Acetylcholinesterase Levels Research Articles

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.

Acaricidal, larvacidal, and repellent activity of green synthesized silver nanoparticles against Hyalomma dromedarii.

We aimed at determination of acaricidal, larvacidal, and repellent activities of green synthesized silver nanoparticles (SNP) against Hyalomma dromedarii as one of the most common ticks in camels. SNP were green synthesized by reducing Lupinus albus extract through the precipitation technique. The acaricidal, larvicidal, and repellent activity of SNP against H. dromedarii was studied through the adult immersion test (AIT), the larval packet test (LPT), the vertical movement behavior of tick's larvae method, anti-acetylcholinesterase (AChE) activity, and oxidative enzyme activity. The green synthesized SNP displayed a spherical form with a size ranging from 25-90 nm; whereas the most distribution of particles size was reported at 50-65 nm. SNP dose-dependently (p<0.001) increased the mortality rate of H. dromedarii adult; whereas at 16 and 32 µg/mL completely killed the adult females. Treatment of exposure of H. dromedarii adult to SNP markedly (p<0.001) declined the mean number, weight, and hatchability of eggs. Treatment of H. dromedarii larvae with SNP reduced the viability rate of larvae with the LC50 and LC90 values of 3.1 and 6.9 µg/mL, respectively. Exposure of H. dromedarii larvae to SNP, especially at ½ LC50 and LC50, markedly (p<0.001) increased the oxidative stress and declined the level of antioxidant enzymes in H. dromedarii larvae; whereas, markedly suppressed the AChE activity of the larvae stage of H. dromedarii in comparison to the control group. These results showed that SNP green synthesized by L. albus extract had promising acaricidal, larvicidal and repellent activity against H. dromedarii adults and larvae as a dose-dependent response. SNP also considrably decreased the level of acetylcholinesterase and antioxidant activity and also provokes oxidative stress in H. dromedarii larvae. However, more investigation must be designed to clear the accurate mechanisms and the efficacy of SNP in practical use.

Comparison of acetylcholinesterase among employees based on job positions and personal protective equipment in fuel station.

The purpose of this study was to compare the levels of acetylcholinesterase (AChE) among employees based on job positions and the wearing of personal protective equipment (PPE) in fuel station areas. The sample group consisted of 200 people sorted into various groups, including (i) Inside fuel dispenser area (I-FDA) group consisting of 100 employees for refueling, cashier, and loading fuel into storage tanks, and (ii) Outside fuel dispenser area (O-FDA) group, consisting of 100 employees working in convenience stores, food stores, coffee shops, and offices, as well as general staff and car washers. Data were collected using interview questionnaires and blood samples were analyzed for AChE activity. The results showed that the I-FDA group had a significantly lower mean of serum AChE (7.38±1.73 U/ml) than the O-FDA group (7.85±1.49 U/ml) (p<0.05). The I-FDA group had a 2.43 times higher risk of abnormal serum AChE than the O-FDA group (OR=2.43, 95%CI=1.05-5.60). When considering the risk factors for job positions, it was found that refueling and cashier positions had lower AChE activity levels than those who did not (p<0.05). In the part, employees for food sales in a closed building and those wearing PPE masks had significantly higher AChE activity levels than those who did not or who wore them (p<0.05). Based on the aforementioned, employers at fuel stations should strictly determine the appropriate measures for wearing a PPE mask. Further, employees should be provided accommodation away from oil supply or enclosed buildings during breaks to reduce the effects on the neurotransmitter.

