Food and Chemical Toxicology最新文献

英文中文

Epigallocatechin gallate-rich fraction alleviates histamine-induced neurotoxicity in rats via inactivating caspase-3/JNK signaling pathways 富含表没食子儿茶素没食子酸酯的成分通过灭活 Caspase-3/JNK 信号通路减轻组胺诱导的大鼠神经毒性

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2024-09-23 DOI: 10.1016/j.fct.2024.115021

Ingestion of prominent levels of histamine (HIS) leads to dangerous effects on biological systems. The most frequent and active catechin in green tea is epigallocatechin gallate which has strong antioxidant properties. Our research intended to investigate the possible neuroprotective effect of epigallocatechin gallate-rich fraction (EGCGR) against HIS-inducing neurotoxicity. Six groups of male rats (n = 5) were used as follows: (1) Distilled water, (2&3) EGCGR (100–200 mg/kg BWT/day, respectively), (4) HIS (1750 mg/kg BWT/week, (5&6) HIS + EGCGR. Administration of HIS for 14 days induced severe neurobehavioral changes including depression, incoordination, and loss of spatial memory. Extensive neuronal degeneration with diffuse gliosis was the prominent histopathological lesion observed and confirmed by strong immunostaining of casp-3, Cox-2, and GFAP. Additionally, the HIS group showed a significantly higher MDA level with lower CAT and GSH activity than the control group. Moreover, HIS promoted apoptosis, which is indicated by increasing JNK, and Bax and decreasing Bcl-2 gene expressions. Otherwise, the oral intake of EGCGR with HIS improved all neurotoxicological parameters induced by HIS. We concluded that HIS could cause neurotoxicity via an upset of the equilibrium between oxidants and antioxidants which trigger apoptosis through modulation of JNK signaling pathway. Furthermore, EGCGR has either direct or indirect antihistaminic effects.

摄入大量组胺（HIS）会对生物系统产生危险影响。绿茶中最常见的活性儿茶素是表没食子儿茶素没食子酸酯，它具有很强的抗氧化性。我们的研究旨在探讨富含表没食子儿茶素没食子酸酯（EGCGR）对 HIS 引起的神经毒性可能具有的神经保护作用。我们使用了六组雄性大鼠（n = 5），具体如下：(1）蒸馏水；（2&3）EGCGR（分别为100-200毫克/千克体重/天）；（4）HIS（1750毫克/千克体重/周）；（5&6）HIS + EGCGR。连续 14 天服用 HIS 会诱发严重的神经行为变化，包括抑郁、不协调和空间记忆丧失。广泛的神经元变性和弥漫性胶质增生是观察到的主要组织病理学病变，并通过 casp-3、Cox-2 和 GFAP 的强免疫染色得到证实。此外，与对照组相比，HIS 组的 MDA 水平明显升高，CAT 和 GSH 活性降低。此外，HIS 还能促进细胞凋亡，表现为 JNK 和 Bax 基因表达增加，Bcl-2 基因表达减少。此外，口服 EGCGR 与 HIS 可改善 HIS 诱导的所有神经毒理学参数。我们得出的结论是，HIS可通过破坏氧化剂和抗氧化剂之间的平衡来引起神经中毒，而抗氧化剂可通过调节JNK信号通路来触发细胞凋亡。此外，EGCGR还具有直接或间接的抗组胺作用。

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引用次数: 0

Oral toxicity of the acetone extract of Coffea arabica var. Oro Azteca leaves in CD-1 mice 阿拉伯咖啡变种 Oro Azteca 叶丙酮提取物对 CD-1 小鼠的口服毒性。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2024-09-21 DOI: 10.1016/j.fct.2024.115018

The investigation of coffee leaves as a source of bioactive principles represents a relatively unexplored area of research. The study assesses the potential adverse effects of an aqueous acetone extract derived from Coffea arabica var. Oro Azteca leaves. The phenolic composition of the extract was identified and quantified by UPLC-MS/MS, and its acute and repeated-dose effects were evaluated in six-week-old CD-1 mice (n = 11 for acute evaluation and n = 20 female and n = 20 male for repeated-dose evaluation). The extract demonstrated no significant toxicity, maintaining consistent body weight and exhibiting a hepatoprotective effect by reducing ALT levels at a dose of 500 mg/kg. Some hyperactivity was observed at the highest doses, but overall, the extract enhanced the immune response and showed no histological alterations, except for mild inflammation in certain organs. The extract, which contains abundant quinic acid, chlorogenic acid, epicatechin, procyanidin B2, and mangiferin, has been deemed safe for consumption.

