Journal of Applied Toxicology最新文献_第8页

Dose-Dependent Hepatorenal Damage Induced by Erythrosine: A Study of Biochemical, Oxidative Stress, DNA Damage, and Histopathological Effects in Wistar Rats 红素所致剂量依赖性肝肾损害：Wistar大鼠生化、氧化应激、DNA损伤和组织病理学影响的研究

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-01-22 DOI: 10.1002/jat.4754

Mandeep Singh, Pooja Chadha

{"title":"Dose-Dependent Hepatorenal Damage Induced by Erythrosine: A Study of Biochemical, Oxidative Stress, DNA Damage, and Histopathological Effects in Wistar Rats","authors":"Mandeep Singh, Pooja Chadha","doi":"10.1002/jat.4754","DOIUrl":"10.1002/jat.4754","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to provide insights into the hepatorenal toxicity induced by erythrosine, a synthetic red dye commonly used in food and pharmaceuticals, which has raised concerns over its potential health risks. Twenty-four rats were randomly divided into four groups (<i>n</i> = 6). The first group was the control group and the other group received one of three doses of erythrosine based on acceptable daily intake (¼ ADI, ½ ADI, and ADI, 0.1 mg/kg body weight). This study examined biological activity via biochemical enzyme analysis, oxidative stress indices, DNA damage, and histopathology. Compared with the control group, erythrosine administration increased the serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein, urea, creatinine, and uric acid at the highest erythrosine dose. The catalase and the superoxide dismutase activity decreased in both tissues at the highest dose. The glutathione-S-transferase activity increased at the ¼ ADI dose and decreased at higher doses in both tissues. In contrast, acetylcholinesterase activity was greater in erythrosine-treated rats than in control rats. Oxidative stress indices indicated increased lipid peroxidation, hydrogen peroxide content, and lactate dehydrogenase activity. The comet assay was used to assess DNA damage, revealing significant damage in the erythrosine-treated groups. Histopathological examination revealed necrotic and degenerative changes in the liver and kidney tissues. The findings underscore dose-dependent hepatorenal toxicity and highlight the novelty of demonstrating a comprehensive link between erythrosine exposure, oxidative stress, and DNA damage. These results emphasize the need for cautious evaluation of synthetic dye consumption due to potential health risks.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"884-897"},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Systematic Review of the Epidemiology of Hair Relaxer Use and Hormone-Sensitive Reproductive Outcomes Among Black Adult Women in the United States. 美国黑人成年女性使用头发松弛剂和激素敏感生殖结果的流行病学系统综述。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-01-19 DOI: 10.1002/jat.4744

Ashley M Hernandez, Sierra J Smith, Moin S Vahora, Devan Campbell, Callan F Krevanko, Ryan C Lewis, Jennifer S Pierce

{"title":"Systematic Review of the Epidemiology of Hair Relaxer Use and Hormone-Sensitive Reproductive Outcomes Among Black Adult Women in the United States.","authors":"Ashley M Hernandez, Sierra J Smith, Moin S Vahora, Devan Campbell, Callan F Krevanko, Ryan C Lewis, Jennifer S Pierce","doi":"10.1002/jat.4744","DOIUrl":"https://doi.org/10.1002/jat.4744","url":null,"abstract":"<p><p>Hair relaxers are predominantly used by Black women in the United States. It has been recently suggested that exposure to potential endocrine-disrupting compounds from the use of these products may be associated with the development of gynecological and breast cancers and anatomically relevant nonmalignancies. We conducted a systematic literature review using PubMed to identify original studies reporting measures of association between hair relaxer use and relevant adverse outcomes, focusing specifically on Black women in the United States. A total of 1382 studies were initially identified, and after consideration of the exclusion and inclusion criteria, the final set of studies consisted of seven cohort studies and one case-control study. The overall findings suggest that Black women in the United States do not experience an increased risk of breast cancer, ovarian cancer, or uterine cancer due to hair relaxers. One study found a statistically significant association between hair relaxer use and uterine leiomyomata, but there were no other studies identified to support these findings. None of the studies characterized the chemical constituents of hair relaxers. From an epidemiologic perspective, the weight of the evidence does not support the hypothesis that the use of hair relaxers is a risk factor for gynecological and breast cancers in US Black women.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Impact of Genetic Polymorphisms on Genotoxicity (DNA Damage) Induced by Cigarette Smoke in Humans: A Systematic Review. 遗传多态性对人类吸烟引起的遗传毒性（DNA损伤）的影响：系统综述。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-01-17 DOI: 10.1002/jat.4753

