NCIC; n = 19); neurotypical controls-active caries (NCAC; n = 16); cerebral palsy-inactive caries (CPIC; n = 19); and cerebral palsy-active caries (CPAC; n = 16). The visible dental plaque index was determined after drying the tooth surfaces and without any mechanical or chemical disclosing methods. Salivary pH and buffer capacity were measured 1 hour after collection using a digital pH meter. Saliva was used to evaluate oxidative status based on the levels of reactive species, lipid peroxidation and non-enzymatic antioxidants (reduced glutathione and vitamin C)., Results: The CPIC and CPAC groups had lower salivary pH and a higher visible dental plaque index. CP was also associated with an increase in salivary levels of markers of oxidative stress and the modulation of salivary levels of non-enzymatic antioxidants., Conclusion: Cerebral palsy exerts an influence on the salivary profile, oral health and oxidative stress. The individuals with CP had more acidic saliva and a higher dental plaque index, which were positively correlated with caries activity. CP was associated with high salivary levels of reactive species and lipid peroxidation, demonstrating an imbalance in salivary redox that was particularly associated with caries activity. These factors facilitate the development of oral diseases in individuals with cerebral palsy.

Microcystin-LR (MIC-LR) is a hepatotoxin, with toxicity mechanisms linked to oxidative stress. Besides, neurotoxic effects of MIC-LR have recently been described. Herein, we evaluated the effects of environmentally important concentrations of MIC-LR (1, 10, 100, 250, and 500 μg/L) on oxidative stress markers and the survival rate of the nematode Caenorhabditis elegans (C. elegans). In addition, a possible protective effect of the carotenoid lutein (LUT) extracted from marigold flowers against MIC-LR toxicity was investigated. Higher concentrations (250 and 500 μg/L) of MIC-LR induced the generation of reactive oxygen species (ROS) and resulted in a survival loss in C elegans. Meanwhile, all MIC-LR concentrations caused an increase in the superoxide dismutase (SOD) expression, while catalase (CAT) expression was only affected at 500 μg/L. The carotenoid LUT prevented the ROS generation, impairment in the CAT expression, and the survival loss induced by MIC-LR in C. elegans. Our results confirm the toxicity of MIC-LR even in a liver-lacking invertebrate and the involvement of oxidative events in this response. Additionally, LUT appears to be able to mitigate the MIC-LR toxic effects., (Copyright © 2017. Published by Elsevier Ltd.)

Background: This study evaluated the antimicrobial photodynamic therapy (aPDT) effects using the methylene blue (MB) in ethanol 20% on systemic oxidative status and collagen content from gingiva of rats with periodontitis., Methods: Rats were divided into five experimental groups: NC (negative control; no periodontitis); PC (positive control; periodontitis without any treatment); SRP (periodontitis and scaling and root planing), aPDT I (periodontitis and SRP+aPDT+MB solubilized in water), and aPDT II (periodontitis and SRP+aPDT+MB solubilized in ethanol 20%). After 7days of removal of the ligature, the periodontal treatments were performed. At 7/15/30days, gingival tissue was removed for morphometric analysis. The erythrocytes were used to evaluate systemic oxidative status., Results: PC group showed higher lipoperoxidation levels at 7/15/30days. aPDT indicated a protective influence in erythrocytes at 15days observed by the elevation in levels of systemic antioxidant defense. aPDT II group was the only one that restored the total collagen area in 15days, and recovered the type I collagen area at the same time point., Conclusions: aPDT as an adjunct to the SRP can induce the systemic protective response against oxidative stress periodontitis-induced and recover the gingival collagen, thus promoting the healing periodontal, particularly when the MB is dissolved in ethanol 20%., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: To evaluate for the first time in vivo the effects of methylene blue (MB) photosensitizer dissolved in ethanol in antimicrobial photodynamic therapy (aPDT) as adjuvant periodontal treatment, at plasmatic oxidative stress and vascular behavior in rat model., Methods: Wistar rats were divided into negative control (NC, no periodontitis) and positive control (PC, with periodontitis, without any treatment). The other groups had periodontitis and were treated with scaling and root planing (SRP); SRP+aPDT+MB dissolved in water (aPDT I); SRP+aPDT+MB dissolved in ethanol (aPDT II). The periodontitis was induced by ligature at the mandibular right first molar. At 7/15/30days, rats were euthanized, the plasma was used to determine oxidative stress parameters and gingival tissue for histomorphometric analysis., Results: PC showed higher thiobarbituric acid reactive substances levels in 7/15/30days. aPDT II was able to block the lipid peroxidation, especially between 15th and 30th days. Glutathione reduced levels were consumed in PC, aPDT I and II groups throughout the experiment. aPDT II increased the vitamin C levels which were restored in this group in the 30th day. aPDT II group showed the highest number of blood vessels., Conclusion: In summary, the aPDT with MB dissolved in ethanol provides better therapeutic responses in periodontitis treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In recent years, interesterified fat (IF) has been used to replace hydrogenated vegetable fat (HVF), rich in trans isomers, being found in processed foods. Studies involving IF have shown deleterious influences on the metabolic system, similarly to HVF, whereas no studies regarding its influence on the central nervous system (CNS) were performed. Rats from first generation born and maintained under supplementation (3g/Kg, p.o.) of soybean-oil or IF until adulthood were assessed on memory, biochemical and molecular markers in the hippocampus. IF group showed higher saturated fatty acids and linoleic acid and lower docosahexaenoic acid incorporation in the hippocampus. In addition, IF supplementation impaired short and long-term memory, which were related to increased reactive species generation and protein carbonyl levels, decreased catalase activity, BDNF and TrkB levels in the hippocampus. To the best of our knowledge, this is the first study to show that lifelong IF consumption may be related to brain oxidative damage, memory impairments and neurotrophins modifications, which collectively may be present indifferent neurological disorders. In fact, the use of IF in foods was intended to avoid damage from HVF consumption; however this substitute should be urgently reviewed, since this fat can be as harmful as trans fat., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study aimed to assess the influence of maternal dietary fat intake during pregnancy or lactation on memory of adult offspring after chronic mild stress (CMS) exposure. Female Wistar rats were supplemented daily with soybean oil/fish oil (SO/FO) or hydrogenated vegetable fat (HVF) by oral gavage (3.0g/kg body weight) during pregnancy or lactation. On post-natal day (PND) 60, half of the animals were exposed to CMS following behavioral assessments. While the adult offspring born under influence of SO/FO and HVF supplementations during pregnancy showed higher levels of n-3 and n-6 fatty acids (FA) series DHA and ARA metabolites, respectively, in the hippocampus, adult offspring born from supplemented dams during lactation showed higher levels of their precursors: ALA and LA. However, only HVF supplementation allowed TFA incorporation of adult offspring, and levels were higher in lactation period. Adult offspring born from dams supplemented with trans fat in both pregnancy and lactation showed short and long-term memory impairments before and after CMS. Furthermore, our study also showed higher memory impairment in offspring born from HVF-supplemented dams during lactation in comparison to pregnancy. BDNF expression was increased by stress exposure in offspring from both SO/FO- and HVF-supplemented dams during pregnancy. In addition, offspring from HVF-supplemented dams showed decreased TrkB expression in both supplemented periods, regardless of stress exposure. In conclusion, these findings show for the first time that the type of dietary FA as well as the period of brain development is able to change FA incorporation in brain neural membranes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The effect of the antioxidant gallic acid (GA) on Pb toxicity in blood, liver and kidney was investigated in the present study. Rats Wistar received Pb nitrate (50 mg/Kg/day, i.p., 5 days) followed by GA (13.5 mg/Kg, p.o., 3 days) or a chelating agent (EDTA, 55 mg/Kg, i.p.). As result, Pb decreased body weight, hematocrit and blood δ-aminolevulinic acid dehydratase (ALA-D) activity. In addition, high Pb levels were observed in blood and tissues, together with increased (1) lipid peroxidation in erythrocytes, plasma and tissues, (2) protein oxidation in tissues and (3) plasma aspartate transaminase (AST) levels. These changes were accompanied by decreasing in antioxidant defenses, like superoxide dismutase (SOD) activity in tissues and catalase (CAT) activity and reduced glutathione (GSH) in liver. GA was able to reverse Pb-induced decrease in body weight and ALA-D activity, as well as Pb-induced oxidative damages and most antioxidant alterations, however it did not decrease Pb bioaccumulation herein as EDTA did. Furthermore, EDTA did not show antioxidant protection in Pb-treated animals as GA did. In conclusion, GA decreased Pb-induced oxidative damages not by decreasing Pb bioaccumulation, but by improving antioxidant defenses, thus GA may be promising in the treatment of Pb intoxications.

