Alterations Of Acetylcholinesterase Research Articles

Unveiling the ecotoxicological effects of azoxystrobin-based fungicides at realistic concentrations on the land snail, Theba pisana

The ecotoxicological consequences of azoxystrobin on land snails have not yet been addressed. Therefore, the present study aims to provide novel data on the threat of a commercial grade azoxystrobin (AMISTAR) at two environmentally relevant concentrations (0.3 µg/ml) and tenfold (3 µg/ml) on the model species, Theba pisana by physiological, biochemical, and histopathological markers for 28 days. Our results showed a reduction in animal food consumption and growth due to exposure to both azoxystrobin concentrations. It also induced oxidative stress and led to a significant decrease in lipid peroxidation (LPO) levels after 7 days of exposure, while the opposite effect occurred after 28 days. Except for the 7-day exposure, all treated snails had significantly reduced glutathione (GSH) content and increased catalase (CAT) activity at all-time intervals. Glutathione peroxidase (GPx), glutathione-S-transferase (GST) activities, and protein content (PC) were elevated in treated snails at all-time intervals. Moreover, alterations in acetylcholinesterase (AChE) activity between a decrease and an increase were noticed. Additionally, azoxystrobin exerted changes in T. pisana hepatopancreas architecture. Our study suggests that azoxystrobin may have negative ecological consequences for T. pisana and highlights its potential risks to the natural environment.

In-feed antiparasitic veterinary drug emamectin benzoate impairs acetylcholinesterase activity and brain tissue histoarchitecture of Oreochromis niloticus fry

Emamectin benzoate (EB) is an antiparasitic veterinary drug in temperate aquaculture to control ectoparasites. Research on its safety, tolerability and toxicity in tropical aquaculture is growing recently. This study examined the neurological and brain histopathological effects and the accumulation of tissue residues in all-male Oreochromis niloticus fry when fed top-coated EB feeds containing doses ranging from 50 to 500 µg/kg biomass/day for 14 days. A dose-dependent increase in mortalities (3.33–13.75 %) and inhibition in acetylcholinesterase activity (43.80–83.52 %) were documented. In the50-µg group, the muscle EB-residues peaked at 2.77 ng/g and then dropped after dosetermination. Yet, traces of residues were demonstrable in the treated groups even after 21 days of cessation of EB feeding. Histologically, dose-dependent alterations like granular layer degeneration, spongiosis, necrotized areas in the stratum album centrale, stratum griserum centrale stratum griseum superficiale, and stratum marginale and stratum opticum degeneration in the brain tissues were documented. The neuron cells were scattered or degenerated and stretched with a shrunken nucleus in the treated groups. The revocable alterations in acetylcholinesterase and brain histoarchitecture upon the termination of dosing indicated that the fry can able to tolerate and mount adaptive responses to overcome the EB toxicity.

Neuroprotective Effect of Levetiracetam in Combination with Berberine on Scopolamine Induced-Cognitive Impairment in Mice: A Behavioral and Biochemical Approach

Background: Presently, only four drugs have been approved by FDA for Alzheimer’s disease (AD). A drug repurposing approach can be fruitful in searching for promising candidates for AD. Objective: The objective of the work was to evaluate the neuroprotective effect of levetiracetam (LEV) in combination with berberine (BER) in scopolamine-induced cognitive impairment in mice by applying a drug repositioning approach owing to their antioxidant potential. Methods: Cognitive impairment was induced in mice by scopolamine. Morris water maze, elevated plus maze, and Y-maze were used to evaluate behavioral parameters. Assays for acetylcholinesterase (AChE), reduced glutathione (GSH), malondialdehyde (MDA), catalase, nitrite, TNF-α, and brain histopathology were performed. Results: The transfer latency time and percentage of spontaneous alternation were significantly reduced and significant alterations in AChE and MDA levels, GSH concentration, and improvement in nitrite and catalase levels were also evidenced after the treatment of mice with a combination of LEV and BER in comparison to independent drugs, standard and disease control groups. The antioxidant defense was also improved and TNF-α levels were significantly reduced by a combination of LEV and BER. Improvement in neuronal damage by restoration of the cytoarchitecture of the brain was also seen in the histopathological study of the brain of treatment groups. Conclusion: The present study has demonstrated that the combination of LEV and BER has significantly improved cognition in mice by lipid peroxidation inhibition, augmentation of endogenous antioxidant enzymes, the decline in TNF- α levels, and AChE activity in the brain when compared to individual drugs, standard and disease control owing to their strong antioxidant and anti-inflammatory potentials.

