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1.
Food Chem ; 368: 130816, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34416489

RESUMO

Acrylamide (AA), a potential carcinogen, is commonly formed in foods rich in carbohydrates at high heat. It is known that AA-induced mitochondrial dysfunction is responsible for its toxicity. Previously we found AA exposure increased miR-27a-5p expression in livers of SD rats. Here, the regulation mechanism of miR-27a-5p in mitochondrial dysfunction was investigated in rat liver cell lines (IAR20) and SD rats. The results showed that the overexpressed miR-27a-5p contributes to modulating mitochondrial dysfunction and Btf3 is identified as its target gene. The knockdown of Btf3 increases the cleaved PARP1 level and the phosphorylation of ATM and p53, which results in mitochondria-dependent apoptosis. Therefore, the miR-27a-5p-Btf3-ATM-p53 axis might play a vital role in the promotion of AA-induced cell apoptosis through disrupting mitochondrial structure and function. This would provide a potential target for the assessment and intervention of AA toxicity.


Assuntos
MicroRNAs , Acrilamida/toxicidade , Animais , Apoptose , MicroRNAs/genética , Mitocôndrias/genética , Ratos , Ratos Sprague-Dawley
2.
BMC Genomics ; 22(1): 728, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625024

RESUMO

BACKGROUND: The seminal vesicles synthesise bioactive factors that support gamete function, modulate the female reproductive tract to promote implantation, and influence developmental programming of offspring phenotype. Despite the significance of the seminal vesicles in reproduction, their biology remains poorly defined. Here, to advance understanding of seminal vesicle biology, we analyse the mouse seminal vesicle transcriptome under normal physiological conditions and in response to acute exposure to the reproductive toxicant acrylamide. Mice were administered acrylamide (25 mg/kg bw/day) or vehicle control daily for five consecutive days prior to collecting seminal vesicle tissue 72 h following the final injection. RESULTS: A total of 15,304 genes were identified in the seminal vesicles with those encoding secreted proteins amongst the most abundant. In addition to reproductive hormone pathways, functional annotation of the seminal vesicle transcriptome identified cell proliferation, protein synthesis, and cellular death and survival pathways as prominent biological processes. Administration of acrylamide elicited 70 differentially regulated (fold-change ≥1.5 or ≤ 0.67) genes, several of which were orthogonally validated using quantitative PCR. Pathways that initiate gene and protein synthesis to promote cellular survival were prominent amongst the dysregulated pathways. Inflammation was also a key transcriptomic response to acrylamide, with the cytokine, Colony stimulating factor 2 (Csf2) identified as a top-ranked upstream driver and inflammatory mediator associated with recovery of homeostasis. Early growth response (Egr1), C-C motif chemokine ligand 8 (Ccl8), and Collagen, type V, alpha 1 (Col5a1) were also identified amongst the dysregulated genes. Additionally, acrylamide treatment led to subtle changes in the expression of genes that encode proteins secreted by the seminal vesicle, including the complement regulator, Complement factor b (Cfb). CONCLUSIONS: These data add to emerging evidence demonstrating that the seminal vesicles, like other male reproductive tract tissues, are sensitive to environmental insults, and respond in a manner with potential to exert impact on fetal development and later offspring health.


Assuntos
Glândulas Seminais , Transcriptoma , Acrilamida/toxicidade , Animais , Citocinas , Feminino , Masculino , Camundongos , Reprodução/genética
3.
J Agric Food Chem ; 69(40): 12012-12020, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34586797

