Brain Acetylcholinesterase Activity Research Articles

Effects of burnt tire-ash on Na+/K+, Ca2+-ATPase, serum immunoglobulin and brain acetylcholinesterase activities in clarias gariepinus (Burchell, 1822)

Aquatic pollution may continue to deepen following the emergence of new class of toxicants. The present study investigated the effect of water-soluble fraction of burnt tire-ash on Clarias gariepinus. The fish were exposed to sublethal doses; 0.00 g/L, 2.24 g/L, 1.12 g/L and 0.56 g/L of tire-ash solution, representing 1/5, 1/10 and 1/20 of 11.2 g/L median lethal concentration (96 LC50), for 28 days, followed by 14 days recovery trial. Biological sampling was done on exposure day 1, 14 and 28, and on day14 recovery period for biochemical analysis such as the liver and gill Na+/K+ and Ca2+-ATPase, serum immunoglobulin (IgM) and brain acetylcholinesterase (AChE) of the experimental fish. Also, body biomass and behavior were evaluated. The behavioral responses exhibited by the fish to BTA exposure include reduced feeding, hypoactivity, air gulping and skin discoloration, which was observed to be concentration dependent. The body weight of 2.24 g/L and 1.12 g/L BTA-exposed fish decreased significantly than 0.56 g/L exposed fish and the control. Furthermore, findings revealed evident induction of Na+/K+ and Ca2 +-ATPase activities in both tissues, elevation of serum immunoglobulin content and inhibition of AChE activity in the brain of the exposed fish relative to the control. However, it was also observed that the biochemical parameters normalized after the recovery period. In conclusion, water-soluble fraction of burnt tire-ash produced toxicological effects in the experimental model, hence the present study provides the ecotoxicological insight of tire ash.

Design, Synthesis and Evaluation of Benzimidazole Hybrids to Inhibit Acetylcholinesterase and COX for Treatment of Alzheimer's Disease.

A simultaneous administration of an acetylcholinesterase (AChE) inhibitor and a NSAID as a drug cocktail has been documented to exhibit significantly protective effects in AD patients. But it suffers from poor patent compliance, pharmacodynamics and pharmacokinetic issues. The present study is aimed to design and synthesize a hybrid molecule capable of exhibiting both AChE inhibition and anti-inflammatory activities for de-accelerating the progression of AD. The synthesized molecules will be evaluated for in vitro and in vivo models. The present study involves the coupling of ibuprofen or naproxen to varied disubstituted amines (AChE inhibitor pharmacophore) through benzimidazole to develop two series of compounds i.e. IB01-IB05 and NP01-NP05. The synthesized compounds were characterized using FTIR, 1H-NMR, 13C-NMR and MS. All compounds were evaluated for in vitro AChE inhibitory and COX inhibitory activities. The most active compound was taken for in vivo evaluation. Compounds of series IB01-IB05 are found more potent as compared to NP01-NP05. The maximally potent compound IB04 in in vitro evaluation is selected for in vivo evaluation of memory restoration activity using scopolamine-induced amnesia model in mice. It significantly reverses the scopolamine-induced changes (i.e., escape latency time, mean time spent in target quadrant, brain AChE activity and oxidative stress) in a dose-dependent manner. IB04 at 8 mg/kg is significantly effective in lowering AD manifestation in comparison to donepezil. The findings indicate that Benzimidazole hybrids utilizing ibuprofen and pyrrolidine moiety may prove a useful template for the development of new chemical moieties against AD with multiple potencies.