将咖啡叶作为生物活性成分来源的研究是一个相对尚未开发的研究领域。本研究评估了从阿拉伯咖啡变种 Oro Azteca 叶子中提取的丙酮水提取物的潜在不良影响。通过 UPLC-MS/MS 对萃取物的酚类成分进行了鉴定和定量，并在六周大的 CD-1 小鼠（急性评估为 11 只，重复剂量评估为 20 只雌性小鼠和 20 只雄性小鼠）身上评估了萃取物的急性和重复剂量效应。该提取物无明显毒性，体重保持稳定，在 500 毫克/千克的剂量下可降低谷丙转氨酶（ALT）水平，表现出保护肝脏的作用。在最高剂量时，观察到一些亢进现象，但总体而言，提取物增强了免疫反应，除了某些器官出现轻微炎症外，未显示组织学改变。这种提取物含有丰富的奎宁酸、绿原酸、表儿茶素、原花青素 B2 和芒果苷，被认为可以安全食用。

引用次数: 0

Barley based gluten free beer – A blessing or an uncontrollable risk? 以大麦为原料的无麸质啤酒--是福音还是无法控制的风险？

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2024-09-20 DOI: 10.1016/j.fct.2024.115019

Recent reports have highlighted that beer labelled “gluten-free”, crafted with enzymatic treatments to remove gluten, may contain polypeptides that could be immunotoxic to individuals with coeliac disease. As strict adherence to a gluten-free diet is the only way to manage this condition, accurate labelling is crucial to those with coeliac disease. This paper aims to discuss the presence, levels and immunogenicity of gluten peptides found in gluten-reduced barley beers. While advances have been made in the detection and quantification of gluten peptides in beer, there are still challenges to the interpretation of gluten measurements as well as to assess whether peptides are immunotoxic in vivo. To make progress, future efforts should involve a combination of in vivo toxicity assessment of the degraded proteins, development of standardised gluten-free production strategies to minimise variability in gluten fragment presence, guidance on how to control the outcome as well as to develop appropriate reference materials and calibrators.

最近的一些报道强调，标有 "无麸质 "的啤酒在经过酶处理以去除麸质的过程中，可能含有对患有乳糜泻的人具有免疫毒性的多肽。由于严格遵守无麸质饮食是控制这种疾病的唯一方法，因此准确的标签对患有乳糜泻的人来说至关重要。本文旨在讨论谷蛋白还原大麦啤酒中谷蛋白肽的存在、含量和免疫原性。虽然在啤酒中麸质肽的检测和定量方面取得了进展，但在解释麸质测量结果以及评估肽在体内是否具有免疫毒性方面仍面临挑战。为了取得进展，今后的工作应包括对降解蛋白质进行体内毒性评估、制定标准化的无麸质生产策略以最大限度地减少麸质片段存在的变异性、指导如何控制结果以及开发适当的参考材料和校准物。

引用次数: 0

Update to RIFM fragrance ingredient safety assessment, hexyl butyrate, CAS Registry Number 2639-63-6 RIFM 香料成分安全评估更新，丁酸己酯，化学文摘社登记号 2639-63-6。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2024-09-19 DOI: 10.1016/j.fct.2024.115013

引用次数: 0

RIFM fragrance ingredient safety assessment, furfural, CAS Registry Number 98-01-1 RIFM 香料成分安全性评估，糠醛，化学文摘社登记号 98-01-1。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2024-09-19 DOI: 10.1016/j.fct.2024.115014

引用次数: 0

Zearalenone promotes endometrial cancer cell migration and invasion via activation of estrogen receptor-mediated Rho/ROCK/PMLC signaling pathway 玉米赤霉烯酮通过激活雌激素受体介导的 Rho/ROCK/PMLC 信号通路促进子宫内膜癌细胞迁移和侵袭。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2024-09-19 DOI: 10.1016/j.fct.2024.115017

