Food and Chemical Toxicology最新文献_第2页

Predictive biomarkers for valproic acid-induced hepatotoxicity in Chinese epileptics: the role of metabolites and genetic polymorphisms. 中国癫痫患者丙戊酸肝毒性的预测性生物标志物：代谢物和遗传多态性的作用。

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2025-07-29 DOI: 10.1016/j.fct.2025.115670

Dingsheng Wen, Zhuojia Chen, Ziyi Chen, Xue Bai, Hongliang Li, Juan Chen, Qiling Dai, Guoping Zhong, Jiaming Qin, Guanzhong Ni, Min Huang, Liemin Zhou, Xueding Wang

{"title":"Predictive biomarkers for valproic acid-induced hepatotoxicity in Chinese epileptics: the role of metabolites and genetic polymorphisms.","authors":"Dingsheng Wen, Zhuojia Chen, Ziyi Chen, Xue Bai, Hongliang Li, Juan Chen, Qiling Dai, Guoping Zhong, Jiaming Qin, Guanzhong Ni, Min Huang, Liemin Zhou, Xueding Wang","doi":"10.1016/j.fct.2025.115670","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115670","url":null,"abstract":"<p><p>Valproic acid (VPA) is a widely used antiepileptic drug, but its hepatotoxicity limits usage. This study explored biomarkers and genetic factors associated with VPA-induced liver injury in 200 Chinese epileptic patients on VPA monotherapy. We analyzed VPA and its metabolites (4-ene-VPA, 3-OH-VPA, 4-OH-VPA, 2-PGA), liver function, and 22 gene polymorphisms. Patients with abnormal liver function (ANLFT) had significantly higher 4-ene-VPA levels than those with normal liver function (NLFT). The GG genotype of CPT1A rs2228502 was associated with elevated 4-ene-VPA levels. SNPs in ACOT1, PPARα, FFAR2, NQO1, and NRF2 showed significant differences between groups. Logistic regression identified NRF2 rs59288687 and NQO1 rs10517 as protective factors against hepatotoxicity. In conclusion, elevated 4-ene-VPA and genetic variants, including CPT1A rs2228502, NRF2 rs59288687, and NQO1 rs10517, influence hepatotoxicity risk, providing insights for individualized treatment strategies.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115670"},"PeriodicalIF":3.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of Natural Products in Modulating Metal Nanoparticle Toxicity: A Review of Mechanisms and Evidence. 天然产物在调节金属纳米颗粒毒性中的作用：机制和证据综述。

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2025-07-29 DOI: 10.1016/j.fct.2025.115662

Mohamed A Abdel-Hakeem, Nermin Gamal, Moez Elsaadani, Shimaa Abdel-Ghany, Aya Afifi, Sara Hisham, Rehab M Ramadan, Hussein Sabit

{"title":"The Role of Natural Products in Modulating Metal Nanoparticle Toxicity: A Review of Mechanisms and Evidence.","authors":"Mohamed A Abdel-Hakeem, Nermin Gamal, Moez Elsaadani, Shimaa Abdel-Ghany, Aya Afifi, Sara Hisham, Rehab M Ramadan, Hussein Sabit","doi":"10.1016/j.fct.2025.115662","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115662","url":null,"abstract":"<p><p>Metallic nanoparticles (MNPs) are widely used in medicine, industry, and consumer goods due to their unique nanoscale properties. However, these same features pose potential health risks through mechanisms such as oxidative stress, inflammation, and cellular damage. This review highlights how MNPs interact with biological systems, leading to toxicity that affects DNA, proteins, and organs-particularly the brain, liver, and immune system. Key physicochemical properties, including particle size, surface charge, and exposure route, influence the extent of toxicity. To address these risks, we explore the protective potential of natural products-especially polyphenols, vitamins, and herbal extracts-that counteract MNP-induced damage by scavenging reactive oxygen species and modulating inflammatory pathways. Evidence from in vitro, in vivo, and clinical studies demonstrates the capacity of these compounds to mitigate nanoparticle toxicity. We also discuss the promise of green synthesis approaches to enhance biocompatibility. By integrating knowledge from nanotoxicology and natural pharmacology, this review presents a dual strategy for safer nanotechnology: understanding toxicological mechanisms and applying biocompatible natural mitigators. These insights can guide future design of safer nanoparticles and therapeutic interventions.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115662"},"PeriodicalIF":3.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fluoride-induced vascular endothelial injury and the protective mechanism of blueberry anthocyanins 氟致血管内皮损伤及蓝莓花青素的保护机制。

