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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and repetitive behaviors. In this study, we assessed the effect of lutein-loaded nanoparticles on ASD-like behaviors induced by prenatal valproic acid (VPA) exposure in female offspring rats and the possible involvement of oxidative stress and apoptosis. Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600mg/kg), on the gestational day 12.5. The VPA-exposed female offspring rats were divided into two subgroups and received either lutein-loaded nanoparticles (5mg/kg) or saline by oral gavage, for 14 days. The animals were submitted to the three-chamber test and open field to evaluate ASD-like behaviors. The hippocampus was removed for the determination of oxidative stress indicators (ROS; TBARS; SOD and Nrf2) and apoptosis biomarkers (Hsp-70; p38-MAPK; Bax and Bcl-2). The exposure to lutein-loaded nanoparticles reversed sociability deficit, social memory deficit, and anxiety-like and repetitive behaviors induced by VPA, and restored the oxidative stress indicators and apoptosis biomarkers in the hippocampus. This neurochemical effect must be associated with the reversal of ASD-like behaviors. These results provide evidence that lutein-loaded nanoparticles are an alternative treatment for VPA-induced behavioral damage in female rats and suggest the involvement of oxidative stress.

The potential of 4-PSQ on psychomotor and non-motor behaviors of PD, such as spontaneous locomotor activity, learning, memory, and anxiety.

Hypothyroidism is a condition that affects multiple systems, including the central nervous system, causing, for example, cognitive deficits closely related to Alzheimer's disease. The flavonoid chrysin is a natural compound associated with neuronal improvement in several experimental models. Here, we evaluated the effect of chrysin on cognitive impairment in hypothyroid female mice by exploring neuroplasticity. Hypothyroidism was induced by continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. On the 32nd day, the animals showed low plasma levels of thyroid hormones (hypothyroid mice) than the control group (euthyroid mice). Subsequently, mice were intragastrically administered with vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. At the end of the treatments, behavioral tests were performed: open-field test (OFT) and morris water maze (MWM). Then, the levels of neurotrophins (BDNF and NGF) in the hippocampus and prefrontal cortex were measured and tested the affinity of chrysin with neurotrophinergic receptors through molecular docking. Hypothyroid mice showed memory deficit in the MWM and reduced neurotrophins levels in the hippocampus and prefrontal cortex, meanwhile, the chrysin treatment was able to reversed the deficit of spatial memory function and increased the levels of BDNF in hipocamppus and NGF in both structures. Additionally, molecular docking analysis showed that chrysin potentially binds to the active site of the TrkA, TrkB, and p75NTR receptors. Together, these findings suggest that chrysin reversed behavioral and neurochemical alterations associated with memory deficit induced by hypothyroidism, possibly by modulating synaptic plasticity in the neurotrophinergic system.

Neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) are responsible for behavioral deficits in children. Imidacloprid is a nicotinic acetylcholine receptor agonist, capable of causing behavioral changes in Drosophila melanogaster, similar to the ADHD-like phenotypes. We assess whether behavioral damage induced by imidacloprid exposure in Drosophila melanogaster is associated with neurochemical changes and whether these changes are similar to those observed in neurodevelopmental disorders such as ASD and ADHD. The fruit flies were divided into four groups, exposed to either a standard diet (control) or a diet containing imidacloprid (200, 400 or 600 ρM) and allowed to mate for 7 days. After hatching, the progeny was subjected to in vivo and ex vivo tests. The ones exposed to imidacloprid showed an increase in hyperactivity, aggressiveness, anxiety and repetitive movements, as well as, a decrease in social interaction. Furthermore, exposure to imidacloprid decreased dopamine levels, cell viability and increased oxidative stress in the flies' progeny. These results demonstrated that the behavioral damage induced by imidacloprid exposure involves a reduction in dopamine levels and oxidative stress and that these neurochemical changes are in line with the events that occur in ASD and ADHD-like phenotypes in other models.

Manganese (Mn) is an essential element that, in excess, seems to be involved in the development of different neurodegenerative conditions. Gamma-oryzanol (Ory) was previously reported to possess antioxidant and neuroprotective properties. Thus, we conducted this study to test the hypothesis that Ory can also protect flies in an Mn intoxication model. Adult wild-type flies were fed over 10 days with Mn (5 mM) and/or Ory (25 μM). Flies treated with Mn had a decrease in locomotor activity and a higher mortality rate compared to those in controls. Mn-treated flies also had a significant increase in acetylcholinesterase (AChE) activity, in Mn accumulation and in oxidative stress markers. Moreover, flies treated with Mn exhibited a significant decrease in dopamine levels and in tyrosine hydroxylase activity, as well as in mitochondrial and cellular viability. Particularly important, Ory protected against mortality and avoided locomotor and biochemical changes associated with Mn exposure. However, Ory did not prevent the accumulation of Mn. The present results support the notion that Ory effectively attenuates detrimental changes associated with Mn exposure in Drosophila melanogaster, reinforcing its neuroprotective action/potential.