(+)-Dehydrofukinone (DHF) is a major component of the essential oil of Nectandra grandiflora (Lauraceae), and exerts a depressant effect on the central nervous system of fish. However, the neuronal mechanism underlying DHF action remains unknown. This study aimed to investigate the action of DHF on GABAA receptors using a silver catfish (Rhamdia quelen) model. Additionally, we investigated the effect of DHF exposure on stress-induced cortisol modulation. Chemical identification was performed using gas chromatography-mass spectrometry and purity was evaluated using gas chromatography with a flame ionization detector. To an aquarium, we applied between 2.5 and 50 mg/L DHF diluted in ethanol, in combination with 42.7 mg/L diazepam. DHF within the range of 10-20 mg/L acted collaboratively in combination with diazepam, but the sedative action of DHF was reversed by 3 mg/L flumazenil. Additionally, fish exposed for 24 h to 2.5-20 mg/L DHF showed no side effects and there was sustained sedation during the first 12 h of drug exposure with 10-20 mg/L DHF. DHF pretreatment did not increase plasma cortisol levels in fish subjected to a stress protocol. Moreover, the stress-induced cortisol peak was absent following pretreatment with 20 mg/L DHF. DHF proved to be a relatively safe sedative or anesthetic, which interacts with GABAergic and cortisol pathways in fish.

Amphetamine (AMPH) is an addictive psychostimulant drug whose use has been related to neurotoxicity. Experimentally, AMPH increases anxiety-like symptoms, showing addictive properties. In the last decades, the growing consumption of processed foods has provided an excess of saturated and trans fats in detriment of essential fatty acids, which may modify the lipid profile of brain membranes, thus modifying its permeability and dopaminergic neurotransmission. Here, we assessed the influence of brain incorporation of different fatty acids (FA) on AMPH self-administration. Three groups of young male rats were orally supplemented from weaning with a mixture of soybean oil (SO, rich in n-6 FA) and fish oil (FO, rich in n-3 FA), hydrogenated vegetable fat (HVF, rich in trans fatty acids--TFA), or water (control group). These animals were born from dams that were supplemented with the same fat from pregnancy to lactation. Anxiety-like symptoms and locomotor index were assessed in elevated plus maze and open-field (OF), respectively, while brain molecular expressions of dopaminergic receptors, dopamine transporter (DAT), and BDNF were determined in the cortex and hippocampus. HVF increased the frequency of AMPH self-administration and was associated with reinforcement and withdrawal signs as observed by increased anxiety-like symptoms. Contrarily, SO/FO decreased these parameters. Increased BDNF protein together with decreased DAT expression was observed in the hippocampus of HVF group. Based on these findings, our study points to a harmful influence of trans fats on drug addiction and craving symptoms, whose mechanism may be related to changes in the dopaminergic neurotransmission.

Purpose: To evaluate the toxicity of chronic consumption of processed foods that are rich in trans fat on the lipid composition of brain membranes, as well as its functional repercussions., Methods: A second generation of male rats born from mothers and grandmothers supplemented with soybean oil (SOC, an isocaloric control group) or hydrogenated vegetable fat (HVF, rich in TFA) (3g/kg; p.o.) were kept under oral treatment until 90 days of age, when they were exposed to an AMPH-induced model of mania., Results: The HVF group presented 0.38% of TFA incorporation in the striatum, affecting Na(+)/K(+) ATPase activity, which was decreased per se and following AMPH-exposure. The HVF group also showed increased protein carbonyl (PC) and brain-derived neurotrophic factor (BDNF) mRNA levels after AMPH administration, while these oxidative and molecular changes were not observed in the other experimental groups. Additionally, a negative correlation between striatal Na(+)/K(+) ATPase activity and PC levels (r(2)=0.49) was observed., Conclusion: The prolonged consumption of trans fat allows TFA incorporation and increases striatal oxidative status, thus impairing the functionality of Na(+)/K(+)-ATPase and affecting molecular targets as BDNF mRNA. We hypothesized that the chronic intake of processed foods (rich in TFA) facilitates the development of neuropsychiatric diseases, particularly bipolar disorder., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Pruritus and discomfort are often present in patients with xerosis and atopic dermatitis. Several studies suggest an important role of diet in skin pathophysiology., Objective: This study evaluated the effect of dietary fatty acids in the skin physiology via an itch-related animal model with and without supplementation with fish oil (FO), a source of polyunsaturated fatty acids (PUFA), especially omega 3 (n-3)., Methods: Male Wistar rats were divided into two groups-non-supplemented (control) and supplemented with FO (3g/kg/day) by gavage for 90 days. Every 30 days, scratching and skin parameters (transepidermal water loss (TEWL), hydration, and local blood flow) were evaluated before and after dorsal skin exposure to acetone to induce the itch-related dry skin. At the end of the study, animals were sacrificed, and skin samples collected for fatty acids composition analysis by GC-FID., Results: FO supplementation reduced the TEWL and increased the skin hydration, with significant changes from day 60 on, while skin microcirculation registered no changes. It also alleviated the acetone induced skin barrier alteration, revealed by a faster resolution of TEWL and hydration, and elimination of itch-related scratching induced by dry skin. These changes were associated with the shift in the skin fatty acids incorporation pattern (richer in n-3 with n-6/n-3<5) resulting from the FO supplementation., Conclusion: Skin barrier dynamics seem to be influenced by FO n-3 PUFA, with suppressive effects on the scratching behaviour induced by dry skin. Hence, long-term supplementation with n-3 PUFA rich nutrients might reinforce and restore cutaneous integrity and function., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aims: We investigated whether trans-fat supplemented over two generations of rats could alter neuronal membranes and influence mania-like behaviors, as well as the effects of lithium (Li)., Main Methods: Two generations of female rats were supplemented with soybean oil (SO-C, rich in n-6 fatty acids - FA) or hydrogenated vegetable fat (HVF, rich in trans-fatty acids - TFA). Male rats born from the 1st and 2nd generations were maintained in the same supplementation until adulthood, when they were exposed to an amphetamine (AMPH)-induced model of mania and co-treated with Li or not., Key Findings: AMPH increased locomotion of both generations and this influence was higher in the HVF than in the SO-C group. Conversely, AMPH increased long-term memory in SO-C group of the 2nd generation. HVF supplementation allowed hippocampal TFA incorporation in rats of both generations (0.1 and 0.2%, respectively). Oxidative parameters indicated higher levels of protein carbonyl (PC) in the HVF group with no changes in catalase (CAT) activity in the 1st generation. In the 2nd generation, AMPH increased PC levels of both experimental groups, whereas CAT activity was lower per se in the HVF group only. The co-treatment with Li leveled out all behavioral parameters, PC levels and CAT activity indicating a significant neuroprotective role., Significance: These findings suggest that chronic HVF consumption allows a rising incorporation of TFA in the brain, which may be reflected on the neuropsychiatric conditions related to mania, whereas the effects of Li are not modified in the course of this harmful dietary habit., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Recently, we have described the influence of dietary fatty acids (FA) on mania-like behavior of first generation animals. Here, two sequential generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy and during lactation. In adulthood, half of each group was exposed to an amphetamine (AMPH)-induced mania animal model for behavioral, biochemical and molecular assessments. FO supplementation was associated with lower reactive species (RS) generation and protein carbonyl (PC) levels and increased dopamine transporter (DAT) levels, while HVF increased RS and PC levels, thus decreasing catalase (CAT) activity and DAT levels in hippocampus after AMPH treatment. AMPH impaired short- (1 h) and long- (24 h) term memory in the HVF group. AMPH exposure was able to reduce hippocampal BDNF- mRNA expression, which was increased in FO. While HVF was related to higher trans FA (TFA) incorporation in hippocampus, FO was associated with increased percentage of n-3 polyunsaturated FA (PUFA) together with lower n-6/n-3 PUFA ratio. Interestingly, our data showed a positive correlation between brain-derived neurotrophic factor (BDNF) mRNA and short- and long-term memory (r(2)  = 0.53; P = 0.000/r(2)  = 0.32; P = 0.011, respectively), as well as a negative correlation between PC and DAT levels (r(2)  = 0.23; P = 0.015). Our findings confirm that provision of n-3 or TFA during development over two generations is able to change the neuronal membrane lipid composition, protecting or impairing the hippocampus, respectively, thus affecting neurothrophic factor expression such as BDNF mRNA. In this context, chronic consumption of trans fats over two generations can facilitate the development of mania-like behavior, so leading to memory impairment and emotionality, which are related to neuropsychiatric conditions., (© 2014 Wiley Periodicals, Inc.)