Neuroprotective evaluation of Marsilea quadrifolia L. and Salvinia molesta D.S Mitchel in aluminium chloride induced Alzheimer disease

Phenolic compounds are very effective for the cure of various neurological and pathological diseases. Current study was conducted to estimate the Phenolic compounds through HPLC and to perform the anti-Alzheimer activity from two aquatic Leptosporangiate ferns; Marsilea quadrifolia L. and Salvinia molesta D. Crushed leaves were subjected to Microwave Assisted Extraction to prepare plant leave ethanolic extract of plants under study. Aluminum chloride induced Alzheimer’s disease model in rats by estimating behavioural and biochemical parameters were measured for ethanolic extract of both plants. Different behavioural tests were performed for neuromuscular coordination estimation and hole board test for exploratory behaviour were performed. The levels of AChE inhibitory activity and antioxidant enzymes were estimated on brain homogenates and Histopathological analysis were also performed. Phenolic compounds of leaf extracts were noted for HPLC chromatograms of standard compounds with Gallic acid (33.76 ± 0.08) higher in M. quadrifolia L. and Salicylic acid (12.45 ± 0.07) higher in S. molesta D. S Mitchel. Histopathological analysis showed that M. quadrifolia and S. molesta reversed the neurofibrillary tangles, degenerative changes, neuronal loss and neuroinflammation in the brain architecture. Both ferns at a dose of 500 mg/kg and 1000mg/kg significantly improved the Aluminium chloride induced neurotoxicity by modulating cognitive disabilities and motor dysfunctions, and normalized the biochemical alteration of acetylcholinesterase and antioxidant enzymes. In conclusion, both plants M. quadrifolia and S. molesta improved behavioural and biochemical parameters and therefore will be effective in treatment of neurodegenerative disorders via countless underlying mechanistic pathways.

Folic acid attenuated learning and memory impairment via inhibition of oxidative damage and acetylcholinesterase activity in hypothyroid rats.

Hypothyroidism has been reported to be associated with cognitive decline. Considering the role of folic acid (FA) in cognitive performance, the present study was designed to investigate the effects of FA on hypothyroidism-induced cognitive impairment, oxidative damage, and alterations in acetylcholinesterase (AChE) activity in rat model of propylthiouracil (PTU)-induced hypothyroidism. In this study, PTU (0.05% in drinking water) and FA (5, 10, and 15mg/kg, oral gavage) were administered for the rats during 7weeks. Then, behavioral performance was tested using Morris water maze (MWM) and passive avoidance (PA) tasks. Finally, oxidative stress indicators and AChE activity were assayed in the brain tissues. The impairing effect of hypothyroidism on cognitive performance was markedly alleviated by FA especially at higher doses. In the MWM test, FA reduced escape latency and travelled distance, compared to the non-treated hypothyroid group. In the PA test, latency to enter dark chamber was significantly enhanced by FA compared to the non-treated hypothyroid group (p < 0.05-p < 0.001). Besides, FA attenuated AChE activity and malondialdehyde level but it increased activity of superoxide dismutase enzyme and total thiol content (p < 0.05-p < 0.001). In conclusion, our findings revealed that FA could improve learning and memory ability in hypothyroid rats. The observed protective effects may have been mediated through regulation of oxidative stress and AChE activity.

