Neurotoxicity In Rats Research Articles

Nigella sativa oil protects against emamectin benzoate-Induced neurotoxicity in rats.

This study evaluated the ameliorative impact of Nigella sativa oil (NSO) on emamectin benzoate (EMB) neurotoxicity. Thirty-five male rats were randomly allocated into 5 groups (n = 7). G1 (control): received distilled water; G2: received NSO (3 ml. Kg-1 B.W.) for 6 weeks; G3: received EMB (9 mg kg-1 B.W.) for 6 weeks; G4: was co-treated with NSO and EMB for 6 weeks; G5: was treated with EMB for 4 weeks then, received NSO for 2 weeks. All treatments were given orally every other day. EMB increased serum urea, creatinine levels; brain dopamine, serotonin, malondialdehyde levels; brain expression levels of caspase 3 and TNF-α. While, it decreased serum total protein, albumin, brain GABA, AChE, GSH-Px, CAT, and SOD levels. Histopathological findings revealed hemorrhage, congestion, severe degeneration, and edema of the brain tissues. NSO reversed the EMB-induced biochemical and histopathological alterations. This NSO effect is mostly due to its antioxidant, antiinflammatory, and antiapoptotic activities. These findings suggest NSO as a potential protective and therapeutic agent for EMB-induced neurotoxicity.

The protective effect of p-coumaric acid on toluene-induced hepatotoxicity, nephrotoxicity and neurotoxicity in rats

Objective. The aim of this study was to determine the protective effect of p-coumaric acid (p-CA) against toluene-induced hepatotoxicity, nephrotoxicity and neurotoxicity in rats. Materials and methods. A total of 32 Sprague-Dawley male rats, 8 in each group, were used. 4 groups were formed as control, toluene, p-CA and toluene+p-CA. Animals in the control group, toluene group and p-CA group were given 0.9% NaCl, 0.9 mg/kg b.w toluene and 100 mg/kg b.w p-CA orally for 21 days, respectively. The animals in toluene+p-CA group were received p-CA for 3 days and from day 4, toluene and p-CA were applied together daily until day 25. On the 25th day, the study was terminated, blood and tissue samples were collected. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine levels in serum, glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) and glutathione (GSH) levels in the tissue samples were determined. Results. In this study, it was determined that there were significant increases in ALT and AST activities, and creatinine levels in toluene-induced group compared to control group. Moreover, there was a decrease in the GSH-Px activities and GSH levels, and an increase in the MDA levels compared to the control group. However, in the toluene+p-CA group, significant decreases in aminotransferases activities, creatinine and MDA levels, and significant increases in GSH-Px activities and GSH levels were determined compared to the toluene group. Conclusions. It has been determined that p-CA has a protective effect against toluene-induced hepatotoxicity, nephrotoxicity and neurotoxicity.

Protective properties of Spondias mombin Linn leaves on redox status, cholinergic dysfunction and electrolyte disturbance in cyanide-intoxicated rats.

Cyanide is an environmental neurotoxin which has been reported to arrest the normal functioning of the brain. This study investigated the protective properties of methanol and flavonoid-rich extracts of the leaves of Spondias mombin on redox status, cholinergic dysfunction and electrolyte disturbance in cyanide-induced neurotoxicity in rats. Male Wistar rats were orally pre-treated with Spondias mombin methanol leaf extract (SMC) (50, 100 and 150 mg/kg), flavonoid-rich extract (SMF) (25, 50 and 75 mg/kg) or quercetin (20 mg/kg), followed by intraperitoneal administration of 2 mg/kg potassium cyanide. Cyanide intoxication caused brain damage in rats as echoed in the deleterious alterations to activities/levels of endogenous antioxidants and biomarkers/enzymes linked with electrolyte imbalance and neurotoxicity. Pre-treatment with SMC and SMF significantly attenuated these KCN-induced imbalances (p < 0.05). The results suggested that the protection conferred by SMC and SMF probably involves attenuation of oxidative stress and regulation of ionic homeostasis. SMF displayed a better apparent ameliorative activity than SMC and 75 mg/kg SMF offered the best protection suggesting that flavonoids probably contributed to the protective effect of Spondias mombin leaf.

