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1.
Artigo em Chinês | MEDLINE | ID: mdl-32062896

RESUMO

Objective: To investigate the clinical manifestations, electrophysiology results, treatment and prognosis of acrylamide-induced toxic peripheral neuropathy. Methods: The clinical data of 9 patients with acrylamide-induced toxic peripheral neuropathy, who were collected in Jinhua Municipal Central Hospital from January 2015 to August 2018, were retrospectively reviewed. Results: This disease was characterized by distal limb numbness, some patients with hypoalgesia or allergy, deep sense loss, reduction or disappearance of tendon reflexes, and peeling. One case had muscle weakening and another case had cerebellar ataxia. Examination of electromyography showed only one case had spontaneous potential. Examination of nerve conduction showed that the amplitude decreased by 34 (38.6%) and the velocity decreased by 2 (2.3%) , the percentage of amplitude decreased was significantly higher than that of velocity decreased. The amplitude of sensory nerve decreased by 30 (57.7%) and motor nerve decreased by 4 (11.1%) , the percentage of sensory nerve amplitude decreased was significantly higher than that of motor nerve. After the treatment of nutrition, circulation improvement, numbness relief, glucocorticoid and other drugs, the numbness of the patients was relieved, but it did not completely disappear. Poor recovery of pain, deep sensation and tendon reflex in all patients. The results of reexamination of electromyography in 3 cases were worse than before. Therefore, it is suggested that peripheral nerve damage is irreversible. Conclusion: This disease is characterized by distal limb numbness. Electrophysiological results suggest that the damage of sensory nerve axon is the main cause of the disease. Up to now, there is no effective drug to treat this disease, therefore, it is very important to do a good job of protection.


Assuntos
Acrilamida/toxicidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/terapia , China , Eletromiografia , Humanos , Condução Nervosa , Estudos Retrospectivos
2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(2): 219-223, 2020 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-32074714

RESUMO

Risk assessment is a necessary technical means to protect human health and environmental safety. Traditional risk assessment based on toxicity data obtained from animal experiments was difficult to meet the need for risk assessment for a large number of chemicals due to the low throughput, long cycle, high cost and uncertainty of extrapolation to human exposure dose. The proposed risk assessment frameworks, the model of action (MOA) and the adverse outcome pathway (AOP), pointed the way for us to develop new and efficient evaluation methods. In this review, the basic concepts and contents of MOA and AOP, as well as the relationship between them, were introduced. Taking acrylamide (AA) as an example, this review briefly described the application of MOA/AOP framework in chemical risk assessment, so as to provide theoretical guidance for better application of MOA/AOP framework in chemical risk assessment.


Assuntos
Acrilamida/toxicidade , Medição de Risco/métodos , Rotas de Resultados Adversos , Humanos , Testes de Toxicidade
3.
Toxicol Lett ; 320: 103-108, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816332

RESUMO

Acrylamide is included on the State of California's Proposition 65 list as a carcinogen. Acrylamide is found in cigarette smoke and in many types of foods, including breads, cereals, coffee, cookies, French fries, and potato chips. In 1990, California's Office of Environmental Health Hazard Assessment (OEHHA) established a no significant risk level (NSRL) of 0.2 µg/day for acrylamide. Since then, multiple cancer studies have been published. In this report, we developed an updated NSRL for acrylamide. Using benchmark dose modeling and a weight-of-evidence, non-threshold approach to identify the most sensitive species, cancer slope factors (CSFs) were derived based on combined incidences of statistically significant neoplastic lesions in the Harderian gland, lung, and stomach in male mice. We then used a toxicokinetic (TK)-based scaling approach to convert the animal CSF to a human equivalent CSF, which served as the basis for the NSRL of 1.1 µg/day at the cancer risk level of 1 in 100,000. This NSRL can be used in quantitative exposure assessments to assess compliance with Proposition 65 to ascertain either the need for or exemption from the Proposition 65 labeling requirement and drinking water discharge prohibition.