The influence of trans fatty acids (TFA) on lipid profile, oxidative damage and mitochondrial function in the skin of rats exposed to ultraviolet radiation (UVR) was assessed. The first-generation offspring of female Wistar rats supplemented from pregnancy with either soybean oil (C-SO, rich in n-6 FA; control group) or hydrogenated vegetable fat (HVF, rich in TFA) were continued with the same supplements until adulthood, when half of each group was exposed to UVR for 12 weeks. The HVF group showed higher TFA cutaneous incorporation, increased protein carbonyl (PC) levels, decreased functionality of mitochondrial enzymes and antioxidant defenses of the skin. After UVR, the HVF group showed increased skin thickness and reactive species (RS) generation, with decreased skin antioxidant defenses. RS generation was positively correlated with skin thickness, wrinkles and PC levels. Once incorporated to skin, TFA make it more susceptible to developing UVR-induced disorders., (© 2015 The American Society of Photobiology.)

Since that fast food consumption have raised concerns about people's health, we evaluated the influence of trans fat consumption on behavioral, biochemical and molecular changes in the brain-cortex of second generation rats exposed to a model of mania. Two successive generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy, lactation to adulthood, when male rats from 2nd generation received amphetamine (AMPH-4 mg/kg-i.p., once a day, for 14 days) treatment. AMPH increased locomotor index in all animals, which was higher in the HVF group. While the FO group showed increased n-3 polyunsaturated fatty acid (PUFA) incorporation and reduced n-6/n-3 PUFA ratio, HVF allowed trans fatty acid (TFA) incorporation and increased n-6/n-3 PUFA ratio in the brain-cortex. In fact, the FO group showed minor AMPH-induced hyperactivity, decreased reactive species (RS) generation per se, causing no changes in protein carbonyl (PC) levels and dopamine transporter (DAT). FO supplementation showed molecular changes, since proBDNF was increased per se and reduced by AMPH, decreasing the brain-derived neurotrophic factor (BDNF) level following drug treatment. Conversely, HVF was related to increased hyperactivity, higher PC level per se and higher AMPH-induced PC level, reflecting on DAT, whose levels were decreased per se as well as in AMPH-treated groups. In addition, while HVF increased BDNF-mRNA per se, AMPH reduced this value, acting on BDNF, whose level was lower in the same AMPH-treated experimental group. ProBDNF level was influenced by HVF supplementation, but it was not sufficient to modify BDNF level. These findings reinforce that prolonged consumption of trans fat allows TFA incorporation in the cortex, facilitating hyperactive behavior, oxidative damages and molecular changes. Our study is a warning about cross-generational consumption of processed food, since high trans fat may facilitate the development of neuropsychiatric conditions, including bipolar disorder (BD)., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

In recent decades, the increased consumption of processed foods, which are rich in hydrogenated vegetable fat (HVF), has led to a decreased consumption of fish and oilseed, rich in omega-3 fatty acids. This eating habit provides an increased intake of trans fatty acids (TFA), which may be related to neuropsychiatric conditions, including inattention and hyperactivity. In this study, we evaluated the potential connection between prolonged trans fat consumption and development of hyperactivity-like symptoms in rats using different behavioral paradigms. Trans fat intake for 10 months (Experiment 1), as well as during pregnancy and lactation across two sequential generations of rats, (Experiment 4) induced active coping in the forced swimming task (FST). In addition, HVF supplementation was associated with increased locomotion before and after amphetamine (AMPH) administration (Experiment 2). Similarly, HVF supplementation during pregnancy and lactation were associated with increased locomotion in both young and adult rats (Experiment 3). Furthermore, trans fat intake across two sequential generations increased locomotor and exploratory activities following stressors (Experiment 4). From these results, we suggest that chronic consumption of trans fat is able to enhance impulsiveness and reactivity to novelty, facilitating hyperactive behaviors., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Chronic consumption of processed food causes structural changes in membrane phospholipids, affecting brain neurotransmission. Here we evaluated noxious influences of dietary fats over two generations of rats on amphetamine (AMPH)-conditioned place preference (CPP). Female rats received soybean oil (SO, rich in n-6 fatty acids (FA)), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans fatty acids (TFA)) for two successive generations. Male pups from the 2nd generation were maintained on the same supplementation until 41 days of age, when they were conditioned with AMPH in CPP. While the FO group showed higher incorporation of n-3 polyunsaturated-FA (PUFA) in cortex/hippocampus, the HVF group showed TFA incorporation in these same brain areas. The SO and HVF groups showed AMPH-preference and anxiety-like symptoms during abstinence. Higher levels of protein carbonyl (PC) and lower levels of non-protein thiols (NPSH) were observed in cortex/hippocampus of the HVF group, indicating antioxidant defense system impairment. In contrast, the FO group showed no drug-preference and lower PC levels in cortex. Cortical PC was positively correlated with n-6/n-3 PUFA ratio, locomotion and anxiety-like behavior, and hippocampal PC was positively correlated with AMPH-preference, reinforcing connections between oxidative damage and AMPH-induced preference/abstinence behaviors. As brain incorporation of trans and n-6 PUFA modifies its physiological functions, it may facilitate drug addiction., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: The present study describes the isolation of linalool from the essential oil of Lippia alba (Mill.) N. E. Brown, and its anesthetic effect in silver catfish (Rhamdia quelen) in comparison with essential oil. The potentiation of depressant effects of linalool with a benzodiazepine (BDZ) and the involvement of GABAergic system in its antagonism by flumazenil were also evaluated., Study Design: Prospective experimental study., Animals: Juvenile silver catfish unknown sex weighing mean 9.24 ± 2.83 g (n = 6 for each experimental group per experiment)., Methods: Column chromatography was used for the isolation of S-(+)-linalool. Fish (n = 6 for each concentration) were transferred to aquaria with linalool (30, 60, and 180 μL L(-1)) or EO of L. alba (50, 100, and 300 μL L(-1)) to determine the induction time for anesthesia. After induction, the animals were transferred to anesthetic-free aquaria to assess their recovery time. To observe the potentiation, fish were exposed to linalool (30, 60, and 180 μL L(-1)) in the presence or absence of BDZ (diazepam 150 μm). In another experiment, fish exposed to linalool (30 and 180 μL L(-1) or BDZ were transferred to an anesthetic-free aquaria containing flumazenil (5 μm) or water to assess recovery time., Results: Linalool had a similar sedation profile to the essential oil at a proportional concentration in silver catfish. However, the anesthesia profile was different. Potentiation of linalool effect occurred only when tested at low concentration. Fish exposed to BDZ showed faster anesthesia recovery in water with flumazenil, but the same did not occur with linalool., Conclusions and Clinical Relevance: The use of linalool as a sedative and anesthetic for silver catfish was effective at 30 and 180 μL L(-1), respectively. The mechanism of action seems not to involve the benzodiazepine site of the GABAergic system., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Polyunsaturated fatty acids (FAs) are cell membrane components involved in brain functions. We hypothesized that long-term trans fat consumption is able to modify the membrane FAs composition impairing behavioral parameters related to aging. In this study, a comparison of behavioral parameters at 10 and 15 months of trans fat consumption by male Wistar rats was made. Animals were fed for 10 and 15 months from weaning with diets containing either 20% w/w soybean oil (SO), rich in n-6 PUFA, hydrogenated vegetable fat (HVF), rich in trans FAs, or a standard diet (control - C). At both evaluation times, HVF-fed rats showed progressively increased parameters of orofacial dyskinesia, fear and anxiety-like symptoms. The HVF diet reduced locomotor and exploratory activities progressively over 10 and 15 months of supplementation, while the standard and SO diets did not. In this study, we showed that chronic trans FAs consumption from weaning is able to favor the development of neuromotor and neuropsychiatric diseases, whose intensity was time dependent.

