Brain AChE Activity Research Articles

Evaluation of Glucosamine Effect Against Heart and Brain Damage Induced by Y-radiation or Aluminium Chloride in Female Rats

Abstract Glucosamine is known as anti-inflammatory, antioxidant and as neuroprotective as well as using to treat many of diseases. This work aimed to investigate the remedial effect of glucosamine (20mg/kg b.wt) against the damage induced by a single dose of γ-radiation (8Gy) or aluminium chloride (AlCl3) (100mg/kg b.wt) in the heart and brain tissues of female rats. Serum aspartate aminotransferase (AST), cholesterol, triglycerides (TGs), LDH and creatine kinase (CPK) were measured. Moreover, gene expression of amyloid protein precursor (APP) and seladin-1 were estimated in the brain tissue. Also, acetylcholinesterase activity (AChE) and p-tau protein expression were estimated in brain homogenate. Metallothioneine (MT) was estimated in the heart and brain tissues. Heart and brain histopathological examination was performed. Irradiation significantly decreased serum AST, CPK and LDH, as well as MT levels in heart and brain tissues. Also, gene expression of seladin-1 decreased. On the other hand, irradiation significantly increased serum TGs level and brain AchE activity, tau protein, and β-amyloid percursor (APP). AlCl3 administration (21 days) induced disturbance in most of the estimated parameters, especially AST, TGs, and MT. Glucosamine treatment with irradiation or AlCl3 improved most of the measured parameters. In addition, histopathological examination confirmed the biochemical results. In conclusion: Glucosamine could be used to improve the heart and brain damages induced by γ-radiation exposure or AlCl3.

805: Fetal brain cholinergic regulation following maternal inflammation and magnesium neuroprotection

To determine pregnancy ontogeny of AChE and its regulator miR-132 expression in maternal serum and fetal brain under basal and inflammatory conditions and to study the effect of Magnesium (Mg), a known neuroprotective agent, on AChE and miR-132 expression in the fetal brain. Pregnant rats at 16, 18 and 20 days of gestation (60 total: 8 groups, n=5) received injections of i.p. lipopolysaccharide (LPS; 500 ug/kg) or saline (SAL) at time 0. Dams were randomized to s.c. saline or Mg (270 mg/kg loading followed by 27 mg/kg q20 min) for 2 hours prior to and 2 hours following LPS /saline injections. Rats were sacrificed 4 hours following LPS/SAL injection. Fetal brains were harvested from the treatment groups (LPS/SAL, LPS/Mg, SAL/Mg, SAL/SAL) for AChE and miR-132 mRNA expression (real-time RT-PCR) and maternal serum analyzed for AChE levels. Maternal serum AChE increased from e16 to e18 and e20 (169+25, 232+51,263+59 mg/ml, p< 0.05, respectively). Fetal brain AChE and miR-132 mRNA expression increased (p< 0.05) from e16 to e18 and then decreased at e20 (p< 0.05) (AChE 1.0±0.01, 1.21±.0.02, 0.78±0.16; miR-132 1.0±0.01, 1.19±0.03, 0.86±0.1, respectively). At e16 maternal LPS decreased fetal brain AChE (0.62±0.1), and miR-132 mRNA expression (0.72±0.11) compared to control (p< 0.05). Maternal Mg alone increased both fetal brain AChE and miR-132 mRNA expression at e16 (AChE1.7±0.15; miR-132 1.7±0.16) compared to both control and LPS fetal brains (p< 0.05). Mg treatment to LPS dams (LPS/Mg) increased fetal brain AChE and miR-132 levels (1.15±0.04;1.25±0.1 respectively, p< 0.05) compared to both LPS/SAL and SAL/SAL groups. The same pattern was demonstrated at e18 and e20. No significant change was demonstrated in maternal serum AChE levels following LPS or Mg compared to control. These findings suggest that fetal brain AChE activity is not regulated by miR-132. Mg treatment increases fetal brain AChE mRNA levels under basal conditions and in response to maternal LPS, suggesting that reduced ACh may increase fetal brain inflammatory responses.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Protective Effect of Edaravone on Cyclophosphamide Induced Oxidative Stress and Neurotoxicity in Rats.

