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.

CaMKIIα mediates spermidine-induced memory enhancement in rats: A potential involvement of PKA/CREB pathway.

Memory consolidation is associated with the regulation of protein kinases, which impact synaptic functions and promote synaptogenesis. The administration of spermidine (SPD) has been shown to modulate major protein kinases associated with memory improvement, including the Ca2+-dependent protein kinase (PKC) and cAMP-dependent protein kinase (PKA), key players in the cAMP response element-binding protein (CREB) activation. Nevertheless, the initial mechanism underlying SPD-mediated memory consolidation remains unknown, as we hypothesize a potential involvement of the memory consolidation precursor, Ca2+/calmodulin-dependent protein kinase II-α (CaMKIIα), in this process. Based on this, our study aimed to investigate potential interactions among PKC, PKA, and CREB activation, mediated by CaMKIIα activation, in order to elucidate the SPD memory consolidation pathway. Our findings suggest that the post-training administration of the CaMKII inhibitor, KN-62 (0.25 nmol, intrahippocampal), prevented the memory enhancement induced by SPD (0.2 nmol, intrahippocampal) in the inhibitory avoidance task. Through western immunoblotting, we observed that phosphorylation of CaMKIIα in the hippocampus was facilitated 15 min after intrahippocampal SPD administration, resulting in the activation of PKA and CREB, 180 min after infusion, suggesting a possible sequential mechanism, since SPD with KN-62 infusion leads to a downregulation in CaMKIIα/PKA/CREB pathway. However, KN-62 does not alter the memory-facilitating effect of SPD on PKC, possibly demonstrating a parallel cascade in memory acquisition via PKA, without modulating CAMKIIα. These results suggest that memory enhancement induced by SPD administration involves crosstalk between CaMKIIα and PKA/CREB, with no PKC interaction.

From gains to gaps? How Selective Androgen Receptor Modulator (SARM) YK11 impact hippocampal function: In silico, in vivo, and ex vivo perspectives.

Selective Androgen Receptor Modulators (SARMs), particularly (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic-acid-methyl-ester (YK11), are increasingly popular among athletes seeking enhanced performance. Serving as an Androgen Receptor (AR) agonist, YK11 stimulates muscle growth while inhibiting myostatin. Our study delved into the impact of YK11 on the rat hippocampus, analyzing potential alterations in neurochemical mechanisms and investigating its synergistic effects with exercise (EXE), based on the strong relationship between SARM users and regular exercise. Utilizing Physiologically Based Pharmacokinetic (PBPK) modeling, we demonstrated YK11 remarkable brain permeability, with molecular docking analysis revealing YK11 inhibitory effects on 5-alpha-reductase type II (5αR2), suggesting high cell bioavailability. Throughout a 5-week experiment, we divided the animals into the following groups: Control, YK11 (0.35 g/kg), EXE (swimming exercise), and EXE + YK11. Our findings showed that YK11 displayed a high binding affinity with AR in the hippocampus, influencing neurochemical function and modulating aversive memory consolidation, including the downregulation of the BDNF/TrkB/CREB signaling, irrespective of EXE combination. In the hippocampus, YK11 increased pro-inflammatory IL-1ß and IL-6 cytokines, while reducing anti-inflammatory IL-10 levels. However, the EXE + YK11 group counteracted IL-6 effects and elevated IL-10. Analysis of apoptotic proteins revealed heightened p38 MAPK activity in response to YK11-induced inflammation, initiating the apoptotic cascade involving Bax/Bcl-2/cleaved caspase-3. Notably, the EXE + YK11 group mitigated alterations in Bcl-2 and cleaved caspase-3 proteins. In conclusion, our findings suggest that YK11, at anabolic doses, significantly alters hippocampal neurochemistry, leading to impairments in memory consolidation. This underscore concerns about the misuse risks of SARMs among athletes and challenges common perceptions of their minimal side effects.

Exposure to Bisphenol F and Bisphenol S during development induces autism-like endophenotypes in adult Drosophila melanogaster.