This study investigated the influence of neonatal handling on amphetamine-induced conditioned place preference (CPP), as well as the consequent anxiety-like symptoms and oxidative status related to drug abstinence in young rats. Male pups were exposed to tactile stimulation (TS) or neonatal isolation (NI) for 10 min every day from postnatal day one (PND1) to PND21. After being weaned (PND22), pups were separated by handling type until PND40, when treatment with amphetamine (AMPH-4 mg/kg/mL ip, for 8 days) or vehicle (NaCl 0.9% ip, 1 mL/Kg) in CPP started. AMPH-conditioning evoked drug-preference (in 24h and 96 h) and abstinence symptoms in unhandled (UH) animals, followed by oxidative damage in the cortex, hippocampus and striatum. TS showed beneficial influence, as observed by the decreased drug-preference (24 and 96 h) in relation to UH and NI, showing no abstinence symptoms in this last period, as observed by the reduced anxiety-like symptoms. The oxidative status indicated a protective influence of TS on brain tissues: lower lipid peroxidation (LP) and reduced protein carbonylation (PC) in the cortex, hippocampus and striatum. Furthermore, TS also increased antioxidant defenses in brain tissues and blood: i) increased plasma levels of vitamin C; ii) increased activity of catalase (CAT) and iii) higher levels of glutathione (GSH) in red blood cells (RBC). Moreover, there were positive correlations of AMPH-CPP with PC and LP levels in all the brain areas assessed. In summary, TS modifies AMPH-preference in the CPP paradigm, reducing drug abstinence behaviors, and stimulating the antioxidant defense system, thus protecting the brain areas closely related to addiction in young rats. Studies about TS and addiction in animal models should be extended to the molecular level., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We evaluated the influence of dietary fats on ultraviolet radiation (UVR)-induced oxidative damage in skin of rats. Animals from two consecutive generations born of dams supplemented with fats during pregnancy and breastfeeding were maintained in the same supplementation: soybean-oil (SO, rich in n-6 FA, control group), fish-oil (FO, rich in n-3 FA) or hydrogenated-vegetable-fat (HVF, rich in TFA). At 90 days of age, half the animals from the 2nd generation were exposed to UVR (0.25 J/cm(2)) 3×/week for 12 weeks. The FO group presented higher incorporation of n-3 FA in dorsal skin, while the HVF group incorporated TFA. Biochemical changes per se were observed in skin of the HVF group: greater generation of reactive oxygen species (ROS), lower mitochondrial integrity and increased Na(+)K(+)-ATPase activity. UVR exposure increased skin wrinkles scores and ROS generation and decreased mitochondrial integrity and reduced-glutathione levels in the HVF group. In FO, UVR exposure was associated with smaller skin thickness and reduced levels of protein-carbonyl, together with increased catalase activity and preserved Na(+)K(+)-ATPase function. In conclusion, while FO may be protective, trans fat may be harmful to skin health by making it more vulnerable to UVR injury and thus more prone to develop photoaging and skin cancer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We investigated the influence of neonatal handling on cocaine-induced conditioned place preference (CPP), anxiety-like symptoms and oxidative status related to drug abstinence in young rats. Pups were submitted to tactile stimulation (TS) or neonatal isolation (NI10 or NI60) after birth, and then were submitted to CPP performed with cocaine. TS group did not show place preference, while unhandled (UH), NI10 and NI60 rats did. Handling was related to anxiety-like symptoms per se in UH and NI60 groups and this behavior was also observed in the cocaine-conditioned rats exposed to the same handlings. Both TS and NI10 pups treated or not with cocaine showed less anxiety-like behavior than animals submitted to other handlings. TS reduced protein carbonyl (PC) in cortex and NI60 increased PC in both striatum and hippocampus of cocaine-treated rats. Among cocaine-treated rats, both times of NI increased plasma lipoperoxidation levels, which was reduced by TS in erythrocytes. TS increased the catalase activity in brain areas, while other handlings did not change this. Both TS and NI10 increased plasma vitamin C levels. These findings indicate that neonatal handling can modify anxiety-like symptoms related to cocaine preference and abstinence, and its protective influence, especially TS, on the antioxidant system., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We evaluated the influence of fish oil (FO, rich in n-3 FA), soybean oil (SO, rich in n-6 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) on the oxidative status and viability of skin cells of mice exposed to ultraviolet radiation (UVR). Mice were supplemented with FO, SO or HVF for three months and exposed to UVR (2.72 mJ/cm(2)) for 2 days. One day after the last UVR session, the FO group showed higher levels of n-3 fatty acids (FA), while the HVF showed higher incorporation of trans FA (TFA) in dorsal skin. UVR increased lipid peroxidation and protein carbonyl levels of the HVF and to a lesser extent of the control and SO groups. Although all irradiated groups showed increased skin thickness, this increase was slighter in FO mice. UVR exposure reduced skin cell viability of the control, SO and HVF groups, while FO prevented this. Catalase activity was reduced independently of the supplementation and SOD level was increased in C and FO groups after UVR exposure; FO prevented the UVR-induced increase in glutathione levels, which was observed in skin of the control, SO and HVF mice. Our results showed the beneficial effects of FO supplementation, as well as the harmful effects of trans FA, whose intensity can increase vulnerability to skin diseases.