A kaempferol derivative isolated from Lysimachia ramosa (Wall ex. Duby) induced alteration of acetyl cholinesterase and nitric oxide synthase in Raillietina echinobothrida

Lysimachia ramosa has been used as a traditional medicine among the tribal population of Meghalaya, northeast India, for the control of helminthosis. The anthelmintic efficacy of L. ramosa has been documented earlier. In the present study, the active compound from L. ramosa has been isolated and identified using mass and NMR spectra. It’s in vitro anthelmintic activity was evaluated against Raillietina echinobothrida, one of the most pathogenic cestode of domestic fowl. The isolated active compound was characterized to be a kaempferol derivative which showed potent anthelmintic activity against R. echinobothrida by changing surface ultrastructure and also inhibiting the activity of two neurotransmitter enzymes: acetyl cholinesterase (AChE) and nitric oxide synthase (NOS), both of which are known to perform dynamic roles in the intracellular communication mediated through neuromuscular system. Motility reduction, deformation in the surface architecture, extensive ultrastructural alterations and reduced histochemical stain intensity in both AChE and NOS was observed in the treated parasites. Biochemical result also revealed alteration in the enzyme activities in the treated parasites. Further, depletion in the nitric oxide (NO) production in the bioactive component exposed tissues of R. echinobothrida was also detected. The results provided evidence that the bioactive compound could be further explored to control helminthosis at a large scale.

Memory-Enhancing Effect of a Phytosome Containing the Combined Extract of Mulberry Fruit and Ginger in an Animal Model of Ischemic Stroke with Metabolic Syndrome.

The prevalence of dementia following cerebral ischemia in metabolic syndrome (MetS) condition is increasing, and most of the cases are often severe. Unfortunately, no effective strategy for treating this condition is available. Based on the positive modulation effect of a polyphenol-rich substance on dementia and the improvement in bioavailability and stability of polyphenols induced by the phytosome technique together with the use of the synergistic concept, we hypothesized that a phytosome containing the combined extract of mulberry fruit and ginger (PMG) should mitigate dementia and memory impairment following ischemic stroke in MetS. MetS was induced in male Wistar rats weighing 180-200 g by exposure to a 16-week feeding period of high-carbohydrate high-fat (HCHF) diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg·kg−1 BW 21 days before and 21 days after the occlusion of the right middle cerebral artery (Rt. MCAO). Then, their spatial memory was determined and the possible underlying mechanisms explored via the alterations of acetylcholinesterase (AChE), neuron density, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), and signal transduction via extracellular signal-regulated kinase (ERK) pathway in both the cerebral cortex and the hippocampus. It was found that PMG significantly enhanced memory. It also decreased AChE, IL-6, and MDA but increased SOD, CAT, GSH-Px, neuron density, and phosphorylation of ERK. These data suggested the cognitive enhancing effect of PMG. The possible underlying mechanisms might occur partly via the improvement of cholinergic function via the ERK pathway together with the decrease in neurodegeneration induced by the reduction of oxidative stress and inflammation. However, a subchronic toxicity study is also required to assure the safety of PMG consumption before moving forward to a clinical trial study.

Inosine protects against impairment of memory induced by experimental model of Alzheimer disease: a nucleoside with multitarget brain actions.

Inosine is a naturally occurring purine nucleoside formed by adenosine breakdown. This nucleoside is reported to exert potent effects on memory and learning, possibly through its antioxidant and anti-inflammatory actions. The objective is to evaluate the effects of inosine on the behavioral and neurochemical parameters in a rat model of Alzheimer's disease (AD) induced by streptozotocin (STZ). Adult male rats were divided into four groups: control (saline), STZ, STZ plus inosine (50mg/kg), and STZ plus inosine (100mg/kg). STZ (3mg/kg) was administered by bilateral intracerebroventricular injection. The animals were treated intraperitoneally with inosine for 25days. Memory, oxidative stress, ion pump activities, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) activities and expression were evaluated in the cerebral cortex and hippocampus. The memory impairment induced by STZ was prevented by inosine. An increase in the Na+, K+-ATPase, and Mg-ATPase activities and a decrease in the Ca2+-ATPase activity were induced by STZ in the hippocampus and cerebral cortex, and inosine could prevent these alterations in ion pump activities. Inosine also prevented the increase in AChE activity and the alterations in AChE and ChAT expression induced by STZ. STZ increased the reactive oxygen species, nitrite levels, and superoxide dismutase activity and decreased the catalase and glutathione peroxidase activities. Inosine treatment conferred protection from these oxidative alterations in the brain. Our findings demonstrate that inosine affects brain multiple targets suggesting that this molecule may have therapeutic potential against cognitive deficit and tissue damage in AD.

