Acetylcholinesterase Levels Research Articles

Commercial Formulation of Chlorpyrifos Alters Neurological Behaviors and Fertility.

Pesticides are known to result in toxic insult. We aimed to evaluate Judo 40, the commercial formulation of chlorpyrifos on the neurological activities, fertility, and hormone levels of male rats. Male Wistar rats were treated orally with 1 mL of 20 or 50 mg/kg Judo 40. The doses were administered four times, twice a day. Sexual and exploratory behavior indices, fertility indices, serum androgen levels, blood acetylcholinesterase (BChE) levels, and neurological and muscular effects were evaluated. Serum testosterone and luteinizing hormone were significantly reduced in the rats receiving 50 mg/kg Judo 40. A reduction in viable implantation sites and live pups born were evident in the female rats mated with the male rats treated with the highest dose. Similarly, in the rats treated with the highest dose of Judo 40, a significant reduction in plasma BChE enzyme was observed. According to the results, prolonged Judo 40 exposure can cause impairment of the neurological alterations and sex hormones leading to impaired fertility. Therefore, chemical handlers should be educated on protection and risk minimization.

Antiepileptic potential of Bacopa monnieri in the rat brain during PTZ-induced epilepsy with reference to cholinergic system and ATPases

Epilepsy is a chronic central nervous system disorder that occurs not only with the imbalance of glutamatergic neurons and inhibitory gamma-aminobutyric acid (γ-GABA) neurons, but also with abnormal Central cholinergic neuronal regulation. Since long term usage of antiepileptic drugs cause high incidence of pharmacoresistance and untoward side effects, attention has been paid in recent years to screen bioactive compounds from natural medicinal plants for the treatment of several neurological disorders including Epilepsy. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-convulsant effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurvedic treatments related to neurological complications. The present study is designed to assess the neurotoxicity of Pentylene tetrazole (PTZ), an epileptic compound with particular reference to Cholinergic system and ATPases in different brain regions of rat to explore the possible antiepileptic effect of different extracts of BM in comparison with Diazepam (DZ) (Reference control). The activity levels of Acetyl cholinesterase (AChE) and ATPases were decreased in different regions of brain during PTZ induced epilepsy which were increased in epileptic rats pretreated with different extracts of Bacopa monnieri except EAE and AE. In addition Acetylcholine (ACh), levels were increased during PTZ induced epilepsy when compared with normal control and levels were reversed on pretreatment with different extracts of BM. Recoveries of these parameters suggest that the bioactive factors present in the extracts offer neuroprotection by interrupting the pathological cascade that occurs during epileptogenesis.

Effect of Anoectochilus roxburghii flavonoids extract on H2O2 - Induced oxidative stress in LO2 cells and D-gal induced aging mice model

