Acrylamide-induced Neurotoxicity Research Articles

The effects of acrylamide-mediated dorsal root ganglion neurons injury on ferroptosis.

Acrylamide (ACR) is a water-soluble chemical applied in industrial and laboratory processes. The neurotoxicity induced by acrylamide involves both peripheral and central nervous system. Hence, there is a growing urgency to investigate the mechanisms of acrylamide-induced neurotoxicity and search novel therapeutic target for the nerve repair. The effects of ACR on the proliferation, reactive oxygen species (ROS) and iron production of dorsal root ganglia (DRG) neurons and Schwann cells were determined. 5-Ethynyl-2'-deoxyuridine (EDU) staining and transwell assay were applied to detect the proliferation and migration capacity of DRG cells. Ferrostatin-1 (Fer-1) was used to suppress ferroptosis induced by ACR. RT-PCR analysis was performed to examine the expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and glial cell line-derived neurotrophic factor (GDNF). Moreover, Iron, ROS, malondialdehyde (MDA) and glutathione (GSH) contents were measured to reveal the regulation of ferroptosis in ACR-related nerve injury. ACR inhibited the proliferation and migration of DRG neurons and the supplementation of Fer-1 reversed the effects induced by ACR. Besides, the treatment of Fer-1 effectively increased the expression of NGF, BDNF, VEGF and GDNF. Furthermore, ACR increased the iron level, MDA and ROS contents while inhibited the level of GSH. It was unveiled that ACR attenuated the proliferation, migration and neuron repair of DRG neurons through regulating ferroptosis. The modulation of ferroptosis might be a promising therapeutic strategy and provide references for future treatment of acrylamide-induced nerve damage.

Ameliorative activity of medicinal plant fraction for neuroprotection against acrylamide-induced neurotoxicity in Drosophila melanogaster\u2014a comparative study

BackgroundMedicinal plant extracts used in folk medicine seem to be crucial since those are generally accepted by people without worrying about the toxicity. In our present study, we have compared the neuroprotective role of the rhizome of Curculigo orchioides Gaertn. and leaf extracts of Olea dioica Roxb., against acrylamide-induced neurotoxicity in Drosophila melanogaster.ResultsIn-vivo neurotoxic study was carried out using 7-day-old flies (wild-type D. melanogaster). Prior to co-after exposing the flies with acrylamide (8 mM) along with or without OLE-2 and CU-3 fractions (0.2, 0.4 and 0.6% w/v), the heads of flies of both the control and treated groups were homogenized for biochemical assay. ACR-treated groups have shown higher elevation in AChE, SOD, LPO, and CAT activity when compared to control and treated (plant fraction) groups. Biochemical and histopathology studies show that both the plant fractions (OLE-2 and CU-3) have neuroprotective action against acrylamide.ConclusionThe present study has demonstrated that dietary supplementation with plant fraction of OLE-2 and CU-3 has increased antioxidant enzymes and decreased AChE activity in D. melanogaster. This activity could be part of the probable mechanisms of action by which OLE-2 and CU-3 fractions have extended the lifespan and locomotory activity in fruit flies. These fruit flies continue to provide an exciting system for metabolic studies and should be more extensively exploited. Based on these results, further studies on the identified bioactive compounds from these two plants are being planned.

Protective effects of selenium on acrylamide-induced neurotoxicity and hepatotoxicity in rats.

Objective(s):Acrylamide (ACR), has wide uses in different industries. ACR induced several toxicities including neurotoxicity and hepatotoxicity. The probable protective effects of selenium on ACR-induced neurotoxicity and hepatotoxicity in rats were evaluated.Materials and Methods:Male Wistar rats were studied for 11 days in 8 groups: 1. Control, 2. ACR (50 mg/kg, IP), 3-5. ACR+ selenium (0.2, 0.4, 0.6 mg/kg, IP), 6. ACR+ the most effective dose of selenium (0.6 mg/kg, IP) three days after ACR administration, 7. ACR+ vitamin E (200 mg/kg IP, every other day) 8. Selenium (0.6 mg/kg IP). Finally, behavioral tests were done. The levels of malondialdehyde (MDA), glutathione (GSH), Bcl-2, Bax and caspase 3 proteins in liver and cerebral cortex tissues were measured. Also, the amount of albumin, total protein, alanine transaminase (ALT) and aspartate transaminase (AST) enzymes were determined in serum. Results:ACR caused the severe motor impairment, increased MDA level and decreased GSH content, enhanced Bax/Bcl-2 ratio and caspase 3 proteins in brain and liver tissues. Besides, the level of AST was elevated while the total serum protein and albumin levels were decreased. Administration of selenium (0.6 mg/kg) (from the first day of the experiment and the third day) significantly recovered locomotor disorders, increased GSH content, and reduced MDA level. Also, selenium decreased Bax/Bcl-2 ratio and caspase 3 levels in brain and liver tissues.Conclusion:The oxidative stress and apoptosis pathways have important roles in neurotoxicity and hepatotoxicity of ACR. Selenium significantly reduced ACR-induced toxicity through inhibition of oxidative stress and apoptosis.