Zearalenone (ZEA), has emerged as a potential endocrine-disrupting chemical (EDC). Previous results show ZEA effects on endometrial stromal cell apoptosis, migration, and growth of endometriosis. Despite the reported presence of ZEA in Endometrial Cancer (EC) patient's blood and tissues, ZEA-induced EC promotion and its mechanism/s remain elusive. In this study, Ishikawa cells were used to investigate the ZEA effects on Ishikawa cell migration, invasion, and the underlying mechanism involved in these events. Ishikawa cells were exposed to low concentrations of ZEA (5, 25, and 125 nM) for 48 h, and morphological alterations, migration, invasion, markers associated with epithelial-mesenchymal transition (EMT), E-cadherin, Vimentin, RhoA/ROCK/PMLC pathway activation were analyzed. ZEA (25 nM) exposure caused morphological alterations like stress fiber, filopodia formation, loss of cell adhesion, and a significant increase in migration and invasive potential in extracellular matrix-coated porous membranes. Moreover, ZEA exposure also increases the Rho-GTPase activity and expression of pathway mediators, GEFH1, RhoA, ROCK1+2, CDC42, and PMLC/MLC. Furthermore, pre-treatment with specific pharmacological inhibitors for Estrogen receptor-alpha (ER-α) and ROCK attenuate the ZEA-induced stress fiber formation and altered expression of E-cadherin, Vimentin, and Rho/ROCK/PMLC pathway mediators. These findings suggest that Rho/ROCK/PMLC signaling pathways are involved in ZEA-induced Ishikawa cell migration and invasion.

玉米赤霉烯酮（ZEA）已成为一种潜在的内分泌干扰化学物质（EDC）。先前的研究结果表明，ZEA 会影响子宫内膜基质细胞的凋亡、迁移和子宫内膜异位症的生长。尽管有报道称子宫内膜癌（EC）患者的血液和组织中存在 ZEA，但 ZEA 诱导的子宫内膜癌促进作用及其机制仍未确定。本研究使用石川细胞来研究 ZEA 对石川细胞迁移、侵袭的影响以及这些事件的内在机制。将石川细胞暴露于低浓度的棣亚乙酸（5、25和125nM）48小时后，对其形态学改变、迁移、侵袭、与上皮-间质转化（EMT）相关的标记物、E-钙粘连蛋白、Vimentin、RhoA/ROCK/PMLC通路激活进行分析。暴露于 ZEA（25nM）会导致形态学改变，如应力纤维、丝状体的形成、细胞粘附力的丧失，以及在细胞外基质包被的多孔膜中迁移和侵袭潜能的显著增加。此外，暴露于 ZEA 还会增加 Rho-GTPase 的活性以及 GEFH1、RhoA、ROCK1+2、CDC42 和 PMLC/MLC 等通路介质的表达。此外，雌激素受体-α（ER-α）和 ROCK 的特异性药理抑制剂可减轻 ZEA 诱导的应力纤维形成以及 E-钙粘蛋白、波形蛋白和 Rho/ROCK/PMLC 通路介质的表达变化。这些研究结果表明，Rho/ROCK/PMLC 信号通路参与了 ZEA 诱导的石川细胞迁移和侵袭。

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引用次数: 0

EGCG alleviates Ochratoxin A-induced pyroptosis in rat's kidney by inhibiting NLRP3/Caspase-1/GSDMD signaling pathway EGCG通过抑制NLRP3/Caspase-1/GSDMD信号通路，缓解赭曲霉毒素A诱导的大鼠肾脏热毒症。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2024-09-18 DOI: 10.1016/j.fct.2024.115006