Assuntos
Acrilamida/toxicidade , Carcinógenos/toxicidade , Modelos Teóricos , Neoplasias/induzido quimicamente , Acrilamida/farmacocinética , Animais , Testes de Carcinogenicidade , Carcinógenos/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Camundongos , Ratos Endogâmicos F344 , Medição de Risco , Toxicocinética
4.
Environ Sci Pollut Res Int ; 26(34): 35151-35162, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31686333

RESUMO

Acrylamide (AA) is a heat-induced toxin formed during thermal processing of many commonly consumed foods, including meat products, French fries, potato crisps, bread, cereals, cookies, and coffee. There is thus potentially high dietary exposure of humans to AA, which can induce significant oxidative stress. Hesperidin (HS) and diosmin (DS) are flavone glycosides that have antioxidant properties. The aim of this study was to investigate the protective effects of HS and DS against AA toxicity. Fifty-six adult male Wistar albino rats were divided into seven groups. The first group was orally administered 0.5% (w/v) dimethyl sulfoxide (DMSO) and considered as the control group. The second and third groups were orally administered 10 mg/kg/day of HS or DS, respectively. The fourth group received 20 mg/kg/day of AA orally for 14 days. The fifth and sixth groups were given 10 mg/kg/day of HS or DS, respectively, followed by AA. The seventh group was given both HS and DS after AA administration. AA intoxication significantly (p ≤ 0.05) increased serum levels of liver function enzymes (ALT, AST, and ALP), kidney function products (urea and creatinine), oxidative DNA damage marker (OHdG), proinflammatory markers (TNF-α, IL-1ß, and IL-6), lipid peroxidation marker (malondialdehyde), and nitric oxide (NO). On the other hand, it significantly (p ≤ 0.05) decreased levels of reduced glutathione (GSH) in the liver, kidney, and brain. The activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) in the liver, kidney, and brain tissues were also reduced. HS and DS supplementation prevented lipid peroxidation, normalized the serum parameters altered by AA, and enhanced the tissue concentrations and activities of antioxidant biomarkers. It could be concluded that HS and DS have potent protective effects against oxidative stress, lipid peroxidation, and DNA damage induced by AA toxicity in rats.


Assuntos
Acrilamida/toxicidade , Diosmina/farmacologia , Substâncias Perigosas/toxicidade , Hesperidina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Encéfalo/efeitos dos fármacos , Catalase/metabolismo , Creatinina/metabolismo , Dano ao DNA/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
5.
Folia Neuropathol ; 57(2): 196-204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556578

RESUMO

INTRODUCTION: Exposure to acrylamide is increasing worldwide as a result of its heavy use in industry and formation in carbohydrate-rich food cooked at high temperature. Despite its neurotoxicity, no studies have shown its toxic effects on dopaminergic neurons yet. Therefore, the current study was carried out to show whether acrylamide adversely affects primary cultured dopaminergic neurons. MATERIAL AND METHODS: Acrylamide (0.001, 0.01, 0.1, 1, 2 mM) was added to two different groups of primary mesencephalic cell cultures on the 9th day in vitro for 24 and 48 h, respectively. Moreover, a group of cultures was treated with lower concentrations of acrylamide (0.01, 0.05, 0.1, 0.5 mM) on the 6th day in vitro for 5 consecutive days to investigate its long-term effects on dopaminergic neurons. Following each treatment, culture media were obtained for measuring lactate dehydrogenase, and cultured cells were stained immunocytochemically against tyrosine hydroxylase and neuronal nuclear antigens. RESULTS: Treatment of cultures with acrylamide for 48 h significantly reduced the number of dopaminergic neurons, adversely altered the morphology of the surviving neurons and increased levels of lactate dehydrogenase in the culture media. Similar treatment of cultures with acrylamide also resulted in lower numbers of total neuronal cells as shown by a reduced expression of the neuronal nuclear antigen. Prolonged treatment of cultures with lower concentrations of acrylamide slightly reduced the survival of dopaminergic neurons but increased the release of lactate dehydrogenase into the culture media as well. CONCLUSIONS: The current study shows, for the first time, neurotoxicity of acrylamide on dopaminergic neurons in the primary mesencephalic cell culture.


Assuntos
Acrilamida/toxicidade , Morte Celular/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Mesencéfalo/efeitos dos fármacos , Animais , Células Cultivadas , Neurônios Dopaminérgicos/citologia , L-Lactato Desidrogenase/análise , Mesencéfalo/citologia , Camundongos
6.
Molecules ; 24(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547332

RESUMO

Some studies have demonstrated that acrylamide (AA) was correlated with oxidative stress, resulting in physical damage. The jackfruit flake was an immature pulp that contained a high level of antioxidant activity. This study aimed to assess the defensive efficacy of jackfruit flake in AA-induced oxidative stress before and after simulated gastrointestinal digestion. Our results indicate that the total polyphenol content of Jackfruit flake digest (Digestive products of jackfruit flake after gastrointestinal, JFG) was diminished; however, JFG had raised the relative antioxidant capacity compared to Jackfruit flake extract (JFE). Additionally, the results of High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) implied that a proportion of compounds were degraded/converted into other unknown and/or undetected metabolites. Further, by high content analysis (HCA) techniques, JFG markedly reduced cytotoxicity and excessive production of reactive oxygen species (ROS) in cells, thereby alleviating mitochondrial disorders. In this study, it may be converted active compounds after digestion that had preferable protective effects against AA-induced oxidative damage.