Acute Toxicity Test and Nootropic Activity of Ethanolic Extract of Astragalus membranaceus Bunge on Scopolamine-Induced Amnesia in Rats

The dried roots of Astragalus membranaceus Bunge, belongs to the family fabaceae enhances the memory function and this could be mediated through brain cholinergic system. Historically in China it is used as a medicine for treatment of different types of diseases. It gives good protection against aging and age related diseases. Astragalus membranaceus Bunge root extract was investigated to reveal its nootropic effect and acute toxicity study. The powdered roots were tested for the phytochemical constituents. Carbohydrates, proteins, amino acids, glycosides, saponins, volatile oils, alkaloids, sterols and flavonoids were present. The acute toxicity study of ethanolic extract was carried out according to the OECD test guideline 423. There were no signs of toxicity of rats even with a maximum dose of 2000 mg/kg of the extract during 14 days. For evaluation of nootropic activity, ethanolic extract was administered by oral route to scopolamine induced amnesic rat model. The reduction of acetylcholinesterase activity in the rat brain supports the elevated plus maze (EPM) and passive avoidance test by improving memory function by lowering acetylcholinesterase activity. Present study shows Astragalus membranaceus Bunge root extract possesses significant nootropic activity in scopolamine induced amnesia rat models.
 Keywords: Astragalus membranaceus Bunge, EPM, passive avoidance, nootropic, acetyl Cholinesterase and Scopolamine.

Hematotoxic, oxidative and genotoxic damage in rainbow trout (Oncorhynchus mykiss) after exposure to 3-benzoylpyridine

Pyridine is a basic heterocyclic organic compound. The pyridine ring is present in many important compounds, including agricultural chemicals, medicines and vitamins. Due to their widespread industrial use, bioaccumulation and non-target toxic effects are being considered as a great risk to human and environmental health. In this study, we aimed to evaluate the hematological, oxidative and genotoxic damage potentials by different concentrations (1, 1.5, and 2 g/L) of the ketone 3-Benzoylpyridine (3BP) on rainbow trout (Oncorhynchus mykiss). Alterations in the biomarker levels of oxidative DNA damage (8-hydroxy-2′-deoxyguanosine (8-OHdG)), apoptosis (Caspase-3), malondialdehyde (MDA) as well as antioxidant enzyme activities including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), myeloperoxidase (MPO), paraoxonase (PON), and arylesterase (AR) were assessed in brain, liver, gill and blood tissues. Acetylcholinesterase (AChE) activity was also determined in brain tissue. In addition, we analyzed micronucleus (MN) rates and hematological indices of total erythrocyte count (RBC), total leukocyte count (WBC), hemoglobin (Hb), hematocrit (Hct), total platelet count (PLT), mean cell hemoglobin concentration (MCHC), mean cell hemoglobin (MCH), and mean cell volume (MCV) in blood. LC50-96h value of 3BP was calculated as 5.2 g/L from the data obtained. A significant decrease in brain AChE activity was determined in clear time and dose dependent manners. While SOD, CAT, GPx, PON, and AR levels were decreased, MDA, MPO, 8-OHdG and Caspase-3 levels were increased in all tissues (p < 0.05). Again, the 3BP led to increases of MN formation at all applied concentrations in the rates of between 45.4 and 72.7%. Significant differences (p < 0.05) were found out in between all studied hematology parameters between 3BP-exposed and the control fish. In conclusion, ours study firstly indicated that the treatment doses of 3BP induced distinct hematological and oxidative alterations as well as genotoxic damage in rainbow trout.

Steel wools microfibers causes iron overload and induces biochemical changes in Gallus gallus domesticus chicks (Galliformes: Phasianidae)

Steel wool (SW) has a broad-spectrum of applicability, particularly as abrasives, cleaning household utensils and surfaces in general. However, when present in the natural environment, they can be ingested by animals, such as birds, and may represent a risk to the survival of individuals. Accordingly, in this study, we attempted the hypothesis that the ingestion of SW microfibers (SWMs) by Gallus gallus domesticus chicks (model system used) alters growth/development, induces redox imbalance and cholinesterasic effect, as well as promotes iron overload in different organs. For this, the animals received SWMs twice (within a 24-h interval) in an amount corresponding to 12% of their total stomach volume. At the end of the experiment, we observed less weight gain and less head growth, increased production of hydrogen peroxide (in the brain, liver, crop, and gizzard), nitrite (liver, crop, proventriculus and gizzard), malondialdehyde (brain, liver, muscle, proventriculus, and gizzard), along with increased superoxide dismutase activity in the liver, muscle and crop of animals exposed to SWMs. Such results were associated with iron overload observed in different organs, especially in liver, crop, and gizzard. Furthermore, we evidenced an anti-cholinesterasic effect in birds that ingested the SWMs, marked by a reduction in the acetylcholinesterase activity (in brain). Thus, our study sheds light on the (eco)toxicological potential of SWMs in avifauna, conceding us to associate their ingestion (despite ephemeral and occasional) with damage to the health of individuals, requiring a greater attention spotted to disposal of these materials in ecosystems.