Thiago Guedes Pinto, Lorrany da Silva Avanci, Ana Claudia Muniz Renno, Debora Cristina Hipolide, Jean Nunes Dos Santos, Patricia Ramos Cury, Rogerio Aparecido Dedivitis, Daniel Araki Ribeiro

{"title":"The Impact of Genetic Polymorphisms on Genotoxicity (DNA Damage) Induced by Cigarette Smoke in Humans: A Systematic Review.","authors":"Thiago Guedes Pinto, Lorrany da Silva Avanci, Ana Claudia Muniz Renno, Debora Cristina Hipolide, Jean Nunes Dos Santos, Patricia Ramos Cury, Rogerio Aparecido Dedivitis, Daniel Araki Ribeiro","doi":"10.1002/jat.4753","DOIUrl":"https://doi.org/10.1002/jat.4753","url":null,"abstract":"<p><p>The present systematic review aims to put together human population studies that include some relationship between genetic polymorphisms and genotoxicity as well as to evaluate the quality of the published studies induced by cigarette smoke exposure in vivo. The present systematic review was built according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Different genotoxicity assays were used by different authors, although the major goal was the genotoxicity assessment by means of micronucleus, comet, sister chromatid exchange, and chromosomal aberration assays. Also, different genetic polymorphisms were analyzed by different authors, being closely related to xenobiotics metabolizing and DNA repair genes. Our aim, therefore, was to collect these data so that a quality assessment could be properly carried out. Out of the 18 included studies, 15 reported genotoxicity due to cigarette smoking, and all of these reported some association between a genetic polymorphism and the aforementioned genotoxicity. Also, 14 studies were classified as either strong or moderate, which suggests the aforementioned findings can be trusted in regard to the studies' quality. Taken as a whole, the results suggest that genes associated with detoxification genes and DNA repair genes play a substantial role in the determination of an individual's susceptibility to genomic damage due to cigarette smoking.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

26-Week Repeated-Dose Toxicity Study of a Novel Antiarrhythmic Drug Sulcardine Sulfate in Sprague–Dawley Rats 新型抗心律失常药物硫酸硫卡定对Sprague-Dawley大鼠26周重复剂量毒性研究

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-01-16 DOI: 10.1002/jat.4750

Liangyu Zhang, Leilei Gu, Hongqun Qiao

{"title":"26-Week Repeated-Dose Toxicity Study of a Novel Antiarrhythmic Drug Sulcardine Sulfate in Sprague–Dawley Rats","authors":"Liangyu Zhang, Leilei Gu, Hongqun Qiao","doi":"10.1002/jat.4750","DOIUrl":"10.1002/jat.4750","url":null,"abstract":"<div>\u0000 \u0000 <p>Sulcardine sulfate (Sul) is a novel antiarrhythmic agent blocking multiple channels and exhibits unique pharmacological properties such as lower APD-dependent prolongation and reduced arrhythmia risk. Sul is currently in Phase III clinical trials, yet studies on its long-term toxicological profile and potential target organs remain unexplored. This study investigated the related toxicity of Sul in Sprague Dawley (SD) rats through repeated oral administration for 26 weeks, followed by a 4-week recovery period. Consistent with the clinical intended mode of administration, Sul was administered via oral gavage at daily doses of 0, 175, 350, and 700/525 mg/kg in rats. On account of clinically observed body weight loss of male and female rats in the high-dose group compared with the control group, with one female rat in the high-dose group dying after 8 weeks of administration, the high dose was adjusted to 525 mg/kg. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in male rats significantly increased in the medium- and high-dose groups, whereas female rats in these groups showed a significant rise in alkaline phosphatase (ALP) levels, accompanied by varying degrees of weight gain in the liver and lungs. Additionally, brownish-red pigment deposition was observed in hepatocytes and Kupffer cells across all dosing groups, along with foam cell deposition in the alveolar cavities. Concomitant toxicokinetics showed that the drug accumulated to some extent in the animals. Consequently, the liver and lungs were identified as potential target organs, and the no observed adverse effect level (NOAEL) was determined to be 175 mg/kg.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"866-883"},"PeriodicalIF":2.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Reactive Metabolites Cause Idiosyncratic Drug-Induced Liver Injury via Inflammasome Activation in Antigen-Presenting Cells 反应性代谢物通过抗原呈递细胞的炎性体激活引起特异性药物诱导的肝损伤。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-01-16 DOI: 10.1002/jat.4751

Ryuji Kato

引用次数: 0

Bioinformatic Analysis for Exploring Target Genes and Molecular Mechanisms of Cadmium-Induced Nonalcoholic Fatty Liver Disease and Targeted Drug Prediction 镉诱导非酒精性脂肪性肝病靶基因和分子机制的生物信息学分析及靶向药物预测

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-01-13 DOI: 10.1002/jat.4752