Background:Cyclophosphamide (CPA) is the most widely prescribed cancer chemotherapeutic agent which shows serious neurotoxic side effect. Generation of reactive oxygen species at the cellular level is the basic mechanism of cyclophosphamide induced neurotoxicity. Edaravone is the synthetic drug used for brain stroke and has potent antioxidant property.Objective:This study aimed to investigate the effect of edaravone on neurobehavioral and neuropathological alteration induced by cyclophosphamide in male rats.Methods:Twenty eight Sprague-Dawley rats were equally divided into four groups of seven rats in each. The control group received saline, and other groups were given CPA intraperitoneally (100 mg/kg), CPA (100 mg/kg) intraperitoneally + Edaravone (10 mg/kg) orally, or Edaravone (10 mg/kg) orally for one month.Results:Our data showed that CPA significantly elevated brain AChE activity in the hippocampal region. A decrease in the total antioxidant capacity and a reduction in the CAT, SOD, and GPX activity occurred in the brains of the rats exposed to CPA. CPA-treated rats showed a significant impairment in long-term-memory and motor coordination. These results were supported by histopathological observations of the brain. Results revealed that administration of edaravone reversed AChE activity alternation and ameliorated behavioral and histopathological changes induced by CPA.Conclusion:This study suggests that co-administration of edaravone with cyclophosphamide may be a useful intriguing therapeutic approach to overcome cyclophosphamide induced neurotoxicity.

Interactive Effects of Sertraline and Diphenhydramine on Biochemical and Behavioral Responses in Crucian Carp (Carassius auratus).

The ecotoxicity of psychiatric pharmaceuticals to aquatic organisms is being increasingly recognized. However, current ecological studies focus on the effects of individual psychiatric pharmaceuticals, with little attention being given to their combined effects. In this study, the interactive effects of two psychiatric pharmaceuticals, sertraline (SER) and diphenhydramine (DPH), on bioconcentration and biochemical and behavioral responses were investigated in crucian carp (Carassius auratus) after seven days of exposure. DPH was found to increase the accumulation of SER in fish tissues relative to SER-alone exposure. In addition, the mixture of SER and DPH significantly changed the activities of antioxidant enzymes and led to significant increases in malondialdehyde content, relative to SER alone. Concerning the neurotoxicity, relative to SER-alone exposure, brain AChE activity was significantly enhanced in fish following the combined exposure. Regarding behavioral responses, swimming activity and shoaling behavior were significantly altered in co-exposure treatments compared with the SER alone. Moreover, the inhibition effects on the feeding rates were increased in co-exposure treatments compared to SER alone. Collectively, our results suggest that the mixtures of psychiatric pharmaceuticals may pose more severe ecological risks to aquatic organisms compared to these compounds individually.

Azelnidipine Ameliorates Dementia in Streptozotocin Treated Rats: Interplay between Oxidative Stress and Calcium

Deregulation of brain Ca2+ homeostasis is linked with oxidative stress, mitochondrial dysfunction, neurodegeneration, loss of synaptic plasticity, and cholinergic deficits. Earlier chronic administration of calcium channel blockers (L-type CCBs) has afforded relief in Alzheimer’s disease (AD) symptoms. Azelnidipine (AZL) is a long duration L-type Ca2+ channel blocker recently included in anti-hypertensive therapy. The present study reveals the role of AZL in the management of ICV-STZ induced AD in rats. Wistar rats of either sex (aged 12–15 weeks and weight range 260–280 g) were divided into 6 groups in single blind fashion and stereotaxic surgery was performed. Streptozotocin (3 mg/kg) was injected (ICV) in five groups and one group was administered with ACSF. AZL was administered (1.5, 3 and 6 mg/kg; p.o.) to separate groups of ICV-STZ pre-treated rats for 14 successive days. Memory of rats was measured using elevated plus maze and novel object recognition task. After behavioral evaluation, the animals were sacrificed and whole brains were isolated for estimation of AChE activity, TBARS and GSH levels. ICV-STZ treatment increased the brain AChE activity, TBARS level, decreased GSH level, and thereby impaired the memory of rats. The Ca2+ antagonistic property of AZL attenuated the STZ induced derangement of biochemical parameters and resurrected the memory functions in rats. This study exhibited that long-term blockade of the L-type Ca2+ channels using azelnidipine mitigates AD type dementia owing to its neuroprotective and antioxidant properties.