Neurotoxicity of tetramethylammonium ion on larval and juvenile zebrafish: Effects on neurobehaviors and multiple biomarkers

Tetramethylammonium hydroxide (TMAH) is an important compound that utilized and released by the rapidly expanding semiconductor industry, which could hardly be removed by the conventional wastewater treatment techniques. As a cholinergic agonist, the tetramethylammonium ion (TMA+) has been reported to induce toxicity to muscular and respiratory systems of mammals and human, however the toxicity on aquatic biota remains poorly known. We investigated the neurotoxic effects of TMA+ exposure on zebrafish, based on neurobehavior tests and a series of biomarkers. Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L, and significant alterations on swimming path angles (straight and deflective movements) occurred even at 10 mg/L. The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species (ROS) and malondialdehyde (MDA), significantly negatively related with the activities of antioxidant enzymes, but not significantly correlated with the level of acetylcholinesterase (AChE). Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress, rather than the alterations of neurotransmitter. At the highest exposure concentration (200 mg/L), TMA+ evoked more severe toxicity on zebrafish juveniles, showing significantly stronger elevation on the MDA activity, and greater inhibitions on the activities of antioxidant enzymes and AChE, suggesting juveniles were more susceptible to TMA+ exposure than larval zebrafish.

Comparing Longitudinal Measures of Cholinesterase as Biomarkers for Insecticide Exposure Among Latinx Children in Rural Farmworker and Urban Nonfarmworker Communities in North Carolina.

In a 2-group prospective design, this study compared seasonal cholinesterase levels of Latinx children in rural farmworker families and comparable urban children to assess the impact of environmental exposure to cholinesterase-inhibiting insecticides. Quarterly blood samples and passive dosimeter wristbands were collected over 2 years in 8-year-old children (74 rural, 62 urban). Laboratory analysis assessed total cholinesterase, acetylcholinesterase, and butyrylcholinesterase from blood samples, and insecticides from wristbands. In spring and summer, total cholinesterase and acetylcholinesterase levels were depressed in rural children compared with winter and fall. Butyrylcholinesterase was depressed in rural children in fall compared with spring and summer. Adjustment for insecticide exposure did not affect these associations. Environmental exposures to cholinesterase-inhibiting insecticides have measurable biochemical effects on blood cholinesterases in rural children from farmworker families.

Croton hirtus attenuating streptozotocin-induced neuroinflammation in rats

ObjectiveThe present study was aimed to investigate the neuroprotective effect of Croton hirtus (CH) extract against streptozotocin (STZ) in rats. Methods(i) The sub-chronic toxicity consisted of 24 adult rats of either sex weighing from 160 to 200 g were divided into four groups with six rats in each group. Rats in group 1 received Dimethyl sulfoxide (DMSO) mixed with saline; rats in groups 2, 3, and 4 received 100, 200, and 400 mg/kg of methanolic extract of CH (MECH) orally by gavage administration for 28 d, respectively. The functional observation battery and locomotor activity were graded as part of their neurobehavioral activity and the brain regions, including cortex and hippocampus, were analyzed for neuropathological abnormalities. (ii) The main research consisted of 30 adult male Wistar rats weighing from 160 to 200 g, which were divided into five groups and six rats in each group, including control (I), STZ (II), Donepezil (III), MECH (100 mg/kg, IV), and MECH (200 mg/kg, V) groups. Rats in group I received citrate buffer orally and DMSO mixed with saline for 14 d. Rats in group II received STZ via intracerebroventricular injection (3 mg/kg, bilateral ICV-STZ) on days 1 and 3 followed by DMSO mixed with saline for 14 d. Rats in groups III, IV, and V received STZ administration on days 1 and 3 followed by Donepezil [3 mg/(kg·d), p.o.] and MECH [100 and 200 mg/(kg·d), p.o.] for 14 d. Rats were tested for learning and memory parameters such as Morris water maze (MWM) and passive avoidance test (PAT). They were sacrificed after completing behavioural experiments; brains were harvested to estimate the acetylcholinesterase (AChE), lipid peroxidation (LPO), glutathione (GSH), and superoxide dismutase (SOD) by using UV-Visible Spectrophotometer; caspase-3 was evaluated by total fluorescence emission spectra; amyloid β (Aβ) levels were detected using enzyme-linked immuosorbent assay (ELISA); and histopathological examination was conducted in the CA1 region of the hippocampus. Results(i) The sub-chronic toxicity results revealed that open field test parameters including line crossing, rearing, entering the middle square, defecating, or urinating did not differ significantly in the MECH rats (P > 0.05). The histopathological observation did not show any lesions in the neuronal cells and inflammation in both the regions in MECH rats compared with control rats. (ii) The main study findings demonstrated that STZ-treated rats showed a significant increase in impairment in learning and memory parameters (P < 0.001), the levels of AChE, caspase-3, Aβ (1-40 and 1-42), and LPO were increased significantly (P < 0.001), and significant decrease was found in the levels of SOD (P < 0.001) and GSH (P < 0.01). Moreover, neuronal damage was found in the hippocampus. In contrast, STZ-induced behavioural and biochemical impairments in rats were considerably decreased by treatment with MECH dose-dependently. ConclusionMECH significantly prevented the memory deficit induced by STZ due to antioxidant action. Restoration of cholinergic functioning may be the cause of behavioural improvement. Therefore, MECH may be able to treat cognitive disorders like Alzheimer's disease (AD).