Assuntos
Antioxidantes/análise , Artocarpus/química , Estresse Oxidativo/efeitos dos fármacos , Acrilamida/toxicidade , Apoptose/efeitos dos fármacos , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Digestão , Humanos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Espectrometria de Massas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Membranas Mitocondriais/efeitos dos fármacos , Permeabilidade , Polifenóis/análise , Espécies Reativas de Oxigênio/metabolismo , Estômago/efeitos dos fármacos
7.
J Agric Food Chem ; 67(31): 8510-8519, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31294559

RESUMO

Acrylamide, mainly formed in Maillard browning reaction during food processing, causes defects in liver circadian clock and mitochondrial function by inducing oxidative stress. Resveratrol is a polyphenol that has powerful antioxidant and anti-inflammatory activity. However, the preventive effects of resveratrol on acrylamide-triggered oxidative damage and circadian rhythm disorders are unclear at the current stage. The present research revealed that resveratrol pretreatment prevented acrylamide-induced cell death, mitochondrial dysfunction, and inflammatory responses in HepG2 liver cells. Acrylamide significantly triggered disorders of circadian genes transcription and protein expressions including Bmal1 and Cry 1 in primary hepatocytes, which were prevented by resveratrol pretreatment. Moreover, we found that the beneficial effects of resveratrol on stimulating Nrf2/NQO-1 pathway and mitochondrial respiration complex expressions in acrylamide-treated cells were Bmal1-dependent. Similarly, the inhibitory effects of resveratrol on inflammation signaling NF-κB were Cry1-dependent. In conclusion, these results demonstrated resveratrol could be a promising compound in suppressing acrylamide-induced hepatotoxicity and balancing the circadian clock.


Assuntos
Fatores de Transcrição ARNTL/imunologia , Acrilamida/toxicidade , Transtornos Cronobiológicos/imunologia , Criptocromos/imunologia , Hepatócitos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Resveratrol/farmacologia , Fatores de Transcrição ARNTL/genética , Animais , Transtornos Cronobiológicos/tratamento farmacológico , Transtornos Cronobiológicos/genética , Transtornos Cronobiológicos/fisiopatologia , Ritmo Circadiano/efeitos dos fármacos , Criptocromos/genética , Células Hep G2 , Hepatócitos/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/genética , Mitocôndrias/imunologia
8.
Ecotoxicol Environ Saf ; 182: 109416, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31301596

RESUMO

The main objectives of this study were to purify the glutathione S-transfereses (GSTs) and assess the effect of high doses of acrylamide (ACR) on male albino Wistar rat liver, kidney, testis and bran GST activities, and expression analysis of GST. ACR (50 mg/300 ml) was ingested for 40 days (20 doses) in drinking water on alternative days, on 40 day post ingestion the control and treated tissues were collected for GST purification by affinity column and biochemical characterization of GSTs by substrate specificities, and GST expression by immuno dot blots. In the analysis of the purified GSTs, we observed that liver GSTs were resolved in to three bands known as Yc, Yb and Ya; kidney GSTs were resolved in to two bands known as Yc and Ya; testis and brain GSTs were resolved as four bands known as Yc, Yb, Yß and Yδ on 12.5% sodium dodecyl sulfate polyacrylamide gel (SDS PAGE). In the analysis of biochemical characterization, we observed a significant decrease (p < 0.05) in the specific activities of liver GST isoforms with the substrates 1-chloro 2,4-dinitrobenzene (CDNB), bromosulfophthalein (BSP), p-nitrophenyl acetate (pNPA), p-nitrobenzyl chloride (pNBC) and cumene hydroperoxide (CHP), but showed no activity with ethacrynic acid (ECA) and significant decrease (p < 0.05) in the specific activities of kidney GST isoforms with the substrates CDNB, pNPA, pNBC and CHP, but showed no activity with BSP and ECA, and a significant decrease (p < 0.05) in the specific activities of testis and brain GST isoforms with the substrates CDNB, BSP, pNPA, pNBC, ECA and CHP. In the analysis of immuno dot blots, we observed a decreased expression of liver, kidney, testis and brain GSTs. Through the affinity purification and biochemical characterization, we observed a tissue specific distribution of GSTs that is liver GSTs possess Yc, Yb and Ya sub units known as alpha (α) and mu (µ) class GSTs; kidney GSTs possess Yc and Ya sub units known as (α) alpha class GST; testis and brain GSTs possess Yc, Yb, Yß and Yδ sub units known as alpha (α), mu (µ) and pi (π) class GSTs. Purification studies, biochemical characterization and immuno dot blot analysis were revealed the GSTs were sensitive to high doses of ACR and the high level exposure to ACR cause the damage of detoxification function of GST due to decreased expression and hence lead to cellular dysfunction of vital organs.