Evaluation of the effects of Cyclotrichium niveum on brain acetylcholinesterase activity and oxidative stress in male rats orally exposed to lead acetate

Cyclotrichium niveum is an endemic plant for Turkey and it appears to have in vitro antioxidant and acetylcholinesterase inhibition properties. To the best of our knowledge, there has been no study on the in vivo effects of this plant. Therefore, the purpose of this study was to evaluate the effects of C. niveum on lead (Pb)-acetate-induced potential alterations in brain acetylcholinesterase activity, as well as oxidative stress in male rats. The rats were randomly assigned to control, Pb-acetate, C. niveum and Pb-acetate+ C. niveum groups. Pb-acetate was provided in drinking water (500 ppm), and C. niveum was administered via orogastric gavage (4 ml/kg) for 30 days. The acetylcholinesterase activity in the brain significantly decreased only in the Pb-acetate group. The malondialdehyde level significantly increased, and the reduced glutathione activity decreased in the Pb-acetate group. The reduced glutathione and glutathione-S-transferase activities of the C. niveum group were higher than the control group. No Pb was detected on a ppb level in the brain tissue of the control and C. niveum groups, while it was detected in the brains of the rats in the Pb-acetate and Pb-acetate+ C. niveum groups (185+8.98 ppb and 206+56.65 ppb, respectively). The data collected in this study suggested that C. niveum may reduce inhibition of brain AChE activity and oxidative stress against Pb-acetate-induced alterations in the brain of male rats.

Pretreatment with pyridostigmine bromide has no effect on seizure behavior or 24 hour survival in the rat model of acute diisopropylfluorophosphate intoxication

Acute intoxication with organophosphate cholinesterase inhibitors (OPs) is a significant human health threat, and current medical countermeasures for OP poisoning are of limited therapeutic efficacy. The rat model of acute intoxication with diisopropylfluorophosphate (DFP) is increasingly being used to test candidate compounds for efficacy in protecting against the immediate and long-term consequences of acute OP toxicity. In this model, rats are typically pretreated with pyridostigmine bromide (PB), a reversible cholinesterase inhibitor, to enhance survival. However, PB pretreatment is not likely in most scenarios of civilian exposure to acutely neurotoxic levels of OPs. Therefore, the goal of this study was to determine whether PB pretreatment significantly increases survival in DFP-intoxicated rats. Adult male Sprague Dawley rats were injected with DFP (4 mg/kg, s.c.) or vehicle (VEH) followed 1 min later by combined i.m. injection of atropine sulfate (2 mg/kg) and 2-pralidoxime (25 mg/kg). Animals were pretreated 30 min prior to these injections with PB (0.1 mg/kg, i.m.) or an equal volume of saline. DFP triggered rapid and sustained seizure behavior irrespective of PB pretreatment, and there was no significant difference in average seizure behavior score during the first 4 h following injection between DFP animals pretreated with PB or not. PB pretreatment also had no significant effect on survival or brain AChE activity at 24 h post-DFP exposure. In summary, PB pretreatment is not necessary to ensure survival of rats acutely intoxicated with DFP, and eliminating PB pretreatment in the rat model of acute DFP intoxication would increase its relevance to acute OP intoxication in civilians.

Cholinesterase inhibition in chicks treated with manganese chloride

The aim of the study was to examine the effect of manganese chloride in drinking water at 1 g/L on the plasma and brain chicks AChE activity in vivo and in vitro. At 14-day-old manganese caused significant decrease in the acetycholinestrase activity in the brain of chicks about 36%. While there was no significant inhibition in plasma AChE. Dichlorvos at 7 mg/kg, orally significantly inhibited plasma and brain AChE activity. Dichlorvos at 0.5 and 1 µl significantly inhibited plasma and brain cholinesterase activity in vitro, while manganese not affected on the cholinesterase activity in vitro. manganese with dichlorvos caused decrease in ration of AchE inhibited at 7 days old in brain and plasma AChE to 59% and 69% respectively, while increased in the ratio of inhibition at 14 days old in brain and plasma AChE activity of chicks to 64% and 91% respectively. The results suggested that manganese chloride caused decrease inhibition of AChE activity in brain of chicks manganese with dichlorvos causes decrease in the inhibited ratio of plasma and brain at 7 days old while causes increased the ratio of inhibition at 14 days old.