Ethnopharmacological relevanceAnoectochilus roxburghii (A. roxburghii) is a popular folk medicine in many Asian countries, which has been used traditionally for treatment of some diseases such as diabetes, tumors, hyperlipemia, and hepatitis. The ethanol extract from A. roxburghii was recently shown to exert better ability to scavenge free radicals in vitro and possess antioxidant on natural aging mice in vivo. Aim of the studyThis study is to characterize the chemical composition, and investigate the protective effect of the A. roxburghii flavonoids extract (ARF) against hydrogen peroxide (H2O2)-induced oxidative stress in LO2 cells in vitro and D-galactose (D-gal)-induced aging mice model in vivo, and explore the underlying mechanisms. Materials and methodsThe chemical components of the flavonoids extract fromA. roxburghii were detected by ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). H2O2 was used to establish an oxidative stress model in LO2 cells. Cytotoxic and protective effects of ARF on the LO2 cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Moreover, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in cell supernatants were measured by commercial reagent kits. Kun-Ming mice were induced to aging with D-gal (400 mg/kg, BW) by subcutaneous injection for 58 days. From the 28th day to the 58th day of D-gal treatment, ARF (122.5, 245 and 490 mg/kg, BW) and vitamin E (100 mg/kg, BW) were orally administrated to aging mice once a day for consecutive 30 days. After 25 days of the treatment with ARF, learning and memory were assessed using Morris Water Maze (MWM). At the end of the test period, the animals were euthanized by cervical dislocation, and the levels of SOD, GSH-PX, and MDA in serum, liver homogenates and brain homogenates were measured. The levels of monoamine oxidase (MAO) and acetylcholinesterase (AchE) were determined in brain homogenates. Skin and liver histopathological morphology were observed by H&E staining. Furthermore, antioxidant-related gene expression levels in the liver were carried out by quantitative real-time polymerase chain reaction (qRT-PCR). ResultsNine flavonoids were identified in the extracts of A. roxburghii. In vitro assay, a high concentration of ARF (>612.5 μg/ml) reduced the survival rate and had toxic effects on LO2 cells. In addition, ARF (245 μg/ml, 490 μg/ml) and Vitamin C (200 μg/ml) markedly inhibited generations of MDA and increased activities of SOD, GSH-PX in H2O2-induced LO2 cells supernatants. In vivo assay, ARF (122.5 mg/kg, 245 mg/kg and 490 mg/kg) and Vitamin E (100 mg/kg) not only ameliorated learning and memory ability but also improved skin and liver pathological alterations. Strikingly, ARF significantly decreased MDA and MAO levels, markedly enhanced antioxidant enzyme (SOD and GSH-PX) activities. Further, compared to the D-gal group, ARF could obviously up-regulate glutathione peroxidase-1 (GPx-1) and glutathione peroxidase-4 (GPx-4) mRNA levels. ConclusionsThese findings suggested that ARF protects LO2 cells against H2O2-induced oxidative stress and exerts the potent anti-aging effects in D-gal aging mice model, which may be related to the inhibition of oxidative stress. Flavonoid compounds may contribute to the anti-oxidative capability and modulating aging.

SAT-133 BLOOD ACETYLCHOLINESTERASE ACTIVITY AND COMPARATIVE eGFR IN RURAL FARMERS WITH LOW, INTERMEDIATE, AND HIGH EXPOSURE TO ORGANOPHOSPHOROUS CONTAINING AGROCHEMICALS

Organophosphorous containing agrochemicals (OCAs) are commonly used by farmers to prevent destruction of farm products by pests and weeds. Their role as risk factors of kidney disease is currently being evaluated. Blood acetylcholinesterase inhibition is a recognized marker of exposure to organophosphorous containing chemicals. We conducted a study to determine the proportion of rural farmers who use these agents, their blood acetylcholinesterase activities and comparative estimated glomerular filtration rate (eGFR) in those with low, intermediate, and high exposure. A cross-sectional study of nine rural farming communities in Southwestern Nigeria. Degree of exposure was categorized using the following criteria: (a) Years of active farming - Low (0-10 years) and High (> 10 years), (b) Use of protective garment - Low (Yes), High (No). A score of low for both parameters was categorized as low exposure, a score of low and high in both parameters was graded as intermediate exposure, while a score of high in both parameters was graded as high exposure. All participants were evaluated for kidney function using CKD-EPI equation to calculate the eGFR. Blood acetylcholinesterase activity was evaluated by the modified Ellman’s method. Five hundred and seventy two farmers participated in the study. Two hundred and twenty five (39.3%) were males while 347 (60.7%) were females. Mean age of participants was 52 ± 17.5 (range 18 – 100) years. Years of active farming ranged from 0.5 to 80 years, with a median of 25 years. Blood acetylcholinesterase activity ranged from 0 – 20.1 (mean 3.5 ± 3.5) µmol/min/mL in all participants. Four hundred participants (69.9%) stated that they used organophosphate containing agrochemicals. Exposure was low in 32 (8%), intermediate in 161 (40.6%), and high in 200 (50%) of these participants. Blood acetylcholinesterase activities / eGFR levels in low, intermediate, and high exposures are shown in the table. Statistically, blood acetylcholinesterase activities were similar in those with high compared to those with low exposure (P = 0.338). However, eGFR was significantly lower in those with high compared to those with low exposure (P = 000). Use of organophosphate containing agrochemicals was high in the rural farmers examined. There was a decline in eGFR with higher exposure. However, blood acetylcholinesterase activity levels did not appear to differ significantly among the different groups of exposure studied. There is a need for a prospective study to determine the normal range of blood acetylcholinesterase levels in unexposed individuals to define the minimum duration of exposure to organophosphate agrochemicals neccessary for significant surpression of blood of acetylcholinesterase levels in the rural farmers.