Amelioration of cognitive deficit in zebrafish by an undescribed anthraquinone from Juglans regia L.: An in-silico, in-vitro and in-vivo approach

An undescribed anthraquinone assigned as 1-Hydroxy-5,5-dimethyl-5,6,7,8-tetrahydro-9,10-anthraquinone (compound 1) was isolated from ethylacetate extract of Juglans regia L. The structure of the compound was established on the basis of 1D, 2D NMR (HSQC, HMBC, COSY), ESI-QTOF-MS/MS spectroscopy. The molecular docking studies of compound 1 indicated similar molecular interactions as that of co-crystalized inhibitor. Compound 1 showed hydrogen bonds with residues PHE295, GLY121, π-σ interactions with TYR 341, π-π interactions with HIS 447 residues, and π-alkyl with TRP86 and TYR 337. On the basis of in-silico interaction studies of compound 1 with proteins, it was tested using acetylcholinesterase inhibition assay, acrylamide-induced neurotoxicity test of zebrafish larva, and scopolamine-induced cognitive deficit model of adult zebrafish. The compound 1 showed potent acetylcholinesterase inhibition activity, prevented acrylamide-induced neurotoxicity and improved learning and memory functions in T-maze test. The results established compound 1 to be a potential neuroprotective natural product for amelioration of cognitive impairment.

Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice.

Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 or 300 ppm in drinking water and co-administered with subcutaneous injections of sulforaphane, a known activator of the Nrf2 signaling pathway at 0 or 25 mg/kg body weight daily for 4 weeks. Assessments for neurotoxicity, hepatotoxicity, oxidative stress as well as messenger RNA-expression analysis for Nrf2-antioxidant and pro-inflammatory cytokine genes were conducted. Relative to mice exposed only to acrylamide, co-administration of sulforaphane protected against acrylamide-induced neurotoxic effects such as increase in landing foot spread or decrease in density of noradrenergic axons as well as hepatic necrosis and hemorrhage. Moreover, co-administration of sulforaphane enhanced acrylamide-induced mRNA upregulation of Nrf2 and its downstream antioxidant proteins and suppressed acrylamide-induced mRNA upregulation of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the cerebral cortex. The results demonstrate that activation of the Nrf2 signaling pathway by co-treatment of sulforaphane provides protection against acrylamide-induced neurotoxicity through suppression of oxidative stress and inflammation. Nrf2 remains an important target for the strategic prevention of acrylamide-induced neurotoxicity.

Morin protects against acrylamide-induced neurotoxicity in rats: an investigation into different signal pathways.

The presented study investigates the effects of morin against toxicity induced by acrylamide (ACR) in the brains of Sprague Dawley rats. In this study, neurotoxicity was induced by orally administering 38.27 mg/kg/b.w ACR to rats through gastric gavage for 10 days. Morin was administered at the same time and at different doses (50 and 100 mg/kg/b.w) with ACR. Biochemical and Western blot analyses showed that ACR increased malondialdehyde (MDA), p38α mitogen-activated protein kinase (p38α MAPK), nuclear factor kappa-B (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), p53, caspase-3, bcl-2 associated X protein (Bax), Beclin-1, light chain 3A (LC3A), and light chain 3B (LC3B) levels and decreased those of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), b-cell lymphoma-2 (Bcl-2), mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) in brain tissue and therefore induced neurotoxicity by causing oxidative stress, inflammation, apoptosis, and autophagy. On the other hand, it was determined that morin positively affected the levels of these markers by displaying antioxidant, anti-inflammatory, anti-apoptotic, and anti-autophagic properties and had a protective effect on ACR-induced neurotoxicity. As a result, morin is an effective substance against brain damage caused by ACR, yet further studies are needed to use it effectively.

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.