Neurophysiological responses in the brain tissues of rainbow trout (Oncorhynchus mykiss) treated with bio-pesticide

The aim of this study was to investigate neurophysiological responses in rainbow trout brain tissue exposed to natural/botanical pesticides. Fish were exposed to botanical and synthetic pesticides over a 21-day period. At the end of the treatment period, oxidative DNA damage (indicated by 8-OHdG (8-hydroxy-2'-deoxyguanosine), AChE activity (acetylcholinesterase) and transcriptional parameters (gpx (glutathione peroxidase), sod (superoxide dismutase), cat (catalase), HSP70 (heat shock protein 70) and CYP1A (cytochromes P450)) was investigated in control and application groups. Our results indicated that brain AChE activities decreased very significantly in fish treated with both insecticide types when compared with control (p < 0.05). 8-OHdG activity increased in a dose/time-dependent situation in the brain tissues of Oncorhynchus mykiss (p < 0.05). In addition, with regards to gene expression, gpx sod and, cat expressions were down-regulated, whereas CYP1A and HSP70 gene expression were up-regulated in fish treated with both insecticides when compared to the control group (p < 0.05). The data for this study suggests that bio-pesticides can cause neurophysiological changes in fish brain tissue.

Characterization of brain acetylcholinesterase of bentonic fish Hoplosternum littorale: Perspectives of application in pesticides and metal ions biomonitoring

Acetylcholinesterase (AChE; EC 3.1.1.7) is a serine hydrolase, whose main function is to modulate neurotransmission at cholinergic synapses. It is, therefore, the primary target of some pesticides and heavy metals. Its inhibition in aquatic organisms has been used as an indicator of the presence of these pollutants in water bodies. The present study aimed to characterize physicochemical and kinetic parameters of brain AChE in the benthic fish Hoplosternum littorale and to analyze the in vitro effects of pesticides (dichlorvos, diazinon, chlorpyrifos, parathion-methyl, temephos, carbaryl, carbofuran, aldicarb, diflubenzuron, novaluron and pyriproxyfen) and metal ions (As3+, Cd2+, Cu2+, Fe2+, Mn2+, Mg2+, K+, Pb2+, Hg2+, Zn2+) investigating the potential of this enzyme as environmental biomarker based on current regulations. Specific substrates and inhibitors have indicated AChE to be the predominant cholinesterase (ChE) in the brain of H. littorale. Peak activity was observed at pH 8.0 and 30 °C. The enzymatic activity is otherwise moderately thermostable (≈ 50% activity at 45 °C). The enzyme can reduce the activation energy of acetylthiocholine hydrolysis reaction to 8.34 kcal mol−1 while reaching a rate enhancement of 106. Among the pesticides under study, dichlorvos presented an IC50 value below the maximum concentrations allowed by legislation. This study presents the first report on the inhibition of brain AChE activity from Siluriformes by the pesticides novaluron and pyriproxyfen. Mercury ion also exerted a strong inhibitory effect on its enzymatic activity. The H. littorale enzyme thus has the potential to function as an in vitro biomarker for the presence of the pesticide dichlorvos as well as mercury in areas of mining and industrial discharge.

Seasonal implications on toxicity biomarkers of Loricariichthys anus (Valenciennes, 1835) from a subtropical reservoir