Cholinesterase activity as a potential biomarker for neurotoxicity induced by pesticides in vivo exposed Oreochromis niloticus (Nile tilapia): assessment tool for organophosphates and synthetic pyrethroids

ABSTRACT Organophosphates (OPs) and synthetic pyrethroids (SPs) are the most popular broad spectrum pesticides, used in agriculture as they have a strong pesticidal activity while also being biodegradable in the environment. The present study aimed to demonstrate the effects of these pesticides on the Acetylcholinesterase (AChE) activity in brain, gills and body muscles of Oreochromis niloticus – an important enzyme for the assessment and biomonitoring pollution caused by neurotoxins in the environment. The fish were exposed for 24 and 48 h to the LC0 concentrations of the malathion (1.425 mg/L), the chlorpyrifos (0.125 mg/L) and the λ-cyhalothrin (0.0039 mg/L), respectively. The activity of the AChE was significantly increased (p < 0.05) at 24 h and decreased at 48 h (except for the chlorpyrifos-treated brain and gills while tissues had shown no activity at 48 h’s exposure) in all pesticides-treated tissues. The maximum increase in the activity and inhibition in the AChE activity were recorded as +92% and −52% in the chlorpyrifos and the lambda-cyhalothrin exposed brain tissues, respectively. Thus, the alterations in the AChE activities indicated that the applied pesticides are highly neurotoxic to fish and the enzyme (AChE) could be used as a useful biomarker for estimation of water pollution.

Effect of grewia hirsuta vahl ethanolic root extract on cognition in scopolamine induced amnesia

Objective Alzheimer's illnesses are becoming medical nightmares because there is no exact solution and existing nootropic medicines (Piracetam, tacrine, and metrifonate) have significant drawbacks. The goal of this study was to see if the ethanolic root extract of Grewia hirsuta (ERGH) could improve memory in rats who had been given scopolamine.&#x0D; Materials and procedures At rats, ERGH was given orally in dosages of 200 and 400 mg/kg for 28 days, followed by Scopolamine (18 mg/kg i.p.) from the 25th to the 27th day. The usual nootropic drug was piracetam (200 mg/kg). The elevated plus maze (EPM), Morris water maze (MWM), and passive avoidance (PA) paradigms are used to assess cognitive functioning. Invivo anti-oxidant activity and brain acetylcholine esterase (AchE) activity were assessed.&#x0D; Results: At the indicated doses, ERGH extract showed a substantial memory-enhancing activity by decreasing the transfer latency in EPM, increasing the escape latency in MWM, and increasing the shock-free zone in PA. In scopolamine-induced amnesia rats, pretreatment with ERGH resulted in a significant drop in AchE enzyme, an increase in enzymatic antioxidant, and a decrease in MDA levels.&#x0D; Conclusion Because of its several favorable benefits, such as memory-improving properties, anticholinesterase activity, and antioxidant activity, ERGH may prove to be a useful drug in the current study, and it would be important to investigate its potential in the care of Alzheimer's patients.