Acrylamide and its metabolite induce neurotoxicity via modulation of protein kinase C and AMP-activated protein kinase pathways

Acrylamide is known as a neurotoxicant found in commonly consumed food as well as in human body. However, the underlying mechanisms involved in neurotoxicity by acrylamide and its metabolite, glycidamide remain largely unknown. In this study, we have examined the interplay between CYP2E1, AMPK, ERK and PKC in acrylamide-induced neurotoxicity associated with autophagy in PC12 cells. Acrylamide-induced cell death was mediated by CYP2E1 expression and the activation of ERK, PKC-ɑ and PKC-δ, whereas AMPK knockdown exacerbated the acrylamide-induced neurotoxic effects. PKC-ɑ, but not PKC-δ, plays an upstream regulator of ERK and AMPK. Moreover, AMPK activation suppressed ERK, and CYP2E1 and AMPK bilaterally inhibit each other. Furthermore, acrylamide increased autophagy with impaired autophagic flux, evidenced by the increased beclin-1, LC3-II and p62 protein. Acrylamide-induced neuronal death was ameliorated by 3-methyladenine, an autophagy inhibitor, whereas neuronal death was exacerbated by chloroquine, a lysosomal inhibitor. Interestingly, PKC-δ siRNA, but not PKC-ɑ siRNA, dramatically reduced acrylamide-induced beclin-1 and LC3-II levels, whereas AMPK siRNA further increased beclin-1, LC3-II and p62 protein levels. Glycidamide, a major metabolite, mimicked acrylamide only with a higher potency. Taken together, acrylamide- and glycidamide-induced neurotoxicity may involve cytotoxic autophagy, which is mediated by interplay between PKCs and AMPK pathways.

The effect of Hippophae rhamnoides L. extract on acrylamideinduced brain injury in rats.

ABSTRACTPurpose:Reactive oxygen species (ROS), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) have been shown in the pathogenesis of acrylamide neurotoxicity. Hippophae rhamnoides L. extract (HRE) has a cytoprotective effect by stabilizing the production of ROS, IL-1β and TNF-α. The objective of the article was to investigate the effect of HRE on acrylamide-induced brain damage in rats biochemically and histopathologically.Methods:To the HRE+acrylamide only (ACR) group (n=6) of the animals, HRE was administered orally at a dose of 50 mg / kg into the stomach by gavage. The same volume of solvent (olive oil) was administered orally to the ACR (n=6) and healthy (HG) (n=6) groups. One hour after HRE administration, acrylamide was given orally at a dose of 20 mg/kg to HRE+ACR and ACR groups in the same way. This procedure was repeated once a day for 30 days. At the end of this period, brain tissues extracted from animals killed with 50 mg/kg thiopental anesthesia were examined biochemically and histopathologically.Results:It has been shown that HRE prevents the increase of malondialdehyde (MDA), myeloperoxidase (MPO), IL-1β and TNF-α with acrylamide and the decrease of total glutathione (tGSH) and glutathione reductase (GSHRd) levels in brain tissue.Conclusions:HRE may be useful in the treatment of acrylamide-induced neurotoxicity.

Notoginsenoside R1 Protects Against the Acrylamide-Induced Neurotoxicity via Upregulating Trx-1-Mediated ITGAV Expression: Involvement of Autophagy.

Acrylamide (ACR) is a common chemical used in various industries and it said to have chronic neurotoxic effects. It is produced during tobacco smoking and is also generated in high-starch foods during heat processing. Notoginsenoside R1 (NR1) is a traditional Chinese medicine, which is used to improve the blood circulation and clotting. The objective of this study was to investigate the mechanism of ACR-triggered neurotoxicity and to identify the protective role of NR1 by upregulating thioredoxin-1 (Trx-1). Our results have shown that NR1 could block the spatial and cognitive impairment caused by ACR administration. Bioinformatics analysis revealed that Trx-1 regulated autophagy via Integrin alpha V (ITGAV). NR1 could resist the ACR-induced neurotoxicity by upregulating thioredoxin-1 in PC12 cells and mice. The autophagy-related proteins like autophagy-related gene (ATG) 4B, Cathepsin D, LC3 II, lysosomal-associated membrane protein 2a (LAMP2a), and ITGAV were restored to normal levels by NR1 treatment in both PC12 cells and mice. Besides, we also found that overexpression of Trx-1 resisted ACR-induced autophagy in PC12 cells and downregulation of Trx-1 triggered autophagy induced by ACR in PC12 cells. Therefore, it could be concluded that Trx-1 was involved in the autophagy pathway. Besides, we also found that ITGAV was an intermediate node linking Trx-1 and the autophagy pathway.