Assuntos
Acrilamida/toxicidade , Glutationa Transferase/metabolismo , Animais , Eletroforese em Gel de Poliacrilamida , Glutationa/metabolismo , Isoenzimas , Rim/metabolismo , Fígado/metabolismo , Masculino , Nitrobenzenos , Nitrofenóis , Ratos , Ratos Wistar , Especificidade por Substrato , Testículo/metabolismo , Distribuição Tecidual
9.
BMC Pharmacol Toxicol ; 20(1): 38, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262364

RESUMO

BACKGROUND: This study aimed to examine femoral bone microstructure of mice after single and simultaneous administration to acrylamide and ethanol since both substances are often consumed separately and/or together by humans. Interactive effects of these toxins were analysed after one remodeling cycle. METHODS: Twenty clinically healthy adult mice were randomly divided into four groups following 2 weeks administration of toxins: A group - mice were fed with acrylamide (40 mg/kg bw); E group - mice were ethanol-fed (15% ethanol); AE group - mice were simultaneously fed with both toxins, and a C group - control (without acrylamide and/or ethanol supplementation). Generally, 2D and 3D imaging methods were used to determine cortical and trabecular bone tissues microstructure. Biochemical analyses of plasma parameters were also realized using commercially available ELISA tests and spectrophotometrically. RESULTS: Single and simultaneous exposure to acrylamide and ethanol affected only cortical bone microstructure. No significant changes in trabecular bone morphometry were detected among all groups. In mice from the A group, increased endocortical remodeling associated with a higher level of serum calcium and vasoconstriction of primary osteon's vascular canals (POVC) were identified. On the contrary, increased cortical porosity consistent with a decreased relative bone volume, bone mineral density (BMD) and lower levels of alkaline phosphatase (ALP), glutathione (GSH), calcium in plasma and also with vasodilation of POVC were observed in the E group. In the AE group, the highest density of secondary osteons associated with a lower BMD and decreased levels of ALP, GSH were documented. The parameters of POVC and Haversian canals approximated to the C group. In addition, single and simultaneous exposure to both toxins caused liver disease consistent with a higher values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in plasma of all experimental groups. CONCLUSIONS: Single administration to acrylamide and ethanol had negative effects on cortical bone structure of mice after one remodeling cycle. However, we identified possible antagonistic impact of these toxins on the structure of the cortical bone.


Assuntos
Acrilamida/toxicidade , Osso Cortical/efeitos dos fármacos , Etanol/toxicidade , Fêmur/efeitos dos fármacos , Animais , Remodelação Óssea , Osso Esponjoso/anatomia & histologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/efeitos dos fármacos , Osso Cortical/diagnóstico por imagem , Osso Cortical/patologia , Interações de Medicamentos , Fêmur/diagnóstico por imagem , Fêmur/patologia , Masculino , Camundongos , Microtomografia por Raio-X
10.
Cutan Ocul Toxicol ; 38(4): 375-383, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31223032

RESUMO

Purpose: A comet assay is one of the genotoxicity methods for evaluating the potential of chemicals to induce DNA strand breaks. To investigate the usefulness of comet assays for evaluating the genotoxic potential of ophthalmic solutions, a three-dimensional (3D) reconstructed human corneal epithelial model (3D corneal model) was exposed to conditions mimicking topical ocular instillation administration. Methods: The 3D corneal model was exposed to acridine orange, ethidium bromide, hydrogen peroxide, 1,1'-dimethyl-4,4'-bipyridinium dichloride (paraquat), 4-nitroquinoline 1-oxide (4-NQO), acrylamide and methyl methanesulfonate (MMS). To mimic the ocular surface condition to which ophthalmic solutions are administered, the exposure time was set to 1 minute. Likewise, human corneal epithelial (HCE-T) cells, as monolayer cultured cells, were exposed to the same chemicals, for comparison. Results: In the 3D corneal model, the amount of DNA fragments was statistically significantly increased in cells treated with each of the test chemicals except acrylamide. In HCE-T cells, the amount of DNA fragments was statistically significantly increased in acridine orange-, ethidium bromide-, hydrogen peroxide-, 4-NQO- and MMS-treated cells but not in paraquat- or acrylamide-treated cells. In the 3D corneal model, the lowest concentrations at which we observed DNA damage were about 100 times higher than the concentrations in HCE-T cells. Since the 3D corneal model is morphologically similar to human corneal tissue, form a multilayer and having tight junctions, it may be that the test chemicals only permeated about 1% into the 3D corneal model. Conclusion: These results suggest that the comet assay using 3D cell culture models may reflect in vivo conditions better than do monolayer cultured cells, and that the comet assay may be useful for the evaluation of genotoxic potential of topical ophthalmic solution.