Sleep Deprivation Affects Brain Acetylcholinesterase Activity and Cognitive Ability in Young and Aged Rats

Sleep plays an important role in maintaining neuronal circuitry, signalling and helps maintain overall health and wellbeing. Sleep deprivation (SD) disturbs the circadian physiology and exerts a negative impact on brain and behavioural functions. SD impairs the cellular clearance of misfolded neurotoxin various proteins which are involved in major neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease. SD affects the immunological and redox system resulting in neuroinflammation and oxidative stress. The aim of the present study is to investigate sleep deprivation (SD) induced oxidative stress in different parts of the brain and in vivo behavioural changes associated with aging. Lipid peroxidation and reduced antioxidant status were significantly (p&lt;0.05) increased along with the altered learning and memory ability. The most affected part of the brain was hippocampus followed by cerebral cortex. Acetyl cholinesterase was found to be altered in SD treated rats. These are remarkably correlated with the cognitive impairment. Aging is the affects more deleterious effect. It is also evident that SD induces premature aging in the study.

P‐Coumaric acid protects against D‐galactose induced neurotoxicity by attenuating neuroinflammation and apoptosis in mice brain

AbstractBackgroundD‐galactose (D‐gal) induced senescence in rodents is a widely used Alzheimer’s model. Chronic administration of D‐gal causes neuroinflammation leading to cognitive deficit and memory impairment.MethodPresent study investigated the neuroprotective effects of the natural phenol, p‐Coumaric acid (PCA) and its underlying mechanism against the chronic D‐gal induced senescence in Swiss albino mice. D‐gal (150 mg/kg) was administration s.c.ly to mice for 42 consecutive days.ResultD‐gal produced cognitive impairment as observed in Morris water maize (MWM) and Y maze test, which was ameliorated by concurrent treatment with PCA (80 mg/kg, and 100 mg/kg, p.o.). Importantly, PCA treatment attenuated the D‐gal induced oxidative stress and significantly inhibited acetylcholinesterase (AChE) activity in mice brain. Furthermore, PCA treatment significantly lowered levels of inflammatory marker nuclear factor kappa B (NFκB) and reduced levels of proapoptotic enzyme caspase 3. We also observed that PCA treatment exhibited β‐secretase enzyme (BACE1) inhibitory effect. However, PCA treatment failed to decrease the level of advanced glycation end products (AGE) both in vitro and in vivo.ConclusionCurrent study demonstrated the significant neuroprotective effect of PCA against D‐galactose induced neuroinflammation, cognitive impairment and apoptosis.

Antioxidant and Anti-inflammatory Properties Mediate the Neuroprotective Effects of Hydro-ethanolic Extract of Tiliacora triandra Against Cisplatin-induced Neurotoxicity.

BackgroundCisplatin (CDDP) is an efficacious anticancer agent used widely in chemotherapy despite its severe side effect related to neurotoxicity. Redox imbalance and inflammatory mechanism have been implicated in the pathophysiology of CDDP-induced neurotoxicity. Herein, we investigated whether Tiliacora triandra (TT) extract could inhibit CDDP-induced redox-mediated neurotoxicity and behavioural deficit in rats.Materials and MethodsCDDP-induced redox-mediated neurotoxicity and behavioral deficit in rats. Rats were administered TT for five consecutive weeks (250 and 500 mg/kg bw), while weekly i.p. injection of CDDP commenced on the second week (2.5 mg/kg bw) of the TT administration.ResultsCCDDP caused significant body weight reduction and cognitive diminution as revealed by Morris water maze and Y maze tests. In the CDDP-induced cognitive impairment (CICI) rats, there were remarkable increases in the brain levels of TNF-α, IL-6 and IL-1β and malondialdehyde (MDA), whereas catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities considerably decreased compared to normal control. The brain acetylcholinesterase (AChE) activity in CDDP control rats was significantly increased compared to the normal control. The expression of caspase-3 and p53 proteins was upregulated by CDDP injection, whereas Bcl2 was downregulated coupled with histopathological alterations in the rat brain. Interestingly, treatment with TT significantly abated neurobehavioral deficits, MDA and cytokine levels and restored CAT, GPx, GSH, SOD, and AChE activities compared to the CDDP control rats. Caspase-3 level as well as Bcl2 and p53 expressions were modulated with alleviated changes in histopathology.ConclusionThe findings highlight neuroprotective and cognitive function improvement efficacy of TT against CICI via redox-inflammatory balance and antiapoptotic mechanism in rats.