RESUMO

Acrylamide has been reported as an important dietary risk factor from carbohydrate-rich processing food. However, systemic biological effects on the serum metabolomics induced by acrylamide have poorly been understood. In the present study, we evaluated the metabolic profiles in a rat serum after exposure to acrylamide using ultrahigh-performance liquid chromatography combined with quadrupole-orbitrap high-resolution mass spectrometry. The serum biochemical parameters of the treated and control groups were also determined using an automatic biochemical analyzer. Compared with the control group, 10 metabolites were significantly upregulated, including citric acid, d-(-)-fructose, gluconic acid, l-ascorbic acid 2-sulfate, 2-hydroxycinnamic acid, valine, l-phenylalanine, prolylleucine, succinic acid, and cholic acid, while 5 metabolites were significantly downregulated, including 3-hydroxybutyric acid, 4-oxoproline, 2,6-xylidine, 4-phenyl-3-buten-2-one, and N-ethyl-N-methylcathinone in the serum of 4-week-old rats exposed to acrylamide in the high-dose group (all P < 0.05). Importantly, acrylamide exposure affected metabolites mainly involved in the citrate cycle, valine, leucine, and isoleucine biosyntheses, phenylalanine, tyrosine and tryptophan biosyntheses, and pyruvate metabolism. These results suggested that exposure to acrylamide in rats exhibited marked systemic metabolic changes and affected the cardiovascular system. This study will provide a theoretical basis for exploring the toxic mechanism and will contribute to the diagnosis and prevention of acrylamide-induced cardiovascular toxicity.


Assuntos
Acrilamida , Sistema Cardiovascular , Acrilamida/toxicidade , Animais , Biomarcadores , Cromatografia Líquida de Alta Pressão , Metaboloma , Metabolômica , Ratos
4.
Chemosphere ; 284: 131346, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34217936

RESUMO

Food is often exposed to multiple types of contaminants, and the coexistence of contaminants may have antagonistic, additive or synergistic effects. This study investigated the combinatorial toxicity of the three most widespread exogenous contaminants, decabrominated diphenyl ether (BDE-209), bisphenol A (BPA), and acrylamide (ACR) to HepG2 cells. A mathematical model (Chou-Talalay) and high-content analysis (HCA) were used to probe the nature of the contaminants' interactions and their cytotoxicity mechanisms, respectively. The results highlighted that for the individual pollutants, the cytotoxicity order was BDE-209> BPA > ACR, and varying combinations of contaminants exhibited additive/synergistic effects. In general, combining multiple contaminants significantly increased intracellular reactive oxygen species (ROS), Ca2+ flux, DNA damage and Caspase-3, and decreased mitochondrial membrane potential (MMP) and nucleus roundness, indicating that the additive or synergistic mechanism of the combined contaminations was disturbance to multiple organelles. This study emphasizes the complexity of human exposure to food contaminants and provides a scientific basis for formulating strict regulatory standards.


Assuntos
Acrilamida , Éteres Difenil Halogenados , Acrilamida/toxicidade , Compostos Benzidrílicos/toxicidade , Éteres Difenil Halogenados/toxicidade , Humanos , Fenóis , Espécies Reativas de Oxigênio
5.
Andrologia ; 53(9): e14176, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34309867

RESUMO

Exposure to acrylamide (Ac) through food is almost inevitable and this kind of toxicity may cause lifelong harm. In present study, we researched effects of Crocin (Cr) on testis histopathology in Ac-induced testis of rats. Adult male rats were grouped as: group 1, 1 ml saline only; group 2, 50 mg/kg Cr only; group 3, 25 mg/kg Ac only and group 4, 25 mg/kg Ac + 50 mg/kg Cr. All administrations were given as 1 ml/day by gavage for 21 days. It was found that Ac adversely influenced the levels of FSH, testosterone and LH in the blood serum; malondialdehyde (MDA), total antioxidant status (TOS), oxidative stress index (OSI)/ glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS) oxidant/antioxidant parameters in testis tissue (p < .01) and the histopathological parameters like Johnson's score, seminiferous tubule diameter, seminiferous epithelial height and H-score for caspase-3 immunoreactivity. In contrary, Cr treatment resulted in increase in testosterone, follicle stimulating hormone (FSH), luteinizan hormone (LH) levels and SOD, CAT, GSH, TAS levels (p < .01) and improved all the histopathological changes. In conclusion, Cr has a promising protective potential against Ac-caused toxic damages in testicular tissue.


Assuntos
Acrilamida , Testículo , Acrilamida/toxicidade , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Carotenoides/farmacologia , Catalase/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Testículo/metabolismo
6.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206048

RESUMO

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.