Comparative Study on Diet Added with Organic and Inorganic Selenium Forms Provided to Carps Exposed to Fipronil Insecticide

Carps belonging to species Cyprinus carpio (carp) were fed on organic and inorganic selenium forms for 60 days to enable evaluating the biochemical profile of tissues exposed to fipronil (FPN) insecticide. Diphenyl diselenide [(PhSe)2] (3.0 mg/kg) and sodium selenite (Na2SeO3) (0.75 mg/kg) were used as organic and inorganic selenium forms, respectively. Overall, the adopted organic and inorganic selenium forms were similarly capable of reestablishing oxidant and antioxidant stress parameters close to control levels. Fish exposed to fipronil have shown decreased acetylcholinesterase (AChE) activity in brain and muscle tissues. Brain tissues of fish supplemented with Na2SeO3 or (PhSe)2 diets presented reestablished AChE levels in comparison to those of fish fed on standard diet. Liver tissues of fish fed on standard diet presented decreased δ-ALA-D activity after their exposure to FPN, whereas diets added with two selenium forms were efficient in reestablishing the levels of standard diets. Therefore, (PhSe)2 and Na2SeO3 have potential to be used as supplementation factors in diets to feed C. carpio.

REVERSAL OF CISPLATIN-INDUCED MEMORY IMPAIRMENT BY GALLIC ACID IN EXPERIMENTAL RAT MODEL

Objective: The objective of the study was to evaluate the protective effect of gallic acid on cisplatin-induced memory impairment (MI) in the rat model.
 Methods: Five groups of Wistar albino rats (n=6) were employed and the duration of the study was 22 days, excluding the pre-treatment period. Animals were pretreated with gallic acid for a period of 5 days and continued daily (200 mg/kg) for 22 days. The cisplatin (3 mg/kg) was given once in a week for 3 consecutive weeks to induce MI, whereas donepezil was used as standard. The evaluation was done by a change in body weight, memory activity by Morris water maze (MWM), locomotor activity by actophotometer, antioxidant activity by thiobarbituric acid reactive substance (TBARS), glutathione (GSH), and estimation of acetylcholinesterase (AChE) activity in brain homogenate.
 Results: Administration of cisplatin has induced MI by increasing in escape latency time, decrease in time spent in the target quadrant in the MWM task and it was reversed by gallic acid treatment. Decreased locomotor activity by cisplatin was also increased by gallic acid when tested by actophotometer. Cisplatin administration has induced oxidative stress by increasing TBARS and decreasing GSH levels. Gallic acid due to its proven antioxidant activity reversed the effects of cisplatin. The AChE level was significantly increased in the control group, whereas treatment groups have shown a decrease in AChE level.
 Conclusion: Gallic acid may serve as a primary agent to treat the cognitive impairment and oxidative stress associated memory dysfunctions. However, more extensive studies are needed before utilization in the clinical trial.

Mitigation of lead neurotoxicity by the ethanolic extract of Laurus leaf in rats.

The present study was conducted in order to assess the chemical composition of Laurus, its antioxidant activities, and benefit from the Laurus extract effect on neurotoxicity caused by lead acetate (Pb). Chemical profile was assayed by using liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS). In this study, 40 male rats were divided into four groups (10 rats per each group): (1) control group, (2) Laurus group: rats treated with 250mg/kg b. wt. of Laurus leaves extract, (3) Pb group: rats treated with 100mg/kg b. wt. of lead acetate, (4) Pb+Laurus group: rats treated with 250mg/kg b. wt. of Laurus leaves extract in addition to lead acetate for 30 days. At the end of experiment, some estimates were calculated from blood samples, brain tissue, and histological examination. The results showed that the extract is highly affluent in total flavonoids, total phenolic, and also has antioxidant activity. The LC-MS appeared a wide range of compounds in the extract. The oxidative stress resulted from exposure to lead acetate has been reported to cause reduction in body and brain weights, levels of RBCs, acetylcholinesterase (AChE), GSH, SOD, and CAT in addition to increase in levels of WBCs and MAD. Moreover, Laurus leaves extract notably lessened the biochemical changes caused by lead acetate in the blood, homogenate, and brain tissue (P<0.05). The current study indicates the antioxidant activity of Laurus leaves extract and assumes that it has a defensive role against the oxidative damage caused by lead in a rat's brain.