Involvement of the Cholinergic Parameters and Glial Cells in Learning Delay Induced by Glutaric Acid: Protection by N-Acetylcysteine.

Dysfunction of basal ganglia neurons is a characteristic of glutaric acidemia type I (GA-I), an autosomal recessive inherited neurometabolic disease characterized by deficiency of glutaryl-CoA dehydrogenase (GCDH) and accumulation of glutaric acid (GA). The affected patients present clinical manifestations such as motor dysfunction and memory impairment followed by extensive striatal neurodegeneration. Knowing that there is relevant striatal dysfunction in GA-I, the purpose of the present study was to verify the performance of young rats chronically injected with GA in working and procedural memory test, and whether N-acetylcysteine (NAC) would protect against impairment induced by GA. Rat pups were injected with GA (5μmolg body weight-1, subcutaneously; twice per day; from the 5th to the 28th day of life) and were supplemented with NAC (150mg/kg/day; intragastric gavage; for the same period). We found that GA injection caused delay procedural learning; increase of cytokine concentration, oxidative markers, and caspase levels; decrease of antioxidant defenses; and alteration of acetylcholinesterase (AChE) activity. Interestingly, we found an increase in glial cell immunoreactivity and decrease in the immunoreactivity of nuclear factor-erythroid 2-related factor 2 (Nrf2), nicotinic acetylcholine receptor subunit alpha 7 (α7nAChR), and neuronal nuclei (NeuN) in the striatum. Indeed, NAC administration improved the cognitive performance, ROS production, neuroinflammation, and caspase activation induced by GA. NAC did not prevent neuronal death, however protected against alterations induced by GA on Iba-1 and GFAP immunoreactivities and AChE activity. Then, this study suggests possible therapeutic strategies that could help in GA-I treatment and the importance of the striatum in the learning tasks.

Probable mechanisms involved in the antipsychotic-like activity of morin in mice.

Evidence derived from preliminary studies suggests that morin, a neuroactive flavonoid with proven antioxidant and antiinflammatory properties possess antipsychotic-like activity. The present study was designed to evaluate the probable mechanisms involve in the antipsychotic-like activity of morin in ketamine model of schizophrenia. The effects of morin, haloperidol and risperidone on neurobehavioral and anti-schizophrenia-like effects were evaluated in mice (n = 7) following intraperitoneal (i.p.) administration of morin (25-100 mg/kg), haloperidol (1 mg/kg) and risperidone (0.5 mg/kg) alone or in combination with ketamine (20 mg/kg, i.p.) for 10 days. Neurobehavioral and schizophrenia-like activities consisting of open-field (positive symptoms), Y-maze, novel-object recognition (cognitive symptoms), social interaction (negative symptoms) tests were assessed. Also, wood-block catalepsy and rota-rod tests were employed to evaluate extrapyramidal side effects of morin. Thereafter, brain levels of biomarkers of oxidative, nitrergic and acetylcholinesterase alterations as well as histomorphological changes in the striatum and prefrontal-cortex were determined. Administration of morin and risperidone alone but not haloperidol significantly (p > 0.05) prevented ketamine-induced hyperlocomotion, social withdrawal and cognitive impairments relative to controls, and were devoid of extrapyramidal side effects. Morin alone or in combination with ketamine significantly increased glutathione concentration, superoxide dismutase and catalase activities compared with saline- or ketamine-treated mice. Moreover, morin alone or in combination with ketamine also significantly decreased malondialdehyde, nitrite and acetylcholinesterase alterations in mice brains. Furthermore, morin prevented ketamine-induced brain neuronal alterations in the striatum and prefrontal-cortex. Together, our findings suggest that morin may demonstrate antipsychotic-like therapeutic effect via modulation of oxidative/nitrergic, cholinergic actions and neuroprotection.