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2025-07-29 DOI: 10.1016/j.fct.2025.115665

Chao Zhang , Yue Wang , Fengya Huang , Yaoyuan Zhang , Mingyue Huang , Yunzhu Liu , Linet Angwa , Yanhui Gao , Dianjun Sun , Yuting Jiang

{"title":"Fluoride-induced vascular endothelial injury and the protective mechanism of blueberry anthocyanins","authors":"Chao Zhang , Yue Wang , Fengya Huang , Yaoyuan Zhang , Mingyue Huang , Yunzhu Liu , Linet Angwa , Yanhui Gao , Dianjun Sun , Yuting Jiang","doi":"10.1016/j.fct.2025.115665","DOIUrl":"10.1016/j.fct.2025.115665","url":null,"abstract":"<div><h3>Background</h3><div>Long-term fluoride exposure poses significant risks to the cardiovascular system, with vascular endothelial damage being the critical initiating factor in fluoride induced CVDs. Fluoride's oxidative stress mediated toxicity disrupted endothelial function, highlighting the urgent need for protective strategies. Acy, known for its antioxidant properties, offered potential cardiovascular protection against fluoride induced damage. Previous studies by our group had identified the p53/miR-200c-3p pathway as a key molecular mechanism in fluoride-triggered endothelial injury.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate how fluoride induced vascular endothelial injury and to evaluate the protective role of Acy in counteracting these detrimental effects.</div></div><div><h3>Study design</h3><div>We established both in vivo (fluoride exposed Wistar rats) and in vitro (ECs) models of fluoride toxicity, with Acy intervention.</div></div><div><h3>Results</h3><div>Fluoride exposure caused severe oxidative stress and endothelial dysfunction, which were significantly mitigated by Acy treatment. Notably, Acy alleviated fluoride-induced pathological damage in the vascular endothelium. Mechanistically, Acy exerted its protective effects by suppressing the fluoride-activated p53/miR-200c-3p pathway.</div></div><div><h3>Conclusion</h3><div>Fluoride exposure led to substantial cardiovascular injury, primarily through oxidative stress and endothelial dysfunction. Acy, as a nutritional intervention, effectively counteracted fluoride induced damage, providing novel insights into both the pathogenesis of fluoride toxicity and potential therapeutic strategies for fluorosis.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"204 ","pages":"Article 115665"},"PeriodicalIF":3.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthetic azo dye amaranth disrupts neuronal plasticity causing alpha-synuclein aggregation and cognitive disability in an in vivo zebrafish model 在斑马鱼体内模型中，合成偶氮染料苋菜红破坏神经元可塑性，导致α -突触核蛋白聚集和认知障碍

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2025-07-28 DOI: 10.1016/j.fct.2025.115669

Sanjay Gopi , S. Prethiba , S. Madesh , Bader O. Almutairi , Ki Choon Choi , Jesu Arockiaraj