Administering crocin ameliorates anxiety-like behaviours and reduces the inflammatory response in amyloid-beta induced neurotoxicity in rat.

Anxiety, hippocampus synaptic plasticity deficit, as well as pro-inflammatory cytokines, are involved in Alzheimer's disease (AD). The present study is designed to evaluate the possible therapeutic effect of crocin on anxiety-like behaviours, hippocampal synaptic plasticity and neuronal shape, as well as pro-inflammatory cytokines in the hippocampus using in vivo amyloid-beta (Aβ) models of AD. The Aβ peptide (1-42) was bilaterally injected into the frontal-cortex. Five hours after the surgery, the rats were given intraperitoneal (IP) crocin (30mg/kg) daily up to 12days. Elevated plus maze results showed that crocin treatment after bilateral Aβ injection significantly increased the percentage of spent time into open arms, frequency of entries, and percentage of entries into open arms as compared with the Aβ group. In the open field test, the Aβ+crocin group showed a higher percentage of spent time in the centre and frequency of entries into central zone as compare with the Aβ treated animals. Administering crocin increased the number of soma, dendrites and axonal arbores in the CA1 neurons among the rats with Aβ neurotoxicity. Cresyl violet (CV) staining showed that crocin increased the number of CV-positive cells in the CA1 region of the hippocampus compared with the Aβ group. Silver-nitrate staining indicated that crocin reduced neurofibrillary tangle formation induced by Aβ. Crocin treatment attenuated the expression of TNF-α and IL-1β mRNA in the hippocampus compared with the Aβ group. Our results suggest that crocin attenuated Aβ-induced anxiety-like behaviours and neuronal damage, and synaptic plasticity loss in hippocampal CA1 neurons may via its anti-inflammatory effects.

Extraction, isolation and evaluation of anti-toxic principles from Moringa oleifera (MOF6) and Myristica fragrans (Trimyristin) upregulated Acetylcholinesterase concentrations in Sodium arsenite-induced neurotoxicity in rats.

This study evaluated the neuroprotective effects of MOF6 (isolated from Moringa oleifera leaves) and Trimyristin (isolated from Myristica fragrans seeds) on Acetylcholinesterase concentrations in cerebral cortices of rats with Sodium arsenite-induced neurotoxicity. Sixty-five adult male rats (150 g-250 g) were randomly divided into thirteen groups comprising of five rats per group. Groups 1 and 3 received physiological saline and 1 ml/200 g bodyweight of Olive oil respectively for 9 weeks. Group 2 received 20 mg/kg bodyweight of Sodium arsenite (SA) for 6 weeks and left untreated for another 3 weeks. Groups 4-5 received 20 mg/kg bodyweight of SA for 3 weeks followed by treatments with 5.0 and 7.5 mg/kg bodyweight of MOF6 respectively for 6 weeks. Groups 6-7 received 20 mg/kg bodyweight of SA for 3 weeks followed by treatments with 15 and 30 mg/kg bodyweight of Trimyristin respectively for 6 weeks. Groups 8-11 received 5.0 and 7.5 mg/kg bodyweight of MOF6; 15 and 30 mg/kg bodyweight of Trimyristin respectively for 9 weeks. Groups 12-13 received 7.5 mg/kg bodyweight of MOF6 and 30 mg/kg bodyweight of Trimyristin respectively for 6 weeks followed by co-administration of each extract dose with 20 mg/kg bodyweight of SA for another 3 weeks. Histological examination of cerebral cortices and biochemical analyses of Acetylcholinesterase concentrations were carried out in all rats. Computed data were analyzed using Microsoft Excel 2016 with statistical significance at p≤0.05. Histo-pathological evaluations revealed normal histo-architecture of cerebral cortices of all rats. Results showed statistically significant (p≤0.05) increases in Acetylcholinesterase concentrations in rats of Groups 1-10 and 12 compared with Group 2 (2.78±1.76 𝜇mole/min/g). 7.5 mg/kg bodyweight of MOF6 showed the best therapeutic and neuro-regenerative potential against SA-induced neurotoxicity.Conclusions: Our findings implied that MOF6 and Trimyristin reversed downregulation of Acetylcholinesterase concentrations in SA-induced neurotoxicity in rats; and possess neuro-protective and neuro-regenerative potentials.