Assuntos
Inflamação/genética , Isotiocianatos/farmacologia , Fator 2 Relacionado a NF-E2/genética , Síndromes Neurotóxicas/genética , Sulfóxidos/farmacologia , Acrilamida/toxicidade , Animais , Modelos Animais de Doenças , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Camundongos , Microglia/metabolismo , Microglia/patologia , NF-kappa B/genética , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/patologia , Óxido Nítrico Sintase Tipo II/genética , Estresse Oxidativo/genética , Transdução de Sinais/efeitos dos fármacos
7.
Environ Pollut ; 287: 117591, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34153608

RESUMO

Acrylamide (ACR) is a widely used environmentally hazardous compound that is known to be neurotoxic, genotoxic, carcinogenic, and reproductive toxicity. It is widely present in soil, water, agents used in chemical industries, and food. It can be distributed to all organs and tissues, and can cause damage to various human systems and those of other animals. Previous metabolomics studies have mainly focused on metabolites in serum and urine, but have lacked comprehensive analysis of major organs and tissues. In the current study, a gas chromatography-massspectrometry method was used to investigate mechanisms underlying organ toxicity, in an effort to identify potentially sensitive biomarkers in the main target tissues of rats after ACR exposure. Male Sprague-Dawley rats were assigned to two groups; a control group and a group treated with 20 mg kg-1 ACR intragastrically for 6 weeks. Metabolite changes in the two groups were statistically analyzed. The respective numbers of altered metabolites in the hippocampus, cortex, kidney, serum, heart, liver, and kidney fat were 21, 21, 17, 5, 15, 14, and 6. There were 14 metabolic pathways related to amino acid, fatty acid, purine, and energy metabolism, revealing that the toxic mechanism of ACR may involve oxidative stress, inflammation, and amino acid metabolism and energy disorders.


Assuntos
Acrilamida , Metabolômica , Acrilamida/toxicidade , Animais , Biomarcadores , Masculino , Metaboloma , Ratos , Ratos Sprague-Dawley
8.
Environ Int ; 155: 106668, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34120003

RESUMO

INTRODUCTION: Four epidemiological studies have shown a negative association between prenatal acrylamide exposure and birth size. In order to shed light on the possible underlying mechanism(s), we analysed associations between acrylamide biomarkers and biomarkers related to fetal growth. METHODS: In newborns of the ENVIRONAGE birth cohort (n ranges from 215 to 434), we investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels in cord blood) and thyroid hormones (TSH, T3, T4 and the ratio of T4 to T3 in cord plasma), insulin-related factors (cord plasma insulin and IGF1, and placental IGF2), neurotrophins (cord plasma BDNF, and placental NGF, NT3 and NT4), and cord plasma homocysteine and progesterone, using multiple linear regression analysis. In addition, we investigated whether the biomarkers mediated the associations between prenatal acrylamide exposure and birth outcomes. RESULTS: We observed lower cord plasma TSH (-10.2% [95% CI: -15.0, -4.3]) and higher placental NGF levels (10.0% [95% CI 3.7, 17.4]) for a twofold increase of acrylamide adducts, a decrease in the ratio of cord plasma free T4 and free T3 with higher acrylamide and glycidamide adducts of -2.9% (95% CI: -5.7, -0.1) and -3.9% (95% CI: -6.2, -1.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively, and higher cord plasma free T3 with increases in both acrylamide and glycidamide adducts of 2.8% (95% CI: 0.2, 5.6) and 3.6% (95% CI: 0.8, 6.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively. Additionally, a twofold increase in glycidamide adducts was associated with lower cord plasma insulin levels, particularly among newborns of non-smoking mothers (-11.2% [95% CI: -19.5, -0.1]). Cord plasma insulin seemed to mediate the association between glycidamide adducts and birth weight. CONCLUSIONS: A decrease in cord plasma insulin levels may be (a marker of) a mechanism by which gestational acrylamide exposure is associated with decreased fetal growth. The possible health consequences of the associations between gestational acrylamide exposure and thyroid hormones and neurotrophins warrant future study.