Cropping systems based on intensive land use and continuous application of agricultural chemicals inflict a threat to aquatic organisms since these substances will inevitably be carried in to water bodies where they can accumulate, particularly in lentic sites. Pesticides exposure in aquatic animals can cause changes that can be quantified through biomarkers. Thus, this study aimed to investigate the effects of season on oxidative stress and neurotoxicity biomarkers in Loricariichthys anus from a subtropical reservoir surrounded by agricultural areas in southern Brazil. Ten armored catfish were collected from six sites in February and August 2016. Pesticides present in the water, sediment and muscle were identified and quantified. No pesticides were detected either in sediment nor in muscle. During the winter, the water contained atrazine, imidacloprid, simazine, azoxystrobin, and propoxur; however, in summer, only atrazine was present in the water. In the winter, there was an increase in the hepatic GST activity and in GPx that kept lipid peroxidation (TBARS) constant and, in the summer, there was an increase in metallothioneins levels. In the gills, variables related to summer were possibly responsible for the elevation of GST, GPx and TBARS; during the winter, there was greater carbonylation of proteins. In the winter, the increased AChE activity in brain and muscle tissue was related to carbonylation of proteins in brain. Although the amount of pesticides detected in the water was low, chronic exposure in addition to environmental variations can cause direct and indirect effects on L. anus population.

Nanoparticle-Delivered 2-PAM for Rat Brain Protection against Paraoxon Central Toxicity.

Solid lipid nanoparticles (SLNs) are among the most promising nanocarriers to target the blood-brain barrier (BBB) for drug delivery to the central nervous system (CNS). Encapsulation of the acetylcholinesterase reactivator, pralidoxime chloride (2-PAM), in SLNs appears to be a suitable strategy for protection against poisoning by organophosphorus agents (OPs) and postexposure treatment. 2-PAM-loaded SLNs were developed for brain targeting and delivery via intravenous (iv) administration. 2-PAM-SLNs displayed a high 2-PAM encapsulation efficiency (∼90%) and loading capacity (maximum 30.8 ± 1%). Drug-loaded particles had a mean hydrodynamic diameter close to 100 nm and high negative zeta potential (-54 to -15 mV). These properties contribute to improve long-term stability of 2-PAM-SLNs when stored both at room temperature (22 °C) and at 4 °C, as well as to longer circulation time in the bloodstream compared to free 2-PAM. Paraoxon-poisoned rats (2 × LD50) were treated with 2-PAM-loaded SLNs at a dose of 2-PAM of 5 mg/kg. 2-PAM-SLNs reactivated 15% of brain AChE activity. Our results confirm the potential use of SLNs loaded with positively charged oximes as a medical countermeasure both for protection against OPs poisoning and for postexposure treatment.

Protective effect of a phenolic extract containing indoline amides from Portulaca oleracea against cognitive impairment in senescent mice induced by large dose of D-galactose /NaNO2

Ethnopharmacological relevance:Portulaca oleracea L. is a potherb and also a widely used traditional Chinese medicine. In accordance with its nickname “longevity vegetable”, pharmacological study demonstrated that this plant possessed antioxidant, anti-aging, and cognition-improvement function. Active principles pertaining to these functions of P. oleracea need to be elucidated. Aim of the study:The present study evaluated the effect of a phenolic extract (PAAs) from P. oleracea which contained specific antioxidant indoline amides on cognitive impairment in senescent mice. Materials and methods:PAAs was prepared through AB-8 macroporous resin column chromatography. Total phenol content was determined using colorimetric method, and contents of indoline amides were determined using HPLC-UV method. Senescent Kunming mice with cognitive dysfunction were established by intraperitoneal injection of D-galactose (D-gal, 1250mg/kg/day) and NaNO2 (90mg/kg/day) for 8 weeks, L-PAAs (360mg/kg/day), H-PAAs (720mg/kg/day), and nootropic drug piracetam (PA, 400mg/kg/day) as the positive control were orally administered. Spatial learning and memory abilities were evaluated by Morris water maze experiment. Activities of AChE, SOD, CAT, and levels of GSH and MDA in the brain or plasma were measured. Hippocampal morphology was observed by HE staining. Results:Chronic treatment of large dose of D-gal/NaNO2 significantly reduced lifespan, elevated AChE activity, decreased CAT activity, compensatorily up-regulated SOD activity and GSH level, increased MDA level, induced neuronal damage in hippocampal CA1, CA3 and CA4 regions, and impaired cognitive function. Similar to PA, PAAs prolonged the lifespan and improved spatial memory ability. Moreover, PAAs improved learning ability. H-PAAs significantly reversed compensatory increase in SOD activity to the normal level, elevated serum CAT activity, and reduced MDA levels in brain and plasma, more potent than L-PAAs. Besides these, PAAs evidently inhibited hippocampal neuronal damage. However, it had no effect on brain AChE activity. Conclusion:PAAs as the bioactive principles of P. oleracea attenuated oxidative stress, improved survival rate, and enhanced cognitive function in D-gal/NaNO2-induced senile mice, similar to piracetam. This phenolic extract provides a promising candidate for prevention of aging and aging-related cognitive dysfunction in clinic.