Assuntos
Ensaio Cometa/métodos , Epitélio Anterior/efeitos dos fármacos , Soluções Oftálmicas/toxicidade , 4-Nitroquinolina-1-Óxido/toxicidade , Laranja Acridina/toxicidade , Acrilamida/toxicidade , Administração Oftálmica , Linhagem Celular , Córnea , Dano ao DNA , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Epitélio Anterior/citologia , Epitélio Anterior/metabolismo , Etídio/toxicidade , Humanos , Peróxido de Hidrogênio/toxicidade , Técnicas In Vitro , Metanossulfonato de Metila/toxicidade , Paraquat/toxicidade , Quinolonas/toxicidade
11.
Environ Health Perspect ; 127(6): 67002, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31166132

RESUMO

BACKGROUND: Transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2) plays a key role in detoxification of electrophiles via formation of glutathione (GSH) adducts and subsequent excretion into extracellular spaces. We found that reactive sulfur species (RSS), such as cysteine persulfides produced by cystathionine [Formula: see text] (CSE), capture environmental electrophiles through formation of sulfur adducts. However, contributions of Nrf2 and CSE to the blockage of environmental electrophile-mediated toxicity remain to be evaluated. OBJECTIVES: The aim of this study was to clarify roles that CSE and Nrf2 play in the protection against various environmental electrophiles. We also wished to clarify the molecular basis of the developmental window of toxicity through investigating expression levels of Nrf2, RSS-producing enzymes, and sulfur nucleophiles during developmental stages of mice. METHODS: Wild-type (WT), CSE knockout (KO), Nrf2 KO, Nrf2/CSE double KO (DKO) mice, and their primary hepatocytes were analyzed in this study. Cadmium (Cd), methylmercury (MeHg), 1,4-naphthoquinone, crotonaldehyde, and acrylamide were used. We conducted Western blotting, real-time polymerase chain reaction (PCR), 3-(4,5-dimethylthiazol-2-yl)-2,5-triphenyl tetrazolium bromide (MTT) assays, liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis, alanine transaminase (ALT) activity, histopathological analysis, and rotarod test. RESULTS: Primary hepatocytes from DKO mice were significantly more sensitive to the environmental electrophiles than each single KO counterpart. Both Nrf2 and CSE single KO mice were highly susceptible to Cd and MeHg, and such sensitivity was further exacerbated in the DKO mice. Lower-level expressions of CSE and sulfur nucleophiles than those in adult mice were observed in a window of developmental stage. CONCLUSIONS: Our mouse model provided new insights into the response to environmental electrophiles; while Nrf2 is recognized as a key transcription factor for detoxification of environmental electrophiles, CSE is crucial factor to repress their toxicity in a parallel mode. In addition, the sensitivity of fetuses to MeHg appears to be, at least in part, associated with the restricted production of RSS due to low-level expression of CSE. https://doi.org/10.1289/EHP4949.


Assuntos
Cistationina gama-Liase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Acrilamida/toxicidade , Aldeídos/toxicidade , Animais , Cádmio/toxicidade , Cistationina gama-Liase/genética , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Compostos de Metilmercúrio/toxicidade , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Naftoquinonas/toxicidade , Sulfetos/química
12.
J Biochem Mol Toxicol ; 33(7): e22326, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31081568

RESUMO

The aim of this study was to investigate the possible therapeutic effects of curcumin (CUR), against acrylamide (AA)-induced toxic effects on Leydig cells. The AA and CUR-treated cells were evaluated for cell viability, lipid peroxidation, reactive oxygen species (hydroxyl radical and hydrogen peroxide), antioxidant levels (glutathione peroxidase, glutathione-S-transferase, and catalase), apoptosis/necrosis rates and phosphorylation status of mitogen-activated protein kinases (MAPKs). Leydig cells were exposed to four concentrations of AA (1, 10, 100, 1000 µM) in the presence and absence of CUR (2.5 µM) for 24 hours. According to the present result, AA concentration-dependently, increased the oxidative stress parameters and suppressed the antioxidant enzyme levels, meanwhile induced apoptosis and activated the phosphorylation of extracellular signal-regulated kinase, p38, and c-Jun NH 2 -terminal kinase. Moreover, CUR ameliorated the detrimental effects of AA. Thus, AA-induced apoptosis through activation of the MAPK signaling pathway and CUR has a protective effect against AA-induced damage in Leydig cells.