Neuroprotective Activity of the Methanolic Extract of Indigofera aspalathoides against Scopalamine induced Alzheimer's Disease in Experimental Rats

The plant Indigofera aspalathoides is a traditional medicine with tremendous therapeutic potential which finds it use in treatment of various ailments such as antibacterial, antioxidant, anti-inflammatory, antidiabetic, and anticancer activities. There are no reports that related to the use of this plant in treating patients with Alzheimer’s disease (AD). Hence present study was aimed to scientifically evaluate the neuroprotective effect of the methanolic extract of Indigofera aspalathoides against scopalamine induced Alzheimer’s disease in experimental rats using behavioral tests like elevated plus maze, Y-maze, and rota-rod tests. In addition to this, biochemical evaluation for acetylcholinesterase activity and histopathological evaluation of brain were done. The results suggests that methanolic extract Indigofera aspalathoides (200mg/kg B.wt and 400mg/kg B.wt) used in this study shows significant improvement of various behavioral parameters like locomotion, anxiety, memory, motor integrity and coordination etc when compared to control group. MEIA inhibited brain AChE enzyme, thereby elevating Ach concentration in brain homogenate and ultimately improved memory of rats. Further, more or less normal histological structure of the hippocampus and all amyloid plaques and neurofibrillary tangles that are formed under the influence of scopolamine disappeared in the rats pretreated with MEIA (200mg/kg B.wt and 400mg/kg B.wt). It can be concluded that our results strongly support the anti-Alzheimer’s potential of the methanolic extract of the plant I.aspalathoides and its use in traditional medicine.

Enhanced trophic transfer of chlorpyrifos from resistant Hyalella azteca to inland silversides (Menidia beryllina) and effects on acetylcholinesterase activity and swimming performance at varying temperatures

Chlorpyrifos, an organophosphate (OP) insecticide, is prevalent in aquatic systems globally and is often implicated in aquatic toxicity during storm events. Chlorpyrifos induces toxicity by inhibition of acetylcholinesterase (AChE) activity, which has been related to alterations to fish swimming performance. Resistance to organophosphate insecticides, including chlorpyrifos, is prevalent in populations of the epibenthic amphipod Hyalella azteca in areas with known OP exposure. Previous studies have demonstrated an elevated bioaccumulation potential of insecticide-resistant prey items, however the potential for trophic transfer of chlorpyrifos from OP-resistant prey items and associated neurotoxic effects in fish predators has not been studied. Consequently, the present study aimed to determine the potential for trophic transfer of chlorpyrifos from OP-resistant H. azteca to a known predator, the inland silverside, Menidia beryllina at two temperatures (18 and 23 °C) to simulate temperature changes associated with global climate change (GCC). Fish were fed either 14C-chlorpyrifos-dosed H. azteca or control animals for 7 d, after which total bioaccumulation, percent parent chlorpyrifos, brain AChE activity and swimming performance (ramp-Ucrit) were determined. Fish fed chlorpyrifos-dosed H. azteca bioaccumulated chlorpyrifos ranging from 29.9 to 1250 ng/g lipid, demonstrating the potential for trophic transfer. Lower bioaccumulation and greater biotransformation were observed in M. beryllina at 23 °C as compared to 18 °C, though this was not statistically significant. A significant 36.5% reduction in brain AChE activity was observed in fish fed chlorpyrifos-dosed H. azteca at 23 °C only, which may be attributed to increased biotransformation of parent chlorpyrifos to more potent AChE-inhibiting metabolites. Dietary chlorpyrifos exposure had no significant effect on swimming performance in M. beryllina, though ramp-Ucrit was significantly increased by 25% at 23 as compared to 18 °C. These findings confirm the potential for trophic transfer of chlorpyrifos from OP-resistant prey to fish predators and the potential for elevated temperatures to exacerbate the neurotoxic effects of chlorpyrifos.