Trachyspermum ammi Seeds Supplementation Helps Reverse Scopolamine, Alprazolam and Electroshock Induced Amnesia.

The present study was designed to explore the beneficial effects of successive 10 days administration of Trachyspermum ammi seed's powder (TASP) along with diet (at the dose of 0.5%, 1.0% and 2.0% w/w) on learning and memory of mice. A total of 306 mice divided in 51 equal groups were employed in the study. Passive avoidance paradigm (PAP) and Object recognition Task (ORT) were employed as exteroceptive models. The brain acetylcholinesterase activity (AChE), serum cholesterol, brain monoaldehyde (MDA), brain reduced glutathione (GSH) and brain nitrite were estimated and Alprazolam, Scopolamine and Electroshock induced amnesia was employed to describe the actions. Treatment of TASP significantly increased step down latency of PAA and significantly increased discrimination index of ORT in groups with or without amnesia when compared to respective control groups. Furthermore, TASP administration resulted in significant fall in brain AChE activity, brain MDA level and brain nitrite level with simultaneous rise in brain GSH level, thereby decreased oxidative damage. A significant decrease in serum cholesterol was also observed. Ajowan supplementation may prove a remedy for the management of cognitive disorders owing to have pro-cholinergic, antioxidant and hypo-lipidemic activities.

Protective effect of hydro-alcoholic extract of Salvia haematodes Wall root on cognitive functions in scopolamine-induced amnesia in rats

Diminished cholinergic transmission may be responsible for development of amnesia. Hence, the present study was undertaken to investigate the possible protective effect of hydro-alcoholic extract of Salvia haematodes Wall root (HESH) on cognitive functions in scopolamine-induced amnesia in adult Sprague Dawley rats. The rats were divided randomly into five groups each consisting of five rats (n = 5). Rats of the groups I, II, III, IV, and V received orally normal saline (10 ml/kg b. wt.), normal saline (10 ml/kg), standard drug rivastigmine (1.5 mg/kg), HESH (20 mg/kg), and HESH (40 mg/kg), respectively once a day for fourteen days. Then, they were subjected to single dose of scopolamine (1 mg/kg b. wt. ip) except in group I on fourteenth day 60 min after respective normal saline or drug administration. They were observed for the effects on step down latency (SDL), locomotor activity and brain AChE activity for the learning and memory. The acquisition SDL, retention SDL and locomotor activity were significantly (p < 0.01) decreased while AChE activity was significantly (p < 0.01) increased in scopolamine-treated group II as compared to normal control group I. The acquisition SDL, retention SDL and locomotor activity were significantly (p < 0.01) increased while, AChE activity was significantly (p < 0.01) decreased with all the doses of HESH and in rivastigmine-treated group as compared to scopolamine-treated group II. Hydro-alcoholic extract of S haematodes root possesses protective effect on cognitive functions and may prove to be a useful memory restorative agent in the management of cognitive dysfunctions as in amnesia and Alzheimer's diseases.

Impact of scorpion venom as an acute stressor on the neuroendocrine-immunological network

Although immunomodulatory property and many other pharmaceutical applications of scorpion venom have been addressed before, no studies were reported about its application as a neuroimmunomodulator at therapeutic dose. In this study, we conceptualized the property of scorpion venom, capable of inducing the acute pain and neurotoxicity can cause acute stress resulting in the modulation of immune cells through HPA axis. The whole venom from Hottentotta rugiscutis, a widely seen scorpion in the region of eastern Karnataka, was extracted and injected a single dose of 1 mg/kg b.w. to Swiss albino mice and then erythrocytes and leukogram were measured. Whole brain AChE activity, corticosterone, cytokines and NO levels in plasma were also evaluated at various time points. Hrv didn't show any histopathological changes in the lymphoid organs and at the site of injection. However, lymphocytes and neutrophils did get altered at 2 h post-injection. Plasma corticosterone, cytokine levels such as IL-1β, IL-6, TNF-α and IL-10 and the AChE activity were significantly increased in a time-dependent manner. Based on these results, it may be predicted, Hrv's ability to cause acute stress resulted in the activation of HPA axis, which stimulates the release of glucocorticoid hormones which in turn elicits the immunomodulation of leukocytes by altering the levels of pro and anti-inflammatory cytokines. Thus, we can conclude, the impact of acute stress induced by Hrv can intercommunicate the signals between neuroendocrine-immune systems.