Evaluvation of Anti-amnesic activity of Ayurvedic formulation Saraswathaghrita in the scopolamine-induced rat model

Aim: The current research aims to evaluate and scientifically validate the ani-amnestic potential of ayruvedic formulation Saraswathaghrita (SG) in the scopolamine-induced rat model. Materials and methods: The animals were pretreated with different doses of SG (100mg/kg, 200mg/kg, and 400mg/kg) for seven days before scopolamine induction. For induction of amnesia, scopolamine was injected i.p (single dose of 2mg/kg) in rats for seven consecutive days. 1 hour before induction different doses of SG were administrated (p.o). On the 7th day after 1-hour of induction, various behavioral studies, biochemical estimations, neurotransmitter evaluations, and histopathological studies were performed. Results: The escape latency time in the Morris water maze was significantly increased in 400mg/kg SG treated group compared to the scopolamine-induced group (31.667± 1.174). Treatment with various doses of SG significantly decreases the no. of attempts and latency time (3.167± 0.307 and 7.700±0.383, 2.667±0.211 and 6.617±0.387 and 2.333±0.211 5.267±0.616). Treatment with SG results in regaining the levels of endogenous antioxidant levels to normal values compared to the scopolamine-induced group. In the case of acetylcholinesterase activity, SG treated group, there was a significantly decreased level of acetylcholinesterase (0.611±0.027) compared with the scopolamine-induced group (1.142±0.049). The neuroprotective effect of SG was confirmed by histopathology. The inflammatory cells were absent, glial and astrocytes possess proper morphological features in SG treated group. Conclusion: SG possesses potent anti-cholinesterase inhibition potential and anti-oxidant properties which leads to its anti-amnestic property in the scopolamine-induced rat model.

An Evaluation of a Pesticide Training Program to Reduce Pesticide Exposure and Enhance Safety among Female Farmworkers in Nan, Thailand.

Although exposure to chemical pesticides is known to cause negative effects on human health, farmers in Ban Luang, Nan, Thailand, continue to use them regularly to protect crops. This study focused on mothers who were engaged in farm tasks and had children between the ages of 0 to 72 months, with the objective of reducing pesticide exposure. This study was conducted from May 2020 to October 2020 in the Ban Fa and Ban Phi sub-districts in Ban Luang due to the high use of pesticides in these areas. A systematic random sampling technique was used to recruit 78 mothers exposed to pesticides. Thirty-nine mothers from Ban Fa district were randomly assigned to the intervention group and 39 from Ban Phi to the control group over a 3-month period. This study applied a pesticide behavioral change training program for the intervention group. To assess the effectiveness of the program, the study compared the results of a questionnaire regarding knowledge, attitude, and practice (KAP) and health beliefs related to pesticide exposure as well as the levels of acetylcholinesterase (AChE) and butyryl cholinesterase (BChE) enzymes, biomarkers of exposure to pesticides, before and after the intervention using ANCOVA statistical test. Furthermore, to evaluate the effectiveness of the intervention program, a paired t-test was used to investigate the in-home pesticide safety assessment. After the intervention, we observed no significant change in AChE; however, a significant improvement in BChE (p < 0.05), a marker of short-term recovery, was observed. Pesticides can cause a reduction in AChE and BChE, however, after eliminating pesticides, BChE takes a shorter time (about 30-50 days) to recover than AChE (around 90-120 days). Therefore, increases in the measured concentrations of AChE and/or BChE suggest the presence of less chemicals from pesticides in the human body. The study also found a significant improvement in KAP and beliefs about chemical pesticide exposure after the intervention (p < 0.05). Furthermore, using a paired t-test, we found a significant increase in pesticide safety practices (p < 0.05) in the intervention group and a borderline significant increase regarding in-home safety (p = 0.051) in the control group. Based on the results, the constructs of the intervention program were effective and could be applied in other agricultural areas in less developed countries. However, due to time limitations during the COVID-19 pandemic, further studies should be conducted to enable data collection over a longer time, with a larger number of subjects providing the ChE levels for the non-agricultural season.