{"title":"Synthetic azo dye amaranth disrupts neuronal plasticity causing alpha-synuclein aggregation and cognitive disability in an in vivo zebrafish model","authors":"Sanjay Gopi , S. Prethiba , S. Madesh , Bader O. Almutairi , Ki Choon Choi , Jesu Arockiaraj","doi":"10.1016/j.fct.2025.115669","DOIUrl":"10.1016/j.fct.2025.115669","url":null,"abstract":"<div><div>Amaranth (AMR) or Acid red 27 is a synthetic dye widely used in the textile, pharmaceutical, and food industries. Its high solubility contributes to its environmental persistence as a pollutant, and its widespread use in confectioneries, due to its vibrant color, raises concerns about overexposure, particularly in children. Despite its prevalence, health and ecological risks of AMR remain poorly studied. We investigated the developmental and neurobehavioral effects of AMR <em>in-vivo</em> zebrafish. Assessments of acute and chronic toxicity revealed a dose-dependent increase in mortality and developmental abnormalities. Oxidative stress was evident from ROS accumulation, glutathione depletion (1.14 ± 0.28 U/mg of protein; <em>p = 0.0012</em>), and increased lipid peroxidation (2.80 fold; <em>p < 0.0001)</em> at 100 mg/L. Neurobehavioral analysis revealed cognitive impairment and altered locomotor activity. Molecular analysis using key markers revealed potential disruptions in neuroplasticity. Immunohistochemical analysis revealed elevated GFAP expression (2.42 fold; <em>p < 0.0001)</em> and accumulation of α-synuclein (2.63 fold; <em>p < 0.0001)</em> at 100 mg/L, indicating astrocyte activation and gliosis, suggesting key pathological mechanisms implicated in major neurodegenerative diseases such as Parkinson's disease. These findings highlight AMR's neurotoxic potential at environmentally relevant concentrations, underscoring the urgent need to reassess its regulatory safety limits and environmental impact.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"204 ","pages":"Article 115669"},"PeriodicalIF":3.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144748582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dietary exposure to heterocyclic amines by the Portuguese population: comparison of different exposure assessment methods 葡萄牙人群饮食中对杂环胺的暴露：不同暴露评估方法的比较

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2025-07-28 DOI: 10.1016/j.fct.2025.115667

Marta Pinto da Costa , Daniela Correia , Catarina Carvalho , Sofia Vilela , Vânia Magalhães , Milton Severo , Carla Lopes , Duarte Torres

{"title":"Dietary exposure to heterocyclic amines by the Portuguese population: comparison of different exposure assessment methods","authors":"Marta Pinto da Costa , Daniela Correia , Catarina Carvalho , Sofia Vilela , Vânia Magalhães , Milton Severo , Carla Lopes , Duarte Torres","doi":"10.1016/j.fct.2025.115667","DOIUrl":"10.1016/j.fct.2025.115667","url":null,"abstract":"<div><div>To estimate dietary exposure to heterocyclic amines (HAs) in the Portuguese population, three methods of attributing HAs occurrence data to consumed food items were compared. Participants are part of the National Food, Nutrition and Physical Activity Survey (n = 5005, 3-84y). Food consumption was collected through two non-consecutive 24 h dietary recalls or food diaries. HAs occurrence was extracted from the literature. Margins of exposure (MOE) were estimated for different cancer types. Three methods were considered: 1.FoodEx2 Hierarchy model (FH) - random HAs values were attributed to missing data, considering the closest item in the occurrence dataset according to the FoodEx2 hierarchy; 2.FoodEx2 Hierarchy Median model (FHM) - median HAs values of the closest items in the dataset were attributed to missing data; 3.Regression Tree model (RTM) - an RTM was used to predict mean occurrence values of homogeneous food groups based on the FoodEx2 hierarchy. The FH method presents higher dietary exposure for the 95th percentile and lower MOE values, appearing to estimate better. Red and white meat were the main contributors to HAs intake. The Portuguese population's dietary exposure to HAs seems to be safe. However, MOE values for prostate cancer in children may raise concern about potential future adult risk from early-life exposures.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"204 ","pages":"Article 115667"},"PeriodicalIF":3.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144748757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PAK1 mediates ivermectin-induced DNA damage in porcine oocytes during meiotic maturation PAK1介导猪卵母细胞减数分裂成熟过程中伊维菌素诱导的DNA损伤