Neuroprotective Effects of Nicorandil in Chronic Cerebral Hypoperfusion-Induced Vascular Dementia

Ischemia-induced chronic cerebral hypoperfusion (CCH) is associated with reduced cerebral blood flow and vascular dementia (VaD). Brain mitochondrial potassium (adenosine triphosphate-sensitive potassium [KATP]) channels have a beneficial role in various brain conditions. The utility of KATP channels in CCH-induced VaD is still unknown. The aim of this study is to investigate the role of nicorandil, a selective KATP channel opener, in CCH-induced VaD. The method of 2-vessel occlusion (2VO) was used to induce CCH in mice. Cognitive impairment was assessed using Morris water maze. Serum nitrosative stress (nitrite/nitrate), brain cholinergic dysfunction (acetylcholinesterase [AChE] activity), brain oxidative stress (thiobarbituric acid reactive substances, glutathione [GSH], catalase [CAT], and superoxide dismutase [SOD]), inflammation (myeloperoxidase [MPO]), and infarct size (2,3,5-triphenyltetrazolium chloride staining) were assessed. 2-vessels-occluded animals have shown significant cognitive impairment, serum nitrosative stress (reduced nitrite/nitrate), cholinergic dysfunction (increased brain AChE activity), and increased brain oxidative stress (reduction in GSH content and SOD and CAT activities with a significant increase in lipid peroxidation), along with a significant increase in MPO activity and infarct size. However, nicorandil treatment has significantly attenuated various CCH-induced behavioral and biochemical impairments. It may be said that 2VO provoked CCH leading to VaD, which was attenuated by the treatment of nicorandil. So, modulation of KATP channels may provide benefits in CCH-induced VaD.

Antagonism of Endothelin (ETA and ETB) Receptors During Renovascular Hypertension-Induced Vascular Dementia Improves Cognition.

Diseases of cardio, as well as the cerebrovascular system, are known as the primary possibility for deficits in cognitive processes and dementia of vascular nature. Endothelin-1 (ET-1) and its receptors are extensively expressed in brain. The present study has been structured to explore the effects of bosentan, an ET-1 antagonist on two-kidneyone- clip: 2K1C method induced hypertension provoked vascular dementia (VaD). 2K1C was modelled to induce renovascular hypertension. Mean arterial blood pressure (MABP) was assessed using BIOPAC system. Cognitive impairment was assessed employing Elevated plus maze-EPM as well as Morris water maze-MWM. Brain cholinergic dysfunction (activity of acetylcholinesterase-AChE), oxidative stress (thiobarbituric acid reactive substances-TBARS level, glutathione-GSH content, superoxide dismutase-SOD as well as catalase-CAT activity), aortic oxidative stress (superoxide anion level), serum nitrosative stress (nitrite/nitrate level), brain inflammation (myeloperoxidase-MPO), vascular endothelial dysfunction (endothelium-dependent relaxation) and infarct size (2,3,5- triphenyltetrazolium chloride-TTC staining) were assessed. Renal artery ligated animals have shown elevated oxidative stress in the aorta (superoxide anion-SA) and brain (augmented TBARS, with decreased GSH, SOD, and CAT). Similarly, 2K1C-renovascular hypertension has shown a considerable rise in brain inflammation (MPO activity) and brain AChE activity with a significant fall in serum nitrite/ nitrate contents. Administration of bosentan considerably diminished 2K1C hypertension induced alterations in MABP, cognitive impairment, and dysfunction of endothelium. Treatment with bosentan has also restored 2K1C induced a rise in brain TBARS, AChE, MPO activity, reduction in brain GSH, SOD and CAT as well as brain damage. It may be concluded that ET-1 antagonism may be regarded as possible agents for managing renovascular hypertension induced VaD.