Impairment of visual and neurologic functions associated with agrochemical use.

To determine whether exposure to occupational levels of agrochemicals is associated with a range of low- (contrast and colour) and higher-level visual functions, particularly the detection of global form and motion coherence. We compared the performance of workers exposed to occupational levels of pesticides and non-exposed individuals on visual tasks that measured colour discrimination (Farnsworth Munsell 100 and Lanthony D15 desaturated) and the contrast sensitivity function (1-16 cpd). Global form and motion detection thresholds were measured using Glass-pattern and global dot motion stimuli. Neurotoxicity symptoms and biological markers associated with pesticide exposure were quantified using the Q16 modified questionnaire and via tests for levels of acetylcholinesterase in blood and substance P from the tear film, respectively. Workers exposed to pesticides had significantly more neurotoxic symptoms than non-exposed workers. No significant difference between groups for acetylcholinesterase levels was found, but there was a significant group difference in Substance P. The exposed group also had significantly poorer contrast sensitivity, colour discrimination and higher coherence detection thresholds for global form and motion perception. Exposure to occupational levels of agrochemicals in workers with signs of neurotoxicity is associated with low and high visual perception deficits.

Codium fragile Suppresses PM2.5-Induced Cognitive Dysfunction by Regulating Gut-Brain Axis via TLR-4/MyD88 Pathway.

This study was conducted to evaluate the cognitive dysfunction improvement effect of aqueous extract of Codium fragile (AECF) by regulating the imbalance of the gut-brain axis in chronic particulate matter (PM)2.5-exposed mice. The physiological compounds of AECF were identified as hexadecanamide, oleamide, octadecanamide, stearidonic acid, and linolenic acid by the ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC Q-TOF MSE) analysis. To evaluate the effect of PM2.5 on the antioxidant system, superoxide dismutase (SOD) contents, reduced glutathione (GSH) contents, and malondialdehyde (MDA) contents were measured in colon and brain tissues. AECF significantly ameliorated the imbalance of the antioxidant systems. Also, AECF improved intestinal myeloperoxidase (MPO) activity, the abundance of the gut microbiome, short-chain fatty acids (SCFAs) contents, and tight junction protein expression against PM2.5-induced damage. In addition, AECF prevented PM2.5-induced inflammatory and apoptotic expression via the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88) pathway in colon and brain tissues. Additionally, AECF enhanced the mitochondrial function, including the mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) contents in brain tissues. Furthermore, AECF regulated the cholinergic system, such as acetylcholine (ACh) contents, acetylcholinesterase (AChE) activity, and protein expression levels of AChE and choline acetyltransferase (ChAT) in brain tissues. To evaluate the effect of cognitive dysfunction caused by PM2.5-induced intestinal dysfunction, behavior tests such as Y-maze, passive avoidance, and Morris water maze tests were performed. From the results of the behavior tests, AECF ameliorated spatial learning and memory, short-term memory, and long-term learning and memory function. This study confirmed that AECF reduced PM2.5-induced cognitive dysfunction by regulating gut microbiome and inflammation, apoptosis, and mitochondrial function by enhancing the gut-brain axis. Based on these results, this study suggests that AECF, which contains fatty acid amides, might be a potential material for ameliorating PM2.5-induced cognitive dysfunction via gut-brain axis improvement.