Exploring the possible neuroprotective and antioxidant potency of lycopene against acrylamide-induced neurotoxicity in rats’ brain

Acrylamide (Ac) is a carbonyl compound extracted from hydrated acrylonitrile with a significantly high chemical activity. It is widely existed and used in food processing, industrial manufacturing and laboratory personnel work. However, lycopene (Ly) is a most potent natural antioxidant among various common carotenoids extracted from red plants. Nevertheless, little is known about the relationship of Ac-induced neurotoxicity and the ameliorative role of Ly in the regulation of oxidative and antioxidant capacity during Ac exposure. Therefore, this work sought to investigate the neurotoxicity induced by Ac exposure and the potential modulatory role of Ly by reversing the brain dysfunctions during Ac exposure. For this purpose, forty male albino rats were assigned into four equal groups. Control group received distilled water, Ly group was given with a daily dose of 10 mg/kg bw, Ac group was given with a daily dose of 25 mg/kg bw, and Ac-Ly group was gavaged Ac plus Ly at the same doses as the former groups. All treatments were given orally for 21 consecutive days. The concentrations of antioxidants (reduced glutathione and glutathione peroxidase) and oxidative stress (malondialdehyde, nitric oxide and protein carbonyl) biomarkers, as well as neurotransmitters (serotonin and dopamine) and acetylcholinesterase (AChE) were measured in the brain homogenates. An immunohistochemical staining was applied with anti-GFPA antibody to determine the severity of astrocytosis. The in vivo study with rat model demonstrated that Ac exposure significantly decline the hematological parameters, brain neurotransmitters concentrations and AChE activity, as well as levels of antioxidant biomarkers but markedly elevate the levels of oxidative stress biomarkers. Moreover, marked histological alterations and astrocytosis were observed through the increased number of GFAP immunopositively cells in cerebral, cerebellar and hippocampal tissues compared with the other groups. Interestingly, almost all of the previously mentioned parameters were retrieved in Ac-Ly group compared to Ac group. These findings conclusively indicate that Ly oral administration provides adequate protection against the neurotoxic effects of Ac on rat brain tissue function and structure through modulations of oxidative and antioxidant activities.

Effects of PI3K/AKT/mTOR pathway regulation of HIF-1α on Lanthanum-induced neurotoxicity in rats

This study examined the effects of the AKT/mTOR/HIF-1α signaling pathway on learning and memory in offspring rats induced by lanthanum from neuroethology and molecular biology perspectives. 32 pregnant adult Wistar rats were divided into four groups randomly: control group (NC), 0.25%, 0.5% and 1.0% LaCl3 groups (n = 8). All rats were poisoned through free drinking from day 0 of pregnancy to postnatal day 21 (suckling period). All offspring rats were poisoned through free drinking from delactation to postnatal day 48. Offspring rats aged 49-days-old were used as sampling objects to construct an LaCl3 poisoning model of offspring rats. Changes in hippocampal neurons, apoptosis of hippocampal neurons, learning and memory abilities of LaCl3-poisoned animals were measured by Nissl staining, TUNEL method and the shuttle box test, respectively. Expressions of PI3K, AKT, and mTOR, HIF-1α, and VEGF in the hippocampus were tested by qPCR and Western blot. Distributions of PI3K and p-AKT in hippocampal neurons were observed through the immunohistochemical method. With increasing LaCl3 dose, lightning strike time and active avoidance incubation period of offspring rats in the different LaCl3 groups were significantly prolonged. The Nissl body positive neurons of hippocampal neurons gradually declined while apoptosis in cells increased. The expressions of both mRNA (PI3K, AKT, mTOR, HIF-1α, VEGF) and proteins (PI3K, p-AKT, p-mTOR, HIF-1α, VEGF) in the hippocampus of the LaCl3 groups were significantly lower than those of NC group (p < 0.05). LaCl3 poisoning can induce developmental injuries in hippocampal neurons and can increase cell apoptosis. As a result, learning and memory abilities of offspring rats, as well as the expressions of PI3K/AKT/mTOR, are decreased, thus inhibiting activation of HIF-1α and influencing the expression of the downstream VEGF gene.