Bisphenol F (BPF) and Bisphenol S (BPS) are being widely used by the industry with the claim of "safer substances", even with the scarcity of toxicological studies. Given the etiological gap of autism spectrum disorder (ASD), the environment may be a causal factor, so we investigated whether exposure to BPF and BPS during the developmental period can induce ASD-like modeling in adult flies. Drosophila melanogaster flies were exposed during development (embryonic and larval period) to concentrations of 0.25, 0.5, and 1 mM of BPF and BPS, separately inserted into the food. When they transformed into pupae were transferred to a standard diet, ensuring that the flies (adult stage) did not have contact with bisphenols. Thus, after hatching, consolidated behavioral tests were carried out for studies with ASD-type models in flies. It was observed that 1 mM BPF and BPS caused hyperactivity (evidenced by open-field test, negative geotaxis, increased aggressiveness and reproduction of repetitive behaviors). The flies belonging to the 1 mM groups of BPF and BPS also showed reduced cognitive capacity, elucidated by the learning behavior through aversive stimulus. Within the population dynamics that flies exposed to 1 mM BPF and 0.5 and 1 mM BPS showed a change in social interaction, remaining more distant from each other. Exposure to 1 mM BPF, 0.5 and 1 mM BPS increased brain size and reduced Shank immunoreactivity of adult flies. These findings complement each other and show that exposure to BPF and BPS during the development period can elucidate a model with endophenotypes similar to ASD in adult flies. Furthermore, when analyzing comparatively, BPS demonstrated a greater potential for damage when compared to BPF. Therefore, in general these data sets contradict the idea that these substances can be used freely.

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.

Bisphenol F and Bisphenol S exposure during development reduce neuronal ganglia integrity and change behavioral profile of Drosophila melanogaster larvae.

The behavior and neuronal ganglia integrity of Drosophila melanogaster larvae exposed to Bisphenol F (BPF) and Bisphenol S (BPS) (0.25, 0.5 and 1 mM) was evaluated. Larvae exposed to BPF and BPS (0.5 and 1 mM) showed hyperactivity, reduced decision-making capacity and were not responsive to touch (no sensitivity to physical stimuli). There was also a reduction in the tunneling capacity induced by 1 mM of BPF and BPS (innate behaviors for survival). Behaviors resulting from changes in neuronal functioning, thermotaxis and phototaxis showed that BPS was more harmful compared to BPF. Furthermore, the concentration of 1 mM BPS generated greater damage to neuronal ganglia when compared to BPF. This difference may be related to the LC50 of the 10.04 mM BPS and 15.07 mM BPF. However, these behavioral changes presented by the larvae here are characteristic of those presented in neurodevelopmental disorders. Our findings are novel and refute the possibility that BPF and BPS are safer alternatives.

Evaluation of oxidative stress level: reactive oxygen species, reduced glutathione, and D-dimer in patients hospitalized due to COVID-19.

Elevated D-dimer levels at hospital admission may also indicate a higher likelihood of progressing to a severe or critical state. This study aimed to assess reactive oxygen species (ROS), non-enzymatic antioxidant reduced glutathione (GSH), and D-dimer levels in COVID-19 patients upon admission, examining their association with mortality outcomes. Data was collected from the medical records of 170 patients hospitalized in a referral hospital unit between March 2020 and December 2021. Patients were divided into two groups: the ward bed group (n = 87), comprising 51% with moderate clinical conditions, and the intensive care unit (ICU) group (n = 83), comprising 49% with severe conditions. The mean age was 59.4 years, with a male predominance of 52.4%. The overall death rate was 43%, with 30.6% in the moderate group and 69.4% in the severe group. The average time from symptom onset to hospitalization was 6.42 days. Results showed that non-survivors had high D-dimer and ROS counts, longer ICU stays, and worse saturation levels at admission. In conclusion, elevated ROS and D-dimer levels may contribute to worse outcomes in critically ill patients, potentially serving as specific and sensitive predictors of poor outcomes upon admission.

Evaluation of oxidative stress indicators as toxicity parameters after chronic exposure of Drosophila melanogaster to free curcumin and curcumin-loaded nanocapsules.