Neuroprotective effect of organic and inorganically grown tea on oxidative damage in rat model of Alzheimer’s disease

Production of improved valued tea is in high demand due to its pharmacological properties against various neurodegenerative diseases like Alzheimer’s disease. In this study, an attempt was made to compare the protective effect of the tea grown under organic and inorganic nutrient management practices against intra-cerebroventricular (i.c.v) colchicine induced memory impairment and oxidative damage in rat model of Alzheimer’s disease (AD). Results showed that chronic intraperitoneal (i.p) administration of tea extract (20 mg/kg i.p) significantly improved the cognitive dysfunction and memory impairment in colchicine treated AD rat model. This beneficial effect occurred with an increase in α-secretase activity, Superoxide dismutase, Catalase activities, and a decrease in Acetylcholinesterase level, Aβ -42 level, Cox-2-linked neuro-inflammation by intraperitoneal injection of tea extract grown organically and inorganically. The amyloid Aβ concentration in the rat model of AD was 84 ± 1.7 pg/mg protein. With administration of tea extract, the amyloid Aβ concentration decreased significantly to 55 ± 1.5, 52 ± 1.3 and 49 ± 1.5 pg/mg protein with the field level management of inorganic, integrated and organic nutrients, respectively. In this study celecoxib (20 mg/kg i.p) is used as a reference standard. This study stated organic tea as a promising neuroprotective agent or adjuvant to prevent AD.

Investigation on beneficial role of l-carnosine in neuroprotective mechanism of ischemic postconditioning in mice: possible role of histidine histamine pathway

Objective The present study was undertaken to investigate the possible role of histidine-histamine pathway in the neuroprotective effects produced by L-carnosine hand in hand with ischemic postconditioning in the animal model of cerebral ischemia. Methods Cerebral ischemia was induced in swiss albino mice by performing BCCAO surgery. Morris water-maze test was utilized to assess the learning ability and memory of the animals. The whole brain acetylcholinesterase (AChE) activity, TBARS, GSH levels and MPO activity were evaluated as the biochemical parameters. For histopathological evaluation of the cerebral infarct size, TTC staining was employed. Results Administration of L-carnosine (500 mg/kg, i.p.) successfully attenuated the manifestations of cerebral ischemia. Higher levels of AChE, TBARS, and MPO were observed in BCCAO treated animals, which were successfully attenuated by treatment with L-carnosine and ischemic postconditioning. Whereas administration of L-carnosine and ischemic postconditioning significantly increased the level of GSH in BCCAO treated animals. Moreover, treatment with ranitidine, an H2 blocker (30 NMol, i.c.v) antagonized the neuroprotective actions of L-carnosine evidenced by decrease in MWM performance, increase in the level of AChE and oxidative stress, while decrease in GSH level in brain. The cerebral infarct size was found to be more in BCCAO inflicted animals, which was improved by the administration of L-carnosine, while the cerebral infarct size worsened by treatment with ranitidine (3 nmol, i.c.v.). Conclusion It is concluded that L-carnosine exerts neuroprotective effect via involvement of histidine-histamine pathway since the beneficial effects of L-carnosine were abolished by the H2-blocker.

Pesticide Use and Serum Acetylcholinesterase Levels among Flower Farm Workers in Ethiopia-A Cross-Sectional Study.