Ochratoxin A (OTA) exposure is inevitable due to its contamination in foods, and there is no treatment for the OTA induced organ toxicity. We evaluate the effect of epigallocatechin gallate (EGCG) on the nephrotoxicity caused by OTA, and to reveal the relationship of this effect with the NLRP3/Caspase-1/GSDMD pathway dependent pyroptosis. 40 male Wistar albino rats divided into 5 groups (n = 8, per group) 0.5 mg/kg/day OTA were administered to the rats and 50 mg/kg and 100 mg/kg EGCG were administered to the groups by gavage orally for 14 days. Serum urea and creatinine levels increased significantly with OTA exposure. Similarly, it was determined that significant changes in oxidative stress parameters with OTA exposure in kidney tissue. Also, there was a significant increase in kidney tissue TGF-β, NF-κB, IL-1β, IL-18, NLRP3, Caspase-1 and GSDMD mRNA expressions with OTA exposure. EGCG administration augmented a dose-dependent decrease in the aforementioned parameters. NLRP3/Caspase-1/GSDMD pathway is induced in the kidneys due to OTA exposure were shown with this study. Potent antioxidant EGCG could alleviate the pathways specified with this study in OTA nephrotoxicity and its supplementation may be effective strategies for the protection.

由于赭曲霉毒素A（OTA）在食品中的污染，人们不可避免地会接触到它，而目前还没有治疗OTA引起的器官毒性的方法。我们评估了表没食子儿茶素没食子酸酯（EGCG）对OTA引起的肾毒性的影响，并揭示了这种影响与NLRP3/Caspase-1/GSDMD途径依赖性热蛋白沉积的关系。将40只雄性Wistar白化大鼠分为5组（n = 8，每组8只），每公斤每天给药0.5毫克OTA，每组口服50毫克/公斤和100毫克/公斤EGCG，连续给药14天。大鼠的血清尿素和肌酐水平随着暴露于 OTA 而明显升高。同样，肾组织中的氧化应激参数也随着暴露于 OTA 而发生了显著变化。此外，接触 OTA 后，肾组织中 TGF-β、NF-κB、IL-1β、IL-18、NLRP3、Caspase-1 和 GSDMD mRNA 的表达量也明显增加。服用 EGCG 可增加上述参数的剂量依赖性下降。本研究表明，接触 OTA 会诱导肾脏中的 NLRP3/Caspase-1/GSDMD 通路。强效抗氧化剂EGCG可以缓解本研究中指出的OTA肾毒性途径，补充EGCG可能是保护肾脏的有效策略。

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引用次数: 0

Hepatotoxic assessment in a microphysiological system: Simulation of the drug absorption and toxic process after an overdosed acetaminophen on intestinal-liver-on-chip 微生理系统中的肝毒性评估：模拟过量对乙酰氨基酚在肠肝芯片上的吸收和毒性过程。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2024-09-18 DOI: 10.1016/j.fct.2024.115016

To compensate the limitation of animal models, new models were proposed for drug safety evaluation to refine and reduce existing models. To mimic drug absorption and metabolism and predict toxicokinetic and toxic effects in an in vitro intestinal-liver microphysiological system (MPS), we constructed an intestinal-liver-on-chip and detected the acute liver injury process after an overdose of acetaminophen (APAP). Caco-2 and HT29-MTX-E12 cell lines were utilized to establish intestinal equivalents, along with HepG2, HUVEC-T1, and THP-1 induced by PMA and human hepatic stellate cell to establish liver equivalents. The APAP concentration was determined using high-performance liquid chromatography, and the toxicokinetic parameters were fitted using the non-compartmental analysis method by Phoenix. Changes in liver injury biomarkers aspartate aminotransferase and alanine aminotransferase, and liver function marker albumin indicated that the short-term culture of the two organs-on-chip model was stable for 4 days. Reactive oxygen species signaling was enhanced after APAP administration, along with decreased mitochondrial membrane potential, activated caspase-3, and enhanced p53 signaling, indicating a toxic response induced by APAP overdose. In the gut-liver MPS model, we fitted the toxicokinetic parameters and simulated the hepatotoxicity procedure following an APAP overdose, which will facilitate the organ-on-chips application in drug toxicity assays.