The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats

BackgroundAcrylamide (ACR) formed during heating of tobacco and carbohydrate-rich food as well as widely applied in industries has been known as a well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats.MethodsCurcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40 mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the cerebral homogenates were detected using ELISA assay.ResultsACR-induced weigh loss, deficits in motor function as well as pathological alterations in brains were significantly improved in rats administrated with 50 and 100 mg/kg curcumin. TUNEL-positive apoptotic cells in curcumin-treated ACR intoxicated brains were less than those in the ACR model group. Curcumin administration especially at the dose of 100 mg/kg upregulated the TERT mRNA expression and enhanced the number of TERT-positive cells in ACR-intoxicated cortex tissues. Moreover, curcumin treatment reduced the concentrations of TNF-α, IL-1β and MDA, while increased the GSH contents as well as the SOD and GSH-Px activities in the cerebral homogenates, in comparison to ACR control group.ConclusionsThese data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. Maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

Upregulation of Antioxidant Gene Expressions and Enzyme Activity Against Acrylamide-Induced Neurotoxicity in Mice after Grape Seed Extract Treatment

Background: The risk of occupational exposure to acrylamide is high and long-term acrylamide exposure can cause neurotoxicity. Thus, therapeutic agents that can protect against acrylamide-induced neurotoxicity are needed. Objective: To investigate whether Grape Seed Extract (GSE) protects against acrylamide-induced neurotoxicity in mice. Methods: Mice were divided into saline, GSE, acrylamide, GSE followed by acrylamide, acrylamide followed by GSE, and simultaneous acrylamide and GSE treatment groups. Gene expression and antioxidant enzyme levels were then determined using RT-PCR and biochemical assays. Results: Gpx1 (P < 0.05), Prdx3 (P < 0.01), SOD1 (P < 0.05), and CAT (P < 0.05) significantly upregulated in GSE-treated mice, compared to those in untreated controls. In contrast, Gpx1 (P < 0.05), Prdx3 (P < 0.05), SOD1 (P < 0.05), and CAT (P < 0.05) significantly downregulated in acrylamide-treated mice compared to those in untreated controls. Results of the treatment with GSE before exposure to acrylamide or simultaneously with acrylamide indicated that GSE restored Gpx1, Prdx3, SOD1, and CAT expression to similar levels as those in the control group. GSE treatment after exposure to acrylamide did not exert any neuroprotective effects against acrylamide, as revealed by significant downregulation of Gpx1 (P < 0.05), Prdx3 (P < 0.01), SOD1 (P < 0.05), and CAT (P < 0.05) compared to that in untreated controls. Animals treated with grape seed before acrylamide treatment showed no significant change in LPO activities and a significant increase in GSH levels, compared to those in untreated controls. Conclusion: GSE exerted neuroprotective effects against acrylamide-induced neurotoxicity. Acrylamide caused oxidative stress 20 days post-exposure. However, grape seed treatment before exposure to acrylamide restored all test parameters to levels similar to control values.

Neuroprotective effects of notoginsenoside R1 by upregulating Trx-1 on acrylamide-induced neurotoxicity in PC12.

Acrylamide (ACR) is a water-soluble chemical that is commonly used in chemical and cosmetic manufacture. Many studies have been carried out to investigate the neurotoxicity mechanisms of ACR, resulting in oxidative stress and nerve damages. One of the commonly used traditional Chinese medicines is notoginsenoside R1 (NR1). However, its mitochondrial-mediated apoptotic effect caused in ACR-induced neurotoxicity has not been reported. Our results have shown that NR1 resisted the neurotoxicity induced by ACR by upregulating the levels of thioredoxin-1 (Trx-1) in Rat adrenal chromaffin cell tumor (PC12) cells. NR1 inhibited the increase in levels of Bax, caspase-9, and caspase-3, which was instigated by ACR. Moreover, NR1 inhibited the decrease in levels of B-cell lymphoma 2 and Trx-1 induced by ACR. The downregulation of Trx-1 aggravated the mitochondrial-mediated apoptosis and increased the expression of the above molecules, which was induced by ACR. In contrast, overexpression of Trx-1 attenuated the mitochondrial-mediated apoptosis and inhibited the expression of the mentioned molecules induced by ACR. Our results suggested that NR1 protected ACR-induced mitochondrial apoptosis by upregulating Trx-1.

Minocycline protects against acrylamide-induced neurotoxicity and testicular damage in Sprague-Dawley rats.