The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson's disease: a cross-sectional PET study

Markers of neuroinflammation are increased in some patients with LRRK2 Parkinson's disease compared with individuals with idiopathic Parkinson's disease, suggesting possible differences in disease pathogenesis. Previous PET studies have suggested amplified dopamine turnover and preserved serotonergic innervation in LRRK2 mutation carriers. We postulated that patients with LRRK2 mutations might show abnormalities of central cholinergic activity, even before the diagnosis of Parkinson's disease. Between June, 2009, and December, 2015, we recruited participants from four movement disorder clinics in Canada, Norway, and the USA. Patients with Parkinson's disease were diagnosed by movement disorder neurologists on the basis of the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. We used the PET tracer N-11C-methyl-piperidin-4-yl propionate to scan for acetylcholinesterase activity. The primary outcome measure was rate of acetylcholinesterase hydrolysis, calculated using the striatal input method. We compared acetylcholinesterase hydrolysis rates between groups using ANCOVA, with adjustment for age based on the results of linear regression analysis. We recruited 14 patients with LRRK2 Parkinson's disease, 16 LRRK2 mutation carriers without Parkinson's disease, eight patients with idiopathic Parkinson's disease, and 11 healthy controls. We noted significant between-group differences in rates of acetylcholinesterase hydrolysis in cortical regions (average cortex p=0·009, default mode network-related regions p=0·006, limbic network-related regions p=0·020) and the thalamus (p=0·008). LRRK2 mutation carriers without Parkinson's disease had increased acetylcholinesterase hydrolysis rates compared with healthy controls in the cortex (average cortex, p=0·046). Patients with LRRK2 Parkinson's disease had significantly higher acetylcholinesterase activity in some cortical regions (average cortex p=0·043, default mode network-related regions p=0·021) and the thalamus (thalamus p=0·004) compared with individuals with idiopathic disease. Acetylcholinesterase hydrolysis rates in healthy controls were correlated inversely with age. LRRK2 mutations are associated with significantly increased cholinergic activity in the brain in mutation carriers without Parkinson's disease compared with healthy controls and in LRRK2 mutation carriers with Parkinson's disease compared with individuals with idiopathic disease. Changes in cholinergic activity might represent early and sustained attempts to compensate for LRRK2-related dysfunction, or alteration of acetylcholinesterase in non-neuronal cells. Michael J Fox Foundation, National Institutes of Health, and Pacific Alzheimer Research Foundation.

Alterations in acetylcholinesterase and butyrylcholinesterase activities in chronic obstructive pulmonary disease: relationships with oxidative and inflammatory markers.

This work focused on finding a relationship between acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities and the development and severity of COPD. The possible link of these enzymes to oxidative and inflammatory processes was also investigated. The study included 229 healthy controls and 153 COPD patients. Erythrocyte AChE and plasma BChE activities were determined using spectrophotometric methods. Markers related to the oxidative status including thiobarbituric acid-reactive substances (TBARS), total protein carbonyls (PCs), advanced oxidation protein products (AOPP), reduced glutathione, nitric oxide, and peroxynitrite were measured. We also evaluated the activity of glutathione peroxidase, catalase, and superoxide dismutase in the plasma and erythrocytes. Serum levels of IL-6 and TNF-α were measured by the enzyme-linked immunosorbent assay. COPD patients showed increased AChE and BChE activities in comparison to healthy controls. Interestingly, AChE activity was higher in COPD smokers than in nonsmokers, while no difference was revealed for BChE. In addition, our results showed an inverse correlation between AChE activity and the levels of IL-6 in COPD smokers. Positive correlations were found, in COPD smokers, between plasma BChE activity and the levels of several biomarkers of protein oxidative damage including AOPP and PC. Our findings suggest that the alterations in AChE and BChE activities may be related to the oxidative and inflammatory processes in COPD patients rendering these enzymes as markers of COPD disease.

