Toxicological analysis of chronic exposure to polymeric nanocapsules with different coatings in Drosophila melanogaster.

Nanotechnology involves the utilization of nanomaterials, including polymeric nanocapsules (NCs) that are drug carriers. For modify drug release and stability, nanoformulations can feature different types of polymers as surface coatings: Polysorbate 80 (P80), Polyethylene glycol (PEG), Chitosan (CS) and Eudragit (EUD). Although nanoencapsulation aims to reduce side effects, these polymers can interact with living organisms, inducing events in the antioxidant system. Thus far, little has been described about the impacts of chronic exposure, with Drosophila melanogaster being an in vivo model for characterizing the toxicology of these polymers. This study analyzes the effects of chronic exposure to polymeric NCs with different coatings. Flies were exposed to 10, 50, 100, and 500 µL of NCP80, NCPEG, NCCS, or EUD. The survival rate, locomotor changes, oxidative stress markers, cell viability, and Nrf2 expression were evaluated. Between the coatings, NCPEG had minimal effects, as only 500 µL affected the levels of reactive species (RS) and the enzymatic activities of catalase (CAT) and glutathione S-transferase (GST) without reducing Nrf2 expression. However, NCEUD significantly impacted the total flies killed, RS, CAT, and Superoxide dismutase from 100 µL. In part, the toxicity mechanisms of these coatings can be explained by the imbalance of the antioxidant system. This research provided initial evidence on the chronic toxicology of these nanomaterials in D. melanogaster to clarify the nanosafety profile of these polymers in future nanoformulations. Further investigations are essential to characterize possible biochemical pathways involved in the toxicity of these polymeric coatings.

Oxidative damage analysis and cell viability of Drosophila melanogaster exposed to three different endodontic sealers: an in vivo and ex vivo study.

The aim of this work was to evaluate the toxicological action of AH Plus (AHP), Bio-C Sealer (BCS), and EndoSequence BC Sealer (ESB), using Drosophila melanogaster as the model organism performing in vivo and ex vivo analysis. D. melanogaster were exposed for 10 days to three concentrations (5 mg/ml, 10 mg/ml, and 20 mg/ml) of AHP, BCS, and ESB sealers mixed with 10 ml of standard diet. During this period, the mortality of flies was evaluated. On the 11th day, the locomotor activity test was performed and the flies were euthanized for oxidative damage analysis (reactive species and lipid peroxidation) and cell viability (resazurin reduction). For the mortality curves evaluation, the log-rank test (Mantel-Cox) was used. For the analysis of other data, a one-way analysis of variance (ANOVA) was applied, followed by Tukey's post hoc test (α = 0.05). Regarding mortality, there were no significant differences. The locomotor activity was reduced, mainly in the two highest concentrations of AHP and BCS. Besides, reactive species generation was bigger in the AHP 20 mg/ml group. AHP induced a lipid peroxidation increase in all three concentrations tested, when compared to other sealers. Considering cell viability, the two highest concentrations of AHP reduced this parameter; while in other sealers, viability was reduced only in the highest concentration. AHP showed changes in oxidative markers that led to greater damage to the flies.

Early exposure to trans fat causes cognitive impairment by modulating the expression of proteins associated with oxidative stress and synaptic plasticity in Drosophila melanogaster.

Evidence has shown that consuming trans fatty acids (TFA) during development leads to their incorporation into the nervous tissue, resulting in neurological changes in flies. In this study, Drosophila melanogaster was exposed to different concentrations of hydrogenated vegetable fat (HVF) during development: substitute hydrogenated vegetable fat (SHVF), HVF 10 %, and HVF 20 %. The objective was to evaluate the effects of early trans fat exposure on cognition and associated pathways in flies. The results showed that early TFA exposure provoked a cerebral redox imbalance, as confirmed by increased reactive species (HVF 10 and 20 %) and lipid peroxidation (SHVF, HVF 10, and 20 %), reduced nuclear factor erythroid 2-related factor 2 immunoreactivity (HVF 10 and 20 %), and increased heat shock protein 70 (HVF 20 %), which was possibly responsible for decreasing superoxide dismutase (SHVF, HVF 10, and 20 %) and catalase (HVF 20 %) activities. Furthermore, the presence of TFA in nervous tissue impaired learning (HVF 10 and 20 %) and memory at 6 and 24 h (SHVF, HVF 10, and 20 %). These cognitive impairments may be linked to reduced Shank levels (HVF 20 %) and increased acetylcholinesterase activity (SHVF, HVF 10 and 20 %) observed. Our findings demonstrate that early exposure to trans fat leads to cerebral redox imbalance, altering proteins associated with stress, synaptic plasticity, and the cholinergic system, consequently leading to cognitive impairment in flies.

The Amazonian Camu-Camu Fruit Modulates the Development of Drosophila melanogaster and the Neural Function of Adult Flies under Oxidative Stress Conditions.