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2025-07-25 DOI: 10.1016/j.fct.2025.115653

Tianhang Yu, Yijing He, Heran Li, Qinfeng Sun, Miaoyu Chen, Weihan Wang, Qiao Li, Shiqiang Ju

{"title":"PAK1 mediates ivermectin-induced DNA damage in porcine oocytes during meiotic maturation","authors":"Tianhang Yu, Yijing He, Heran Li, Qinfeng Sun, Miaoyu Chen, Weihan Wang, Qiao Li, Shiqiang Ju","doi":"10.1016/j.fct.2025.115653","DOIUrl":"10.1016/j.fct.2025.115653","url":null,"abstract":"<div><div>Ivermectin (IVM), a broad-spectrum antiparasitic agent, is widely utilized in agriculture and animal husbandry. However, the presence of its residues in the environment and food sources may pose potential risks to animal health. Although various cytotoxic effects of IVM have been reported, there is limited information available regarding whether IVM exposure can exert toxic effects on mammalian oocytes. In this study, porcine oocytes were exposed to varying concentrations of IVM for 44 h during <em>in vitro</em> maturation. The results showed that 10 μM IVM significantly inhibited oocyte maturation, as evidenced by the inhibition of first polar body (PB1) extrusion, cytoskeletal disorganization, and meiotic progression arrest. Furthermore, IVM treatment increased expression of γ-H<sub>2</sub>AX but decreased P21-activated kinase 1 (PAK1) in oocytes, while inhibiting DNA homologous recombination (HR) repair process. Interestingly, these negative effects of IVM were significantly alleviated by the increased expression of PAK1. However, co-treatment with Mirin, an inhibitor of HR repair, reversed the alleviating effect of PAK1 overexpression on oocyte meiotic maturation and DNA damage.</div><div>In conclusion, IVM exposure adversely affects the maturation of porcine oocytes and induced DNA damage. Additionally, PAK1 is involved in IVM-induced DNA damage in oocytes, and its mediating role is closely related to the regulation of HR repair.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"204 ","pages":"Article 115653"},"PeriodicalIF":3.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CDDO-Me triggers ROS-dependent ferroptosis and apoptosis in cervical cancer via targeting PI3K/Nrf2 pathway CDDO-Me通过靶向PI3K/Nrf2通路触发ros依赖性宫颈癌铁下垂和凋亡

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-07-24 DOI: 10.1016/j.fct.2025.115664

Wenxuan Li , Mengying Wang , Pan Du , Anna Han , Xinyue Feng , Liyan Chen

{"title":"CDDO-Me triggers ROS-dependent ferroptosis and apoptosis in cervical cancer via targeting PI3K/Nrf2 pathway","authors":"Wenxuan Li , Mengying Wang , Pan Du , Anna Han , Xinyue Feng , Liyan Chen","doi":"10.1016/j.fct.2025.115664","DOIUrl":"10.1016/j.fct.2025.115664","url":null,"abstract":"<div><h3>Context</h3><div>Cervical cancer (CC) ranks as one of the most common types of malignant tumors affecting women. CDDO-Me is derived from oleanolic acid, a pentacyclic triterpenoid obtained by chemical structural modification, which has been shown anti-tumor effects.</div></div><div><h3>Results</h3><div>CC cell proliferation was decreased by CDDO-Me both in vitro and in vivo. Mechanistically, CDDO-Me led to a reduction of intracellular mitochondrial volume and crista, or an increase of membrane density. The levels of ROS, Fe<sup>2+</sup>, MDA were increased while GSH was decreased. Meanwhile, the levels of protein expression of GPX4, Nrf2, NQO1 and FTH1 were observably inhibited by CDDO-Me. Specifically, ferroptosis triggered by CDDO-Me was reverted by DFO. It has been demonstrated that CDDO-Me-induced apoptosis and ferroptosis in CC cells is contingent upon the PI3K/AKT-mediated Nrf2/NQO1 pathway.</div></div><div><h3>Conclusions</h3><div>CDDO-Me induces CC cell lines apoptosis and ferroptosis through the PI3K/Nrf2 signaling pathway, for exerting anti-proliferation effects.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"204 ","pages":"Article 115664"},"PeriodicalIF":3.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intestinal metabolomic profiling provides insights into the molecular mechanisms for hyperuricemia-induced intestinal barrier dysfunctions in a hyperuricemia mouse model 肠道代谢组学分析为高尿酸血症小鼠模型中高尿酸血症诱导的肠屏障功能障碍的分子机制提供了见解。