This study investigated the protective effects of minocycline against acrylamide (ACR)-induced neurotoxicity and testicular damage in Sprague-Dawley rats. Forty rats were divided into five groups (eight rats each). Group I received saline (0.5 mL/rat) daily for 10 days and served as the untreated control group. Group II received ACR (30 mg/kg body weight (b.w.)) daily for 10 days. Group III received ACR (30 mg/kg b.w.) daily for 10 days and subsequently minocycline (60 mg/kg b.w.) for five days. Group IV received ACR (30 mg/kg b.w.) daily for 10 days followed by saline for five days and served as the control group for the ACR-minocycline-treated group. Group V received minocycline (60 mg/kg b.w.) for five days. All treatments were administered orally. Rats in group I and V showed normal locomotor behavior and normal histology of the brain and testes. Administration of ACR (Group II and IV) resulted in weight loss and gait abnormalities. Furthermore, neuronal degeneration in the hippocampus and cerebellum and degeneration of the seminiferous tubular epithelium with formation of spermatid giant cells were observed. Ultrastructurally, ACR specifically damaged spermatogonia and spermatocytes. Acrylamide was also seen to cause a significant increase of malondialdehyde levels in the brain and testes. Treatment of ACR-administered rats with minocycline (Group III) significantly alleviated the loss of body weight and improved locomotor function. Minocycline also ameliorated neuronal degeneration and seminiferous tubular damage and decreased malondialdehyde concentrations. In conclusion, minocycline protects against neurotoxic effects of acrylamide and seminiferous tubular damage. Decreasing lipid peroxidation by minocycline might play a role in such protection.

The antioxidant and neuroprotective effects of Zolpidem on acrylamide-induced neurotoxicity using Wistar rat primary neuronal cortical culture

Zolpidem is an introduced medication for the therapy of sleeping disorders. Its pharmacological effects are consequently characterized by a quick onset and a half-life of 2.4 h. Previous studies revealed the antioxidant and neuroprotectant effects of zolpidem. In this research, we wanted to demonstrate the exact sub-cellular/molecular mechanism of this medication using the primary neuronal cortical culture.For this purpose, firstly, the cortical neurons were isolated from the postnatal Wistar rat pups. Thereafter, different neural toxicity endpoints caused by acrylamide including ROS formation, lipid peroxidation, mitochondrial membrane potential collapse, lysosomal membrane integrity, and apoptosis were determined. All of these parameters are upstream events of cellular apoptosis which justifies neurodegeneration involved in many diseases such as Alzheimer's and Parkinson's.Our results demonstrated that zolpidem at concentrations of 1 and 2 mM prevented all the acrylamide-induced above referenced neural toxic events leading to neuronal apoptosis.These results revealed that zolpidem has the antioxidant and neuroprotectant properties that make it a promising prophylactic agent for preventing neurodegenerative complications. Considering the important role of oxidative stress in the development or progression of diseases, if the medication used as a treatment of a disease has antioxidant properties at the same time, it will certainly have much greater healing effects.

Apoptosis and astrogliosis perturbations and expression of regulatory inflammatory factors and neurotransmitters in acrylamide-induced neurotoxicity under ω3 fatty acids protection in rats

This study was aimed to investigate the potential ameliorative effects of omega-3 (ω3) fatty acids against acrylamide (ACR)-induced neurotoxicity. Thirty-two adult male Sprague Dawley rats were randomly assigned into four groups (n = 8) as follows: control, ω3 fatty acids (1000 mg/kg bwt/day orally), ACR-treated (50 mg/kg bwt/day IP) and ACR plus ω3 fatty acids group. Treatments were performed every other day for 21 consecutive days. ACR induced abnormal gait and elevated serum levels of proinflammatory cytokines (IL-6 and TNF-α), brain and spinal cord MDA levels and decreased brain and spinal cord GSH levels. Moreover, it reduced neurotransmitters (acetylcholine, GABA, serotonin and noradrenaline levels) and increased AChE activity in brain tissues. Histopathologically, ACR caused various degenerative changes, necrosis and glial cell activation in the cerebrum, cerebellum, hippocampus, spinal cord and sciatic nerve. Likewise, the histomorphometric analysis was constant with ACR-induced neurotoxicity. The ACR induced axonal atrophy and myelin disruption and decreased g-ratio of the sciatic nerve. Immunohistochemically, strong positive expressions of apoptotic marker caspase-3 and astroglial GFAP in the examined tissues were detected. Contrariwise, concurrent administration of ω3 fatty acids partially attenuated ACR impacts, as it improved the gait performance, reduced oxidative stress and pro-inflammatory cytokines, and modulate the levels of the neurotransmitters. It also ameliorated the intensity of ACR-induced histopathological and histomorphometric alterations within the examined nervous tissues. It could be concluded that ω3 fatty acids have antioxidant, anti-inflammatory and anti-apoptotic potentials against ACR neurotoxicity via suppression of oxidative stress, lipid peroxidation and pro-inflammatory cytokines, and inhibition of AChE activity and downregulation of caspase-3 and GFAP expressions in the nervous tissues.