Thromboxane A2 synthase inhibition ameliorates endothelial dysfunction, memory deficits, oxidative stress and neuroinflammation in rat model of streptozotocin diabetes induced dementia

RationaleVascular dementia (VaD) is the second leading cause of dementia worldwide. It is very important to find the possible pharmacological agents which may be useful in management and therapy of VaD. ObjectivesThe present study investigates the effect of ozagrel, a selective thromboxane A2 (TXA2) synthase inhibitor, in a rat model of VaD. MethodsSingle intraperitoneal injection of streptozotocin [STZ, (50 mg/kg)] was administered to Wistar rats to induced diabetes-associated vascular endothelial dysfunction and memory impairment. Morris water maze (MWM) test was employed to assess learning and memory. Endothelial dysfunction was assessed in the isolated aorta by observing endothelial-dependent vasorelaxation and levels of serum nitrite. Various biochemical and histopathological estimations were also performed. ResultsSTZ treatment produced endothelial dysfunction, impairment of learning and memory, reduction in body weight and serum nitrite/nitrate, and increase in serum glucose, brain oxidative stress (increased brain thiobarbituric acid reactive species and decreased reduced glutathione levels), brain acetylcholinesterase activity and brain myeloperoxidase activity. Further a significant rise in brain tumor necrosis factor-α & interleukin-6 levels and brain neutrophil infiltration were also observed. Treatment of ozagrel (10 & 20 mg/kg, p. o.)/donepezil (0. 5 mg/kg, i.p., serving as standard) ameliorated STZ induced endothelial dysfunction; memory deficits; biochemical and histopathological changes. ConclusionsIt may be concluded that ozagrel markedly improved endothelial dysfunction; learning and memory; biochemical and histopathological alteration associated with STZ induced dementia and that TXA2 can be considered as an important therapeutic target for the management of VaD.

Cacao powder supplementation attenuates oxidative stress, cholinergic impairment, and apoptosis in d-galactose-induced aging rat brain

Aging, a critical risk factor of several diseases, including neurodegenerative disorders, affects an ever-growing number of people. Cacao supplementation has been suggested to improve age-related neuronal deficits. Therefore, this study investigated the protective effects of raw cacao powder on oxidative stress-induced aging. Male Sprague–Dawley rats were divided into 4 groups: Control (C), d-galactose-induced aging (G), d-galactose injection with 10% (LC), and 16% (HC) cacao powder mixed diet. d-galactose (300 mg/3 mL/kg) was intraperitoneally injected into all but the control group for 12 weeks. Cacao supplemented diets were provided for 8 weeks. The levels of serum Malondialdehyde (MDA), Advanced Glycation End-products (AGEs), brain and liver MDA, the indicators of the d-galactose induced oxidative stress were significantly decreased in LC and HC but increased in G. The Acetylcholinesterase (AChE) activity of brain showed that the cholinergic impairment was significantly lower in LC, and HC than G. Furthermore, the expression levels of catalase (CAT), phospho-Akt/Akt, and procaspase-3 were significantly increased in LC and HC. In conclusion, cacao consumption attenuated the effects of oxidative stress, cholinergic impairment and apoptosis, indicating its potential in future clinical studies.

Arbutin protects brain against middle cerebral artery occlusion-reperfusion (MCAo/R) injury