Assuntos
Acrilamida , Placenta , Acrilamida/toxicidade , Biomarcadores , Feminino , Sangue Fetal , Desenvolvimento Fetal , Hemoglobinas , Humanos , Recém-Nascido , Gravidez
9.
Expert Opin Drug Metab Toxicol ; 17(7): 857-865, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34102941

RESUMO

BACKGROUND: Acrylamide (AA) is a water-soluble toxic chemical that is considered one of the most important food contaminants. Furthermore, AA is considered a major public health risk. METHODS: This study was designed to evaluate the effects of AA on cytotoxicity, oxidative damage and genotoxicity in human lymphocytes and also to evaluate the protective effects of the chrysin (CH). Lymphocytes after isolation from the blood were treated with AA (50 µM), AA (50 µM) plus CH (10, 25, 50 µM) and CH (50 µM), and parameters such as cell viability, mitochondrial and lysosomal damage, as well as oxidative damage to DNA were examined. RESULTS: The results showed that CH was able to reduce cytotoxicity, reactive oxygen species (ROS) levels, lipid peroxidation (LPO) level, collapse in mitochondrial membrane potential (MMP) and oxidative damage of DNA caused by AA in human lymphocytes. Also, co-treatment of the AA-exposed human lymphocytes with CH increases the glutathione (GSH) levels. CONCLUSION: Results suggest that CH (10, 25, 50 µM) shows a protective role in AA-induced cytotoxicity, oxidative stress, mitochondrial damage and DNA oxidative damage.


Assuntos
Acrilamida/toxicidade , Flavonoides/farmacologia , Linfócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Adulto , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Linfócitos/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
10.
J Agric Food Chem ; 69(27): 7765-7776, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34191505

RESUMO

Acrylamide, a well-documented neurotoxicant, is commonly found as a byproduct of the Maillard reaction in carbohydrate-rich foods. Numerous studies have indicated that acrylamide-induced apoptosis accompanied by mitochondrial dysfunction contributes to its neurotoxicity. However, the mechanisms of how acrylamide causes mitochondrial impairment is not well understood. In this study, we observed destroyed redox balance, accumulated mitochondrial reactive oxygen species (ROS), damaged mitochondrial structures, and activated apoptosis in astrocytes following acrylamide treatment. Furthermore, acrylamide decreased the expression of mitochondrial biogenesis- and dynamics-related genes, including PGC-1α, TFAM, Mfn2, and Opa1, and altered the expression of mitochondrial DNA (mtDNA)-encoded mitochondrial respiratory chain complexes, along with the inhibited mitochondrial respiration. Pretreatment with a mitochondrial ROS scavenger mitoquinone dramatically restored the expressions of PGC-1α, TFAM, Mfn2, and Opa1; protected the mitochondrial structure; and decreased acrylamide-induced apoptosis. Further in vivo experiments confirmed that acrylamide decreased the expressions of PGC-1α, TFAM, Mfn2, and Opa1 in rat brain tissues. These results revealed that acrylamide triggered the mitochondrial ROS accumulation to interfere with mitochondrial biogenesis and dynamics, causing mtDNA damage and finally resulting in mitochondrial dysfunction and apoptosis.


Assuntos
Acrilamida , DNA Mitocondrial , Acrilamida/toxicidade , Animais , DNA Mitocondrial/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo
11.
Environ Sci Pollut Res Int ; 28(38): 53249-53266, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34024031