Because consumption of processed foods has increased in the last decades and so far its potential influence on emotionality and susceptibility to stress is unknown, we studied the influence of different fatty acids (FA) on behavioral and biochemical parameters after acute restrain stress (AS) exposure. Two sequential generations of female rats were supplemented with soybean oil (control group; C-SO), fish oil (FO) and hydrogenated vegetable fat (HVF) from pregnancy and during lactation. At 41days of age, half the animals of each supplemented group were exposed to AS and observed in open field and elevated plus maze task, followed by euthanasia for biochemical assessments. The HVF-supplemented group showed higher anxiety-like symptoms per se, while the C-SO and FO groups did not show these behaviors. Among groups exposed to AS, HVF showed locomotor restlessness in the open field, while both C-SO and HVF groups showed anxiety-like symptoms in the elevated plus maze, but this was not observed in the FO group. Biochemical evaluations showed higher lipoperoxidation levels and lower cell viability in cortex in the HVF group. In addition, HVF-treated rats showed reduced catalase activity in striatum and hippocampus, as well as increased generation of reactive species in striatum, while FO was associated with increased cell viability in the hippocampus. Among groups exposed to AS, HVF increased reactive species generation in the brain, decreased cell viability in the cortex and striatum, and decreased catalase activity in the striatum and hippocampus. Taken together, our findings show that the type of FA provided during development and growth over two generations is able to modify the brain oxidative status, which was particularly adversely affected by trans fat. In addition, the harmful influence of chronic consumption of trans fats as observed in this study can enhance emotionality and anxiety parameters resulting from stressful situations of everyday life, which can trigger more severe neuropsychiatric conditions., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

This study evaluated the sedative and anesthetic effects of the essential oils (EO) of Hyptis mutabilis (Rich.) Briq. and their isolated components on silver catfish (Rhamdia quelen). Quantitative chemical differences between the EOs obtained from leaves and inflorescences were verified, and a new chemotype rich in globulol was described. Although there were no significant differences in the time of induction for sedation and anesthesia between the EOs, only the leaf EO at 344 mg/L anesthetized all fish without side effects. Fractionation of the leaf EO was carried out by column chromatography. The isolated compounds [(+)-1-terpinen-4-ol and (-)-globulol] showed different activity from that detected for the leaf EO in proportional concentrations and similar sedation to a eugenol control at 10 mg/L. However, fish exposed to 1-terpinen-4-ol (3 and 10 mg/L) did not remain sedated for 30 min. Anesthesia was obtained with 83-190 mg/L globulol, but animals showed loss of mucus during induction and mortality at these concentrations. Synergism of the depressor effects was detected with the association of globulol and benzodiazepine (BDZ), compared with either drug alone. Fish exposed to BDZ or globulol+BDZ association showed faster recovery from anesthesia in water containing flumazenil, but the same did not occur with globulol. In conclusion, the use of globulol in aquaculture procedures should be considered only at sedative concentrations of 10 and 20 mg/L, and its mechanism of action seems not to involve the GABAA-BDZ system.

The current Western diet often provides considerable amounts of saturated and trans fatty acids (TFA), whose incorporation into neuronal membranes has been implicated in changes of brain neurochemical functions. Such influence has caused concerns due to precipitation of neuropsychiatric disorders, whose data are still unclear. Here we evaluated the influence of different fats on preference parameters for amphetamine (AMPH): adolescent rats were orally supplemented with soybean oil (SO, rich in n-6 FA, which was considered an isocaloric control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in saturated and trans FA) from weaning, which were born of dams supplemented with the same fat from pregnancy and lactation. AMPH preference, anxiety-like symptoms and locomotor index were evaluated in conditioned place preference (CPP), elevated plus maze (EPM) and open-field (OF), respectively, while brain oxidative status was determined in cortex, striatum and hippocampus. HVF increased AMPH-CPP and was associated with withdrawal signs, as observed by increased anxiety-like symptoms. Moreover, SO and FO were not associated with AMPH preference, but only FO-supplemented rats did not show any anxiety-like symptoms or increased locomotion. FO supplementation was related to lower oxidative damages to proteins and increased CAT activity in striatum and hippocampus, as well as increased GSH levels in blood, while HVF was related to increased oxidative status. In conclusion, our study showed the harmful influence of TFA on AMPH-CPP and drug craving symptoms, which can be related to dopaminergic neurotransmission., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The influence of dietary fatty acids (FA) on mania-like behavior and brain oxidative damage were evaluated in rats. First generation of rats born and maintained under supplementation with soybean-oil (SO), fish-oil (FO) or hydrogenated-vegetable-fat (HVF), which are rich in n-6, n-3 and trans (TFA) FA, respectively, until adulthood, were exposed to an amphetamine (AMPH)-induced mania animal model to behavioral and biochemical evaluations. While AMPH caused hyperlocomotion in HVF and, to a less extent, in SO- and FO-groups, a better memory performance was observed in FO group. Among vehicle-groups, HVF increased reactive species (RS) generation and protein-carbonyl (PC) levels in cortex; FO reduced RS generation in hippocampus and decreased PC levels in hippocampus and striatum. Among AMPH-treated animals, HVF exacerbated RS generation in all evaluated brain areas and increased PC levels in cortex and striatum; FO reduced RS generation in hippocampus and decreased PC levels in hippocampus and striatum. FO was related to higher percentage of polyunsaturated fatty acids (PUFA) and docosahexaenoic acid (DHA) in cortex and striatum, while HVF was associated to higher incorporation of TFA in cortex, hippocampus and striatum, besides increased n-6/n-3 FA ratio in striatum. While a continuous exposure to TFA may intensify oxidative events in brain, a prolonged FO consumption may prevent mania-like-behavior; enhance memory besides decreasing brain oxidative markers. A substantial inclusion of processed foods, instead of foods rich in omega-3, in the long term is able to influence the functionality of brain structures related to behavioral disturbances and weaker neuroprotection, whose impact should be considered by food safety authorities and psychiatry experts., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The aim of this study was to compare the effects of manganese (Mn) on silver catfish exposed to different levels of dissolved oxygen. Silver catfish (Rhamdia quelen) were exposed to increasing concentrations of Mn (4.2, 8.4 or 16.2mgL(-1)) under either normoxia (100 percent saturation) or moderate hypoxia (51.87 percent saturation) for 15 days. Under normoxia, Mn exposure increased lipid peroxidation (LP) in brain and kidney; it increased gluthatione (GSH) levels in brain and decreased catalase (CAT) activity in both tissues. Moderate hypoxia was able to prevent Mn-induced LP in brain and to reduce this oxidative parameter in kidney; GSH level was increased in brain, while CAT activity was reduced in both tissues. Activity of isolated mitochondria of liver and gills was reduced by Mn exposure under both levels of dissolved oxygen, but this effect was more prominent in normoxia. As expected, liver, kidney and gills showed an increase of Mn accumulation according to waterborne levels, and these parameters presented positive relationship. The highest waterborne Mn (8.4 and 16.2mgL(-1)) resulted in greater accumulation under normoxia, indicating that moderate hypoxia can stimulate mechanisms capable of reducing Mn accumulation in tissues (though not in blood). Moderate hypoxia can be considered a stress factor and Mn an aquatic anthropogenic contaminant. Therefore we hypothesized that these two conditions together are able to invoke defense mechanisms in juvenile silver catfish, acting in a compensatory form, which may be related to adaptation and/or hormesis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This study investigated the influence of neonatal handling on behavioral and biochemical consequences of chronic mild stress (CMS) in adulthood. Male rat pups were submitted to daily tactile stimulation (TS) or maternal separation (MS), from postnatal day 1 (PND1) to postnatal day 21 (PND21), for 10 min/day. In adulthood, half the number of animals were exposed to CMS for 3 weeks and submitted to behavioral testing, including sucrose preference (SP), elevated plus maze (EPM), and defensive burying tasks (DBTs), followed by biochemical assessments. CMS reduced SP, increased anxiety in EPM and DBT, and increased adrenal weight. In addition, CMS decreased plasma vitamin C (VIT C) levels and increased protein carbonyl (PC) levels, catalase (CAT) activity in hippocampus and cortex, and superoxide dismutase (SOD) levels in cortex. In contrast, both forms of neonatal handling were able to prevent reduction in SP, anxiety behavior in DBT, and CMS-induced adrenal weight increase. Furthermore, they were also able to prevent plasma VIT C reduction, hippocampal PC levels increase, CAT activity increase in hippocampus and cortex, and SOD levels increase in cortex following CMS. Only TS was able to prevent CMS-induced anxiety symptoms in EPM and PC levels in cortex. Taken together, these findings show the protective role of neonatal handling, especially TS, which may enhance ability to cope with stressful situations in adulthood.