The experimental autoimmune encephalomyelitis (EAE) is a model that mimics multiple sclerosis in rodents. Evidence has suggested that the activation of indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme in the kynurenine pathway (KP), plays a crucial role in inflammation-related diseases. The present study aimed to investigate the involvement of the inflammatory process and KP components in a model of EAE in mice. To identify the role of KP in EAE pathogenesis, mice received IDO inhibitor (INCB024360) at a dose of 200 mg/kg (per oral) for 25 days. We demonstrated that IDO inhibitor mitigated the clinical signs of EAE, in parallel with the reduction of cytokine levels (brain, spinal cord, spleen and lymph node) and ionized calcium-binding adaptor protein-1 (Iba-1) gene expression in the central nervous system of EAE mice. Besides, IDO inhibitor causes a significant decrease in the levels of tryptophan, kynurenine and neurotoxic metabolites of KP, such as 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) in the prefrontal cortex, hippocampus, spinal cord, spleen and lymph node of EAE mice. The mRNA expression and enzyme activity of IDO and kynurenine 3-monooxygenase (KMO) were also reduced by IDO inhibitor. These findings indicate that the inflammatory process concomitant with the activation of IDO/KP is involved in the pathogenic mechanisms of EAE. The modulation of KP is a promising target for novel pharmacological treatment of MS.

This study aimed to evaluate the effects of the addition of saturated fat and hydrogenated vegetable fat (HVF) to the diet on depressive and anxiety-like behaviors in Drosophila melanogaster. Flies were exposed to experimental diets: regular diet (RD), or HVF in the concentrations of the substitute (SHVF), HVF 10% and HVF 20%, or Lard (L) in the concentrations of the substitute (SL), L 10% and L 20%, during seven days. Our results showed that flies fed with the HVF diet presented similar behaviors to depression, anxiety, and a higher number of aggressive events. Flies exposed to L showed only depressive-like behavior. Regarding serotonin levels (5HT), there was a significant reduction in the flies exposed to SHVF, HVF 10%, HVF 20%, and L 20%. Regarding the levels of octopamine (OA), there was a significant reduction in the flies exposed to both HVF and L rich diets when compared with the RD group. Also, there was a significant negative correlation between 5HT or OA levels and behaviors of aggressiveness, negative geotaxis, immobility time, light/dark, and grooming in the flies. This study shows that D. melanogaster can serve as a valuable model for understanding psychiatric disorders and that the type of fatty acid (FA) offered in the diet can influence these disorders. This demonstrates the importance of the composition of the FAs in the neural pathways, being able to influence the signaling of neurotransmitters, such as 5HT and OA, and thus, cause behavioral changes.

Background: ultraviolet radiation types A and B (UV) (400–315nm and 315–280nm respectively) are the main components present in sunlight known to cause skin injuries. Arnica montana is a plant that ...

Female and male Drosophila melanogaster were exposed separately for seven days to Bisphenol A (BPA), Bisphenol F (BPF), and Bisphenol S (BPS) at concentrations of 0.25, 0.5, and 1 mM. We observed that males exposed to 0.5 and 1 mM BPS showed lower catalase (CAT) activity and higher superoxide dismutase (SOD) and reactive species (RS); CAT activity decreased for BPF 0.5 and 1 mM. Nevertheless, BPA 0.5 and 1 mM decreased CAT activity, increased RS and lipid peroxidation (LPO), and reduced mitochondrial viability. None of the bisphenols altered the cell viability of male flies, although BPA 0.5 and 1 mM reduced longevity. In female flies, BPA and BPS 0.5 and 1 mM increased RS and LPO levels and decreased CAT activity and glutathione-S-transferase (GST), which may have contributed to lower mitochondrial and cell viability. Furthermore, BPS decreased SOD activity at the 1 mM concentration, and BPA reduced the SOD activity at concentrations of 0.5 and 1 mM. In the BPF 1 mM group, there was a reduction in GST activity and an increase in RS and LPO levels. The toxicological effects were different between sexes, and BPA was more harmful than BPF and BPS in male flies. Thus, our findings showed that females were more susceptible to oxidative cell damage when exposed to BPA and BPS than to BPF, and daily exposure to BPA and BPS at all concentrations reduced female longevity, as well as in BPF 1 mM.

Environmental factors are involved in the pathogenesis of neurodevelopmental disorders in addition to genetic factors. In this sense, we demonstrated here that the embryonic exposure of Drosophila melanogaster to Bisphenol A (BPA) 1 mM resulted in changes in development, behavior, and biochemical markers punctuated below. BPA did not alter the oviposition and viability of the eggs, however, it was evidenced a decrease in the rate of pupal eclosion and life span of the hatched flies of the generation filial 1 (F1). F1 flies also developed behavioral changes such as incompatibility in the social interaction between them, and hyperactivity demonstrated by increased locomotion in open field tests, increased grooming, and aggression episodes. Furthermore, decreases in dopamine levels and tyrosine hydroxylase activity have also been observed in flies' heads, possibly related to oxidative damage. Through analyzes of oxidative stress biomarkers, carried out on samples of flies’ heads, we observed an increase in malondialdehyde and reactive species, decrease in the activity of the superoxide dismutase and catalase, which possibly culminated in the reduction of cell viability. Thus, it is important to emphasize that BPA developed atypical behaviors in Drosophila melanogaster, reinforce the importance of the environmental factor in the development of neurobehavioral diseases.

