OBJECTIVETo investigate acrylamide (ACR)-induced subacute neurotoxic effects on the central nervous system (CNS) at the synapse level in rats.

METHODSThirty-six Sprague Dawley (SD) rats were randomized into three groups, (1) a 30 mg/kg ACR-treated group, (2) a 50 mg/kg ACR-treated group, and (3) a normal saline (NS)-treated control group. Body weight and neurological changes were recorded each day. At the end of the test, cerebral cortex and cerebellum tissues were harvested and viewed using light and electron microscopy. Additionally, the expression of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were investigated.

RESULTSThe 50 mg/kg ACR-treated rats showed a significant reduction in body weight compared with untreated individuals (P < 0.05). Rats exposed to ACR showed a significant increase in gait scores compared with the NS control group (P < 0.05). Histological examination indicated neuronal structural damage in the 50 mg/kg ACR treatment group. The active zone distance (AZD) and the nearest neighbor distance (NND) of synaptic vesicles in the cerebral cortex and cerebellum were increased in both the 30 mg/kg and 50 mg/kg ACR treatment groups. The ratio of the distribution of synaptic vesicles in the readily releasable pool (RRP) was decreased. Furthermore, the expression levels of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were decreased in both the 30 mg/kg and 50 mg/kg ACR treatment groups.

CONCLUSIONSubacute ACR exposure contributes to neuropathy in the rat CNS. Functional damage of synaptic proteins and vesicles may be a mechanism of ACR neurotoxicity.

Acrylamide ; toxicity ; Animals ; Cerebellum ; cytology ; drug effects ; Cerebral Cortex ; cytology ; drug effects ; Drug Administration Schedule ; Gait ; Gene Expression Regulation ; drug effects ; Male ; Neurons ; drug effects ; Neurotoxicity Syndromes ; pathology ; Rats ; Rats, Sprague-Dawley ; Synapses ; drug effects ; Synapsins ; genetics ; metabolism ; Synaptic Vesicles ; drug effects ; physiology ; Weight Loss ; drug effects

OBJECTIVEThe aim of this study is to investigate hepatic and renal toxicity of acrylamide (ACR) , the antagonistic effect and possible mechanism of N-acetylcysteine (NAC) on the toxicity.

METHODSForty female SD rats were randomly divided into four groups. All the rats were administrated by intraperitoneal(i.p.) injection and 1.5 hours later by gavage. The control group was administrated with 0.9% NaCl by i.p. injection and gavaged with 0.9% NaCl. The NAC group was administrated with 200 mg/kg NAC by injection and gavaged with 0.9% NaCl. The ACR group was administrated with 0.9% NaCl by injection and gavaged with 40 mg/kg ACR. The combined treatment group was administrated with 200 mg/kg NAC by i.p. injection and gavaged with 40 mg/kg ACR. The rats were administrated once a day for 2 weeks. After 24 hours of the last administration, the rats were decapitated. The blood was collected, the liver and kidney were separated. The body weight, organ coefficient and serum biochemical parameters were measured, and the pathological changes of the tissues were examined with a microscope. Then the expression of NF-κB p65, IκB-α and COX-2 were detected by Western blot.

RESULTSFrom the second day to the end of the exposure, the body weight of rats in the ACR group was statistically lower than that in the control group (P<0.05) . Compared with the combined treatment group, the body weight in the ACR group statistically decreased in the second and third days (P < 0.05) . The liver and kidney organ coefficients in the ACR group were (4.159%±.371%) and (0.764%±0.068%) respectively, which increased statistically when compared with the control group (P < 0.05) . The contents of ALT, AST and Cr in the serum in the ACR group were (77.370±16.397) U/L、(379.410±57.817) U/L and (77.812±6.391) μmol/L respectively, which were not significantly different with those in the control group and the combined treatment group (P>0.05) . The content of BUN in the serum in the ACR group was (7.005±1.009) mmol/L, which was statistically higher than that in the control group (P<0.05) . Histopathology results showed unclear boundary and nucleus pyknosis in hepatocytes, loose and disordered structures of hepatic cords in the ACR group, but no obvious pathology changes were observed in the kidneys of each group. In the Western blot results, the expression of nuclear NF-κB p65 and COX-2 in the liver in the ACR group was statistically higher than that in the control group and the combined treatment group (P<0.05) , and the expression of IκB-α in the liver in the ACR group statistically decreased compared with the control group and the combined treatment group (P<0.05) . The expression of total NF-κB p65 in the liver in the ACR group was statistically higher than that in the control group (P<0.05) .