P 033 - Oxidative and nitrosative stress damage induced by Tacrolimus in brain of rat: Protective effect of Mycophenolate mofetil

Tacrolimus (TAC) and mycophenolate mofetil (MMF) are used effectively to prevent immunologic rejection after solid-organ transplantation. Some immunosuppressive drugs contribute to the pathophysiology of cerebral injury. In this study, we investigate the efficacy of MMF against TAC induced neurotoxicity in the brains of rats. Statistical analyses showed that rats treated with TAC by oral gavage at a dose of 60 mg/kg b.w. caused an alteration of acetylcholinesterase (AChE) activity, a potential induction of oxidative/nitrosative stress mediated by an increase of malondialdehyde (MDA), protein carbonyls (P.C.) and a decrease of the nitric oxide (NO). In addition, TAC provoked significantly caspase-3 activity in brains of rats. A significant correlation between caspase-3 levels and oxidative/nitrosative markers was observed. However, the co-treatment with MMF at a dose of 50 mg/kg is able to restore the AChE activity and all stress markers and regulated apoptosis in brains. These data indicated that MMF plays a neuroprotective role in brain tissue damage.

Benzo(a)pyrene Exposure Causes Genotoxic and Biochemical Changes in the Midge Larvae of Chironomus sancticaroli Strixino & Strixino (Diptera: Chironomidae).

Benzo(a)pyrene (BaP) is a carcinogenic polycyclic aromatic hydrocarbon, also found in nature due to human activities. BaP adheres to sediments showing toxic effects on benthic organisms, including midge larvae of the family Chironomidae. We tested for toxic effects of benzo(a)pyrene on Chironomus sancticaroli Strixino & Strixino 1981 using biochemical and genotoxic biomarkers, to identify changes in metabolic and antioxidant pathways, besides neurotoxic and DNA damage. Enzyme activity was compared by exposing larvae to four nominal concentrations (0.47, 2.13, 3.41, and 4.73μgl-1) and DNA damage to two concentrations (0.47 and 4.73μgl-1), after exposure at 24, 48, 72, and 96h. BaP caused neurotoxic effect, showing acetylcholinesterase alterations at different treatments. Changes in the biotransformation pathway were detected, with an increased activity of alpha and beta esterase in 48h and reduction of glutathione-S-transferase activity in all periods at the highest concentrations. Damage to the antioxidant system was observed by the increase of the superoxide dismutase and reduction of the catalase, in 48h. Genotoxicity was detected by an increased DNA damage at 48 and 72h. The lowest concentration (0.47μgl-1), even presenting low mortality, also altered the biochemical parameters of the larvae. Thus, these results indicate that BaP causes metabolic, neurotoxic, and genotoxic effects on C. sancticaroli, even at low concentrations and short-term exposure. BaP can cause damage of immature invertebrates, and the ecological dynamics can be affected, since these organisms have trophic importance in the aquatic environment.

Curcumin attenuates memory deficits and the impairment of cholinergic and purinergic signaling in rats chronically exposed to cadmium.

This study investigated the protective effect of curcumin on memory loss and on the alteration of acetylcholinesterase and ectonucleotidases activities in rats exposed chronically to cadmium (Cd). Rats received Cd (1 mg/kg) and curcumin (30, 60, or 90 mg/kg) by oral gavage 5 days a week for 3 months. The animals were divided into eight groups: vehicle (saline/oil), saline/curcumin 30 mg/kg, saline/curcumin 60 mg/kg, saline/curcumin 90 mg/kg, Cd/oil, Cd/curcumin 30 mg/kg, Cd/curcumin 60 mg/kg, and Cd/curcumin 90 mg/kg. Curcumin prevented the decrease in the step-down latency induced by Cd. In cerebral cortex synaptosomes, Cd-exposed rats showed an increase in acetylcholinesterase and NTPDase (ATP and ADP as substrates) activities and a decrease in the 5'-nucleotidase activity. Curcumin was not able to prevent the effect of Cd on acetylcholinesterase activity, but it prevented the effects caused by Cd on NTPDase (ATP and ADP as substrate) and 5'-nucleotidase activities. Increased acetylcholinesterase activity was observed in different brain structures, whole blood and lymphocytes of the Cd-treated group. In addition, Cd increased lipid peroxidation in different brain structures. Higher doses of curcumin were more effective in preventing these effects. These findings show that curcumin prevented the Cd-mediated memory impairment, demonstrating that this compound has a neuroprotective role and is capable of modulating acetylcholinesterase, NTPDase, and 5'-nucleotidase activities. Finally, it highlights the possibility of using curcumin as an adjuvant against toxicological conditions involving Cd exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 70-83, 2017.