Protective effects of nobiletin on cisplatin induced neurotoxicity in rats

Objectives This study was designed to investigate the possible antioxidant, antiapoptotic and neuroprotective effects of nobiletin on cisplatin-induced neurotoxicity rat model by evaluating neurotrophins, antioxidants and histopathology. Methods Forty male Wistar Albino rats were divided into four groups: control, cisplatin (CIS), cisplatin + nobiletin (CIS + NOB) and nobiletin + cisplatin (NOB + CIS). CIS + NOB was applied nobiletin (10 mg/kg, i.p.) during the last four days whereas NOB + CIS was applied nobiletin during the first four days of the study. Cisplatin (4 mg/kg, i.p. twice a day) was administered to the experimental groups on the 5th day of the study. All rats were sacrificed on the 10th day of the study. BDNF, NGF, G6PD, GPx, tGSH and MDA levels were determined in brain. In addition, routin histolopathological analysis and caspase-3 immunoreactivity assay were conducted. Results BDNF concentrations increased in nobiletin-administered groups, compared to Control and CIS and that the increase was statistically significant in NOB + CIS (p < 0.05). It was also found that G6PD activity increased (p < 0.05) in the nobiletin-administered groups, compared to control and CIS. Histopathologically, neuronal degeneration, oedema and gliosis increased in CIS compared to Control, and nobiletin administration decreased neuronal degeneration and oedema compared to CIS (p < 0.05). Cisplatin increased (p < 0.05) caspase-3 immunoreactivity in cerebrovascular endothelium and neurons compared to Control, while nobiletin administration decreased caspase-3 immunoreactivity in cerebrovascular endothelium. Caspase-3 immunoreactivity in neurons decreased only in NOB + CIS (p < 0.05). Conclusion Nobiletin increased BDNF concentration and G6PD activity in brain and when evaluated together with histopathological and immunohistochemical findings, it may have antioxidant, antiapoptotic and neuroprotective effects against cisplatin.

Mechanistic insights into the protective effect of paracetamol against rotenone-induced Parkinson’s disease in rats: Possible role of endocannabinoid system modulation

Parkinson’s disease (PD) is a disabling progressive neurodegenerative disease. So far, PD’s treatment remains symptomatic with no curative effects. Aside from its blatant analgesic and antipyretic efficacy, recent studies highlighted the endowed neuroprotective potentials of paracetamol (PCM). To this end: the present study investigated: (1) Possible protective role of PCM against rotenone-induced PD-like neurotoxicity in rats, and (2) the mechanisms underlying its neuroprotective actions including cannabinoid receptors’ modulation. A dose-response study was conducted using three doses of PCM (25, 50, and 100 mg/kg/day, i.p.) and their effects on body weight changes, spontaneous locomotor activity, rotarod test, tyrosine hydroxylase (TH) and α-synuclein expression, and striatal dopamine (DA) content were evaluated. Results revealed that PCM (100 mg/kg/day, i.p.) halted PD motor impairment, prevented rotenone-induced weight loss, restored normal histological tissue structure, reversed rotenone-induced reduction in TH expression and striatal DA content, and markedly decreased midbrain and striatal α-synuclein expression in rotenone-treated rats. Accordingly, PCM (100 mg/kg/day, i.p.) was selected for further mechanistic investigations, where it ameliorated rotenone-induced oxidative stress, neuro-inflammation, apoptosis, and disturbed cannabinoid receptors’ expression. In conclusion, our findings imply a multi-target neuroprotective effect of PCM in PD which could be attributed to its antioxidant, anti-inflammatory and anti-apoptotic activities, in addition to cannabinoid receptors’ modulation.

Au-TiO2 nanoparticles exposure induced oxidative stress and neurotoxicity in rat

Context The Au-TiO2NPs have a wide range of applications and can easily enter the cells. Due to their properties, they can cause toxicity. Objective It was aimed to test the toxic effects of Au-TiO2 NPs in the brain, heart, kidney and liver of rats in this work. Materials and methods All used rats in this work were treated using diverse concentrations (doses) of NPs (100 and 200 mg/kg bw) for 21 days. SOD, CAT, AChE activities and MDA, H2O2, NO contents were evaluated in different organs. Results The Au-TiO2 NPs exposure induced biochemical changes in different organs of rats in view of oxidative stress and neurotoxicity by the alteration of the activity of the enzyme of neurotransmitter (AChE activity). Conclusion The Au-TiO2 NPs have the potential to interact with rat’s biochemical status and cause undesirable effects. One of those damaging effects was oxidative stress and neurotoxicity. Clinical significance The study signifies the impact of usage of Au-TiO2 NPs in the medical field for further exploration.