Non-motor alterations such as anxiety and memory deficit may represent early indications of Parkinson's disease (PD), and therapeutic strategies that reduce non-motor alterations are promising alternatives for the treatment. Therefore, the search for natural compounds that act on motor and non-motor complications is highly relevant. In this sense, we demonstrated the role of hesperidin (Hsd) as a citrus flavonoid and its pharmacological properties as an antioxidant and neuroprotective agent. Our objective was to evaluate Hsd in developing motor and non-motor alterations in a Drosophila melanogaster model of Parkinson-like disease induced by iron (Fe) exposure. The flies were divided into six groups: control, Hsd (10 µM), L-dopa (positive control, 1 mM), Fe (1 mM), Fe + Hsd, and Fe + L-dopa. Motor coordination tests, memory assessment through aversive phototaxy, and anxiety-like behaviors characterized in flies, such as grooming and aggressiveness, were performed. The Hsd attenuated motor and non-motor alterations, such as motor coordination, memory deficits and anxiety-like behaviors, attenuated monoaminergic deficits, and lowered Fe levels in the head of flies. In addition, Hsd prolonged the life of the flies, thereby standing out from the L-dopa-treated group. Thus, Hsd can protect the dopaminergic system from insults caused by Fe, preventing non-motor alterations in PD; Hsd also reduced Fe levels in the flies' heads, suggesting that iron chelation may represent an important mechanism of action, in addition to its antioxidant action.

Association to early mortality and sedentarism was already demonstrated in the literature; nevertheless, some possible biochemical mechanisms around physical inactivity still need answers. The use of an invertebrate model, such as

Association to early mortality and sedentarism was already demonstrated in the literature; nevertheless, some possible biochemical mechanisms around physical inactivity still need answers. The use of an invertebrate model, such as Drosophila melanogaster, can reproduce reliable responses in inducing an exercise protocol with exogenous antioxidant supplementation. This study main evaluates the effect of exercise (EXE) associated with γ-oryzanol (ORY) supplementation to improve locomotor behavior, antioxidant defenses, and survival in Drosophila melanogaster. Two-day old flies were submitted to a protocol for seven days, divided into five groups: Control, Movement-Limited Flies (MLF), EXE, ORY [25 µM], and EXE + ORY [25 µM]. The survival rate was evaluated, followed by open field and negative geotaxis. Flies were euthanized and subjected to analysis for acetylcholinesterase (AChE) and antioxidant enzymes activity, glycidic and lipid parameters, body weight, reactive species (RS), and lipid peroxidation. EXE and EXE + ORY flies showed increased survival and locomotor activity, improved glycidic and lipid parameters, with a lower RS production, and increased antioxidant defenses compared to Control, and EXE + ORY when compared to the EXE group, obtained an increase in the ratio of protein levels/body weight, decreased ratio of triglyceride levels/body weight and decreased lipid peroxidation. However, MLF showed less survival and decreased locomotor activity, possibly due to increased AChE activity and reduced antioxidant defenses. The EXE and EXE + ORY demonstrate effective results in maintaining endogenous defenses, with increased locomotor activity, supporting evidence on EXE benefits, and supplementation with antioxidant compounds face of health paradigms.HighlightsNew protocol system of exercise on Drosophila melanogaster model.ORY demonstrates synergistic effect with EXE.Exercise with ORY supplementation increases locomotor behavior.Exercise with ORY supplementation decrease oxidative damages on flies. New protocol system of exercise on Drosophila melanogaster model. ORY demonstrates synergistic effect with EXE. Exercise with ORY supplementation increases locomotor behavior. Exercise with ORY supplementation decrease oxidative damages on flies.

Parkinson's is a neurodegenerative disease, characterized by the loss of dopaminergic neurons, cholinergic alterations and oxidative damages. Lutein is widely known by its antioxidants properties. In the present study, we investigated whether lutein-loaded nanoparticles protects against locomotor damage and neurotoxicity induced by Parkinson's disease model in Drosophila melanogaster, as well as possible mechanisms of action. First, the nanoparticles were characterized by physicochemical methods, demonstrating that water affinity was improved by the encapsulation of lutein into the polymeric encapsulant matrix. The fruit flies of 1–4 days old were divided into four groups and exposed to a standard diet (control), a diet containing either rotenone (500 μM), lutein-loaded nanoparticles (6 μM) or rotenone (500 μM) and lutein-loaded nanoparticles (6 μM) for 7 days. The survival percentage was assessed, the flies were submitted to negative geotaxis, open field tasks and the determination of dopamine levels, tyrosine hydroxylase (TH) and acetylcholinesterase activities and oxidative stress indicators (superoxide dismutase, catalase, thiobarbituric acid reactive substances and glutathione S-transferase) were carried out. The exposure to lutein-loaded nanoparticles protected against locomotor damage and the decrease survival rate induced by rotenone, besides, it restored the dopamine levels, TH and acetylcholinesterase activities and oxidative stress indicators. These results provide evidence that lutein-loaded nanoparticles are an alternative treatment for rotenone-induced damage, and suggest the involvement of dopaminergic and cholinergic system and oxidative stress.