Involuntary oral movements are present in several diseases and pharmacological conditions; however, their etiology and efficient treatments remain unclear. Gallic acid is a natural polyphenolic acid found in gall nuts, sumac, oak bark, tea leaves, grapes and wine, with potent antioxidant and antiapoptotic activity. Thus, the present study investigated the effects of gallic acid on vacuous chewing movements (VCMs) in an animal model induced by reserpine. Rats received either vehicle or reserpine (1mg/kg/day, s.c.) during three days, followed by treatment with water or different doses of gallic acid (4.5, 13.5 or 40.5mg/kg/day, p.o.) for three more days. As result, reserpine increased the number of VCMs in rats, and this effect was maintained for at least three days after its withdrawal. Gallic acid at two different doses (13.5 and 40.5mg/kg/day) has reduced VCMs in rats previously treated with reserpine. Furthermore, we investigated oxidative stress parameters (DCFH-DA oxidation, TBARS and thiol levels) and Na(+),K(+)-ATPase activity in striatum and cerebral cortex, however, no changes were observed. These findings show that gallic acid may have promissory use in the treatment of involuntary oral movements., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Haloperidol is the most widely used antipsychotic drug in the treatment of psychiatric disorders. Despite its satisfactory therapeutic effect, its chronic use is related to severe motor side effects. Here, we investigate the incidence of motor side effects of haloperidol-loaded nanocapsules when compared to free haloperidol and the relation with oxidative stress (OS) development. Both vehicle (B-NcFO) and haloperidol loaded polysorbate-coated nanocapsules suspension (H-NcFO) prepared with fish oil as core showed uniform and rounded particles, nanometric size, negative zeta potential, low polydispersity indices and high encapsulation efficiency. Wistar rats received a single dose of free haloperidol (FH), B-NcFO or H-NcFO (0.2 mg/kg ip) and were submitted to acute motor side effects evaluation 1 h after the injection. Lower catalepsy time and oral dyskinesia were observed in H-NcFO-treated group than in FH group; however, both formulations decreased animals' locomotor activity. In a experiment performed subchronically, rats injected daily with H-NcFO (0.2 mg/kg-ip) for 28 days showed decreased oral dyskinesia frequency and catalepsy time and no impairment on locomotor activity as compared to FH group (0.2 mg/kg-ip). FH group showed higher OS, as observed by increased lipid peroxidation and reduced glutathione levels and catalase activity in extrapyramidal region. Our findings showed that nanocapsules may be an efficient form to prevent or minimize haloperidol motor side effects, which are related to OS development, ameliorating psychiatric patients' quality of life., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In this study we evaluated the influence of neonatal tactile stimulation (TS) on behavioral and biochemical effects related to a low dose of diazepam (DZP) in adult rats. Male pups of Wistar rats were handled (TS) daily from PND1 to PND21 for 10 min, while unhandled (UH) rats were not touched. In adulthood, half the animals of each group received a single administration of diazepam (0.25mg/kg body weight i.p.) or vehicle and then were submitted to behavioral and biochemical evaluations. In the TS group, DZP administration reduced anxiety-like symptoms in different behavioral paradigms (elevated plus maze, EPM; staircase and open-field and defensive burying) and increased exploratory behavior. These findings show that neonatal TS increased DZP pharmacological responses in adulthood compared to neonatally UH animals, as observed by reduced anxiety-like symptoms and lower levels of plasma cortisol. TS also changed plasma levels of antioxidant defenses such as vitamin C and glutathione peroxidase, whose increase may be involved in lower oxidative damages to proteins in cortex, subthalamic region and hippocampus of these animals. Here we are showing for the first time that neonatal TS is able to change responsiveness to benzodiazepine drugs in adulthood and provides better pharmacological responses in novel situations of stress., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Development of a hydrogel containing rutin at 0.025% (w/w) and evaluation of its in vivo efficacy in cutaneous wound healing in rats., Methods: Hydrogels were prepared using Carbopol Ultrez® 10 NF and an aqueous dispersion of rutin in polysorbate 80. Hydrogels were characterized by means of pH measurement, rheological and spreadability analysis and rutin content determination by liquid chromatography. The in vivo healing effect was evaluated through the regression of skin lesions in rats and by analysis of oxidative stress., Results and Discussion: Hydrogels showed adequate pH values (5.50-6.50) and pseudoplastic non-Newtonian behavior. After 5 days of treatment of wounds, hydrogels containing rutin presented a higher decrease in the wound area compared to the control hydrogels. Analysis of the oxidative stress showed a decrease in lipid peroxidation and protein carbonyl content as well as an increase in catalase activity after the treatment with the hydrogel containing rutin. Furthermore, this treatment increased total protein levels., Conclusion: This study shows for the first time the feasibility of using dermatological formulations containing rutin to improve skin wound healing.

The objective of this study was to identify the possible involvement of the GABAergic system in the anesthetic effect of Lippia alba essential oil (EO). We propose a new animal model using silver catfish (Rhamdia quelen) exposed to an anesthetic bath to study the mechanism of action of EO. To observe the induction and potentiation of the anesthetic effect of EO, juvenile silver catfish (9.30 ± 1.85 g; 10.15 ± 0.95 cm; N = 6) were exposed to various concentrations of L. alba EO in the presence or absence of diazepam [an agonist of high-affinity binding sites for benzodiazepinic (BDZ) sites coupled to the GABA A receptor complex]. In another experiment, fish (N = 6) were initially anesthetized with the EO and then transferred to an anesthetic-free aquarium containing flumazenil (a selective antagonist of binding sites for BDZ coupled to the GABA A receptor complex) or water to assess recovery time from the anesthesia. In this case, flumazenil was used to observe the involvement of the GABA-BDZ receptor in the EO mechanism of action. The results showed that diazepam potentiates the anesthetic effect of EO at all concentrations tested. Fish exposed to diazepam and EO showed faster recovery from anesthesia when flumazenil was added to the recovery bath (12.0 ± 0.3 and 7.2 ± 0.7, respectively) than those exposed to water (9.2 ± 0.2 and 3.5 ± 0.3, respectively). In conclusion, the results demonstrated the involvement of the GABAergic system in the anesthetic effect of L. alba EO on silver catfish.