Neuroprotective effects of roflumilast against quinolinic acid-induced rat model of Huntington's disease through inhibition of NF-κB mediated neuroinflammatory markers and activation of cAMP/CREB/BDNF signaling pathway.

Huntington's disease (HD) is a progressive neurodegenerative and hyperkinetic movement disorder. Decreased activity of cAMP-responsive element-binding protein (CREB) is thought to contribute to the death of striatal medium spiny neurons in HD. The present study has been designed to explore the possible role of roflumilast against qunilonic acid (QA) induced neurotoxicity in rats intending to investigate whether it inhibits the neuroinflammatory response through activation of the cAMP/CREB/BDNF signaling pathway. QA was microinjected (200nmol/2µl, bilaterally) through the intrastriatal route in the stereotaxic apparatus. Roflumilast (0.5, 1, and 2mg/kg, orally) once-daily treatment for 21days significantly improved locomotor activity in actophotometer, motor coordination in rotarod, and impaired gait performance in narrow beam walk test. Moreover, roflumilast treatment significantly attenuated oxidative and nitrosative stress (p<0.05) through attenuating lipid peroxidation nitrite concentration and enhancing reduced glutathione, superoxide dismutase, and catalase levels. Furthermore, roflumilast also significantly decreased elevated pro-inflammatory cytokines like TNF-α (p<0.01), IL-6 (p<0.01), IFN-γ (p<0.05), NF-κB (p<0.05) and significantly increased BDNF(p<0.05) in the striatum and cortex of rat brain. The results further demonstrated that roflumilast effectively increased the gene expression of cAMP(p<0.05), CREB(p<0.05) and decreased the gene expression of PDE4 (p<0.05) in qRT-PCR. These results conclusively depicted that roflumilast could be a potential candidate as an effective therapeutic agent in the management of HD through the cAMP/CREB/BDNF signaling pathway.

Sodium hydrogen sulfide upregulates cystathionine β-synthase and protects striatum against 3-nitropropionic acid-induced neurotoxicity in rats.

Hydrogen sulfide (H2S) is a neuromodulator that plays a protective role in multiple neurodegenerative diseases including Alzheimer's (AD) and Parkinson's (PD). However, the precise mechanisms underlying its effects against Huntington's disease (HD) are still questioned.This study aimed to examine the neuroprotective effects of sodium hydrogen sulfide (NaHS; H2S donor) against 3-nitropropionic acid (3NP)-induced HD like pathology in rats. Methods: Male Wistar rats were randomly allocated into four groups; (1) normal control receiving saline; (2) NaHS control receiving (0.5 mg/kg/day, i.p.) for 14 days; (3,4) receiving 3NP (10 mg/kg/day, i.p.) for 14 days, with NaHS 30 min later in group 4. NaHS improved cognitive and locomotor deficits induced by 3NP as confirmed by the striatal histopathological findings. These former events were biochemically supported by the increment in cystathionine β-synthase (CBS) gene expression, reduction of glutamate (Glu), dopamine (DA), malondialdehyde (MDA), tumour necrosis factor-alpha (TNF-α), cytochrome-c, cleaved caspase-3 and pc-FOS indicating antioxidant, anti-inflammatory as well as anti-apoptotic effects. Furthermore, NaHS pretreatment improved cholinergic dysfunction and increased brain-derived neurotropic factor (BDNF) and nuclear factor erythroid-2-related factor 2 (Nrf2). These findings suggest that appropriate protection with H2S donors might represent a novel approach to slow down HD-like symptoms.

Metabolomic Profiling and Neuroprotective Effects of Purslane Seeds Extract Against Acrylamide Toxicity in Rat's Brain.