Focal ischemia causes irreversible brain damage if cerebral blood flow is not restored promptly. Acute phase excitotoxicity and pro-oxidant and inflammatory events in the sub-chronic phase elicit coagulative necrosis, vascular injury, cerebral oedema, and neurobehavioral deficits. Earlier, in pre-clinical studies arbutin protected behavioral functions and improved therapeutic outcomes in different models of brain and metabolic disorders. Arbutin is natural hydroquinone that might protect against ischemia-reperfusion (I/R) injury. In this study, cerebro-protective effects of arbutin were evaluated in the middle cerebral artery occlusion-reperfusion (MCAo/R) mouse model. Mice were administered arbutin (50, 100 mg/kg, i.p.) for 21 days, and subjected to MCAo/R or sham surgery on day 14. Results showed brain infarction, blood-brain barrier dysfunction, oedema, and neurological deficits 24 h post-MCAo/R injury that were prevented by arbutin. Behavioral evaluations over the sub-chronic phase revealed MCAo/R triggered spatial and working memory deficits. Arbutin protected the memory against MCAo/R injury and decreased hydroxy-2′-deoxyguanosine, protein carbonyls, inflammatory cytokines (tumor necrosis factor-α, myeloperoxidase, matrix metalloproteinase-9, inducible nitric oxide synthase), and enhanced glutathione levels in the ischemia ipsilateral hemisphere. Arbutin decreased brain acetylcholinesterase activity, glutamate, and enhanced GABA levels against MCAo/R. Arbutin can alleviate I/R pathogenesis and protects neurobehavioral functions in the MCAo/R mouse model.

Brain acetylcholinesterase activity in Wistar rats subacutely exposed to low doses of Pb

Brain acetylcholinesterase activity in Wistar rats subacutely exposed to low doses of Pb

Neuroprotective Potential of Berberine Against Doxorubicin-Induced Toxicity in Rat's Brain.

Chemotherapy-associated neurotoxicity is one of the principal side-effects for doxorubicin (DOX)-treated cancer patients. Despite its poor-penetration across the blood-brain barrier (BBB), DOX is linked to the induction of oxidative stress and neuroinflammation. Berberine (BEB) is a natural polyphenolic alkaloid, which exhibits unique antioxidant activity and anti-inflammatory potential. The present study was performed to investigate the neuroprotective potential of BEB in a rodent model of DOX-induced neurotoxicity. Neurotoxicity was induced in rats via a single acute dose of DOX (20mg/kg/week, i.p.). BEB was administered at 50mg/kg/day orally for 10days before and 4days after DOX administration. Brain acetylcholinesterase (AChE) activities were evaluated. Oxidative stress was investigated via the colorimetric determination of lipid peroxides, glutathione reduced (GSH) contents and catalase (CAT) activities in the brain tissue. In addition, DOX-induced genotoxicity was evaluated using comet assay. DOX produced a significant elevation in AChE activities. Additionally, DOX provoked oxidative stress as evidenced from the significant elevation in lipid peroxidation along with depletion in GSH contents and CAT activities. Moreover, DOX resulted in neuroinflammation as indicated by the elevation of pro-inflammatory mediator glial fibrillary acid protein (GFAP), as well as, the pro-apoptotic nuclear factor kappa B (NF-κB) and caspase-3 in brain tissue. Co-treatment with BEB significantly counteracted DOX-induced oxidative stress, neuroinflammation and genotoxicity. Histopathological and immunohistochemical examination supported the biochemical results. BEB demonstrated neuroprotective potential through exerting cholinergic, anti-oxidative, genoprotective, anti-inflammatory, and anti-apoptotic activities. Our findings present BEB as a promising "pre-clinical" neuroprotective agent against DOX-induced neurotoxicity during anti-neoplastic therapy.

Ivermectin: A multilevel approach to evaluate effects in Prochilodus lineatus (Valenciennes, 1836) (Characiformes, Prochilodontidae), an inland fishery species