CONCLUSIONUnder the conditions of this experiment, ACR may induce hepatic toxicity through the activation of NF-κB signaling pathway, and NAC could antagonize the hepatic toxicity of ACR by inhibiting the NF-κB signaling pathway, whereas the toxic effect of ACR on kidney needs to be further studied.

Acetylcysteine ; pharmacology ; Acrylamide ; toxicity ; Animals ; Cyclooxygenase 2 ; metabolism ; Female ; I-kappa B Proteins ; metabolism ; Kidney ; drug effects ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; NF-KappaB Inhibitor alpha ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Transcription Factor RelA ; metabolism

The purpose of this study was to study the role of neurofilament (NF) mRNA and calpain in NF reduction of acrylamide (ACR) neuropathy. Male Wistar adult rats were injected i.p. every other day with ACR (20 mg/kg·bW or 40 mg/kg·bW) for 8 weeks. NF mRNA expression was detected using RT-PCR and the calpain concentration was determined using western blot analysis. The NF mRNA expression significantly decreased while the level of m-calpain and μ-calpain significantly increased in two ACR-treated rats groups regardless of the ACR dose. The light NF (NF-L) protein expression was significantly correlated with NF-L mRNA expression. Combined with previous data, the concentrations of three NF subunits were negatively correlated with the calpain levels. These findings suggest that NF-L mRNA and calpain mediated the reduction in NF of ACR neuropathy.
Acrylamide ; toxicity ; Animals ; Calpain ; metabolism ; Gene Expression Regulation ; drug effects ; Intermediate Filaments ; genetics ; Male ; Peripheral Nervous System Diseases ; chemically induced ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats

OBJECTIVETo investigate the immunotoxicity of acrylamide (ACR) in female BALB/c mice.

METHODSA total of 200 female mice weighing 18-22 g were randomly divided into four clusters based on body weight, and each weight-based cluster included five groups (10 mice per group): negative control, positive control (cyclophosphamide), low, intermediate, and high dose ACR groups, and all the groups were administered ACR by gavage for 30 days. At the end of the study, the immunotoxicological effects of the ACR were evaluated through immunopathology, humoral immunity, cellular immunity, and non-specific immunity.

RESULTSThe terminal body weight, spleen and thymus weights, lymphocyte counts in the ACR-H group were decreased, pathological changes were observed in lymph glands, thymus and spleen. %T cells in blood lymphocytes were significantly increased in all ACR-treated groups, and a significant reduction of % natural killer(NK) cells and increase of %Th cells were observed in the ACR-H group. interleukin-6(IL-6), Concanavalin A(ConA)-induced splenocyte proliferation and serum half hemolysis value (HC50) were also significantly suppressed in the ACR-H group.

CONCLUSIONACR elicited an inhibitory effect on cellular and humoral immunity of mice after 30 day feeding.

Acrylamide ; toxicity ; Animals ; Body Weight ; drug effects ; CD4-CD8 Ratio ; Cytokines ; blood ; Female ; Immunity, Cellular ; drug effects ; Immunity, Humoral ; drug effects ; Immunophenotyping ; Immunotoxins ; toxicity ; Mice ; Mice, Inbred BALB C ; Organ Size ; drug effects ; Random Allocation ; Spleen ; drug effects ; Thymus Gland ; drug effects ; Toxicity Tests

Acrylamide ; toxicity ; Animals ; Behavior, Animal ; drug effects ; Blotting, Western ; Cytoskeletal Proteins ; blood ; Dose-Response Relationship, Drug ; Electrophoresis, Polyacrylamide Gel ; Gait Ataxia ; blood ; chemically induced ; Male ; Motor Activity ; drug effects ; Neurotoxicity Syndromes ; blood ; etiology ; Rats ; Rats, Wistar

OBJECTIVETo explore the effects of acrylamide on the permeability of blood cerebrospinal fluid barrier (BCB) and tight junction protein ZO-1 of choroid plexus in rats and to provide a theoretical basis for explaining the mechanism of nerve injury induced by acrylamide.