Acrylamide (ACR) is an environmental pollutant with well-demonstrated neurotoxic and neurodegenerative effects in both humans and experimental animals. The present study aimed to investigate the neuroprotective effect of Portulaca oleracea seeds extract (PSE) against ACR-induced neurotoxicity in rats and its possible underlying mechanisms. PSE was subjected to phytochemical investigation using ultra-high-performance liquid chromatography (UPLC) coupled with quantitative time of flight mass spectrometry (qTOF-MS). Multivariate, clustering and correlation data analyses were performed to assess the overall effects of PSE on ACR-challenged rats. Rats were divided into six groups including negative control, ACR-intoxicated group (10mg/kg/day), PSE treated groups (200 and 400mg/kg/day), and ACR + PSE treated groups (200 and 400mg/kg/day, respectively). All treatments were given intragastrically for 60days. PSE markedly ameliorated brain damage as evidenced by the decreased lactate dehydrogenase (LDL), increased acetylcholinesterase (AchE) activities, as well as the increased brain-derived neurotrophic factor (BDNF) that were altered by the toxic dose of ACR. In addition, PSE markedly attenuated ACR-induced histopathological alterations in the cerebrum, cerebellum, hippocampus and sciatic nerve and downregulated the ACR-inclined GFAP expression. PSE restored the oxidative status in the brain as indicated by glutathione (GSH), lipid peroxidation and increased total antioxidant capacity (TAC). PSE upregulated the mRNA expression of protein kinase B (AKT), which resulted in an upsurge in its downstream cAMP response element-binding protein (CREB)/BDNF mRNA expression in the brain tissue of ACR-intoxicated rats. All exerted PSE beneficial effects were dose-dependent, with the ACR-challenged group received PSE 400mg/kg dose showed a close clustering to the negative control in both unsupervised principal component analysis (PCA) and supervised orthogonal partial least square discriminant analysis (OPLS-Da) alongside with the hierarchical clustering analysis (HCA). The current investigation confirmed the neuroprotective capacity of PSE against ACR-induced brain injury, and our findings indicate that AKT/CREB pathways and BDNF synthesis may play an important role in the PSE-mediated protective effects against ACR-triggered neurotoxicity.

Inhibition of PLCβ1 signaling pathway regulates methamphetamine self-administration and neurotoxicity in rats

Studies have shown that the central renin–angiotensin system is involved in neurological disorders. Our previous studies have demonstrated that angiotensin II receptor type 1 (AT1R) in the brain could be a potential target against methamphetamine (METH) use disorder. The present study was designed to investigate the underlying mechanisms of the inhibitory effect of AT1R on various behavioural effects of METH. We first examined the effect of AT1R antagonist, candesartan cilexetil (CAN), on behavioural and neurotoxic effects of METH. Furthermore, we studied the role of phospholipase C beta 1 (PLCβ1) blockade behavioural and neurotoxic effects of METH. The results showed that CAN significantly attenuated METH-induced behavioral disorders and neurotoxicity associated with increased oxidative stress. AT1R and PLCβ1 were significantly upregulated in vivo and in vitro. Inhibition of PLCβ1 effectively alleviated METH-induced neurotoxicity and METH self-administration (SA) by central blockade of the PLCβ1 involved signalling pathway. PLCβ1 blockade significantly decreased the reinforcing and motivation effects of METH. PLCβ1 involved signalling pathway, as well as a more specific role of PLCβ1, involved the inhibitory effects of CAN on METH-induced behavioural dysfunction and neurotoxicity. Collectively, our findings reveal a novel role of PLCβ1 in METH-induced neurotoxicity and METH use disorder.

Tail Coiling Assay in Zebrafish (Danio rerio) Embryos: Stage of Development, Promising Positive Control Candidates, and Selection of an Appropriate Organic Solvent for Screening of Developmental Neurotoxicity (DNT)