The influence of trans fatty acids (FA) on development of orofacial dyskinesia (OD) and locomotor activity was evaluated. Rats were fed with diets enriched with 20% soybean oil (SO; n-6 FA), lard (L; saturated FA) or hydrogenated vegetable fat (HVF; trans FA) for 60 weeks. In the last 12 weeks each group was subdivided into sedentary and exercised (swimming). Brains of HVF and L-fed rats incorporated 0.33% and 0.20% of trans FA, respectively, while SO-fed group showed no incorporation of trans FA. HVF increased OD, while exercise exacerbated this in L and HVF-fed rats. HVF and L reduced locomotor activity, and exercise did not modify. Striatal catalase activity was reduced by L and HVF, but exercise increased its activity in the HVF-fed group. Na(+)K(+)-ATPase activity was not modified by dietary FA, however it was increased by exercise in striatum of SO and L-fed rats. We hypothesized that movement disorders elicited by HVF and less by L could be related to increased dopamine levels in striatum, which have been related to chronic trans FA intake. Exercise increased OD possibly by increase of brain dopamine levels, which generates pro-oxidant metabolites. Thus, a long-term intake of trans FA caused a small but significant brain incorporation of trans FA, which favored development of movement disorders. Exercise worsened behavioral outcomes of HVF and L-fed rats and increased Na(+)K(+)-ATPase activity of L and SO-fed rats, indicating its benefits. HVF blunted beneficial effects of exercise, indicating a critical role of trans FA in brain neurochemistry., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na(+)K(+)-ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na(+)K(+)-ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na(+)K(+)-ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Acute reserpine and subchronic haloperidol are animal models of extrapyramidal disorders often used to study parkinsonism, akinesia and tardive dyskinesia. In humans, these usually irreversible and disabling extrapyramidal disorders are developed by typical antipsychotic treatment, whose pathophysiology has been related to oxidative damages development. So far, there is no treatment to prevent these problems of the psychiatric clinic, and therefore further studies are needed. Here we used the animal models of extrapyramidal disorders cited above, which were performed in two distinct experiments: orofacial dyskinesia (OD)/catalepsy induced by acute reserpine and subchronic haloperidol after (experiment 1) and before (experiment 2) oral treatment with pecan shell aqueous extract (AE), a natural and promissory antioxidant. When administered previously (exp.1), the AE prevented OD and catalepsy induced by both reserpine and haloperidol. When reserpine and haloperidol were administered before the extract (exp.2), the animals developed OD and catalepsy all the same. However, the orofacial parameter (but not catalepsy) in both animal models was reversed after 7 and 14 days of AE treatment. These results indicate that, acute reserpine and subchronic haloperidol administrations induced similar motor disorders, although through different mechanisms, and therefore are important animal models to study the physiopathology of extrapyramidal disorders. Comparatively, the pecan shell AE was able to both prevent and reverse OD but only to prevent catalepsy. These results reinforce the role of oxidative stress and validate the two animal models used here. Our findings also favor the idea of prevention of extrapyramidal disorders, rather than their reversal., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We investigated the antioxidant potential of gallic acid (GA), a natural compound found in vegetal sources, on the motor and oxidative damages induced by lead. Rats exposed to lead (50 mg/kg, i.p., once a day, 5 days) were treated with GA (13.5mg/kg, p.o.) or EDTA (110 mg/kg, i.p.) daily, for 3 days. Lead exposure decreased the locomotor and exploratory activities, reduced blood ALA-D activity, and increased brain catalase (CAT) activity without altering other antioxidant defenses. Brain oxidative stress (OS) estimated by lipid peroxidation (TBARS) and protein carbonyl were increased by lead. GA reversed the motor behavior parameters, the ALA-D activity, as well as the markers of OS changed by lead exposure. CAT activity remained high, possibly as a compensatory mechanism to eliminate hydroperoxides during lead poisoning. EDTA, a conventional chelating agent, was not beneficial on the lead-induced motor behavior and oxidative damages. Both GA (less) and EDTA (more) reduced the lead accumulation in brain tissue. Negative correlations were observed between the behavioral parameters and lipid peroxidation and the lead levels in brain tissue. In conclusion, GA may be an adjuvant in lead exposure, mainly by its antioxidant properties against the motor and oxidative damages resulting from such poisoning., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Fish oil (FO) supplementation could cause an increase in the concentration of plasmatic free fatty acids and, consequently, could compete with pro-inflammatory arachidonic acid (ARA) derived from brain biomembranes metabolism in the cerebrospinal fluid. Essential fatty acids (EFA) (n-3) have been reported by their antioxidant and neuroprotective properties, and therefore the influence of the FO supplementation on the reserpine-induced motor disorders was studied. Wistar rats were orally treated with FO solution for 5 days, and co-treated with reserpine (R; 1 mg/kg/mL) or its vehicle for 3 days (every other day). Reserpine-induced orofacial dyskinesia and catalepsy (P < 0.05) were prevented by FO (P < 0.05). Biochemical evaluations showed that reserpine treatment increased the lipid peroxidation in the cortex and striatum (P < 0.05), while the FO supplementation prevented this oxidative effect in both brain regions (P < 0.05). Our results showed the protective role of FO in the brain lipid membranes, reinforcing the beneficial effect of n-3 fatty acids in the prevention of degenerative and motor disorders.

Haloperidol is an antipsychotic drug associated with the development of movement disorders. We evaluated the effect of its nanoencapsulation on its pharmacological activity and motor side effects. Haloperidol-loaded polysorbate-coated nanocapsules (H-NC) showed nanometric size, negative zeta potential and low polydispersity indices and high encapsulation efficiency (>95%). Rats received a single dose of H-NC (0.2mg/kg ip) and four doses of D,L-amphetamine, AMPH (8.0mg/kg ip), injected every 3h (0, 3, 6 and 9h). The AMPH-induced stereotyped movements were quantified in the intervals of 15 min after each of four doses of AMPH, demonstrating greater pharmacological efficacy of the H-NC over free haloperidol (FH). The acute motor side effects were evaluated 1h after a single dose of H-NC or its free solution (0.2mg/kg ip). The group treated with H-NC presented lower extrapyramidal effects (catalepsy and oral dyskinesia) than those treated with FH. In the last experimental set, rats sub-chronically treated with a daily dose of H-NC (0.2mg/kg ip) for 28 days showed a lower incidence of extrapyramidal effects than those treated with the free drug (0.2mg/kg ip). Our findings showed the potential of using H-NC in the development of a nanomedicine aimed at increasing the efficacy of this antipsychotic drug and reducing its side effects., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Here we evaluate the influence of a new exercise protocol on movement disorders induced by neuroleptic drugs. In this animal model, involuntary movements are closely related to neuronal degeneration and oxidative stress (OS) that can be caused by pre-synaptic D2 receptor blockade increasing dopamine (DA) metabolism. The increase in vacuous chewing movements (VCM) and the reduced locomotor activity induced by haloperidol treatment (12 mg/kg-im, once a week for 4 weeks) was prevented by exercise, 5 times per week, which was initiated four weeks before the first haloperidol administration. Exercise training also prevented the increase of haloperidol-induced lipid peroxidation in the cortex and subcortical region and recovered the catalase activity in the subcortical region. There was a negative correlation between catalase activity in the subcortical region and the VCM frequency (r = 0.50, p < 0.05), as well as a positive correlation between VCM frequency and lipid peroxidation in the cortex (r = 0.64, p < 0.05) and subcortical region (r = 0.71, p < 0.0001). Both haloperidol and exercise increased DA uptake in the striatum, while the co-treatment (exercise plus haloperidol) reduced it. The striatal DA uptake correlated negatively with catalase activity (r = 0.51, p < 0.05), indicating a relationship between oxidative damage and the function of the transporter in the striatum. Our findings show that physical exercise can modulate dopamine uptake, especially when it is altered, and reveal the benefit of this new exercise protocol in the prevention of movement disorders related to oxidative damage., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