Iron (Fe) is used in various cellular functions, and a constant balance between its uptake, transport, storage, and use is necessary to maintain its homeostasis in the body. Changes in Fe metabolism with a consequent overload of this metal are related to neurological changes and cover a broad spectrum of diseases, mainly when these changes occur during the embryonic period. This work aimed to evaluate the effect of exposure to Fe overload during the embryonic period of Drosophila melanogaster. Progenitor flies (male and female) were exposed to ferrous sulfate (FeSO4) for ten days in concentrations of 0.5, 1, and 5 ​mM. After mating and oviposition, the progenitors were removed and the treatment bottles preserved, and the number of daily hatches and cumulative hatching of the first filial generation (F1) were counted. Subsequently, F1 flies (separated by sex) were subjected to behavioral tests such as negative geotaxis test, open field test, grooming, and aggression test. They have evaluated the levels of dopamine (DA), serotonin (5-HT), octopamine (OA), tryptophan and tyrosine hydroxylase (TH), acetylcholinesterase, reactive species, and the levels of Fe in the progenitor flies and F1. The Fe levels of F1 flies are directly proportional to what is incorporated during the period of embryonic development; we also observed a delay in hatching and a reduction in the number of the hatch of F1 flies exposed during the embryonic period to the 5mM Fe diet, a fact that may be related to the reduction of the cell viability of the ovarian tissue of progenitor flies. The flies exposed to Fe (1 and 5 ​mM) showed an increase in locomotor activity (hyperactivity) and a significantly higher number of repetitive movements. In addition to a high number of aggressive encounters when compared to control flies. We can also observe an increase in the levels of biogenic amines DA and 5-HT and an increase in TH activity in flies exposed to Fe (1 and 5 ​mM) compared to the control group. We conclude that the hyperactive-like behavior demonstrated in both sexes by F1 flies exposed to Fe may be associated with a dysregulation in the levels of DA and 5-HT since Fe is a cofactor of TH, which had its activity increased in this study. Therefore, more attention is needed during the embryonic development period for exposure to Fe overload.

Mancozeb (MZ) is a broad-spectrum fungicide used worldwide in several crops. Neurological disorders in humans and animals have been associated with exposure to this compound by mechanisms still not fully understood. Drosophila melanogaster represents a reliable model in toxicological studies, presenting genetic and biochemical similarities with mammals. In this study, D. melanogaster flies were exposed for 15 days to MZ through the food (5 and 10 mg/mL). After that period, the efficiency of mitochondrial respiration complexes and metabolic markers were analyzed and evaluated. Flies presented weight loss, lower glucose, trehalose, and glycogen levels, and augmented levels of triglycerides concerning control (non-treated group). Acetyl-CoA Synthetase (ACeCS-1) and Acyl-Coenzyme Synthetase (ACSL1) contents were unchanged by MZ treatment. Mitochondrial respiration of flies was targeted by MZ treatment, evidenced by a decrease in oxygen consumption and bioenergetics rate and inhibition in mitochondrial complexes I/II. These results suppose that an impairment in mitochondrial respiration jointly with reduced levels of energetic substrates might be a mechanism involved in MZ deleterious effects, possibly by the limitation of ATP's availability, necessary for essential cellular processes., Respiration, ACeCl-1, Mitochondria, Mancozeb, Drosophila melanogaster, Glucose.

Chronic unpredictable mild stress (CUMS) is a valid model for inducing depression-like symptoms in animal models, causing predictive behavioral, neurochemical, and physiological responses to this condition. This work aims to evaluate the possible antidepressant effect of γ-oryzanol (ORY) in the CUMS-induced depressive model in male

The mechanisms underlying the neuroprotective effects of hesperidin in a murine model of PD are not fully elucidated. The current study was carried out to investigate the ability of hesperidin in modulating proinflammatory cytokines, neurotrophic factors, and neuronal recovery in 6-hydroxydopamine (6-OHDA)-induced nigral dopaminergic neuronal loss. Adult male C57BL/6 mice were randomly assigned into four groups: (I) sham/vehicle, (II) sham/hesperidin, (III) 6-OHDA/vehicle, and (IV) 6-OHDA/hesperidin. Mice received a unilateral intrastriatal injection of 6-OHDA and treated with hesperidin (50 mg/kg; per oral) for 28 days. After hesperidin treatment, mice were submitted to behavioral tests and had the striatum removed for neurochemical assays. Our results demonstrated that oral treatment with hesperidin ameliorated the anxiety-related and depressive-like behaviors in 6-OHDA-lesioned mice (p

Chronic unpredictable mild stress (CUMS) is a valid model for inducing depression-like symptoms in animal models, causing predictive behavioral, neurochemical, and physiological responses to this condition. This work aims to evaluate the possible antidepressant effect of γ-oryzanol (ORY) in the CUMS-induced depressive model in male Drosophila melanogaster. We will use the CUMS protocol to continue the study previously conducted by our research group, mimicking a depressive state in these insects. Male flies were subjected to various stressors according to a 10-day randomized schedule and concomitantly treated with ORY or fluoxetine (FLX). After the experimental period, in vivo behavioral tests were performed (open field, forced swimming, aggressiveness test, mating test, male virility, sucrose preference index and light/dark test) and ex vivo analyses measuring serotonin (5HT), dopamine (DA), octopamine (OCT) levels and body weight. We report here that ORY-treated flies and concomitant exposure to CUMS did not exhibit obvious behaviors such as prolonged immobility or increased aggressive behavior, reduced male mating and virility behavior, and anxiolytic behavior, in contrast to ORY, not altering sucrose preference and body weight flies exposed to CUMS. ORY effectively prevented 5HT and OCT reduction and partially protected against DA reduction. The data presented here are consistent and provide evidence for the use of ORY as a potential antidepressant compound.Lay SummaryFlies treated with ORY and concomitant exposure to CUMS did not exhibit obvious depressive-like behaviors, such as prolonged immobility in the FST or increased aggressive behavior, or reduced mating behavior, male virility, or anxiolytic behavior. ORY did not change the preference for sucrose and body weight of flies, about the levels of monoamines in the heads of flies, ORY was effective in preventing the reduction of 5HT and OCT, and we had partial protection of ORY for reducing the levels of DA. Flies treated with ORY and concomitant exposure to CUMS did not exhibit obvious depressive-like behaviors, such as prolonged immobility in the FST or increased aggressive behavior, or reduced mating behavior, male virility, or anxiolytic behavior. ORY did not change the preference for sucrose and body weight of flies, about the levels of monoamines in the heads of flies, ORY was effective in preventing the reduction of 5HT and OCT, and we had partial protection of ORY for reducing the levels of DA.