The flower industry in East Africa has grown in recent years, especially in the production and export of roses. The aim of this study was to assess pesticide use on selected flower farms in Ethiopia. Serum cholinesterase levels in workers were used as a marker of pesticide exposure. This study was a cross-sectional study involving 588 workers from 15 different flower farms. It had a response rate of 95.5%. The participants included 277 males (mean age 26 years; 148 pesticide sprayers and 129 non-sprayers) and 311 females (mean age 25 years; 156 working in greenhouses and 155 working outside the greenhouses). The researchers undertook structured interviews, blood sampling, and walkthrough surveys. Descriptive statistics and Poisson regression were used in the statistical analyses. A total of 154 different trade names of pesticides were found. Of them, 31 (27%) were classified as moderately hazardous by the WHO, and 9% were organophosphates. Serum levels of cholinesterase deviating from 50–140 Michel units were considered abnormal. Abnormal serum cholinesterase levels (above 140 Michel units) were found in 97 participants (16.5%, 95% confidence interval 13.7–19.7%). There were no differences between the four job groups regarding cholinesterase levels. The high prevalence of abnormal serum cholinesterase levels might indicate the presence of pesticide intoxication. Thus, there is a need for routine monitoring of all workers exposed to pesticides, not only sprayers.

Carnosic acid alleviates chlorpyrifos-induced oxidative stress and inflammation in mice cerebral and ocular tissues.

Chlorpyrifos is an organophosphate pesticide whose exposure leads to inhibition of acetylcholinesterase (AChE) enzyme and induces oxidative stress, inflammation, and neurotoxicity. The current study was designed to evaluate the efficacy of carnosic acid (CA) in ameliorating CPF-induced cytotoxicity in mice brain and eye tissues. We allocated 40 male Swiss albino mice to receive DMSO 1% solution, oral CA 60mg/kg/day bw, CPF 12mg/kg/day bw via gastric gavage, or CPF plus CA at 30 and 60mg/kg/day bw. Carnosic acid was administered once/day for 14days, while CPF was administered in the last 7days of the experiment. Biochemical analysis showed that CPF administration was associated with significant increases in the serum concentrations of interleukin-1β, IL-6, and tumor necrosis factor-α, while it was associated with significant reductions in serum AChE levels in mice. Moreover, CPF-intoxicated mice exhibited significantly higher levels of malondialdehyde and nitric oxide in the brain and eye tissues. However, they had significantly lower levels of reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase in comparison with normal controls. Pretreatment with CA at 30 and 60mg/kg/day bw for 14days significantly alleviated all the aforementioned CPF-induced alterations in a dose-dependent manner; more frequent restorations of the normal control ranges were observed in the higher dose group. In conclusion, CA offers a neuroprotective effect against CPF-induced oxidative stress and inflammation and should be further studied in upcoming experimental and clinical research.

Fucoidan protects against subacute diazinon-induced oxidative damage in cardiac, hepatic, and renal tissues.

Fucoidans (FUC) are organic sulfated polysaccharides from natural seaweeds with multiple biological actions. The current study was performed to assess the chemoprotective, antioxidant, and anti-inflammatory effects of FUC from Laminaria japonicum against diazinon (DZN)-induced injuries to rat cardiac, hepatic, and renal tissues. Forty male Wistar rats were assigned into five groups, receiving saline, oral FUC 200mg/kg/day, subcutaneous DZN 20mg/kg/day, DZN plus FUC 100mg/kg/day, or DZN plus FUC 200mg/kg/day (each treatment was given daily for 4weeks). Data analysis showed that DZN-intoxicated rats exhibited significantly higher (p < 0.05) serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, urea, creatine, creatine kinase, creatine kinase-MB, lactate dehydrogenase, cholesterol, interleukin-6, and tumor necrosis factor-α, as well as lower levels of acetylcholinesterase, compared to control rats. In addition, DZN intoxication was associated with significantly higher (p < 0.05) cardiac, hepatic, and renal tissue concentrations of malondialdehyde and nitric oxide, as well as lower glutathione concentrations, and activities of glutathione peroxidase, superoxide dismutase, and catalase enzymes in comparison to control rats. Treatment with FUC (at 100 or 200mg/kg/day) ameliorated all the aforementioned alterations in a dose-dependent manner. In conclusion, FUC from Laminaria japonicum ameliorated DZN-induced oxidative stress, pro-inflammatory effects, and injuries to the cardiac, hepatic, and renal tissues. These effects may be related to the antioxidant and anti-inflammatory effects of FUC.