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2025-07-24 DOI: 10.1016/j.fct.2025.115666

Hailong Li, Qingli Zhang, Tingting Tang, Lei Zhu, Qu Chen, Haili Zhang, Yan Zhang, Zichu Zhao, Di Xiao, Xinlei Sha, Jingrong Mu, Jingjing Kong

{"title":"Intestinal metabolomic profiling provides insights into the molecular mechanisms for hyperuricemia-induced intestinal barrier dysfunctions in a hyperuricemia mouse model","authors":"Hailong Li, Qingli Zhang, Tingting Tang, Lei Zhu, Qu Chen, Haili Zhang, Yan Zhang, Zichu Zhao, Di Xiao, Xinlei Sha, Jingrong Mu, Jingjing Kong","doi":"10.1016/j.fct.2025.115666","DOIUrl":"10.1016/j.fct.2025.115666","url":null,"abstract":"<div><div>Cadmium exposure could damage the liver, which is suggested to be associated with the hyperuricemia (HUA)-induced intestinal barrier injury. To reveal the mechanism for HUA-induced intestinal barrier injury, the HUA mice constructed by knockout (Ko) of the urate oxidase (<em>Uox</em>) gene and their corresponding controls were used for the metabolomics analysis. Clinical biochemistry from the plasma was assessed, and the histopathological changes of the intestines were evaluated. Metabolomics was performed to explore the intestinal metabolomic profiles from the Uox-Ko mice, and the potential metabolic biomarkers were identified. Compared with controls, Uox-Ko mice showed dramatically increased uric acid, creatinine, and urea nitrogen levels, along with sparse intestinal villi, mucosal and submucosal edema. Metabolomics found the five metabolites were significantly dysregulated in intestines from the Uox-Ko mice, which includes N-acetylornithine, palmitoleic acid, 4-pyridoxic acid, phenylacetylglycine and 3-indoxyl sulphate. These altered pathways were involved fatty acid biosynthesis, biosynthesis of amino acids, arginine biosynthesis, vitamin B6 metabolism and 2-oxocarboxylic acid metabolism. 4-pyridoxic acid was identified as the most promising metabolic biomarker for predicting HUA-induced intestinal barrier damage. Our findings suggest the metabolic disturbances may contribute to the development of HUA-induced intestinal barrier injury, which may shed light on the mechanisms of cadmium-induced liver damage.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"204 ","pages":"Article 115666"},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual Mechanisms of Vitisin A in Managing Alcoholic Liver Disease: Inhibition of Lipogenesis and Complement Activation. 维生素A治疗酒精性肝病的双重机制：抑制脂肪生成和补体激活。

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-07-23 DOI: 10.1016/j.fct.2025.115639

Yuanqin Zhu, Huilin Deng, Jia Liu, Xusheng Li, Xin Huang, Zhaodi Che, Weibin Bai, Rui Jiao