RESUMO

Acrylamide (ACR) has been previously associated with male sexual dysfunction and infertility. Eruca sativa (L.) (arugula or rocket) have been widely used in traditional remedies in Mediterranean region and western Asia and was known for its strong aphrodisiac effect since Roman times. The current study was designed to investigate LC/MS analysis of total ethanol extract Eruca sativa (L.) and the efficiency and mechanism of action of Eruca sativa seed extract (ESS) in reducing hypogonadism induced by acrylamide in male rats. Male Wistar rats were divided into 6 groups (n = 7): control group, Eruca sativa seed extract (ESS) at doses of 100 and 200 mg\kg, acrylamide (ACR), ACR + ESS 100 mg/kg, and ACR + ESS 200 mg/kg. The animals received ACR at a dose of 10 mg/kg b.wt for 60 days. Sperm indices, testicular oxidative stress, testosterone hormone, and testicular histopathology and immunohistochemistry of PCNA and caspase-3 were investigated. Moreover, the expression level of testicular B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) genes was evaluated. In respect to the LC/MS of total ethanol extract Eruca sativa (L.) seed revealed tentative identification of 39 compounds, which belongs to different classes as sulphur-containing compounds, flavonoids, phenolic acid, and fatty acids. Administration of ESS extract (100, 200 mg/kg) improved semen quality, diminished lipid peroxidation, enhanced testicular antioxidant enzyme, restored serum testosterone level, and reduced testicular degeneration and Leydig cell death in the rats intoxicated with ACR. However, the effects of ESS at the dose of 200 mg/kg were similar to that of control group. Furthermore, ESS treatment significantly induced anti-apoptotic effect indicated by elevation of both Bcl-2 and Bax expressions. Nutriceutics of ESS extract protects testis against ACR-induced testicular toxicity via normalizing testicular steroidogenesis, keeping Leydig cells, and improving oxidative stress status.


Assuntos
Acrilamida , Análise do Sêmen , Acrilamida/metabolismo , Acrilamida/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose , Masculino , Estresse Oxidativo , Extratos Vegetais/metabolismo , Ratos , Ratos Wistar , Testículo/metabolismo , Proteína X Associada a bcl-2/metabolismo
12.
Environ Sci Pollut Res Int ; 28(36): 49808-49819, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33939091

RESUMO

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-1ß), 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.


Assuntos
Acrilamida , Fosfatidilinositol 3-Quinases , Acrilamida/toxicidade , Animais , Antioxidantes , Apoptose , Flavonoides , Inflamação , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
13.
Sci Total Environ ; 778: 146304, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34030393

RESUMO

Acrylamide exposure along with resultant potential adverse health effects have attracted global concern, and the World Health Organization calls for more and urgent studies on the health risks from acrylamide. However, the association and mechanism between acrylamide exposure and pulmonary dysfunction remain unclear. Our goals were to investigate the relationship of internal acrylamide exposure with lung function reduction, and the potential mediating role of systematic inflammation in that relationship. Our study was conducted within the Wuhan-Zhuhai cohort. Urinary biomarkers of acrylamide exposure (N-acetyl-S-(2-carbamoylethyl)-l-cysteine, AAMA; N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine, GAMA) and lung function were determined among 3271 general adults, of whom 2595 had test results of systemic inflammatory marker plasma C-reactive protein (CRP). We employed linear mixed models to assess the relations among urinary acrylamide metabolites, pulmonary function and plasma CRP, and PRODCLIN program to evaluate the mediating role of CRP. We observed that urinary acrylamide metabolites were inversely and dose-dependently related to lung function (P trend<0.05). Each 1-unit increment in log-transformed level of AAMA, GAMA, or AAMA+GAMA (ΣUAAM) was significantly (P < 0.05) related to a 59.9-, 64.2-, or 64.3-mL reduction in FVC, and a 53.9-, 59.7-, or 58.5-mL reduction in FEV1, respectively. Such relationships were independent of smoking, and were significant in physically inactive rather than physically active participants. AAMA (ß = 0.10), GAMA (ß = 0.16) and ΣUAAM (ß = 0.12) were significantly (P < 0.05) related to increased CRP, which was significantly (P < 0.05) related to reduced FVC (ß = -55.3) and FEV1 (ß = -40.6). We further found that increased CRP significantly (P < 0.05) mediated 6.34-11.1% of the urinary acrylamide metabolites-associated lung function reductions. For the first time, our findings suggested that exposure to acrylamide in daily life was related to reduced lung function and increased systemic inflammation in general population, and systemic inflammation further mediated acrylamide-associated lung function reduction, indicating a potential mechanistic role of systemic inflammation underlying pulmonary dysfunction from acrylamide exposure.