Cognitive-enhancing effects of fibrauretine on Aβ1–42-induced Alzheimer's disease by compatibilization with ginsenosides

Fibrauretine is the main active ingredient in rattan stems of Fibraurea recisa Pierre. The aim of this study was to evaluate the cognitive-enhancing effects and underlying molecular mechanisms of fibrauretine compatibilized with ginsenosides on Alzheimer's disease (AD) induced in mice with amyloid β-protein (Aβ1–42). The results showed that the spatial learning and memory abilities of AD mice were significantly enhanced after combined treatment with fibrauretine and ginsenosides using the Morris water maze test. The levels of acetylcholinesterase (AChE) and phosphorylated Tau protein (p-Tau) in brain tissue and the levels of nitric oxide (NO), malondialdehyde (MDA), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in plasma were significantly increased in Aβ1–42-induced AD mice, and these effects were reversed after combined treatment with fibrauretine and ginsenosides. By contrast, a significant increase in the levels of catalase (CAT), superoxide dismutase (SOD), choline acetyltransferase (ChAT) and glutathione peroxidase (GSH-Px) was observed in the combined treatment group. The results of haematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) analysis, immunohistochemistry (IHC) and Western blot analysis showed that the apoptosis rate, Bax, nuclear factor kappa-B p65 (NF-κBp65), cleaved caspase-3 and cleaved caspase-9 expression levels were obviously decreased and that the Bcl-2 expression levels were significantly increased in the hippocampi of mice treated with fibrauretine and ginsenosides. The results of this study show that the ameliorative effect of fibrauretine against AD can be significantly enhanced by compatibilization with ginsenosides. The underlying molecular mechanisms of fibrauretine may be related to antioxidation and anti-apoptosis.

Cholinergic Enhancing and Antioxidant Effect of Vigna subterranea (L.) Verdc. (Fabaceae) Landrace Aqueous Extract on Scopolamine-Induced Amnesia in Male Swiss Mice

The present study was conducted to investigate protective effects of the aqueous extract of V. subterranea seeds landrace on amnesia induced by scopolamine in mice. V. subterranea aqueous extract (100, 200 and 400 mg/kg BW) was administered by gavage for nine consecutive days and memory impairment was induced by repeated intraperitoneal injection of scopolamine (1.5 mg/kg). The Y-maze (YM), Morris water maze (MWM), novel object recognition paradigm (NOR) and the T maze (TM) were used to assess learning, memory and retention. Superoxide dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA) levels and Acetylcholine esterase activity was also evaluated in the mice hippocampi homogenates. V. subterranea aqueous extract (400 mg/kg) significantly increased the percentage of spontaneous alternation in the YM task and decreased escape latency in the MWM. Moreover, this dose brought about a significantly improvement in the time spent in the preferred TM arm and discrimination index in the NOR tasks despite repeated scopolamine injection. Additionally, low acetylcholine esterase levels, reduced lipid peroxidation (malondialdehyde) but increased antioxidant enzymes (catalase and superoxide dismutase) activity was observed in hippocampi homogenate of mice pre-treated with the extract. A protective action against hippocampal cell damage was also evident. This finding suggests that the aqueous extract of V. subterranea seed landrace may improve learning and memory.