Ivermectin (IVM) is one of the most widely used antiparasitics worldwide. It is a potent and effective drug for treatment and prevention of internal and external parasitic infections of livestock and humans. IVM is excreted unchanged in manure of treated animals. Thus, residues of IVM may reach aquatic systems, affecting non-target organisms such as fish. Although the presence of IVM in aquatic environments has been reported, a multilevel approach (from cellular to behavioral responses) is necessary to determine the health of exposed organisms and the environmental risks associated. The aim of the present study was to investigate the response of the Neotropical fish Prochilodus lineatus, one of the main target species of South American freshwater fisheries, exposed to environmental concentrations of IVM: low (0.5 μg L−1) and high (1.5 μg L−1). Behavioral responses were assessed in juvenile fish and included water column use, routine swimming, total distance travelled, total activity time and Maximum swimming speed achieved during the escape response. Biochemical/oxidative stress responses assessed included brain acetylcholinesterase (AChE), catalase (CAT) and glutathione S-transferase (GST) activities; total antioxidant competence against peroxyl radicals (ACAP) and lipid oxidative damage (TBARs). Hematological biomarker responses included blood glucose levels, hematocrit, hemoglobin concentration, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and mean corpuscular volume. Condition factor and hepatosomatic index were also calculated. The lowest IVM concentration caused a significant decrease in GST activity and maximum swimming speed during the escape response. Multivariate analysis with biochemical/stress and behavioral data revealed overall effects of IVM treatments. This multilevel analysis shows detrimental effects related to swimming behavior and predator avoidance which could affect population size and size-structure of P. lineatus. To our knowledge this is the first attempt to assess the effects of IVM on Neotropical fishes using an integrative approach based on biomarkers from different levels of biological organization.

Development of flavored yoghurt fortified with microcapsules of triple omega 3‐ 6‐ 9 for preventing neurotoxicity induced by aluminum chloride in rats

Microcapsules of omega-3, -6, and -9 (fish, wheat germ, and olive oils at ratio 2:1:1) were microencapsulated using maltodextrin (MD), whey protein concentrate, gum Arabic (GA), and lactoferrin (LF) as carrier agents. The microcapsules were added to yoghurt that previously flavored by addition of orange essential oil. The characteristics of either the microcapsules or the flavored yoghurt were studied. The protective effect of the microcapsules and the flavored yoghurt in which these microcapsules were added against neurotoxicity mediated by aluminum chloride was assessed. The microcapsules prepared from MD: GA: LF and omega-3, -6, and -9 at ratio 4:1 showed the highest encapsulation efficiency with less separation%, and zeta potential. The flavored yoghurt containing microcapsules recorded high scores in the sensorial evaluation, showed protective effect against aluminum chloride-mediated neurotoxicity, enhanced brain dopamine, and 5-hydroxytriptamine, suppressed the elevation of brain acetylcholinesterase activity and attenuated the oxidative stress markers. Novelty impact statement The flavored yoghurt containing triple omega-3, -6, and -9 microcapsules recorded high sensory attributes, showed neuroprotective effect against the aluminum chloride, attenuated the oxidative stress markers, and enhanced brain dopamine and serotonin.

Concentration-dependent Effects of Dietary L-Ascorbic Acid Fortification in the Brains of Healthy Mice

Ascorbic acid (AA) is a water-soluble vitamin that is concentrated in the brain in large quantities. There have been reports that it is essential for proper brain functioning. However, there is insufficient information on the possible effects of dietary fortification with AA on the health of the brain. This study examined the effects of dietary fortification of rodent chow with AA on neurobehaviour, antioxidant status, lipid peroxidation, and inflammatory/apoptotic markers in the brain of healthy mice. Mice were randomly assigned into four groups of ten animals each. Groups were normal control [fed rodent chow], and three groups were fed AA-fortified chow at 100, 200, and 300 mg/kg of feed, respectively, for eight weeks. Behavioural tests {Open field, Y-maze, radial-arm maze, and elevated plus maze (EPM)} were carried out on day 57. Twenty-four hours after the last behavioural test, animals were euthanised, and the brains were excised and homogenised for assessment of brain acetylcholinesterase activity, lipid peroxidation, antioxidant status, inflammatory and apoptotic markers. Ascorbic acid fortified diet was associated with concentration-dependent changes in body weight, open-field behaviours, working-memory, and anxiety indices. Also, brain levels of malondialdehyde, caspase-3, and TNF-α decreased, while superoxide dismutase activity, total antioxidant capacity, and IL-10 level increased. Dietary AA fortification with concentrations up to 300 mg/kg of feed was associated with sustained improvement in neurobehavioural and biochemical parameters in the brain of healthy mice, reiterating additional health benefits of AA fortification beyond the prevention of nutritional deficiencies.