Resveratrol- and α-viniferin-induced alterations of acetylcholinesterase and nitric oxide synthase in Raillietina echinobothrida

Phytostilbenes, like resveratrol and α-viniferin, which occur mainly in the plants and belong to the families Cyperaceae, Vitaceae, and Gnetaceae are extensively popular for their medicinal and nutritional properties. In Northeast India, the Jaintia tribes consume these phytochemicals through aqueous extract of the medicinal plant Carex baccans to control helminthiasis. The present study aimed to investigate the inhibitory effect of the phytochemicals on neurotransmitters and its related enzymes in helminth parasite Raillietina echinobothrida. Viability of the parasites exposed to the phytostilbenes and extent of inhibition of cholinergic and nitrergic enzymes were evaluated in comparison to reference anthelmintic drug praziquantel and two known enzyme inhibitors, namely Nω-nitro-L-arginine and pyridostigmine. On exposure to resveratrol, α-viniferin, and reference drug praziquantel, the parasites ceased movement at 9.37, 11.38, and 0.24 h followed by death at 23.65, 34.13, and 1.87 h, respectively. Exposed parasites also showed a significant decrease in the activity of acetylcholinesterase (46.101, 65.935, and 63.645%) and nitric oxide synthase (61.241, 55.046, and 29.618%) in comparison to the controls. In addition, a decreased trend in nitric oxide (NO) level was also detected in the tissue of different phytochemical-exposed parasites compared to control. The present study suggests that anthelmintic potential of both the phytochemicals is mediated through inhibition of two vital enzymes which play diverse role in intracellular communications through neuromuscular system.

Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus.

Studies demonstrated that the iron chelating antioxidant restores brain dysfunction induced by iron toxicity in animals. Earlier, we found that iron overload-induced cerebral cortex apoptosis correlated with oxidative stress could be protected by naringenin (NGEN). In this respect, the present study is focused on the mechanisms associated with the protective efficacy of NGEN, natural flavonoid compound abundant in the peels of citrus fruit, on iron induced impairment of the anxiogenic-like behaviour, purinergic and cholinergic dysfunctions with oxidative stress related disorders on mitochondrial function in the rat hippocampus. Results showed that administration of NGEN (50 mg/kg/day) by gavage significantly ameliorated anxiogenic-like behaviour impairment induced by the exposure to 50 mg of Fe-dextran/kg/day intraperitoneally for 28 days in rats, decreased iron-induced reactive oxygen species formation and restored the iron-induced decrease of the acetylcholinesterase expression level, mitochondrial membrane potential and mitochondrial complexes activities in the hippocampus of rats. Moreover, NGEN was able to restore the alteration on the activity and expression of ectonucleotidases such as adenosine triphosphate diphosphohydrolase and 5'-nucleotidase, enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. These results may contribute to a better understanding of the neuroprotective role of NGEN, emphasizing the influence of including this flavonoid in the diet for human health, possibly preventing brain injury associated with iron overload.