为了弥补动物模型的局限性，人们提出了新的药物安全性评价模型，以完善和减少现有模型。为了在体外肠肝微生理系统（MPS）中模拟药物的吸收和代谢，预测毒代动力学和毒性效应，我们构建了肠肝芯片，并检测了过量对乙酰氨基酚（APAP）后的急性肝损伤过程。我们利用 Caco-2 和 HT29-MTX-E12 细胞系建立肠道等效细胞系，并利用 PMA 诱导的 HepG2、HUVEC-T1 和 THP-1 以及人肝星状细胞建立肝脏等效细胞系。采用高效液相色谱法测定了 APAP 的浓度，并采用 Phoenix 非室分析法拟合了毒代动力学参数。肝损伤生物标志物天冬氨酸氨基转移酶和丙氨酸氨基转移酶以及肝功能标志物白蛋白的变化表明，芯片上两个器官模型的短期培养在 4 天内是稳定的。服用 APAP 后，活性氧信号转导增强，线粒体膜电位降低，caspase-3 被激活，p53 信号转导增强，这表明 APAP 过量会诱发毒性反应。在肠道-肝脏 MPS 模型中，我们拟合了毒物动力学参数，模拟了过量服用 APAP 后的肝毒性过程，这将促进芯片上器官在药物毒性检测中的应用。

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引用次数: 0

RIFM fragrance ingredient safety assessment, heptyl acetate, CAS Registry Number 112-06-1. RIFM 香料成分安全评估，醋酸庚酯，化学文摘社登记号 112-06-1。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2024-09-18 DOI: 10.1016/j.fct.2024.115015

A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Freidrich, G A Burton, M A Cancellieri, H Chon, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar, Y Tokura

引用次数: 0

Synergistic neurological threat from Сu and wood smoke particulate matter Сu和木烟颗粒物对神经系统的协同威胁。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2024-09-18 DOI: 10.1016/j.fct.2024.115009

Trace metal Cu and carbonaceous airborn particulate matter (PM) are dangerous neuropollutants. Here, the ability of Cu²⁺ to modulate the neurotoxicity caused by water-suspended wood smoke PM preparations (SPs) and vice versa was examined using presynaptic rat cortex nerve terminals. Interaction of Cu²⁺ and SPs, changes of particle size and surface properties were shown in the presence of Cu²⁺ using microscopy, DLS, and IR spectroscopy. In nerve terminals, Cu²⁺ and SPs per se elevated the ambient levels of excitatory and inhibitory neurotransmitters L-[¹⁴C]glutamate and [³H]GABA, respectively. During combined application, Cu²⁺ significantly enhanced a SPs-induced increase in the ambient levels of both neurotransmitters, thereby demonstrating a cumulative synergistic effect and significant interference in the neurotoxic threat associated with Cu²⁺and SPs. In fluorimetric measurements, Cu²⁺ and SPs also demonstrated cumulative synergistic effects on the membrane potential, mitochondrial potential, synaptic vesicle acidification and ROS generation. Therefore, synergistic effects of Cu²⁺ and SPs on the most crucial presynaptic characteristics and neurohazard of multiple pollutants through excitatory/inhibitory imbalance, disruption of the membrane and mitochondrial potential, vesicle acidification and ROS generation were revealed. Increased expansion and burden of neuropathology may result from underestimation of synergistic interference of the neurotoxic effects of Cu²⁺ and carbonaceous smoke PM.

痕量金属 Cu 和含碳空气颗粒物（PM）是危险的神经污染物。在这里，我们利用突触前大鼠皮层神经末梢研究了 Cu2+ 调节水悬浮木烟颗粒制剂（SPs）引起的神经毒性的能力，反之亦然。使用显微镜、DLS 和红外光谱显示了 Cu2+ 和 SPs 的相互作用、颗粒大小和表面性质在 Cu2+ 存在下的变化。在神经末梢中，Cu2+和SPs本身分别提高了兴奋性和抑制性神经递质L-[14C]谷氨酸和[3H]GABA的环境水平。在联合应用时，Cu2+ 会显著增强 SPs 引起的这两种神经递质环境水平的升高，从而显示出累积协同效应，并显著干扰与 Cu2+ 和 SPs 相关的神经毒性威胁。在荧光测量中，Cu2+ 和 SPs 还对膜电位、线粒体电位、突触小泡酸化和 ROS 生成产生了累积协同效应。因此，Cu2+ 和 SPs 通过兴奋/抑制失衡、膜电位和线粒体电位破坏、突触小泡酸化和 ROS 生成，对突触前最关键的特征和多种污染物的神经危害产生了协同效应。由于低估了 Cu2+ 和含碳烟雾 PM 的神经毒性效应的协同干扰，可能导致神经病变的扩大和负担加重。

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