Assuntos
Acetilcisteína , Acrilamida , Acrilamida/toxicidade , Adulto , Biomarcadores , Estudos de Coortes , Humanos , Inflamação/induzido quimicamente
14.
Toxicology ; 456: 152785, 2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-33872730

RESUMO

Acrylamide (ACR), a recognized neurotoxicant in humans and experimental animals, is widely used in industry and in food generated through Maillard reaction. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the cellular defense system and activates antioxidants and cytoprotective genes. The exact roles of Nrf2 in environmental electrophile-induced neurotoxicity is poorly understood. The aim of this study was to determine the roles of Nrf2 in ACR-induced neurotoxicity including degeneration of monoaminergic axons and sensorimotor dysfunction. Male 10-week-old C57BL/6JJcl Nrf2-knockout mice and wild type (WT) counterparts were each divided into four groups of 12 and provided with drinking water containing acrylamide at 0, 67, 110 or 200 ppm for four weeks. The effects of acrylamide were examined by landing foot spread test, immunohistochemistry for noradrenaline (NA) and serotonin (5-HT)-containing axons and Iba1-positive microglia in the prefrontal cortex as well as quantitative real-time polymerase chain reaction (qRT-PCR) on antioxidant, proinflammatory and anti-inflammatory genes in the prefrontal cortex. Relative to the wild type, exposure of Nrf2-knockout mice to acrylamide increased hindlimb splay length, microglial area and process length as well as decreasing the density of NA and 5-HT-immunoreactive axons to a greater extent. Moreover, deletion of Nrf2 gene suppressed acrylamide-induced mRNA upregulation of Nrf2-antioxidants, NAD(P): quinone oxidoreductase 1 (NQO1), superoxide dismutase-1 (SOD-1) and heme oxygenase-1 (HO-1) as well as anti-inflammatory markers such as, arginase-1 (Arg1), found in the inflammatory zone-1 (Fizz1), chitinase-like 3 (Chi3l3), interleukin-4 receptor alpha (IL-4Rα), cluster of differentiation  206 (CD206) and transforming growth factor beta-1 (TGFß1) while enhancing acrylamide-induced upregulation of pro-inflammatory cytokines, interleukin-1 beta (IL-1ß), tumor necrosis-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the prefrontal cortex. The results demonstrate susceptibility of mice lacking the Nrf2 gene to acrylamide-induced neurotoxicity and neuroinflammation with the activation of microglia. Moreover, the results suggest the role of Nrf2 not only in induction of antioxidant gene expression, but also in suppression of proinflammatory cytokine gene expression.


Assuntos
Acrilamida/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fator 2 Relacionado a NF-E2/deficiência , Fator 2 Relacionado a NF-E2/genética , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/efeitos dos fármacos , Microglia/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-33921874

RESUMO

Acrylamide is a contaminant as defined in Council Regulation (EEC) No 315/93 and as such, it is considered a chemical hazard in the food chain. The toxicity of acrylamide has been acknowledged since 2002, among its toxicological effects on humans being neurotoxicity, genotoxicity, carcinogenicity, and reproductive toxicity. Acrylamide has been classified as carcinogenic in the 2A group, with human exposure leading to progressive degeneration of the peripheral and central nervous systems characterized by cognitive and motor abnormalities. Bakery products (bread, crispbread, cakes, batter, breakfast cereals, biscuits, pies, etc.) are some of the major sources of dietary acrylamide. The review focuses on the levels of acrylamide in foods products, in particular bakery ones, and the risk that resulting dietary intake of acrylamide has on human health. The evolving legislative situation regarding the acrylamide content from foodstuffs, especially bakery ones, in the European Union is discussed underlining different measures that food producers must take in order to comply with the current regulations regarding the acrylamide levels in their products. Different approaches to reduce the acrylamide level in bakery products such as the use of asparginase, calcium salts, antioxidants, acids and their salts, etc., are described in detail.