{"title":"Dual Mechanisms of Vitisin A in Managing Alcoholic Liver Disease: Inhibition of Lipogenesis and Complement Activation.","authors":"Yuanqin Zhu, Huilin Deng, Jia Liu, Xusheng Li, Xin Huang, Zhaodi Che, Weibin Bai, Rui Jiao","doi":"10.1016/j.fct.2025.115639","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115639","url":null,"abstract":"<p><p>Pyranoanthocyanins in aged red wine show superior stability, pigmentation, antioxidative, anti-inflammatory, and hypocholesterolemic properties compared to unmodified anthocyanin precursors in vitro. However, evidence supporting their health benefits in vivo remains limited. This study evaluated the hepatoprotective effects of Vitisin A compared to Cyanidin-3-O-glucoside using Lieber-DeCarli mouse and AML12 cell models. Additionally, mulberry wine anthocyanins and their aged counterparts were evaluated in vivo. All anthocyanin treatments significantly alleviated ethanol-induced hepatic steatosis and improved alcohol metabolism. Notably, Vitisin A markedly reduced plasma AST and ALT levels (p < 0.05), a result not observed with C3G. RNA-seq analysis showed Vitisin A induced significant gene expression changes, especially in complement system and lipid metabolism pathways. It inhibited fatty acid synthesis by upregulating p-AMPK/AMPK and p-ACC/ACC ratios, suppressing FASN expression, and reduced complement activation by downregulating C3 and decreasing C3ar1 and Tnf-α expression, mitigating Kupffer cell-mediated inflammation. In contrast, C3G and ACNS had limited effects on these pathways, particularly in complement modulation. These findings highlight the dual actions of vitisin A in inhibiting de novo lipogenesis and complement activation, demonstrating its superior efficacy over C3G. This study underscores the therapeutic potential of vitisin A as a functional food component for managing alcoholic liver disease.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115639"},"PeriodicalIF":3.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lithium suppresses the Ras-Raf-MEK-ERK signaling in CD4 T cells and impairs the humoral immune system 锂抑制CD4 T细胞中的Ras-Raf-MEK-ERK信号，损害体液免疫系统

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-07-23 DOI: 10.1016/j.fct.2025.115661

Jiaojiao Wu , Yifan Zhao , Jie Zhang , Lihong Tu , Yalin Liu , Chuanxuan Wang , Ting Liu , Wei Wang , Yijia Luo , Yingzi Ju , Peng Xue , Yanyi Xu , Minghua Gu , Weidong Qu , Yubin Zhang

{"title":"Lithium suppresses the Ras-Raf-MEK-ERK signaling in CD4 T cells and impairs the humoral immune system","authors":"Jiaojiao Wu , Yifan Zhao , Jie Zhang , Lihong Tu , Yalin Liu , Chuanxuan Wang , Ting Liu , Wei Wang , Yijia Luo , Yingzi Ju , Peng Xue , Yanyi Xu , Minghua Gu , Weidong Qu , Yubin Zhang","doi":"10.1016/j.fct.2025.115661","DOIUrl":"10.1016/j.fct.2025.115661","url":null,"abstract":"<div><div>Lithium (Li) is a metal that broadly exists in human bodies. To date, the impact of Li on the humoral immune system remains to be defined. In this study, C57BL/6 mice treated with 50 or 200 ppm Li for 3 months and human peripheral blood mononuclear cells (PBMC) treated with Li in vitro were used. Treatment with 200 ppm Li suppressed the production of serum IgG, but not serum IgM in mice; treatment with 200 ppm Li impaired the activation of CD4 T cells and B cells, and the production of germinal center in mice. Mechanistically, treatment with 200 ppm Li impaired the Ras-Raf-MEK-ERK signaling in CD4 T cells and thereby suppressed the humoral immune system in mice. In line with this, in vitro treatment with Li on human PBMC decreased the production of IgG, but not IgM in the supernatants; in vitro treatment with Li on human PBMC suppressed the activation of CD4 T cells and impaired the Ras-Raf-MEK-ERK signaling in CD4 T cells. Collectively, the present study indicated that Li impaired the humoral immune system via repressing the Ras-Raf-MEK-ERK signaling in CD4 T cells, which was a previously unrecognized immunotoxicity of Li.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"204 ","pages":"Article 115661"},"PeriodicalIF":3.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0