We investigated a possible toxic effect induced by chronic exposure to free curcumin and curcumin-loaded nanocapsules in Drosophila melanogaster, enabling safe applications. Flies of both sexes were divided into groups: control group; free curcumin at concentrations of 10, 30, 100, 300, 900, and 3000 µM; curcumin-loaded nanocapsules at concentrations of 10, 30, 100, and 300 µM. Initially, the diet consumption test was evaluated in flies exposed to different concentrations. During the 10-day treatment, the flies were evaluated for percentage survival. After the treatment, behaviors (geotaxis negative and open field), acetylcholinesterase activity (AChE), and oxidative stress parameters (reactive species (RS) and thiobarbituric acid reactive substances (TBARS) levels, Glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) enzymes activity, erythroid-derived nuclear factor 2 (Nrf2) immunoreactivity, and cellular metabolic capacity, were assessed. No significant difference in diet consumption, indicating that the flies equally consumed the different concentrations of free curcumin and the curcumin-loaded nanocapsules. Was observed that free curcumin and curcumin-loaded nanocapsules increased survival, locomotor and exploratory performance, decreased AChE activity, RS and TBARS levels, increased GST, SOD and CAT activity, Nrf2 and viable cells compared to the control. The chronic treatment did not cause toxicity, suggesting that nanoencapsulation of curcumin could be explored.

HDAC3 inhibition protects against peripheral and central alterations in an animal model of obesity.

BACKGROUND: Obesity is a multifactorial disease with epigenetic manifestations that increases the prevalence of associated comorbidities such as metabolic syndrome, cardiovascular dysfunction, and major depression disorder. Given the aforementioned, a search for new pharmacological alternatives for the treatment of this disease is necessary. The current study aimed to evaluate the effects of histone deacetylase-3 (HDAC3) inhibition caused by RGFP966 (a benzamide-type HDAC inhibitor selective for HDAC3) administration, in an animal model of obesity induced by high-fat diet (HFD). METHODS: Adult male mice C57BJ/6 were fed with a normal pellet diet (NPD) or HFD for 120 days. The HDAC3 inhibitor (RGFP966; 10 mg/kg; sc) was administered on the 91st to 120th day of the experiment (per 30 days). After the last inhibitor administration, animals were euthanized, blood was collected, and the hippocampus was removed for biochemical determinations. RESULTS: In an overall manner, the administration of RGFP966 protected against changes in body weight gain, glucose, insulin, lipid profile, adipokines, and increase of hippocampal proinflammatory cytokines levels caused by HFD. CONCLUSION: Therefore, HDAC3 inhibition can represent a promising pharmacological target for the treatment of obesity.

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.

YK11 induces oxidative stress and mitochondrial dysfunction in hippocampus: The interplay between a selective androgen receptor modulator (SARM) and exercise.

Our study investigates potential neurochemical effects of (17α,20E)- 17,20-[(1-methoxyethylidene)bis(oxy)]- 3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11), a selective androgen receptor modulator (SARM), in the rat hippocampus, with a particular focus on oxidative stress and mitochondrial function, as well as its potential effect when combined with exercise (EXE). To validate YK11's anabolic potential, we performed a molecular docking analysis with the androgen receptor (AR), which showed high affinity with YK11, highlighting hydrogen interactions in Arg752. During the five-week protocol, we divided male Wistar rats into the following groups: Control, YK11 (0.35 g/kg), EXE (swimming protocol), and EXE+YK11. The administration of YK11 resulted in alterations in the endogenous antioxidant system, promoting increased oxidative stress and proteotoxic effects, impairing all mitochondrial function markers in the hippocampus. In contrast, EXE alone had a neuroprotective effect, increasing antioxidant defenses and improving mitochondrial metabolism. When combined, EXE+YK11 prevented alterations in some mitochondrial toxicity markers, including MnSOD/SOD2 and MTT reduction capacity, but did not reverse YK11's neurochemical impairments regarding increased oxidative stress and dysfunction of the mitochondrial respiratory chain and mitochondrial dynamics regulatory proteins in the hippocampus. In summary, our study identifies important pathways of YK11's hippocampal effects, revealing its potential to promote oxidative stress and mitochondrial dysfunction, suggesting that the administration of YK11 may pose potential neurological risks for athletes and bodybuilders seeking to enhance performance. These findings highlight the need for further research to assess the safety and efficacy of YK11 and SARM use in humans.

Safer alternatives? Bisphenol F and Bisphenol S induce oxidative stress in Drosophila melanogaster larvae and trigger developmental damage.