Assuntos
Acrilamida , Contaminação de Alimentos , Acrilamida/toxicidade , Pão/análise , Dieta , Contaminação de Alimentos/análise , Humanos
16.
Int J Mol Sci ; 22(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805345

RESUMO

Acrylamide is a commonly used industrial chemical that is known to be neurotoxic to mammals. However, its developmental toxicity is rarely assessed in mammalian models because of the cost and complexity involved. We used zebrafish to assess the neurotoxicity, developmental and behavioral toxicity of acrylamide. At 6 h post fertilization, zebrafish embryos were exposed to four concentrations of acrylamide (10, 30, 100, or 300 mg/L) in a medium for 114 h. Acrylamide caused developmental toxicity characterized by yolk retention, scoliosis, swim bladder deficiency, and curvature of the body. Acrylamide also impaired locomotor activity, which was measured as swimming speed and distance traveled. In addition, treatment with 100 mg/L acrylamide shortened the width of the brain and spinal cord, indicating neuronal toxicity. In summary, acrylamide induces developmental toxicity and neurotoxicity in zebrafish. This can be used to study acrylamide neurotoxicity in a rapid and cost-efficient manner.


Assuntos
Acrilamida/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Síndromes Neurotóxicas/fisiopatologia , Peixe-Zebra/crescimento & desenvolvimento , Acrilamida/farmacologia , Sacos Aéreos/patologia , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Embrião não Mamífero/fisiopatologia , Desenvolvimento Embrionário/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Escoliose/etiologia , Natação , Peixe-Zebra/fisiologia
17.
Food Chem Toxicol ; 151: 112156, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33781805

RESUMO

Acrylamide (AA) is a common endogenous contaminant in food, with a complex toxicity mechanism. The study on liver damage to experimental animals caused by AA has aroused a great attention. Rosmarinic acid (RosA) as a natural antioxidant shows excellent protective effects against AA-induced hepatotoxicity, but the potential mechanism is still unclear. In the current study, the protective effect of RosA on BRL-3A cell damage induced by AA was explored. RosA increased the activity of SOD and GSH, reduced the content of ROS and MDA, and significantly reduced the oxidative stress (OS) damage of BRL-3A cells induced by AA. RosA pretreatment inhibited the MAPK signaling pathway activated by AA, and down-regulated the phosphorylation of JNK, ERK and p38. RosA pretreatment also reduced the production of calcium ions caused by AA. In addition, the key proteins p-IRE1α, XBP-1s, TRAF2 of the IRE1 pathway, and the expression of endoplasmic reticulum stress (ERS) characteristic proteins GRP78, p-ASK1, Caspase-12 and CHOP were also down-regulated by RosA. NAC blocked the activation of the MAPK signaling pathway and inhibited the ERS pathway. RosA reduced the rate of apoptosis and down-regulated the expression of Bax/Bcl-2 and Caspase-3, thereby inhibiting AA-induced apoptosis. In conclusion, RosA reduced the OS and ERS induced by AA in BRL-3A cells, thereby inhibiting cell apoptosis, and it could be used as a potential protective agent against AA toxicity.


Assuntos
Acrilamida/toxicidade , Apoptose/efeitos dos fármacos , Cinamatos/farmacologia , Depsídeos/farmacologia , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Linhagem Celular , Cinamatos/administração & dosagem , Depsídeos/administração & dosagem , Relação Dose-Resposta a Droga , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Estaurosporina/farmacologia
18.
Food Chem ; 352: 129438, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33690072

RESUMO

As one of the medicine homologous foods in China, Atractylodis Macrocephalae Rhizoma (AMR) is usually distributed after thermal processing, which raised the possibility of acrylamide pollution and a potential carcinogenic risk. In this study, a method was developed for the determination of the acrylamide in AMR using graphited multiwalled carbon nanotubes as the dispersive solid phase extraction sorbent and liquid chromatography tandem mass spectrometry. The concentration of acrylamide was investigated at processing conditions of 80℃-210℃ and 5 min-100 min. Method validation results demonstrated the reliability of the method with good linearity, accuracy and precision. Significant increment of acrylamide was found in AMR after thermal processing with the highest concentration at 9826 µg/kg, which led to a margin of exposure at 90.83-181.7 according to the BMDL10 of carcinogenicity at 0.17 mg/kg, indicating a high health risk of taking thermally processed AMR, and monitoring and controlling should be considered.