Naringenin protects AlCl3/D-galactose induced neurotoxicity in rat model of AD via attenuation of acetylcholinesterase levels and inhibition of oxidative stress

Currently prescribed medications for the treatment of Alzheimer’s disease (AD) that are based on acetylcholinesterase inhibition only offer symptomatic relief but do not provide protection against neurodegeneration. There appear to be an intense need for the development of therapeutic strategies that not only improve brain functions but also prevent neurodegeneration. The oxidative stress is one of the main causative factors of AD. Various antioxidants are being investigated to prevent neurodegeneration in AD. The objective of this study was to investigate the neuroprotective effects of naringenin (NAR) against AlCl3+D-gal induced AD-like symptoms in an animal model. Rats were orally pre-treated with NAR (50 mg/kg) for two weeks and then exposed to AlCl3+D-gal (150 mg/kg + 300 mg/kg) intraperitoneally for one week to develop AD-like symptoms. The standard drug, donepezil (DPZ) was used as a stimulator of cholinergic activity. Our results showed that NAR pre-treatment significantly protected AD-like behavioral disturbances in rats. In DPZ group, rats showed improved cognitive and cholinergic functions but the neuropsychiatric functions were not completely improved and showed marked histopathological alterations. However, NAR not only prevented AlCl3+D-gal induced AD-like symptoms but also significantly prevented neuropsychiatric dysfunctions in rats. Results of present study suggest that NAR may play a role in enhancing neuroprotective and cognition functions and it can potentially be considered as a neuroprotective compound for therapeutic management of AD in the future.

Celery ameliorating against neurobehavioral and neurochemical disorders of perinatal lipopolysaccharides exposure in mice offspring

In this study, the role of Lipopolysaccharide (LPS) on the neurochemical disruption and neurobehavioural changes in offspring of mice was analyzed. Totally 30 pregnant mice was selected and divided in to six groups. Apium graveolens was supplemented at various doses to the experimental animals. This experiment was started at the day of pregnancy and was continued up to post-natal day 15. In our experiment three pups from each set of experiment were carefully marked and analyzed its physical, biochemical and behavioral changes. The experimental animals showed decreased body weight, delayed eye opening and delayed hair growth. Also, LPS treated pups showed cliff avoidance and rotating reflexes. Pups exposed to LPS showed heavy learning deficits and memory loss. In the treated pups, decreased level of dopamine, acetylcholinesterase and serotonin in forebrain was observed than celery groups. The present finding showed that the treatment of Celery revealed potent activity on behavior and biochemical disorders. Administration of celery enhanced cognition behavior in experimental animals.

Protective effects of thymoquinone and diallyl sulphide against malathion-induced toxicity in rats.

Malathion is a potent organophosphate insecticide that inhibits acetylcholinesterase (AChE) enzyme. Our experimental objective was to investigate the beneficial effects of diallyl sulphide (DAS) and thymoquinone (TQ) against malathion-induced oxidative stress in rat cerebral, hepatic, and renal tissues. For 30days, rats received corn oil alone (negative control) or malathion by intragastric gavage (200mg/kg daily), either alone (positive control) or combined with oral DAS (200mg/kg daily) or TQ (10mg/kg daily) (treatment groups). Later, blood samples were collected via direct cardiac puncture and tissue samples were obtained for biochemical analysis. Malathion administration was associated with significant increases (p < 0.05) in the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase, cholesterol, urea, creatinine, and 8-OHdG (DNA damage biomarker), as well as significant (p < 0.05) decreases in theserum levels of total proteins, albumin, triglycerides, and AChE. Moreover, it significantly increased thetissue concentrations of malondialdehyde and nitric oxide and reduced tissue glutathione concentration and activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase). Treatment of malathion-intoxicated rats with DAS or TQ significantly minimized these biochemical and oxidative effects with more frequent reversal to normal ranges of serum biomarkers, tissue oxidative markers, and antioxidant enzymes in the TQ group. In conclusion, treatment with DAS or TQ ameliorated the biochemical and oxidative effects of malathion, probably through reducing the generation of reactive oxygen and nitrogen radicals, as well as enhancing the antioxidant defense mechanisms.

Acupotomy Alleviates Energy Crisis at Rat Myofascial Trigger Points.