Bisphenol F (BPF) and Bisphenol S (BPS) are safe alternatives substances? Here Drosophila melanogaster were exposed during development (larval stage) to BPF and BPS (0.25, 0.5 and 1 mM). Upon reaching the last larval stage (3rd stage), markers of oxidative stress and metabolism of both substances were evaluated, along with investigation of mitochondrial and cell viability. This study is attributed to an unprecedented fact: BPF and BPS exposed larvae, both at concentrations of 0.5 and 1 mM, showed higher cytochrome P-450 (CYP450) activity. The GST activity increased in all BPF and BPS concentrations, and reactive species, lipid peroxidation, superoxide dismutase, and catalase activity increased in larvae (BPF and BPS; 0.5, and 1 mM); nonetheless, mitochondrial and cell viability decreased with 1 mM of BPF and BPS. In addition, the reduced number of pupae formed in the 1 mM BPF and BPS groups and melanotic mass formation may be attributed to oxidative stress. From the pupae formed, the hatching rate reduced in the 0.5 and 1 mM BPF and BPS groups. Thus, the possible presence of toxic metabolites may be related to the larval oxidative stress condition, which is detrimental to the complete development of Drosophila melanogaster.

Exposure to Trans Fat During the Developmental Period of Drosophila melanogaster Alters the Composition of Fatty Acids in the Head and Induces Depression-like Behavior.

Given the importance of understanding the disorders caused by trans fatty acids (TFAs), this study sought to add different concentrations hydrogenated vegetable fat (HVF) to the diet of Drosophila melanogaster during the developmental period and evaluate the effects on neurobehavioral parameters. Longevity, hatching rate, and behavioral functions were assessed, such as negative geotaxis, forced swimming, light/dark, mating, and aggressiveness. The fatty acids (FAs) present in the heads of the flies were quantified as well as serotonin (5HT) and dopamine (DA) levels. Our findings showed that flies that received HVF at all concentrations during development showed reduced longevity and hatching rates, in addition to increased depression-like, anxious-like, anhedonia-like, and aggressive behaviors. As for the biochemical parameters, there was a more significant presence of TFA in flies exposed to HVF at all concentrations evaluated and lower 5HT and DA levels. This study shows that HVF during the developmental phase can cause neurological changes and consequently induce behavioral disorders, thereby highlighting the importance of the type of FA offered in the early stages of life.

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.

Lutein-loaded nanoparticles reverse oxidative stress, apoptosis, and autism spectrum disorder-like behaviors induced by prenatal valproic acid exposure in female rats.

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 (600 mg/kg), on the gestational day 12.5. The VPA-exposed female offspring rats were divided into two subgroups and received either lutein-loaded nanoparticles (5 mg/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.

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.

Relationship between toxicity and oxidative stress of the nanoencapsulated colchicine in a model of Drosophila melanogaster.

Drug repurposing allows searching for new biological targets, especially against emerging diseases such as Covid-19. Drug colchicine (COL) presents recognized anti-inflammatory action, while the nanotechnology purpose therapies with low doses, efficacy, and decrease the drug's side-effects. This study aims to evaluate the effects of COL and colchicine nanocapsules (NCCOL) on survival, LC50, activity locomotor, and oxidative stress parameters, elucidating the toxicity profile in acute and chronic exposure in Drosophila melanogaster. Three-day-old flies were investigated into groups: Control, 0.001, 0.0025, 0.005, and 0.010 mg/mL of COL or NCCOL. The survival rate, open field test, LC50, oxidative stress markers (reactive species (RS) production, thiobarbituric acid reactive substances), antioxidant enzyme activity (catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase), protein thiols, nonprotein thiols, acetylcholinesterase activity, and cell viability were measured. As a result, acute exposure to the COL decreases the number of crosses in the open field and increases CAT activity. NCCOL reduced RS levels, increased lipoperoxidation and SOD activity. Chronic exposure to the COL and NCCOL in high concentrations implied high mortality and enzymatic inhibition of the CAT and AChE, and only the COL caused locomotor damage in the open field test. Thus, NCCOL again reduced the formation of RS while COL increased. In this comparative study, NCCOL was less toxic to the antioxidant system than COL and showed notable involvement of oxidative stress as one of their toxicity mechanisms. Future studies are needed to elucidate all aspects of nanosafety related to the NCCOL.