Assuntos
Acrilamida/toxicidade , Antioxidantes/farmacologia , Curcumina/farmacologia , Células Intersticiais do Testículo/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Linhagem Celular , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Camundongos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Food Chem Toxicol ; 130: 308-316, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31102675

RESUMO

A total diet study (TDS) was conducted between 2010 and 2016 to assess the risk associated with chemicals in food of non-breast-fed children from 1 to 36 months living in France. Food samples were collected, prepared "as consumed", and analyzed for chemicals of public health interest. Acrylamide, furan and polycyclic aromatic hydrocarbons (PAHs) were analyzed as heat-induced compounds produced mainly during thermal processing of foods. Dietary exposure was assessed for 705 representative children using food consumptions recorded through a 3-consecutive-days record. As all calculated margins of exposure (MOE) for PAHs exceeded 10 000, dietary exposure of the infant and toddler population was deemed tolerable with regard to the carcinogenic risk. Conversely, the exposure levels to acrylamide and furan were considered as of concern, requiring management measures to reduce the exposure essentially by reducing the formation of heat-induced compounds during food production or preparation processes. Efforts should mainly focus on major contributors to the exposure, i.e. sweet and savoury biscuits and bars, and potatoes and potato products for acrylamide, baby jars of vegetables, with or without meat or fish for acrylamide and furan.


Assuntos
Acrilamida/química , Armazenamento de Alimentos , Furanos/química , Temperatura Alta , Alimentos Infantis/análise , Hidrocarbonetos Policíclicos Aromáticos/química , Acrilamida/toxicidade , Contaminação de Alimentos , França , Furanos/toxicidade , Humanos , Lactente , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Fatores de Risco
14.
Acta Histochem ; 121(5): 595-603, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31109687

RESUMO

Due to the broad toxic relevance of acrylamide, many measures have been taken since the 1900s. These measures increased day by day when acrylamide was discovered in foods in 2002, and its toxic spectrum was found to be wider than expected. Therefore, in some countries, the products with higher acrylamide content were restricted. On the other hand, the effects of acrylamide on the respiratory system cells have yet to be well understood. In this study, we aimed at investigating the effect of acrylamide on lung epithelial BEAS-2B cells. Initially, the cytotoxic effect of acrylamide on BEAS-2B was determined by MTT assay. Then, cellular oxidative stress was measured. Flow cytometry analysis was conducted for Annexin-V and caspase 3/7. Furthermore, Bax, Bcl-2 and Nrf-2 proteins were evaluated by immunocytochemistry. Finally, acrylamide-induced cellular morphological changes were observed under confocal and TEM microscopes. According to MTT results, the IC50 concentration of acrylamide was 2.00 mM. After acrylamide treatment, oxidative stress increased dose-dependently. Annexin V-labelled apoptotic cells and caspase 3/7 activity were higher than untreated cells in acrylamide-treated cells. Immunocytochemical examination revealed a marked decrease in Bcl-2, an increase in Bax and Nrf-2 protein staining upon acrylamide treatment. Furthermore, in confocal and TEM microscopy, apoptotic hallmarks were pronounced. In the present study, acrylamide was suggested to display anti-proliferative activity, decrease viability, induce apoptosis and oxidative stress and cause morphological changes in BEAS-2B cells.


Assuntos
Acrilamida/toxicidade , Apoptose/efeitos dos fármacos , Citotoxinas/toxicidade , Pulmão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Humanos , Pulmão/patologia , Pulmão/ultraestrutura , Microscopia Confocal , Microscopia Eletrônica de Transmissão
15.
Toxicol Mech Methods ; 29(7): 488-498, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31050326