This study aimed to evaluate the antimicrobial activity of 2-phenylethynyl-butyltellurium (PEBT) in Escherichia coli and the relation to its pro-oxidant effect. For this, we carried out disk diffusion test, minimum inhibitory concentration (MIC) assay, and survival curve analysis. We also measured the level of extracellular reactive oxygen species (ROS), activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and level of non-protein thiols (NPSH). PEBT at 1.28 and 0.128 mg/disk exhibited antimicrobial capability in the disk diffusion test, with an MIC value of 1.92 mg/ml, whereas PEBT at 0.96, 1.92, and 3.84mg/ml inhibited bacterial growth after a 9-h exposure. PEBT at 3.84, 1.92, and 0.96 mg/ml increased extracellular ROS production, decreased the intracellular NPSH level, and reduced the SOD and CAT activities. Glutathione or ascorbic acid in the medium protected the bacterial cells from the antimicrobial effect of PEBT. In conclusion, PEBT exhibited antimicrobial activity against E. coli, involving the generation of ROS, oxidation of NPSH, and reduction of the antioxidant defenses in the bacterial cells.

Monosodium glutamate (MSG) is the most widely used additive in the food industry; however, some adverse effects of this additive, including functional, learning, and behavioral alterations, have been observed in experimental animals and humans. Studies have shown learning and memory impairment in adult animals exposed to MSG. However, studies relating exposure to MSG to acetylcholinesterase (AChE) and Na+, K+-ATPase activities and memory damage are still scarce in the literature. The aim of the present study was to assess the possible protective effects of selenofuranoside, an organoselenium compound, against the impairment of long-term memory, Na+, K+-ATPase and AChE activities, and oxidative stress after MSG exposure in rats. MSG (2g/kg) and/or selenofuranoside (5mg/kg) were administered orally to 5-week-old male Wistar rats for 10days. On the 10th day, after the administration of last dose of the drug(s), the rats were subjected to behavioral tests: the open-field test and step-down passive avoidance task (SDPA). The blood, liver, kidney, cortex, and hippocampus were removed to determine the oxidative stress parameters, such as the levels of reactive species, lipid peroxidation, antioxidant enzyme activities, and endogenous nonenzymatic antioxidant content. Furthermore, the cortex and hippocampus were used to determine the Na+, K+-ATPase and AChE activities. The results demonstrate that the administration of MSG led to long-term memory impairment, as shown in the SDPA task, and also hippocampal and cortical Na+, K+-ATPase inhibition. There were no alterations in the AChE activity and oxidative stress parameters. Treatment with selenofuranoside attenuated memory impairment associated with MSG exposure by improving the hippocampal Na+, K+-ATPase activity.

This study has evaluated the action of flavonoid hesperidin on the neurotoxic effects caused by the intake of iron (Fe) in Drosophila melanogaster . Male adult flies, aged 1–3 days, have been divided into four groups of 50 each: (1) control, (2) Hsd 10 μM, (3) Fe 20 mM (4) Hsd 10 μM + Fe 20 mM. During the exposure protocol, the flies have been exposed to a diet containing Hsd and/or Fe for 48 h. The survival and behavioral analyses have been carried out in vivo , and ex vivo . The analyses involved acetylcholinesterase (AChE) activity and Fe levels in the flies' heads and bodies and determination of dopaminergic levels, cellular and mitochondrial viability, activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reactive species levels (RS), thiobarbituric acid reactive substances (TBARS) and contents of total thiols and non-proteic thiols (NPSH) in the flies' heads. A significant negative correlation between Fe levels in the head of the flies and the survival, dopamine levels and antioxidant enzymes in the head of the flies has been found. Additionally, significant positive correlation between Fe levels in the head of the flies with negative geotaxis RS and AChE activity in the head of the flies has been found. It demonstrates that the flies which had higher levels of Fe in their heads have demonstrated more susceptibility to neurotoxicity. An important result from our study is that Hsd treatment promotes a decrease in Fe concentration in the head, restores dopamine levels and cholinergic activity of the flies and improves motor function caused by Fe. Hsd also ameliorates Fe induced mortality, oxidative stress and mitochondrial dysfunction. Our results have demonstrated the neuroprotective effect of Hsd and it suggests that flavonoid acts in different ways to protect against the Parkinson disease caused by Fe exposure such as the direct scavenging of RS and activation of antioxidant enzymes.