It is relatively recent that tail coiling assay in zebrafish (Danio rerio) embryos has been proposed as an alternative method to screen for developmental neurotoxicity (DNT) induced by chemicals. Despite the considerable use of the method, there is no consensus related to the most suitable age of embryos and other experimental parameters. Non-exposed embryos were videotaped for tail-coiling activity from 18 to 54 h post-fertilization (hpf) and after exposure to positive control candidates (caffeine, fluoxetine, and tricaine (MS-222)) and organic solvents (acetone, dimethyl-sulfoxide (DMSO), and ethanol) from 26.0 to 28.5 hpf. Results demonstrated that embryos from 22 to 29 hpf presented a constant coiling activity, with no significant differences between the activity measurements. We also found that stimulant properties of caffeine and the anesthetic effects of MS-222 induced hyperactivity and hypoactivity, respectively. Finally, even using DMSO at 1%, it seems to be safer as a solvent for neurotoxicity evaluation by tail coiling assay. The period from 26.0 to 28.5 hpf was appropriate for a fast protocol of tail coiling assay. Caffeine and MS-222 were demonstrated to be promising positive control candidates, whereas DMSO was considered the most appropriate solvent choice for tail coiling assay.

Electrochemical degradation of psychotropic pharmaceutical compounds from municipal wastewater and neurotoxicity evaluations.

Contaminants of emerging concern (CECs) are released daily into surface water, and their recalcitrant properties often require tertiary treatment. Electrochemical oxidation (EO) is often used as an alternative way to eliminate these compounds from water, although the literature barely addresses the neurotoxic effects of residual by-products. Therefore, this study investigated the performance of EO in the removal of five CECs (alprazolam, clonazepam, diazepam, lorazepam, and carbamazepine) and performed neurotoxicity evaluations of residual EO by-products in Wistar rat brain hippocampal slices. Platinum-coated titanium (Ti/Pt) and boron-doped diamond (BDD) electrodes were studied as anodes. Different current densities (13-75 A m-2), pH values (3-10), electrolyte dosages (NaCl), and matrix effects were assessed using municipal wastewater (MWW). The drugs were successfully degraded after 5 min of reaction for both the Ti/Pt and BDD electrodes when a current density of 75 A m-2 was applied. For Ti/Pt and BDD, neutral and acidic pH demonstrated better CEC removal performance, respectively. Compound degradation using MWW achieved 40% removal after 120 min for Ti/Pt and ranged between 33 and 52% for the BDD anode. For Ti/Pt, neurotoxicity studies using MWW indicated a decrease in reactive oxygen species (ROS) signals. However, when an artificial cerebrospinal fluid (ACSF) medium was reapplied, the signal recovered and increased to a value above the baseline, indicating that cells recovered part of their normal activity but remained in a different condition. For the BDD anode, the treated MWW did not cause significant ROS production variations, suggesting that he EO was effective in eliminating the toxicity of the treated solution.

The modulatory effect of Hydrocotyle sibthorpioides in attenuating the aluminium chloride induced neurotoxicity in rat brain

Hydrocotyle sibthorpioides Lam. (Family: Araliaceae) is used widely in the preparation of food in different cuisines of the world. The study was designed to explore the protective effect of different standardised extracts of H. sibthorpioides on the AlCl3 induced neurotoxicity in Alzheimeric rats. When AlCl3 at a dose of 100 mg/kg body weight was administered i.p. for 60 days showed a significant increase in aluminium (Al) level, acetylcholinesterase (AChE) level and protein expressions of amyloid precursor proteins, β and γ secretase, and β-amyloid (Aβ1–42) in the cortex and hippocampus comparing to the control. Moreover, there was a significant reduction in locomotor activity, muscle coordination and cognition and memory. On the other hand, animals treated with chloroform and methanolic extracts of H. sibthorpiodes given at 200 and 100 mg/kg body weight orally with AlCl3 altered the behavioural impairment caused by Al and Al concentration, activity of AChE, synthesis molecules of Aβ generation. The report of histological studies in hippocampus and cortex supported the neuroprotective role of chloroform and a methanolic extract of H. sibthorpioides, which conserved a normal histoarchitecture pattern of cortex and hippocampus. Finally, it can be concluded that chloroform and methanolic extract of H sibthorpioides can alter memory loss induced by aluminum toxicity by enhancing AChE activity and by its involvement in amyloidogenic pathway.