Evaluation of Nootropic Potential of Aerva persica Roots against D-galactose-induced Memory Impairment.

The primary phytoconstituents reported to have neuroprotective effects are flavonoids and phenolic compounds. Aerva persica roots are reported to be rich in flavonoids and phenolic compounds. Therefore, this study aimed to explore the nootropic potential of Aerva persica roots. The objective of this study was to evaluate the nootropic potential of Aerva persica roots against D-galactose-induced memory impairment. In this study, the roots of Aerva persica were extracted with 70% ethanol. The obtained extract was evaluated for total phenolic content using the Folin-Ciocalteu method and total flavonoid content using the aluminium chloride colorimetric assay. Afterward, the acute oral toxicity of the extract was determined following the Organisation for Economic Co-operation and Development (OECD) guideline 423. Additionally, two doses of Aerva persica (100 and 200 mg/kg body weight (BW)) were evaluated for their nootropic potential against D-galactose-induced memory impairment. The nootropic potential of the crude extract was assessed through a behavioural study and brain neurochemical analysis. Behavioural studies involved the evaluation of spatial reference- working memory using the radial arm maze test and the Y-maze test. Neurochemical analysis was performed to determine the brain's acetylcholine, acetylcholinesterase, glutathione (GSH), and malondialdehyde (MDA) levels. The total phenolic content and total flavonoid content were found to be 179.14 ± 2.08 μg GAE/mg and 273.72 ± 3.94 μg QE/mg, respectively. The Aerva persica extract was found to be safe up to 2000 mg/kg BW. Following the safety assessment, the experimental mice received various treatments for 14 days. The behavioural analysis using the radial maze test showed that the extract at both doses significantly improved spatial reference-working memory and reduced the number of total errors compared to disease control groups. Similarly, in the Y-maze test, both doses significantly increased the alteration percentage and the percentage of novel arm entry (both indicative of intact spatial memory) compared to disease control. In neurochemical analysis, Aerva persica at 200 mg/kg significantly normalised the acetylcholine level (p<0.0001) and GSH level (p<0.01) compared to disease control. However, the same effect was not observed with Aerva persica at 100 mg/kg. Additionally, Aerva persica at 200mg/kg BW significantly decreased the acetylcholinesterase level (p<0.0001) and decreased the brain's MDA level (p<0.01) compared to the disease control, whereas the effect of Aerva persica at 100 mg/kg BW in reducing acetylcholinesterase was non-significant. Based on the results, it can be concluded that the nootropic potential of Aerva persica was comparable to that of the standard drug, Donepezil, and the effect might be attributed to the higher content of flavonoids and phenolic compounds.

Mumefural Improves Recognition Memory and Alters ERK-CREB-BDNF Signaling in a Mouse Model of Chronic Cerebral Hypoperfusion.

Cognitive impairment resulting from chronic cerebral hypoperfusion (CCH) is known as vascular dementia (VaD) and is associated with cerebral atrophy and cholinergic deficiencies. Mumefural (MF), a bioactive compound found in a heated fruit of Prunus mume Sieb. et Zucc, was recently found to improve cognitive impairment in a rat CCH model. However, additional evidence is necessary to validate the efficacy of MF administration for treating VaD. Therefore, we evaluated MF effects in a mouse CCH model using unilateral common carotid artery occlusion (UCCAO). Mice were subjected to UCCAO or sham surgery and orally treated with MF daily for 8 weeks. Behavioral tests were used to investigate cognitive function and locomotor activity. Changes in body and brain weights were measured, and levels of hippocampal proteins (brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase (ERK), cyclic AMP-response element-binding protein (CREB), and acetylcholinesterase (AChE)) were assessed. Additionally, proteomic analysis was conducted to examine the alterations in protein profiles induced by MF treatment. Our study showed that MF administration significantly improved cognitive deficits. Brain atrophy was attenuated and MF treatment reversed the increase in AChE levels. Furthermore, MF significantly upregulated p-ERK/ERK, p-CREB/CREB, and BDNF levels after UCCAO. Thus, MF treatment ameliorates CCH-induced cognitive impairment by regulating ERK/CREB/BDNF signaling, suggesting that MF is a therapeutic candidate for treating CCH.