This study aimed to characterize, evaluate toxicity and optimize the conditions for the growth and production of bacteriocin-like substances by Lactobacillus curvatus P99. The antibacterial activity of the cell-free supernatant (CFS) containing bacteriocin-like substances was evaluated by the agar diffusion technique. The stability of the CFS was also examined after heat treatment, refrigeration, freezing, pH variations, and treatment with different chemical substances. The toxic effect of CFS on Drosophila melanogaster diet was determined by calculating the survival rate of the flies. The effects of pH, temperature, and incubation time were the parameters used to optimize cell growth and production of bacteriocin-like substances through response surface methodology. The CFS was stable for 36 weeks under freezing and refrigeration, as well as under heat treatment, in acidic and basic pH and for all chemical substances tested. Fewer than 50,000 AU/mL of CFS added to D. melanogaster diet showed no toxic effect. The optimum growth condition was pH 6.3 at 29.3 °C for 18.6 h, and the optimum production of bacteriocin-like substances was under pH 6.22 at 30.6 °C for 17.9 h. The data on the optimization of cell growth and the characterization and optimization of bacteriocin-like substances provided information to support the industrial-scale production of this microorganism and its metabolites.

Some studies have showed that intake of blackberry juice (BBJ) can prevent urinary tract infections. However, there is a lack of studies that evaluate the mechanisms by which BBJ has protective effect. Thus, the aim of current study was to evaluate the effects of BBJ supplementation on cisplatin-induced renal pathophysiology in mice. Mice were supplemented with BBJ (10 mL/kg) for seven days. One hour after the last supplementation with BBJ, mice received cisplatin (10 mg/kg, i.p.). Seventy-two hours after cisplatin administration, blood was collected and biochemical analysis were performed (urea and creatinine), kidney was dissected and utilized in histological and oxidative evaluations. Cisplatin caused severe injury in renal tissue, in markers of renal damage (urea and creatinine) generated increased of plasmatic levels. Besides that, the cisplatin induced decreased of enzymes activities in renal tissue (superoxide dismutase, glutathione S-transferase and catalase). In contrast, BBJ supplementation protected against histopathological alterations through decreased in urea and creatinine levels and modulation of catalase enzyme activity. Thus, BBJ supplementation protected the renal system of mice from deleterious effects. We suggest that high concentrations of Cyanidin 3-O-glucoside and Cyanidin 3-O-rutinoside are responsible for antioxidant role of BBJ supplementation in renal pathophysiology induced by cisplatin exposure. Also, these results reinforcing the importance of including BBJ in the human diet aimed at preventing renal diseases.

Mancozeb (MZ) is a broad-spectrum fungicide used worldwide in several crops. Neurological disorders in humans and animals have been associated with exposure to this compound by mechanisms still not fully understood. Drosophila melanogaster represents a reliable model in toxicological studies, presenting genetic and biochemical similarities with mammals. In this study, D. melanogaster flies were exposed for 15 days to MZ through the food (5 and 10 mg/mL). After that period, the efficiency of mitochondrial respiration complexes and metabolic markers were analyzed and evaluated. Flies presented weight loss, lower glucose, trehalose, and glycogen levels, and augmented levels of triglycerides concerning control (non-treated group). Acetyl-CoA Synthetase (ACeCS-1) and Acyl-Coenzyme Synthetase (ACSL1) contents were unchanged by MZ treatment. Mitochondrial respiration of flies was targeted by MZ treatment, evidenced by a decrease in oxygen consumption and bioenergetics rate and inhibition in mitochondrial complexes I/II. These results suppose that an impairment in mitochondrial respiration jointly with reduced levels of energetic substrates might be a mechanism involved in MZ deleterious effects, possibly by the limitation of ATP's availability, necessary for essential cellular processes.

The goals of this work were to evaluate the effects produced by a hyperglycidic diet (HD) on Drosophila melanogaster and to verify the protective effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on this model. Adult flies were divided into eight groups of 50 flies each: (1) RD, (regular diet) (2) RD + 4-PSQ (25 μM), (3) HD 5%, (4) HD 10%, (5) HD 30% (6) HD 5% + 4-PSQ (25 μM), (7) HD 10% + 4-PSQ (25 μM) and (8) HD 30% + 4-PSQ (25 μM). Flies were exposed to a diet containing sucrose and or 4-PSQ for ten days, according to each group. At the end of treatment survival rate, longevity, hatch rate, food intake, glucose and triglyceride levels, as well as, some markers of oxidative stress, such as thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and catalase (CAT) activities, protein thiol (PSH) and non-protein levels (NPSH) and cell viability assays (Resazurin and MTT) were evaluated. It was observed that HD's consumption was associated with lower survival of the flies, lower longevity, and increased levels of glucose, triglycerides, TBARS and increased SOD activities and CAT activities. Treatment with 25 μM 4-PSQ increased the satiety of flies, increased survival, reduced glucose, triglyceride and TBARS levels, increased hatching, and normalized SOD and CAT activities. These results suggest that 25 μM 4-PSQ had a potential antioxidant effect and provided greater satiety by attenuating the effects of high HD consumption on this model.