METHODSThirty two male Sprague-Dawley rats were randomly divided into ACR and control groups. ACR group was exposed to 20 mg/kg ACR daily for 5 days a week by intraperitoneal injection (i.p.) for 4 weeks. Control group was exposed to normal saline. The neurobehavioral tests (including sensatory and motor functions) were performed every week. At the end of exposure, Evan blue (EB) and Sodium fluorescein (NaFI) content in rat CSF were detected for determining the BCB permeability, Real-time PCR was used to measure the expression levels of ZO-1 mRNA in the epithelium cells of choroid plexus, and laser scanning confocal microscope (LSCM) was utilized to observe the distribution of ZO-1 protein.

RESULTSNeurobehavioral tests showed that the tail-flick latencies of ACR group were 27.77% and 53.71% as long as control group in the 3rd week and 4th week, respectively (P < 0.05). The hind lamb splay distances of ACR group were 131.76% and 153.77% as long as control group in the 3rd week and 4th week, respectively (P < 0.05). Evan blue (EB) and Sodium fluorescein (NaFI) content of ACR group were significantly higher than those of control group (P < 0.05). In the 4th week, the expression level of ZO-1 mRNA in ACR group was 0.21 +/- 0.07, which was significantly lower than that (0.31 +/- 0.11) in control group (P < 0.05). In the 4th week, the ZO-1 protein expression level of choroid plexus in ACR group was significantly lower than that in control group (P < 0.05).

CONCLUSIONAcrylamide could increased the BCB permeability of rats, which may be involved in the central nervous injury induced by ACR.

Acrylamide ; toxicity ; Animals ; Blood-Brain Barrier ; drug effects ; Choroid Plexus ; metabolism ; Male ; Permeability ; drug effects ; Rats ; Rats, Sprague-Dawley ; Zonula Occludens-1 Protein ; metabolism

Prohibited substances in cosmetics refer to substances which must not be among the raw material ingredients of cosmetic products. These substances are absorbed mostly through skin, as well as via lung and gastrointestinal tract. Polyacrylamide is ubiquitously used in industry and its decomposition residue acrylamide (ACR) easily finds its way into cosmetic products. ACR can either be oxidized to epoxide glycidamide or conjugated with glutathione, hemoglobin or DNA; ultimately it is excreted in urine. ACR causes neurotoxicity, reproductive toxicity and tumors in rodents. Occupational exposure to ACR causes neurotoxicity in humans; however, epidemiological evidence have not unambiguously answered the question of whether ACR exposure can increase cancer risk for humans.
Acrylamide ; metabolism ; pharmacokinetics ; toxicity ; Acrylic Resins ; chemistry ; China ; Cosmetics ; chemistry ; Humans

OBJECTIVE: To investigate the protective effect of epigallocatechin-3 -gallate (EGCG) on apoptosis of cerebellar granule neurons (CGNs) induced by acrylamide (ACR). METHODS: CGNs were cultured with the addition of 5 mmol/L ACR for 24 hours to set up a cell injury model. Prior to ACR treatment, CGNs were treated with different concentrations of EGCG (0, 5, 10, 25, 50, 100 μmol/L) for 48 hours. Neuronal viability was measured with metylthiazdyltetrazolium (MTT). The activity of SOD and the content of MDA were assayed. Hoechst33342 staining was employed to observe morphological changes of the cell nucleus. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure expression of bcl- 2 mRNA and bax mRNA. RESULTS: At the concentrations of 10, 25 or 50 μmol/L, EGCG played a protective role against ACRinduced CGN injury. Compared with ACR injured group (no EGCG), EGCG improved the cell viability, enhanced SOD activity, decreased the level of MDA as well as the cell apoptosis ratio (P<0.05). Bcl-2 mRNA expression was increased and bax mRNA expression was reduced (P<0.05). 25 μmol/L EGCG had the largest effect. However, 100 μmol/L EGCG did not have a significantly protective effect. CONCLUSION EGCG at appropriate concentration has protective effect against the CGNs on apoptosis induced by ACR.
Acrylamide ; toxicity ; Animals ; Apoptosis ; drug effects ; Catechin ; analogs & derivatives ; pharmacology ; Cells, Cultured ; Cerebellum ; cytology ; drug effects ; Cytoplasmic Granules ; Female ; Male ; Neurons ; cytology ; drug effects ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore effects of acrylamide on synaptic plasticity of rat neuron and its mechanisms.