Neuroprotective effects of Ellagic acid against acrylamide-induced neurotoxicity in rats

ABSTRACT Acrylamide (ACR) is an environmental contaminant and a well-known neurotoxin. Ellagic acid (EA), a natural plant polyphenol, has shown a variety of beneficial effects. The present study was designed to explore whether EA could attenuate ACR-induced neurotoxicity in rats and to explore the underlying mechanisms. Animals were divided into five groups. Group 1 was treated with normal saline (2 mL/kg) for 30 days. Group 2 was treated with ACR (20 mg/kg, orally) for 30 days. Groups 3 and 4 were treated with ACR and EA (10 and 30 mg/kg, orally) for 30 days. Group 5 was treated with EA (30 mg/kg, orally) for 30 days. Open field, rotarod and passive avoidance test were conducted to evaluate behavioral changes, respectively. The brain cortex was used for histological examination. Different oxidative parameters and inflammatory biomarkers were assessed in the brain cortex. ACR-administered rats showed a considerable impairment in exploratory behavior, motor performance as well as cognition. Our data also showed that ACR administration significantly increases malondialdehyde, nitric oxide, interleukin-1β and tumor necrosis factor-α levels. Moreover, it decreases brain glutathione level, superoxide dismutase, glutathione peroxidase, catalase activity. Co-administration of EA (especially 30 mg/kg, p.o.) prevented these changes; however, it did not affect the glutathione peroxidase activity. These results were supported by histopathological observations of the brain. Our results suggest that EA can be useful for protecting brain tissue against ACR-induced neurotoxicity through ameliorative effects on inflammatory indices and oxidative stress parameters.

The role of Crocin in an acrylamide-induced neurotoxicity model in Wistar rats

Aim: The changes in rat brain tissues treated with Crocin (Cr) as a protective agent in an acrylamide (AA) neurotoxicity model were investigated.Material and Methods: The present with of the experimental animal ethics committee at Inonu University, Faculty of Medicine (2016 / A-59). Forty male rats were randomly divided into 4 groups with study was conducted the approval equal number of rats (10): Control, Cr, AA, Cr + AA Groups. Malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), Oxidative stress index (OSI), superoxide dismutase (SOD), catalase (CAT) and protein values were examined in the brain tissues.Results: MDA, TOS and OSI levels increased in brain tissues of AA administered rats when compared to the other groups, while the GSH, TAS, SOD and CAT levels decreased in the group (p 0.05). GSH, TAS, SOD and CAT levels increased, but MDA, TOS and OSI levels decreased in the AA + Cr administered group when compared to the AA group (p 0.05). It was observed that oral AA administration altered the antioxidant/oxidant balance favoring the oxidants in male rat brain tissues, leading to oxidative stress induced neurotoxicity, while Cr administration reestablished the normal antioxidant/oxidant balance, preventing the oxidative stress induced neurotoxicity via detoxification. Conclusion: The present study concluded that the administered Cr dose was sufficient to prevent neurotoxicity and we recommend that adequate amounts of Cr should be consumed to prevent AA-induced toxicity and improve antioxidant capacity.

Assessment of biomarkers in acrylamide-induced neurotoxicity and brain histopathology in rat

The effects of acrylamide (ACR), a synthetic neurotoxic chemical compound on non-enzymatic and enzymatic stress markers and brain histopathology were studied in wistar rats. ACR (50 mg/300 ml) was ingested through drinking water on alternative days and brain tissues were collected on 13th and 27th days post ingestion for analysis. Results revealed that ACR causes significant increase in non-enzymatic stress markers like lipid peroxidation (p

Evaluation of the Neuroprotective Effect of Silybum Marianum Extract on Acrylamide-Induced Neurotoxicity: An In Vitro and In Vivo Study

Evaluation of the Neuroprotective Effect of Silybum Marianum Extract on Acrylamide-Induced Neurotoxicity: An In Vitro and In Vivo Study