This study aims to investigate the protective effect of p-chloro-phenyl-selenoesterol [PCS; 0,2 mg/kg; 10 ml/kg i.g.) in colitis induced by 2,4,6-trinitrobenzene sulfonic acid [TNBS; 2 mg/100 µl 50% ethanol; intrarectally) in mice. Several parameters including weight, length, histological analyses determination, thiobarbituric acid reactive species, reactive species levels, superoxide dismutase, catalase, and myeloperoxidase (MPO) activity of colon were evaluated. The serum levels of tumor necrosis factor alpha [TNF-α) and interleukin 6 [IL-6) were also assessed. Treatment with PCS reduced the clinical and histopathologic severity of TNBS-induced colitis, characterized by colon length reduction and increased colon weight and microscopic intestinal inflammation. The therapeutic effects of PCS in this model were associated with significant decrease in proinflammatory cytokines TNF-α and IL-6 and decrease in MPO activity. Furthermore, combined with improvements in inflammatory parameters, treatment with the PCS was able to decrease oxidative stress and to prevent the decrease in antioxidant defenses in animals with TNBS-induced colitis. This finding suggests that PCS can improve experimental colitis in mice and it could be a potential therapeutic agent for the treatment of patients with IBD. J. Cell. Biochem. 118: 709-717, 2017. © 2016 Wiley Periodicals, Inc.

Isoquinolines are formed endogenously as metabolites of neurotransmitters and are studied because they have structures similar to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and selegiline, a selective inhibitor of MAO-B. This study investigated a possible in vitro inhibitory activity of new 4-organochalcogen-isoquinoline derivatives, containing sulfur 1, selenium 2 or tellurium 3 on MAO-A and B activities. Considering that the non-substituted selenoisoquinoline derivative 2 showed the best inhibitory profile (IC50 = 36.45 μM), new compounds were synthesized by adding substituents (methyl 2a, fluorine 2b, chloro 2c and trifluoromethyl 2d) to the aromatic ring bonded to the selenium atom of compound 2. All tested compounds were selective MAO-B inhibitors, although only the substituted isoquinoline derivative 2b showed IC50 lower than the concentration of 100 μM (IC50 = 82.41 μM). Compounds 2 and 2b were chosen to study the inhibitory profile. These compounds demonstrated reversible and mixed inhibition by decreasing apparent V (app) max and increasing apparent K (app) m, however the non-substituted compound 2 was a more potent inhibitor than the substituted compound 2b (K i = 7.07 and 16.30 μM). In conclusion, selenoisoquinolines 2 and 2b fit in the profile of third generation MAO inhibitors (selective and reversible), which are promising alternatives for treatment of emotional and neurodegenerative disorders.

The synthesis of a new series of organochalcogen-derivatives, 2-alkyl/arylchalcogenyl- N -(4-aryl-1,3-thiazol-2-yl)acetamides 5a – r , provided products in satisfactory yields, which varied from 42% to 95%. All these novel compounds were screened for their in vitro free radical scavenging activity against 2,2-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. Compounds 5 ( m , h , i , f , q , g , l , c , n ) were effective scavengers against the ABTS radical species but less effective on scavenging the DPPH radical, indicating that the antioxidant effect of these compounds were related to protonated radical scavenger activity.

Nandrolone decanoate (ND) belongs to the class II of anabolic–androgenic steroids (AAS), which is composed of 19-nor-testosterone-derivatives. AAS represent a group of synthetic testosterone that is used in clinical treatment. However, these drugs are widely abused among individuals as a means of promoting muscle growth or enhancing athletic performance. AAS in general and ND in particular have been associated with several behavioral disturbances, such as anxiety, aggressiveness and depression. A factor that contributes to the development of depression is the brain activation of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of kynurenine pathway (KP). In the present study, we examined the involvement of KP in depressive phenotype induced by a ND treatment (10 mg/kg/day/s.c., for 28 days) that mimics human abuse system (e.g. supraphysiological doses) in C57B/6J mice. Our results showed that ND caused depressive like-behavior in the tail suspension test and anhedonic-like state measured in the sucrose preference test. ND administration decreased the levels of brain-derived neurotrophic factor and neurotrophin-3 and reduced Na+,K+-ATPase activity in the hippocampus, striatum and prefrontal cortex. We also found that ND elicited KP activation, as reflected by the increase of IDO activity and kynurenine levels in these brain regions. Moreover, ND decreased serotonin levels and increased 5-hydroxyindoleacetic acid levels in the brain. Treatment with IDO inhibitor 1-methyl- dl -trypthophan (1 mg/kg/i.p.) reversed the behavioral and neurochemical alterations induced by ND. These results indicate for the first time that KP plays a key role in depressive-like behavior and neurotoxicity induced by supraphysiological doses of ND in mice.