The aim of this study was to determine the effects of acupotomy on energy crises in rat trigger points (TrPs) by measuring mechanical pain thresholds (MPTs) and levels of acetylcholinesterase (AChE), free sarcoplasmic calcium (Ca2+), adenosine 5′-triphosphate (ATP), adenosine 5′-monophosphate (AMP), substance P (SP), and calcitonin gene-related peptide (CGRP) in rat muscle TrP tissue. Male Sprague Dawley rats (n = 32) were randomly divided into four groups: control, TrP, acupotomy, and lidocaine injection. Enzyme-linked immunosorbent assays were used to measure AChE, and free sarcoplasmic Ca2+ concentrations were determined by fluorescent staining with Fura-2 AM; high-performance liquid chromatography was used to measure ATP and AMP, and SP and CGRP were evaluated by immunohistochemistry. Compared with the control group, free sarcoplasmic Ca2+, AMP, SP, and CGRP were higher in the model group, while MPT, AChE, and ATP were lower. Treatment with acupotomy or lidocaine injection reduced free sarcoplasmic Ca2+, SP, and CGRP and increased MPTs and AChE levels compared with the model group. However, only acupotomy also led to decreased AMP and increased ATP levels relative to the model group. We conclude that acupotomy can alleviate energy crises at TrPs.

Exploiting Citrus aurantium seeds and their secondary metabolites in the management of Alzheimer disease

Fruit by-products are considered nature’s golden gift for human health and a good starting point to discover new drugs depending on the fact that they contain millions of bio-active compounds that are responsible for therapeutic activities. In this context, the main goal of this study is to recycle Citrus aurantium (C. aurantium) seeds to produce pharmaceutical molecules to be used in the prevention of the progressive neurological damage associated with Alzheimer disease (AD). Donepezil (0.75 mg/kg), hesperidin (125 and 250 mg/kg) and limonoids (50 and 100 mg/kg) were used for treatment of rats for 2 weeks prior to concomitant administration of AlCl3 for three successive weeks. Protection against cognitive deterioration was observed among study group with insignificant difference from normal control group and significant difference from positive control group in the Y-Maze test. On the other hand, treatment with both doses of hesperidin (125 and 250 mg/kg) and high dose of limonoids only (100 mg/kg) produced improvement in psychological state, observed by significant increase in ambulation frequency in comparison to positive control group, however it was not as frequent as normal group, as it was significantly less than normal group in the open field test. Regarding acetylcholine esterase (AChE) and beta-amyloid (β amyloid) levels, the effect of limonoids low dose was the best as it didn’t have a significant effect when compared to normal control, also hesperidin in both doses showed insignificant effects on β amyloid levels when compared to normal control group. Our results encourage the use of C. aurantium seeds which are wasted in huge amounts, as Alzheimer prophylactic food additives.

Role of penehyclidine in acute organophosphorus pesticide poisoning.

Penehyclidine is a newly developed anticholinergic agent. We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning (OP) patients. We searched the Pubmed, Cochrane library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical literature (CBM) and Wanfang databases. Randomized controlled trials (RCTs) recruiting acute OP patients were identified for meta-analysis. Main outcomes included cure rate, mortality rate, time to atropinization, time to 60% normal acetylcholinesterase (AchE) level, rate of intermediate syndrome (IMS) and rate of adverse drug reactions (ADR). Sixteen RCTs involving 1,334 patients were identified. Compared with the atropine- or penehyclidine-alone groups, atropine combined with penehyclidine significantly increased the cure rate (penehyclidine+atropine vs. atropine, 0.97 vs. 0.86, RR 1.13, 95% CI [1.07-1.19]; penehyclidine+atropine vs. penehyclidine, 0.93 vs. 0.80, RR 1.08, 95% CI [1.01-1.15]) and reduced the mortality rate (penehyclidine+atropine vs. atropine, 0.015 vs. 0.11, RR 0.17, 95% CI [0.06-0.49]; penehyclidine+atropine vs. penehyclidine, 0.13 vs. 0.08, RR 0.23, 95% CI [0.04-1.28]). Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery, the rate of IMS and the rate of ADR. Compared with a single dose of atropine, a single dose of penehyclidine also significantly elevated the cure rate, reduced times to atropinization, AchE recovery, and rate of IMS. Atropine combined with penehyclidine benefits OP patients by enhancing the cure rate, mortality rate, time to atropinization, AchE recovery, IMS rate, total ADR and duration of hospitalization. Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.