In the last decades, foods rich in omega-3 (ω-3) fatty acids (FA) have been replaced by omega-6 (ω-6) and trans FA, which are found in processed foods. The influence of ω-6 (soybean oil--SO), trans (hydrogenated vegetable fat--HVF) and ω-3 (fish oil--FO) fatty acids on locomotor and oxidative stress (OS) parameters were studied in an animal model of mania. Rats orally fed with SO, HVF and FO for 8 weeks received daily injections of amphetamine (AMPH--4 mg/kg/mL-ip) for the last week of oral supplementation. HVF induced hyperactivity, increased the protein carbonyl levels in the cortex and decreased the mitochondrial viability in cortex and striatum. AMPH-treatment increased the locomotion and decreased the mitochondrial viability in all groups, but its neurotoxicity was higher in the HVF group. Similarly, AMPH administration increased the protein carbonyl levels in striatum and cortex of HVF-supplemented rats. AMPH reduced the vitamin-C plasmatic levels of SO and HVF-fed rats, whereas no change was observed in the FO group. Our findings suggest that trans fatty acids increased the oxidative damage per se and exacerbated the AMPH-induced effects. The impact of trans fatty acids consumption on neuronal diseases and its consequences in brain functions must be further evaluated., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The effects of fish oil supplementation on motor disorders, memory dysfunction, and lipid peroxidation (LP) induced by typical neuroleptics were studied. Wistar rats received a suspension prepared with fish oil containing omega-3 fatty acids, water, and Tween 80 (1%) in the place of drinking water (FO group) or vehicle (C group) for 8 weeks. After 4 weeks of treatment, half of the animals of both groups were treated with haloperidol (H and FO + H groups; experiment 1), fluphenazine (F and FO + F groups; experiment 2), or vehicle (C group), administered once a week (12 mg/kg/im) for 4 weeks, maintaining the treatment with FO. Extrapyramidal motor disorders by haloperidol and fluphenazine were observed by an increase in vacuous chewing movements and catalepsy (P < 0.05). These effects were reduced by FO treatment (P < 0.05). Both neuroleptics displayed impairment in memory retention observed by latency time to find the original location of platform in water-maze task, after 4 days of training performed in the last treatment week. This effect was reduced by FO (P < 0.05) to both haloperidol and fluphenazine treatments. Haloperidol increased the LP in plasma and hippocampus, and these effects were decreased by FO treatment (P < 0.05). Fluphenazine increased the LP in plasma and substantia nigra, which were completely decreased by FO treatment (P < 0.05). The FO decreased the motor disorders, memory dysfunction, and oxidative damage typical neuroleptic-induced. Our results indicate that FO exhibits a neuroprotector role useful on diseases related to oxidative damages, and may be considered in the prevention of motor and memory side effects induced by the antipsychotic treatment.

This study investigated the antioxidant effects of pecan nut (Carya illinoensis) shell aqueous extract (AE) on toxicity induced by cyclophosphamide (CP) in the heart, kidney, liver, bladder, plasma and erythrocytes of rats. Rats were treated with water or pecan shell AE (5%) ad libitum, replacing drinking water for 37 days up to the end of the experiment. On day 30, half of each group received a single administration of vehicle or CP 200 mg/kg-ip. After 7 days, the organs were removed. Rats treated with CP showed an increase in lipid peroxidation (LP) and decrease in reduced glutathione (GSH) levels in all structures. Catalase (CAT) activity was increased in the heart and decreased in liver and kidney. Besides, CP treatment decreased plasmatic vitamin C (VIT C) levels and induced bladder macroscopical and microscopical damages. In contrast, co-treatment with pecan shell AE prevented the LP development and the GSH depletion in all structures, except in the heart and plasma, respectively. CAT activity in the heart and liver as well as the plasmatic VIT C levels remained unchanged. Finally, AE prevented CP-induced bladder injury. These findings revealed the protective role of pecan shell AE in CP-induced multiple organ toxicity.

Objective: This study evaluated the preliminary effects of intense physical training (swimming) on oxidative stress in rats with nutritional deficiencies., Methods: Rats were fed with a standard diet or a diet deficient in vitamins and minerals for 4 months. The deficient diet contained one-fourth of the recommended vitamin and mineral levels for rats. From the second month, half of the animals were subjected to a swimming exercise in a plastic container with water maintained at 34 +/- 1 degrees C for 1 h/d, five times per week, for 11 wk. The rats were subjected to swimming exercise with loads attached to the dorsal region, which were progressively increased according to their body weight (1% to 7%). Sedentary rats were transported to the experimental room and handled as often in a similar way as the exercise group, except that they were not put in water., Results: In the exercised group, blood lactate levels were significantly lower and the heart weight/body weight ratio was significantly higher than in the sedentary group (P < 0.05). Increased lipid peroxidation was observed in the liver, heart, and skeletal muscle of rats fed with the deficient diet, but it was completely reversed by exercise. Exercise also decreased lipid peroxidation levels in the heart and skeletal muscle of rats fed with the standard diet (P < 0.05)., Conclusion: This pilot study leads to the continuity of the studies, because the partial results observed suggest that inadequate nutrition may enhance oxidative stress, and that intense chronic physical training may activate antioxidant defenses, possibly by hormesis.

Considering the important role of oxidative stress in the pathogenesis of several neurological diseases, and the growing evidence of the presence of compounds with antioxidant properties in the plant extracts, the aim of the present study was to investigate the antioxidant capacity of three plants used in Brazil to treat neurological disorders: Melissa officinalis, Matricaria recutita and Cymbopogon citratus. The antioxidant effect of phenolic compounds commonly found in plant extracts, namely, quercetin, gallic acid, quercitrin and rutin was also examined for comparative purposes. Cerebral lipid peroxidation (assessed by TBARS) was induced by iron sulfate (10 microM), sodium nitroprusside (5 microM) or 3-nitropropionic acid (2 mM). Free radical scavenger properties and the chemical composition of plant extracts were assessed by 1'-1' Diphenyl-2' picrylhydrazyl (DPPH) method and by Thin Layer Chromatography (TLC), respectively. M. officinalis aqueous extract caused the highest decrease in TBARS production induced by all tested pro-oxidants. In the DPPH assay, M. officinalis presented also the best antioxidant effect, but, in this case, the antioxidant potencies were similar for the aqueous, methanolic and ethanolic extracts. Among the purified compounds, quercetin had the highest antioxidant activity followed by gallic acid, quercitrin and rutin. In this work, we have demonstrated that the plant extracts could protect against oxidative damage induced by various pro-oxidant agents that induce lipid peroxidation by different process. Thus, plant extracts could inhibit the generation of early chemical reactive species that subsequently initiate lipid peroxidation or, alternatively, they could block a common final pathway in the process of polyunsaturated fatty acids peroxidation. Our study indicates that M. officinalis could be considered an effective agent in the prevention of various neurological diseases associated with oxidative stress.

Regular physical activity exerts beneficial effects for mental and physical health, but an intense exercise can cause oxidative stress (OS) in dopaminergic regions and intensify the harmful effects of reserpine. Reserpine-induced neurotoxicity can be accessed by behavioral and biochemical evaluations. The objective of this study was to examine the effect of a gradual intensifying exercise program on an animal model of oxidative stress. Male rats were submitted to swimming sessions (1 h/day, for eleven weeks), and they were loaded gradually during the adaptation period (two weeks) with a weight corresponding to 1-7% of their body weight tied to their back. After the last training, the animals were treated with two doses of vehicle or reserpine (1 mg/kg-sc), an agent that induces orofacial dyskinesia. After behavioral evaluations, the striatum was dissected for enzymatic and biochemical assays. Development of cardiac hypertrophy demonstrated the effectiveness of the physical training. The gradual intense exercise and reserpine increased lipid peroxidation and striatal catalase activity. The results confirm the importance of catalase activity in orofacial dyskinesia which can be related to lipid peroxidation in striatal dopaminergic brain tissue. These results indicate that intense exercise can have some deleterious effect on striatal dopaminergic system.