Abnormalities in the thyroid hormones, like in hypothyroidism, are closely related to dementia and Alzheimer's disease demonstrating the main symptom of these disorders: memory deficit. In this study we evaluated the effect of chrysin on deficit spatial and aversive memories and the contribution of glutamatergic, cholinergic pathways and Na+, K+-ATPase activity on hippocampus and prefrontal cortex in hypothyroid adult female mice C57BL/6. Hypothyroidism was induced by the continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. The exposure to MTZ was associated to low plasma levels of thyroid hormones (TH) compared to the control group on the 32nd. Subsequently, euthyroid and MTZ-induced hypothyroid mice received (intragastrically) either vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. After treatments mice performed the following behavioral assessments: open-field test (OFT), morris water maze (MWM) and passive avoidance test. Additionally, plasma TH levels were measured again, as well as glutamate levels, Na+,K+-ATPase and acetylcholinesterase (AChE) activities were analyzed in the hippocampus and prefrontal cortex of mice. Mice with hypothyroidism showed a deficit of spatial and aversive memory and chrysin treatment reversed these deficits. It also reduced the levels of glutamate and decreased Na+,K+-ATPase activity in both cerebral structures in the hypothyroid mice compared with the euthyroid ones, with the exception of glutamate in the hippocampus, which was a partial reversal. AChE activity was not altered by treatments. Together, our results demonstrate that chrysin normalized hippocampal glutamate levels and Na+,K+-ATPase activity, which could be involved in the reversal of memory deficit.

The pathogenesis of Parkinson's disease has not been fully clarified yet but its cause is known to be multifactorial. One of these factors is oxidative stress induced by exposure to environmental toxifiers. We studied the effect of Bisphenol A (BPA) at concentrations of 0.5 mM and 1 mM, the concentration of 1 mM corresponding to Lowest Observed Adverse Effect Level (LOAEL) for humans in adult Drosophila melanogaster. The BPA induced oxidative stress was established by increased levels of malondialdehyde, reactive species, and decreased activity of the antioxidant enzymes superoxide dismutase and catalase, and detoxificant enzyme glutathione-S-transferase. Associated with oxidative stress, there was a reduction of acetylcholinesterase activity and a reduction of dopamine levels, which are related to the decreased locomotion activity as observed in negative geotaxis, open field and equilibrium behaviors in group exposed to 1 mM of BPA. Oxidative stress also impaired mitochondrial and cellular metabolic activity in the head causing an increase in the mortality of flies exposed to both BPA concentrations. Therefore, BPA induced Parkinsonian-like changes in flies and it is possible that the oxidative stress is closely related to this effect, providing new insights for future studies.

Neurodegeneration in Parkinson's disease appears to be caused by multiple factors, including oxidative damage and an increase in acetylcholinesterase expression that can culminate in loss of dopaminergic neurons. A selenium-containing quinoline derivative, 7-chloro-4-(phenylselanyl) quinoline (4-PSQ), shows important pharmacological actions mainly attributed to its antioxidant and anticholinesterase properties. Thus, this study investigated the neuroprotective effect of 4-PSQ in a model of Parkinson’s-like disease induced by rotenone (ROT) in Drosophila melanogaster and verified whether these effects are related to selenium levels. Adult flies were divided into: [1] control, [2] 4-PSQ (25 μM), [3] ROT (500 μM), and [4] 4-PSQ (25 μM) + ROT (500 μM) groups and exposed to a diet containing ROT and/or 4-PSQ for 7 days, according to their respective groups. Survival, behavioral, and ex vivo analyses were performed. Dopamine levels, reactive species levels (RS), lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activity, and proteic thiol (PSH) and non-proteic thiol (NPSH) content in the head region were analyzed, while acetylcholinesterase (AChE) activity and selenium levels in the head and body regions were analyzed. 4-PSQ was able to reverse the ROT-induced deficits in flies, reestablish dopamine and selenium levels, reverse cholinergic deficits, improve motor function, and ameliorate mortality. Furthermore, 4-PSQ also reduced RS levels and LPO, and restored the activities of the antioxidant enzymes, SOD and CAT. Interestingly, a positive relationship between dopamine and selenium levels could be seen. Our results demonstrate the neuroprotective effect of 4-PSQ, and we suggest that the compound may act via different mechanisms, such as improving antioxidant defenses and consequently reducing oxidative damages, as well as having an anticholinesterase action, which together can prevent dopamine depletion, as these actions were correlated with the presence of selenium in the 4-PSQ molecule.

The etiopathogenesis of depression may involve repeated exposure to several unpredictable stressors. This study was conducted to investigate changes induced by chronic unpredictable mild stress (CUMS) and to assess behavioral and neurochemical changes that predict depressive-like behavior in Drosophila melanogaster. Male Drosophila melanogaster flies were exposed to CUMS with several stressors (cold, heat, starvation, and sleep deprivation) in an unpredictable and chronic manner for ten days. At the end of treatment, in vivo behavioral tests (open field, aggression, forced swimming, mating, light/dark box, male fertility evaluation, sucrose preference, weight evaluation) and ex vivo analyses (dopamine and serotonin levels) were performed. Using this CUMS model, we obtained results that contribute to the construction of a depressive model in Drosophila, where we reproduce some behavioral phenotypes corresponding to depressive symptoms, such as immobility in the forced swimming test, less exploration in the light/dark test, changes in mating behavior, changes in the aggressiveness test, reduced sucrose preference, and weight-loss, in addition to a significant reduction in the levels of serotonin and dopamine when compared to the control group. Fluoxetine was used in our study as a positive control to demonstrate that CUMS-induced depressive-like behaviors in flies can be reversed by antidepressants. In conclusion, male Drosophila melanogaster exposed to CUMS display a depressive-like phenotype, and, while this poses some limitations as an animal model for depression, it meets some of the criteria required to be a valid model, such as good face and construct validity.