Assuntos
Acrilamida/análise , Atractylodes/química , Temperatura Alta , Rizoma/química , Acrilamida/toxicidade , Nanotubos de Carbono/química , Reprodutibilidade dos Testes , Medição de Risco
19.
Nutrients ; 13(3)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673718

RESUMO

Acrylamide can be carcinogenic to humans. However, the association between the acrylamide and the risks of renal cell, prostate, and bladder cancers in Asians has not been assessed. We aimed to investigate this association in the Japan Public Health Center-based Prospective Study data in 88,818 Japanese people (41,534 men and 47,284 women) who completed a food frequency questionnaire in the five-year follow-up survey in 1995 and 1998. A validated food frequency questionnaire was used to assess the dietary acrylamide intake. Cox proportional hazard regression models were used to estimate hazard ratios and 95% confidence intervals (CIs). During a mean follow-up of 15.5 years (15.2 years of prostate cancer), 208 renal cell cancers, 1195 prostate cancers, and 392 bladder cancers were diagnosed. Compared to the lowest quintile of acrylamide intake, the multivariate hazard ratios for the highest quintile were 0.71 (95% CI: 0.38-1.34, p for trend = 0.294), 0.96 (95% CI: 0.75-1.22, p for trend = 0.726), and 0.87 (95% CI: 0.59-1.29, p for trend = 0.491) for renal cell, prostate, and bladder cancers, respectively, in the multivariate-adjusted model. No significant associations were observed in the stratified analyses based on smoking. Dietary acrylamide intake was not associated with the risk of renal cell, prostate, and bladder cancers.


Assuntos
Acrilamida/toxicidade , Carcinoma de Células Renais/induzido quimicamente , Neoplasias Renais/induzido quimicamente , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Bexiga Urinária/induzido quimicamente , Acrilamida/administração & dosagem , Adulto , Idoso , Carcinoma de Células Renais/epidemiologia , Estudos de Coortes , Coleta de Dados , Dieta , Feminino , Contaminação de Alimentos , Humanos , Japão/epidemiologia , Neoplasias Renais/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/epidemiologia , Administração em Saúde Pública , Fatores de Risco , Inquéritos e Questionários
20.
Environ Sci Pollut Res Int ; 28(28): 38085-38093, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33725300

RESUMO

Acrylamide (AA) is routinely used in laboratories and industries, and its disposal is always a problem; consequently, offering an alternative for their treatment contributes to conducting research in a responsible way. Therefore, in this work, acrylamide solutions were degraded by ultraviolet radiation and hydrogen peroxide (H2O2), and their toxicity was evaluated using a Desmodesmus quadricauda microalgae growth assay. The AA solutions were exposed to different dosages of H2O2 and different exposure times to UV radiation. The degradation was evaluated by liquid chromatography, which allowed the identification of the acrylamide peak and subsequent by-product peaks. A 100% degradation of the 1.5 mg L-1 AA solution with UV/H2O2 (0.034 g L-1) was achieved in just 10 min. The by-products formed did not inhibit the growth of D. quadricauda microalgae. The number of D. quadricauda individuals that grew in acrylamide solutions exposed to 20 and 30 min of UV radiation, with 0.034 g L-1 of H2O2, was very similar to the number of individuals that grew in the control solution. Thus, the treatment proposed in this work using H2O2 combined with ultraviolet radiation degraded acrylamide into by-products with reduced toxicity.


Assuntos
Microalgas , Poluentes Químicos da Água , Acrilamida/toxicidade , Humanos , Peróxido de Hidrogênio , Oxirredução , Fotólise , Raios Ultravioleta
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