RESUMO

The increased incidence of testicular disorders in young men and the possible influence of environmental chemicals, such as dibutyl phthalate (DBP) and acrylamide (AA), requires experimental models for identifying modes of action. Most published reproductive toxicologic studies use RNA samples from the total testis to evaluate testicular gene expression; however, analyses of isolated cell types could provide a more specific tool. Among testicular germ cells, spermatogonia are critical since they represent the onset of spermatogenesis. This study aimed, (1) to establish a technique for spermatogonia isolation; (2) to apply this isolation technique to verify possible gene expression alterations (Pou5f1, Kitlg, Mki-67, Bak1 and Spry4) in prepubertal post-natal day, (PND24) and pubertal (PND45) testes after in utero and postnatal exposure to DBP or AA. The technique was efficient for isolation of a majority of spermatogonia. In utero DBP exposure led to reduced litter body weight at birth, reduced anogenital distance of male pups on PND4, and increased frequency of male nipple retention on PND14 compared to controls. DBP-exposed relative testes weights were reduced only at PND24 compared to control but they did not differ at PND45. DBP-exposed animals showed reduced expression levels of Pou5f1 and Mki67 on PND24, and reduced expression of Pou5f1 and Spry4 on PND45. AA exposure reduced expression of Pou5f1, Mki67, and Spry4 at PND45 although not significantly. Our results suggest that DBP acts by reducing cell proliferation and impairing differentiation in prepubertal and pubertal testes.


Assuntos
Acrilamida/toxicidade , Dibutilftalato/toxicidade , Poluentes Ambientais/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Espermatogônias/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Peso Corporal , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Expressão Gênica/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos Sprague-Dawley , Espermatogônias/patologia , Testículo/embriologia , Testículo/crescimento & desenvolvimento , Testículo/patologia
16.
Food Chem ; 290: 246-254, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31000044

RESUMO

Whether caseinate oligochitosan-glycation of the transglutaminase-type followed by trypsin digestion could lead to better protection against the acrylamide-induced cell barrier damage was investigated. Compared with caseinate digest, glycated caseinate digest had similar amount of Lys and Arg but lower -NH2 (0.557 versus 0.508 mol/kg protein) and total amide (1.12 versus 1.05 mol/kg protein) contents, and contained glucosamine at 5.74 g/kg protein. Acrylamide damaged barrier function of IEC-6 cells efficiently, leading to increased paracellular permeability and lactate dehydrogenase release, decreased trans-epithelial electrical resistance, and destroyed tight junction. The two digests alleviated these barrier dysfunctions via reversing index values. Three cellular proteins (ZO-1, occludin, and claudin-1) crucial to tight junction were up-regulated by the two digests. Furthermore, glycated caseinate digest was always more effective than caseinate digest to improve cell barrier function. This oligochitosan glycation is thus desired, as it ensures glycated protein digest with higher potential to protect intestinal barrier function.


Assuntos
Acrilamida/química , Caseínas/metabolismo , Quitina/análogos & derivados , Acrilamida/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitina/química , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Glicosilação , Humanos , Mucosa Intestinal/citologia , Ocludina/genética , Ocludina/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Peptídeos/farmacologia , Permeabilidade/efeitos dos fármacos , Substâncias Protetoras/química , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo
17.
Andrologia ; 51(7): e13292, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30995698

RESUMO

Thirty rats, with confirmed pregnancies by vaginal smear, were divided into five groups, each including six rats, as the Control, Corn Oil, Vitamin E, Acrylamide, Vitamin E + Acrylamide groups. The births were monitored on the 21st day to select the male rats, and the selected male rats were decapitated at the end of the 8th week. Oxidant-antioxidant parameters, serum hormone levels and histopathological examinations were performed on testis tissues of the rats. It was found that acrylamide (AA) negatively affected the serum hormone levels (Total Testosterone, Progesterone, FSH, LH, Estradiol), oxidant-antioxidant parameters in the tissues (MDA, GSH, NO, SOD, CAT, TAS, TOS) (p < 0.05) and the histological findings (the Johnson's score, seminiferous tubule diameter, histopathological images), and Vitamin E administration resulted with an increase in the total testosterone, progesterone, FSH, LH, GSH, TAS, NO, SOD, CAT levels (p < 0.05) and an improvement in histopathological findings. Currently, it is almost inevitable to be exposed to food-induced AA toxicity and such toxicity is likely to cause lifelong damage. It was concluded that Vitamin E was able to present a protective effect in the testis tissue against AA toxicity; however, further studies are necessary.


Assuntos
Acrilamida/toxicidade , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Testículo/efeitos dos fármacos , Vitamina E/administração & dosagem , Acrilamida/administração & dosagem , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Wistar , Testículo/patologia
18.
Hum Exp Toxicol ; 38(8): 899-913, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30995857