The essential oil from Lippia alba induces biochemical stress in the silver catfish (Rhamdia quelen) after transportation

This study investigated the effects of the essential oil (EO) from Lippia alba on biochemical parameters related to oxidative stress in the brain and liver of silver catfish (Rhamdia quelen) after six hours of transport. Fish were transported in plastic bags and divided into three treatments groups: control, 30 µL L- 1 EO from L.alba and 40 µL L-1 EO from L.alba. Prior to transport, the fish were treated with the EO from L. alba (200 µL L -1 for three minutes), except for the control group. Fish transported in bags containing the EO did not have any alterations in acetylcholinesterase, ecto -nucleoside triphosphate diphosphohydrolase and 5'nucleotidase activity in the brain or superoxide dismutase activity in the liver. The hepatic catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx), nonprotein thiol and ascorbic acid levels were significantly lower compared to the control group. However, the hepatic thiobarbituric acid- reactive substances, protein oxidation levels and the lipid peroxidation/catalase+glutathione peroxidase (LPO/CAT+GPx) ratio were significantly higher in fish transported with both concentrations of the EO, indicating oxidative stress in the liver. In conclusion, considering the hepatic oxidative stress parameters analyzed in the present experiment, the transport of previously sedated silver catfish in water containing 30 or 40 µL L-1 of EO from L. alba is less effective than the use of lower concentrations.

Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: Possible involvement of the acetylcholinesterase and Na+,K+-ATPase activities

The present study investigated the effects of quercetin in the impairment of memory and anxiogenic-like behavior induced by cadmium (Cd) exposure. We also investigated possible alterations in acetylcholinesterase (AChE), Na+,K+-ATPase and δ-aminolevulinate dehydratase (δ-ALA-D) activities as well as in oxidative stress parameters in the CNS. Rats were exposed to Cd (2.5mg/kg) and quercetin (5, 25 or 50mg/kg) by gavage for 45days. Animals were divided into eight groups (n=10–14): saline/control, saline/Querc 5mg/kg, saline/Querc 25mg/kg, saline/Querc 50mg/kg, Cd/ethanol, Cd/Querc 5mg/kg, Cd/Querc 25mg/kg and Cd/Querc 50mg/kg. Results demonstrated that Cd impaired memory has an anxiogenic effect. Quercetin prevented these harmful effects induced by Cd. AChE activity decreased in the cerebral cortex and hippocampus and increased in the hypothalamus of Cd-exposed rats. The Na+,K+-ATPase activity decreased in the cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin prevented these effects in AChE and Na+,K+-ATPase activities. Reactive oxygen species production, thiobarbituric acid reactive substance levels, protein carbonyl content and double-stranded DNA fractions increased in the cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin totally or partially prevents these effects caused by Cd. Total thiols (T-SHs), reduced glutathione (GSH), and reductase glutathione (GR) activities decreased and glutathione S-transferase (GST) activity increased in Cd exposed rats. Co-treatment with quercetin prevented reduction in T-SH, GSH, and GR activities and the rise of GST activity. The present findings show that quercetin prevents alterations in oxidative stress parameters as well as AChE and Na+,K+-ATPase activities, consequently preventing memory impairment and anxiogenic-like behavior displayed by Cd exposure. These results may contribute to a better understanding of the neuroprotective role of quercetin, emphasizing the influence of this flavonoid in the diet for human health, possibly preventing brain injury associated with Cd intoxication.

Sucralose Induces Biochemical Responses in Daphnia magna

The intense artificial sweetener sucralose has no bioconcentration properties, and no adverse acute toxic effects have been observed in standard ecotoxicity tests, suggesting negligible environmental risk. However, significant feeding and behavioural alterations have been reported in non-standard tests using aquatic crustaceans, indicating possible sublethal effects. We hypothesized that these effects are related to alterations in acetylcholinesterase (AChE) and oxidative status in the exposed animals and investigated changes in AChE and oxidative biomarkers (oxygen radical absorbing capacity, ORAC, and lipid peroxidation, TBARS) in the crustacean Daphnia magna exposed to sucralose (0.0001–5 mg L−1). The sucralose concentration was a significant positive predictor for ORAC, TBARS and AChE in the daphnids. Moreover, the AChE response was linked to both oxidative biomarkers, with positive and negative relationships for TBARS and ORAC, respectively. These joint responses support our hypothesis and suggest that exposure to sucralose may induce neurological and oxidative mechanisms with potentially important consequences for animal behaviour and physiology.