Acute toxicity, biochemical and histopathological responses of endosulfan in Chanos chanos

This study investigated 96h median lethal concentration of endosulfan (99%, pure α: β ratio of 7:3) by conducting static non-renewable acute toxicity bio-assay in Chanos chanos juvenile with average weight (110±5.65g). Further, the effect of different definitive doses (18.5, 19.5, 20.5, 21.5 and 22.5µg/L) of endosulfan on metabolic, heamato-immunoligcal and histopathological response were probed. Anti-oxidative enzymes CAT, SOD and GST showed significant (p<0.01) increase of activity in the liver, gill and brain during exposure to endosulfan in a dose and time dependent manner. The brain AChE activity showed significant (p<0.01) inhibition from 18.5 to 22.5µg/L exposure of endosulfan than the control group. LDH and MDH activity gradually increased with consequent increasing dose of endosulfan exposure in the liver, gill and brain. Similarly, ALT, AST and G6PDH activities in both liver and gill increased with consequent increases in the dose of endosulfan exposure. Immunological profile such as blood glucose and serum cortisol level significantly enhanced while respiratory burst activity declined with consequent increasing doses of endosulfan exposure. Histopathological alteration in the gill demonstrated curling of secondary lamellae, thickening of primary epithelium, shorting of secondary lamellae, epithelial hyperplasia, fusion of secondary lamellae, aneurism, and collapsed secondary lamellae due to dose dependent exposure of endosulfan. Liver histology illustrated cloudy swelling and necrosis with pyknotic nuclei to the moderate dose of endosulfan, whereas higher dose of endosulfan (21.5µg/L) displayed severe necrosis of hepatic cells. Overall results clearly indicate that acute exposure of endosulfan led to pronounced deleterious alterations on biochemical, heamato-immunological, and histopathological responses of C. chanos juvenile.

Imazapyr+imazapic herbicide determines acute toxicity in silver catfish Rhamdia quelen

Imazapyr (IMY) and imazapic (IMI) are imidazolinone herbicides which have been associated in a commercial formulation (Kifix®). To date, there are no studies on the toxicity of an IMY+IMI herbicide in fish. This work aimed to assess the acute toxicity (24 and 96h) of IMY+IMI (0, 0.488 and 4.88µg/L) towards Rhamdia quelen through hematological, biochemical, immunological, ionoregulatory and enzymatic indexes. Red blood cell count was lower at 4.88 than at 0.488µg/L (24 and 96h); mean corpuscular volume was lower than control at both concentrations (24h) and at 0.488µg/L (96h); lymphocytes declined at 4.88µg/L comparing to control (96h); and monocytes increased at 4.88µg/L (96h) in comparison with the respective control and with 4.88µg/L at 24h. Aspartate aminotransferase was higher at 0.488µg/L (96h) than the respective control and the respective concentration at 24h; uric acid reduced at 4.88µg/L comparing with 0.488µg/L (96h); and cortisol was lower at 4.88µg/L compared to 0.488µg/L and control (96h). Herbicide exposure lowered plasma bactericidal activity at both concentrations (24h) and at 0.488µg/L (96h); and plasma complement activity declined at 4.88µg/L comparing with 0.488µg/L and control (96h), and was lower at all concentrations at 96h than at 24h. Plasma K+ levels were higher at 4.88µg/L than in the remaining groups (24 and 96h); and Na+ levels decreased at 4.88µg/L compared to control (96h). Na+/K+-ATPase and H+-ATPase activities in gills were lower at 4.88µg/L comparing with control (24h) and with the respective concentration at 96h; and AChE activity in brain was higher at 0.488 and 4.88µg/L than control (24h) and the respective concentrations at 96h, while in muscle it was higher at 0.488 and 4.88µg/L than control (96h) and the respective concentrations at 24h. The present findings demonstrate that, despite IMY+IMI targets the animal-absent AHAS enzyme, such formulation displayed an acute toxic effect upon R. quelen homeostasis by impacting on vital functions such as immune defense, metabolism, ionoregulation and neurotransmission.