RESUMO

Cryptorchidism (CPT), the most common male congenital abnormality, is variably associated with other male reproductive tract problems. We evaluated if cryptorchid rats develop enhanced testicular susceptibility to dibutyl phthalate (DBP) or acrylamide (AA) after extended exposure. Three studies with rats were performed: (1) in utero and postnatal exposure to DBP or AA; (2) establishment of CPT and orchiopexy; and (3) in utero and postnatal exposures to DBP or AA associated with CPT/orchiopexy. Seminiferous tubules were histologically scored according to the severity of lesions: (1) Rats exposed to DBP (score 1.5) or AA (score 1.1) presented mostly preserved spermatogenesis. Some seminiferous tubules showed vacuolated germinative epithelium, germ cell apoptosis, and a Sertoli cell-only (SCO) pattern. (2) CPT (score 3.3) resulted in decreased absolute testes weights, degenerated and SCO tubules, and spermatogenesis arrest that were reversed by orchiopexy (score 1.1). (3) Exposure to DBP or AA with CPT/orchiopexy led to atrophic testes, spermatogenesis arrest, germ cell exfoliation/multinucleation, and SCO tubules (both chemicals score 2.5). Exposure to chemicals such as DBP or AA prevented the recovery of cryptorchid testes by orchiopexy. The possible role of environmental contaminants should be considered when looking for factors that modulate human testicular disorders associated with CPT.


Assuntos
Acrilamida/toxicidade , Criptorquidismo/cirurgia , Dibutilftalato/toxicidade , Testículo/efeitos dos fármacos , Animais , Criptorquidismo/patologia , Modelos Animais de Doenças , Feminino , Masculino , Troca Materno-Fetal , Orquidopexia , Gravidez , Ratos Sprague-Dawley , Testículo/patologia
19.
Biotech Histochem ; 94(5): 352-359, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30864862

RESUMO

Acrylamide is an important industrial chemical; it also is formed in starch-rich foodstuffs during baking, frying and roasting. Most acrylamide exposure occurs by ingestion of processed foods. We investigated possible immunotoxic effects of extended administration of low doses of acrylamide in rats. To do this, we measured alpha-naphthyl acetate esterase (ANAE) and acid phosphatase (ACP-ase) activities in peripheral blood lymphocytes. Male and female weanling Wistar rats were administered 2 or 5 mg acrylamide/kg/day in drinking water for 90 days. Peripheral blood was sampled at the end of the administration period. We found ANAE staining in eosinophils and T-lymphocytes, but not in monocytes, platelets, B-lymphocytes and neutrophils. ACP-ase was found in B-lymphocytes. We found a significant reduction of the ratio of ANAE:ACP-ase in lymphocytes of the experimental animals compared to controls. We found no statistically significant differences between the doses or sexes. We found that acrylamide ingested in processed foods might affect the immune system adversely by decreasing the population of mature T- and B-lymphocytes.


Assuntos
Fosfatase Ácida/metabolismo , Acrilamida/administração & dosagem , Acrilamida/toxicidade , Linfócitos/fisiologia , Naftol AS D Esterase/metabolismo , Fosfatase Ácida/sangue , Administração Oral , Animais , Relação Dose-Resposta a Droga , Feminino , Histocitoquímica , Masculino , Naftol AS D Esterase/sangue , Ratos , Ratos Wistar , Fatores Sexuais
20.
Environ Sci Pollut Res Int ; 26(14): 14184-14193, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30859440

RESUMO

Acrylamide (ACR) is a widespread industrial chemical with recognized adverse effects not only to humans but to other organisms in the environment as well. In the present study, the ecotoxicological effects of dietary exposure to sublethal concentration (1/20 LC50) of ACR on the land snail, Theba pisana after 2 weeks of exposure and 1-week recovery with respect to oxidative stress parameters; lipid peroxidation (LPO), reduced glutathione (GSH), catalase (CAT), and glutathione-S-transferase (GST), cytogenetic parameter; deoxyribonucleic acid (DNA) content, as well as immunological parameters; cell death, phagocytosis, lysosomal membrane stability (LMS), lectins, superoxide anion (O2-) generation, phenoloxidase (PO), peroxidase (POD), and hemocyanin (Hc) were examined. The results showed that ACR significantly increased LPO level and the activity of CAT and GST, cell death, and Hc level, whereas a significant decline in DNA and GSH contents, phagocytic activity, LMS, lectins, O2- generation, POD, and PO activities compared to the controls after 2-week exposure was observed. After 1-week recovery, most of the tested parameters in exposed snails were permanent and not reversible to the control levels. This study suggests that the tested multiple parameters of T. pisana species may be used as biomarkers of ACR exposure. Besides, T. pisana snails could be used as a good sentinel organism for ACR exposure in pollution monitoring studies.


Assuntos
Acrilamida/toxicidade , Poluentes Ambientais/toxicidade , Caramujos/fisiologia , Acrilamida/metabolismo , Animais , Biomarcadores/metabolismo , Catalase/metabolismo , Ecotoxicologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Dose Letal Mediana , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Caramujos/efeitos dos fármacos
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