Camu-camu (Myrciaria dubia) is known for its antioxidant properties, although little is known about its developmental safety effects, particularly on adult neural function under basal redox and oxidative stress conditions. Therefore, this study sought to address this gap by conducting three complementary protocols using Drosophila melanogaster to investigate these effects. The initial assays revealed that second-stage larvae consumed diets supplemented with various concentrations of camu-camu uniformly, establishing a 50% lethal concentration at 4.799 mg/mL. Hence, non-lethal (0.1, 0.5, and 1 mg/mL) and sub-lethal (5 and 10 mg/mL) concentrations were then chosen to evaluate the effects of camu-camu on preimaginal development and adult neural function. Our observations showed that camu-camu impacts the expression of antioxidant enzymes, reactive species, and lipoperoxidation. Notably, sub-lethal concentrations decreased preimaginal viability and locomotor activity, negatively influenced geotaxis and acetylcholinesterase activity, and increased reactive species, catalase, and glutathione S-transferase activity in flies. Additionally, the protective effects of camu-camu against oxidative stress induced by iron (20 mM) were assessed. Flies supplemented with 0.5 mg/mL of camu-camu during the larval period showed improved neural viability and function, and this supplementation was found to protect against oxidative stress. These findings are instrumental in evaluating the safety and efficacy of commercial supplements based on camu-camu, offering significant insights for future research and application.

The implications of exercise in Drosophila melanogaster: insights into Akt/p38 MAPK/Nrf2 pathway associated with Hsp70 regulation in redox balance maintenance.

This study investigated the potential effects of exercise on the responses of energy metabolism, redox balance maintenance, and apoptosis regulation in Drosophila melanogaster to shed more light on the mechanisms underlying the increased performance that this emerging exercise model provides. Three groups were evaluated for seven days: the control (no exercise or locomotor limitations), movement-limited flies (MLF) (no exercise, with locomotor limitations), and EXE (with exercise, no locomotor limitations). The EXE flies demonstrated greater endurance-like tolerance in the swimming test, associated with increased citrate synthase activity, lactate dehydrogenase activity and lactate levels, and metabolic markers in exercise. Notably, the EXE protocol regulated the Akt/p38 MAPK/Nrf2 pathway, which was associated with decreased Hsp70 activation, culminating in glutathione turnover regulation. Moreover, reducing the locomotion environment in the MLF group decreased endurance-like tolerance and did not alter citrate synthase activity, lactate dehydrogenase activity, or lactate levels. The MLF treatment promoted a pro-oxidant effect, altering the Akt/p38 MAPK/Nrf2 pathway and increasing Hsp70 levels, leading to a poorly-regulated glutathione system. Lastly, we demonstrated that exercise could modulate major metabolic responses in Drosophila melanogaster aerobic and anaerobic metabolism, associated with apoptosis and cellular redox balance maintenance in an emergent exercise model.

ß-carotene-loaded nanoparticles protect against neuromotor damage, oxidative stress, and dopamine deficits in a model of Parkinson's disease in Drosophila melanogaster.

ß-carotene-loaded nanoparticles improves absorption by increasing bioavailability. The Drosophila melanogaster model of Parkinson's disease must be helpful in investigating potential neuroprotective effects. Four groups of four-day-old flies were exposed to: (1) control; (2) diet containing rotenone (500 µM); (3) ß-carotene-loaded nanoparticles (20 µM); (4) ß-carotene-loaded nanoparticles and rotenone for 7 days. Then, the percentage of survival, geotaxis tests, open field, aversive phototaxis and food consumption were evaluated. At the end of the behaviors, the analyses of the levels of reactive species (ROS), thiobarbituric acid reactive substances (TBARS), catalase (CAT) and superoxide dismutase (SOD) activity was carried out, as well as an evaluation of the levels of dopamine and acetylcholinesterase (AChE) activity, in the head of flies. Nanoparticles loaded with ß-carotene were able to improve motor function, memory, survival and also restored the oxidative stress indicators (CAT, SOD, ROS and TBARS), dopamine levels, AChE activity after exposure to rotenone. Overall, nanoparticles loaded with ß-carotene showed significant neuroprotective effect against damage induced by the Parkinson-like disease model, emerging as a possible treatment. Overall, ß-carotene-loaded nanoparticles presented significant neuroprotective effect against damage induced by model of Parkinson-like disease, emerging as a possible treatment.

Sex-specific changes in oxidative stress parameters and longevity produced by Bisphenol F and S compared to Bisphenol A in Drosophila melanogaster.

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.

Improvement of non-motor and motor behavioral alterations associated with Parkinson-like disease in Drosophila melanogaster: Comparative effects of treatments with hesperidin and L-dopa.

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.

Bisphenol A exposure during the embryonic period: Insights into dopamine relationship and behavioral disorders in Drosophila melanogaster.

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.

Oxidative stress and decreased dopamine levels induced by imidacloprid exposure cause behavioral changes in a neurodevelopmental disorder model in Drosophila melanogaster.

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.

Iron overload during the embryonic period develops hyperactive like behavior and dysregulation of biogenic amines in Drosophila melanogaster.

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 â€‹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 â€‹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 â€‹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.

Exercise associated with γ-oryzanol supplementation suppresses oxidative stress and prevents changes in locomotion in Drosophila melanogaster.

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.

Protective effect of gamma-oryzanol against manganese-induced toxicity in Drosophila melanogaster.

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.

γ-Oryzanol produces an antidepressant-like effect in a chronic unpredictable mild stress model of depression in Drosophila melanogaster.

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.

Addition of Saturated and Trans-fatty Acids to the Diet Induces Depressive and Anxiety-like Behaviors in Drosophila melanogaster.

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.

Modulation of glutamate levels and Na+,K+-ATPase activity contributes to the chrysin memory recovery in hypothyroidism 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.

Bisphenol A exposure is involved in the development of Parkinson like disease in Drosophila melanogaster.

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.