Aldol-click generated silane: A turn-on fluorescent sensor for Al3+ ion and exploring its anti-Alzheimer activity via molecular docking

Alzheimer's disease (AD) is one of the leading neurodegenerative disorder whose cure is yet to be developed. Elevated levels of Aluminium ion and acetylcholinesterase in brain tissue are main concern for progression of AD. Hence, both detection of Aluminium ion and inhibition of acetylcholinesterase are important research areas that have gained attention. Aldol-generated chalcones and Click-derived triazoles are among the emerging privileged scaffolds for selective and sensitive detection of metal ions and as promising pharmacological drugs. The present work focuses on design and development of ‘chalcogenyl-based triazole coupled organosilane’ that could selectively detect neurotoxic Aluminium ion. The binding strength and ratio between the two was discovered from B–H plot and Job's plot method respectively from fluorescent studies. Further linear calibration curve was utilized to calculate the limit of detection (LOD). The possible binding site of chemosensor for Aluminium ion has been recognized from 1H NMR studies and DFT calculations. Molecular docking, a computational approach was used to scrutinize the synthesized ‘chalcogenyl based triazole coupled organosilane’ as whether it could inhibit the activity of acetylcholinesterase and thus be further examined as potent pharmacological drug in treatment of AD.

Neuroprotective effects of terpenoids against streptozotocin-nicotinamide-induced diabetic rats: An in silico, in vitro and in vivo study

The present study focused to determine the neuroprotective effects of terpenoids in streptozotocin & nicotinamide-induced type-2 diabetes in rats. The in silico studies were carried out for 68 terpenoids using AutoDock 4.2. The in vitro cholinestrerase, α-amylase enzyme inhibitory assays were perfomed using standard procedures. For in vivo neuroprotective studies, male wistar rats were separated into five groups and each group comprised of six animals. Treatment groups were received low dose and high dose α-Bisabolol 100 and 200 mg/kg respectively, and the standard groups received rivastigmine 2 mg/kg, p.o. and metformin group 100 mg/kg, p.o. for 30 consecutive days. Administration of streptozotocin (45 mg/kg, i.p.) and nicotinamide (110 mg/kg, i.p.)-induced the type 2 diabetes in all groups except the control. The behavioural assessments such as Morris water maze, and open field test were performed and biochemical parameters such as acetylcholinesterase levels and enzymatic antioxidants and reduced glutathione level were estimated from brain homogenates. Treatment of diabetic rats with α-Bisabolol was lowered blood glucose level, improved spatial recognition memory in behavioural assessments in a concentration dependent manner. It can be concluded that α-Bisabolol could act as a potential drug candidate in the management of diabetic Alzheimer's disease.

Sesquiterpene nootkatone counteracted the melamine-induced neurotoxicity via repressing of oxidative stress, inflammatory, and apoptotic trajectories