Protective effect of metformin against lithium-induced cerebral neurotoxicity in rats

Protective effect of metformin against lithium-induced cerebral neurotoxicity in rats

Intra-arterial Contrast-enhanced Micro-computed Tomography Can Evaluate Intracranial Status in the Ultra-early Phase of Experimental Subarachnoid Hemorrhage in Rats

The endovascular perforation (EP) model is a common technique for experimental subarachnoid hemorrhage (SAH) in rats, simulating the pathophysiological features observed in the acute phase of SAH. Due to the drawbacks of large variations in the amount of bleeding, the results obtained from this model require severity evaluation. However, no less-invasive procedure could confirm the precise intracranial conditions immediately after establishing the rat EP model. We created a novel method for evaluating SAH immediately after establishing the rat EP model using intra-arterial contrast-enhanced micro-computed tomography (CT). We administered contrast agents continuously via the carotid artery during surgery and performed CT examination immediately after SAH induction. First, bleeding severity was classified by establishing a scoring system based on the CT findings (cSAH scoring system). Subsequently, we determined the actual SAH distribution macroscopically and histologically and compared it with the cSAH scores. Second, we investigated the contrast agent’s neurotoxicity in rats. Finally, we confirmed the correlation between cSAH scores and SAH severity, including neurological status, cerebral vasospasm, and hematoma volume 24 hr after SAH. Intra-arterial contrast-enhanced micro-CT could visualize the distribution of SAH proportionally to the bleeding severity immediately after establishing the EP model. Moreover, the contrast agent administration was determined not to be neurotoxic to rats. The cSAH scoring revealed a significant correlation with the SAH severity in the rat EP model (P <0.01). Thus, our minimally invasive method provided precise information on intracranial status in the ultra-early phase of SAH in rats EP model.

RETRACTED ARTICLE: Pristimerin inhibits neuronal inflammation and protects cognitive function in mice with sepsis-induced brain injuries by regulating PI3K/Akt signalling

We, the authors, Editors and Publisher of the journal Pharmaceutical Biology, have retracted the following article: Weimin Xue, Yaqiang Li & Mei Zhang (2021) Pristimerin inhibits neuronal inflammation and protects cognitive function in mice with sepsis-induced brain injuries by regulating PI3K/Akt signalling, Pharmaceutical Biology, 59:1, 1349-1356, https://doi.org/10.1080/13880209.2021.1981399 Since publication, the authors identified that the results shown in Figure 4 cannot be repeated. As this directly impacts the reproducibility and validity of the reported results and conclusions, the authors alerted the issue to the Editor and Publisher. During the investigation by the journal, additional concerns were raised such as: Similarity in Figure 6 with Figure 6 in the following article published in Frontiers in Neurology: Auti ST and Kulkarni YA (2019) Neuroprotective Effect of Cardamom Oil Against Aluminum Induced Neurotoxicity in Rats. Front. Neurol. 10:399. https://doi.org/10.3389/fneur.2019.00399 Similarity in Figure 5 with figures in the following articles: Figure 8 in Sun, X., Gan, L., Li, N. et al. Tabersonine ameliorates osteoblast apoptosis in rats with dexamethasone-induced osteoporosis by regulating the Nrf2/ROS/Bax signalling pathway. AMB Expr 10, 165 (2020). https://doi.org/10.1186/s13568-020-01098-0 Figure 4a in Liu, X, Wang, B. Fuscoside Attenuates Bone Loss in Bone Defects by Regulating The Rankl/Nlrp3/Opg Pathway in Rats. Cell Journal 23 (2021), 451-456. https://doi.org/10.22074/cellj.2021.7736 Figure 6 in Jiang, T., You, H., You, D. et al. RETRACTED ARTICLE: A miR-1275 mimic protects myocardiocyte apoptosis by regulating the Wnt/NF-κB pathway in a rat model of myocardial ischemia–reperfusion-induced myocardial injury. Mol Cell Biochem 466, 129–137 (2020). https://doi.org/10.1007/s11010-020-03695-w Figure 3 in Fang, X, Zhou, H., at al. MiR-1906 attenuates neuropathic pain in rats by regulating the TLR4/mTOR/ Akt signaling pathway. Translational Neuroscience 10 (2019), 175-179. https://doi.org/10.1515/tnsci-2019-0031 Whilst the authors have fully cooperated with the investigation, when they were asked for an explanation for the similarities for these figures, they were unable to address the concerns raised as they were unable to provide the raw data. In light of the concerns about the integrity of the reported results, all parties have agreed to retract the article to ensure correction of the scholarly record. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.