METHODS24 Wistar rats were divided into control and test groups randomly, 12 rats in each group. The ratio of male and female in each group was 1:1. Acrylamide (30 mg/kg) was administered to rats by intraperitoneal injection in test group and normal saline (5 g/kg) was given to rats in control group. The neurobehavioral and pathologic changes of heart, liver, spleen, lung and kidney were observed. Changes of parameters in synapse were recorded by electron microscope. As an important target of synapse, change of Synapsin I was measured by immunohistochemical method.

RESULTSCompared with the control group (male: 1.00 ± 0.00; female: 1.00 ± 0.00), the gait score was increased significantly in ACR treated group (male: 2.50 ± 0.55, t = -7.24, P < 0.01; female: 3.17 ± 0.41, t = -12.19, P < 0.01). No obvious pathological changes of heart, liver, spleen, lung and kidney were found in all rats. Compared with the control group (male: (0.41 ± 0.09) µm; female: (0.40 ± 0.06) µm), the length of active zone of synapse was decreased significantly in ACR treated group (male: (0.15 ± 0.05) µm, t = 6.59, P < 0.05; female: (0.14 ± 0.07) µm, t = 7.26, P < 0.05). The width and postsynaptic density of synapse in ACR treated group had no significant difference with control group. The location of Synapsin I of control group and ACR treated group was both in gray matter of spinal dorsal horn. Compared with the control group (male: 195.40 ± 12.30; female: 195.19 ± 6.71), the concentration of Synapsin I was decreased significantly in ACR treated group (male: 60.90 ± 29.19, t = 10.40, P < 0.05; female: 67.56 ± 20.23, t = 15.65, P < 0.05).

CONCLUSIONNeuronal synaptic plasticity was found in damage of nervous system induced by acrylamide in rats, which might be associated with the expression of Synapsin I.

Acrylamide ; toxicity ; Animals ; Female ; Male ; Neuronal Plasticity ; drug effects ; Neurons ; drug effects ; Rats ; Rats, Wistar ; Synapses ; drug effects

OBJECTIVETo evaluate the hazardous effects of fried potato chips upon the retina of two developmental stages of the albino rats aged 7 and 14 days from parturition.

METHODSPREGNANT RATS WERE ARRANGED INTO TWO GROUPS: control pregnant rats and consequently their delivered newborns until reaching 7 and 14 days old from parturition and fried potato chips group in which pregnant rats at the 6th day of gestation maintained on diet formed of fried potato chips supplied from the market mixed with standard diet at a concentration of 50% per each till 7 and 14 post-partum. Three fold integrated approaches were adopted, namely, histological, ultrastructural and proteomic analysis.

RESULTSHistological examination of the retina of the experimental offsprings revealed many histopathological changes, including massive degeneration, vacuolization and cell loss in the ganglion cell layer, as well as general reduction in retinal size. At the ultrastructural level, the retina of experimental offsprings exhibited number of deformities, including ill differentiated and degenerated nuclear layer, malformed and vacuolated pigment epithelium with vesiculated and fragmented rough endoplasmic reticulum, degenerated outer segment of photoreceptors, as well as swollen choriocapillaris and loss of neuronal cells. Proteomic analysis of retina of the two experimental developmental stages showed variations in the expressed proteins as a result of intoxication which illustrated the adverse toxic effects of fried potato chips upon the retina.

CONCLUSIONSIt can be concluded that the effect of fried potato chips on the development of retina in rats may be due to the presence of acrylamide or its metabolite.

Acrylamide ; toxicity ; Animals ; Animals, Newborn ; Cooking ; methods ; Diet ; methods ; Female ; Histocytochemistry ; Male ; Pigments, Biological ; Pregnancy ; Proteome ; analysis ; Rats ; Retina ; pathology ; Solanum tuberosum ; chemistry ; Ultrasonography