Melamine (ML), a chemical substance of high nitrogen content, is used as a food adulterant. Former evidences implied that ML could induce a variety of toxic effects including neurotoxicity and cognitive impairment. Therefore, the aim of this study was to delineate the protective effect of the nootkatone (NK) against ML-induced neural adverse effects. Rats were orally pretreated with NK (5 and 10 mg/kg) prior to the oral administration of ML (700 mg/kg) for a period of 28 days. Our findings unveiled remarkable alleviating effect of NK on MK-induced neurobehavioral disturbance in open field test. Furthermore, NK lessened ML-caused increases in the acetylcholine esterase level in the brain tissue of exposed rats. NK also decreased the neural oxidative stress as represented by elevated levels of SOD, CAT, and GSH along with decreased MDA and NO levels. Upregulated mRNA expression levels of neural NRF-2 and HO-1 were noticed after NK administration. Remarkable anti-inflammatory impact was prominent by decreased neural IL-1β, and TNF-α along with downregulated NF-κB and TLR-4 gene expression levels in NK-treated rats. Noteworthily, pre-treatment with NK decreased the immune reaction of RAGE and HMGB-1 induced by oral ML exposure. Brain histological examination validated the obtained biochemical and molecular results. To sum up, these outcomes reveal that NK successfully alleviated the neural damage induced by ML via blocking of oxidative stress, and inflammatory signaling pathways. Consequently, our study may suggest NK as a new effective therapeutic supplement for treatment of ML-mediated neurotoxicity in rats via inhibition of HMGB-1-RAGE/TLR-4/NF-κB.

The Influence of Copper Nanoparticles on Neurometabolism Marker Levels in the Brain and Intestine in a Rat Model.

The aim of this study is to assess the effect of different forms and dosages of copper on the levels of markers depicting the neurodegenerative changes in the brain and the jejunum. The experiment was performed using 40 male Wistar rats fed a typical rat diet with two dosages of Cu used as CuCO3 (6.5 and 13 mg/kg diet) and dietary addition of two CuNP dosages (standard 6.5 and enhanced 13 mg/kg diet), randomly divided into four groups. The levels of neurodegenerative markers were evaluated. Nanoparticles caused a reduction in the level of glycosylated acetylcholinesterase (GAChE), an increase the level of acetylcholinesterase (AChE) and lipoprotein receptor-related protein 1 (LRP1), a reduction in β-amyloid (βAP) in the brain and in the intestine of rats and a reduction in Tau protein in the brain of rats. The highest levels of AChE, the ATP-binding cassette transporters (ABC) and LRP1 and lower levels of toxic GAChE, β-amyloid, Tau, hyper-phosphorylated Tau protein (p-Tau) and the complex of calmodulin and Ca2+ (CAMK2a) were recorded in the tissues of rats receiving a standard dose of Cu. The neuroprotective effect of Cu can be increased by replacing the carbonate form with nanoparticles and there is no need to increase the dose of copper.

Salivary Biomarkers: Noninvasive Ways for Diagnosis of Parkinson's Disease.

Finding reliable biomarkers has a crucial role in Parkinson's disease (PD) assessments. Saliva is a bodily fluid, which might be used as a source of biomarkers for PD. Our article has reviewed several publications on salivary proteins in PD patients and their potential as biomarkers. We find out that α-Syn's proportion in oligomeric form is higher in PD patients' saliva, which is potent to use as a biomarker for PD. The salivary concentration of DJ-1 and alpha-amylase is lower in PD patients. Also, substance P level is more moderate in PD patients. Although salivary flow rate is decreased in PD patients, high levels of heme oxygenase and acetylcholinesterase might be used as noninvasive biomarkers. Salivary miRNAs (miR-153, miR-223, miR-874, and miR-145-3p) are novel diagnostic biomarkers that should be given more attention.

Investigating Neuroprotective Potential of Berberine, Levetiracetam and their Combination in the Management of Alzheimer's Disease Utilizing Drug Repurposing Strategy.

The aim of the present work was to evaluate the neuroprotective potential of berberine, levetiracetam and their combination in lead acetate-induced neurotoxicity by applying a drug repositioning approach. Alzheimer's disease (AD) is a neurodegenerative disease characterized by impairment of memory, disturbances in reasoning, planning, language and perception. Currently, there are only four drugs approved by US-FDA for AD; therefore, there is an extensive need for new drug development. The drug repositioning approach refers to the development of new uses for existing or abandoned pharmaceuticals. Several studies support the neuroprotective abilities of anti-oxidants resulting in neuronal protection against neurotoxins, suppression of oxidative stress and promotion of memory, learning and cognitive functions. Many natural polyphenols are being investigated as a potential therapeutic option for AD. Levetiracetam (LEV), a second-generation antiepileptic drug, is a new molecule that is clearly differentiated from conventional antiepileptic drugs by its pharmacologic properties. LEV also has been previously demonstrated to protect against oxidative stress-induced neurotoxicity in several models of seizures. Berberine (BBR) is an anti-inflammatory and anti-oxidant phytoconstituent. To study the therapeutic effect of berberine, levetiracetam and their physical mixture in lead acetate-induced neurotoxicity in Swiss albino mice for probable application in the management of Alzheimer's disease. Neurotoxicity was induced in Swiss albino mice by lead acetate. Behavioural parameters, such as transfer latency time and percentage alternation, were studied using Morris water maze (MWM), Elevated plus-maze test (EPM) and Y-maze for the assessment of improvement in learning and memory. Concentrations of acetylcholinesterase, MDA and GSH in the brain were also estimated. Brain samples were subjected to histopathological studies. Results revealed that the combination of BBR and LEV exhibited a significant neuroprotective effect by decreasing escape latency time and increasing time spent in the target quadrant in MWM. The combination also decreases transfer latency time in EPM and acetylcholinesterase levels in the brain as compared to standard donepezil. Reduced neuronal damage was also confirmed by the histopathological report. Leveteracitam, berberin and their combination resulted in the significant conservation of various behavioural, biochemical, enzymatic and anti-oxidant parameters that were evaluated. The neuroprotective effect of plain leveteracitam and berberin was significantly better than their combination. The anticipated synergism or additive effect was not observed with the combination of leveteracitam and berberin in lead acetate-induced neurotoxicity.

Oxidative Stress Caused by Lithium Exposure in the Carassius auratus (goldfish) Liver Tissue

Lithium is a therapeutic agent widely used in the treatment of some psychiatric disorders. The aim of this study was to investigate the effects lithium-induced oxidative stress in liver tissue. In this study, Carassius auratus fish was used as a model organism and total 20 control fish and 28 experimental fishes were divided 4 subgroups randomly. Lithium chloride at a concentration of 50 mg/L was added to the glass tank of the experimental group. Fish were placed in two separate glass tanks, 20 in the control group and 28 in the experimental group. Lithium chloride at a concentration of 50 mg/L was added to the glass tank, which is the experimental group. At the 24th, 48th, 72nd and 96th hours of the study, 5 samples from the control group and 7 samples from the experimental group were included in the study in four different time periods. At the end of the study, it was determined that the level of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and acetylcholinesterase(AchE) decreased in the group with lithium exposure, while the levels of Malondialdehyde (MDA) increased. It was determined that oxidative stress occurred in lithium exposure.

Reproductive and Biochemical Toxicity of Biobased Silver Nanoparticles against Toxocara vitulorum

Background: Toxocara vitulorum is a common parasitic worm of buffalo and cattle, causing livestock mortality and morbidity worldwide. Several countries suffered substantial eco-nomic losses due to animal death and reduced meat and milk production. Therefore, it became nec-essary to discover a new alternative drug, especially with the emerging resistance to current medica-tions. The present study aims to evaluate the in vitro anthelmintic effect of different concentrations of biobased silver nanoparticles on T. vitulorum adults. Methods: Different concentrations of silver nanoparticles were synthesised using lemon juice. Groups of male and female adult worms were incubated in 50, 100, and 200 mg/L silver nanoparti-cles for 48 h. The parasite motility, histology, and biochemical parameters were observed and com-pared to the control. Results: The results showed that silver nanoparticles decreased the worm motility, increased mor-tality rate, induced structural damage, caused collagen disruption, and showed elevated levels of as-partate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, total protein, urea, and creatinine, as well as reduced levels of acetylcholinesterase, lactate dehydrogenase, uric acid, total cholesterol, triglycerides, and high-density lipoprotein in a dose-dependent manner. Conclusion: Silver nanoparticles established a significant anthelmintic effect against T. vitulorum and could become one of the up-and-coming antiparasitic drugs in the future.