Le Zhang, Rui Wang, Qian Xue, Yongjie Wang, Jiayunzhu Xu, Chaofan Wang, Xin Fang, Shidi Gao, Haiying Zhang, Li Guo

{"title":"Bioinformatic Analysis for Exploring Target Genes and Molecular Mechanisms of Cadmium-Induced Nonalcoholic Fatty Liver Disease and Targeted Drug Prediction","authors":"Le Zhang, Rui Wang, Qian Xue, Yongjie Wang, Jiayunzhu Xu, Chaofan Wang, Xin Fang, Shidi Gao, Haiying Zhang, Li Guo","doi":"10.1002/jat.4752","DOIUrl":"10.1002/jat.4752","url":null,"abstract":"<div>\u0000 \u0000 <p>Cadmium (Cd) is a widely available metal that has been found to have a role in causing nonalcoholic fatty liver disease (NAFLD). However, the detailed toxicological targets and mechanisms by which Cd causes NAFLD are unknown. Therefore, the present work aims to reveal the main targets of action, cellular processes, and molecular pathways by which cadmium causes NAFLD. As shown in the bioinformatics analysis, there were 74 main targets of action for cadmium-induced NAFLD, hemopoietic cell kinase (HCK), EPH receptor A2 (EPHA2), MYC proto-oncogene (MYC), lysyl oxidase (LOX), dipeptidyl peptidase 7 (DPP7), nuclear factor erythroid 2-related factor 2 (NFE2L2), dual specificity phosphatase 6 (DUSP6), CD2 cytoplasmic tail binding protein 2 (CD2BP2), notch receptor 3 (NOTCH3), and phospholipase A2 group IVA (PLA2G4A) were screened as core genes. Testing these core genes in other databases, three differentially expressed genes, HCK, MYC, and DUSP6 were verified and used as targets for drug prediction in DsigDB; decitabine and retinoic acid were screened as potential therapeutic drugs for NAFLD based on the <i>p</i>-value and the combined score. The results of molecular docking showed that the predicted drugs can bind well to the core targets. In conclusion, cadmium is associated with NAFLD; the identified cadmium-toxicity targets, HCK, MYC, and DUSP6, may serve as biomarkers for the diagnosis of NAFLD and predicted drugs, decitabine and retinoic acid may have a potential role in the treatment of NAFLD.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"858-865"},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 CXCL13 in GC-1 Cell Cycle Arrest Induced by Titanium Dioxide Nanoparticles Through JAK2/STAT3 Signaling Pathway CXCL13通过JAK2/STAT3信号通路在二氧化钛纳米颗粒诱导GC-1细胞周期阻滞中的作用

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-01-07 DOI: 10.1002/jat.4747

Yuzhu Lei, Ruoyun Dong, Chenhao Sun, Yunhua Hu, Yizhong Yan, Guanling Song, Yan Wang

{"title":"The Role of CXCL13 in GC-1 Cell Cycle Arrest Induced by Titanium Dioxide Nanoparticles Through JAK2/STAT3 Signaling Pathway","authors":"Yuzhu Lei, Ruoyun Dong, Chenhao Sun, Yunhua Hu, Yizhong Yan, Guanling Song, Yan Wang","doi":"10.1002/jat.4747","DOIUrl":"10.1002/jat.4747","url":null,"abstract":"<div>\u0000 \u0000 <p>Titanium dioxide nanoparticles (TiO<sub>2</sub> NPs) can induce the cell cycle arrest in spermatogonia, and the JAK2/STAT3 signaling pathway plays a pivotal role in cell cycle progression, but the specific upstream regulatory mechanisms are not completely clarified. The purpose of this study was to investigate whether CXCL13 regulated the JAK2/STAT3 signaling pathway to participate in cell cycle arrest after mouse spermatogonia cell line (GC-1) exposure to TiO<sub>2</sub> NPs. The GC-1 cells were treated with TiO<sub>2</sub> NPs at different concentrations (0, 10, 20, 30, and 40 μg/mL) for 24 h to detect cell viability, cell cycle distribution, CXCL13 protein, JAK2/STAT3 pathway-related proteins, and cell cycle–related proteins. The CXCL13 recombinant protein was used to verify the role of CXCL13 in cell cycle and JAK2/STAT3 signaling pathway. TiO<sub>2</sub> NPs inhibited cell viability; regulated cell cycle–related proteins including remarkably decreased Cyclin D1, CDK4, Cyclin E1, and CDK2 as well as increased p21; and induced cell cycle arrest at the G0/G1 phase. TiO<sub>2</sub> NPs inhibited the levels of CXCL13 protein and weakened the activation of the JAK2/STAT3 signaling pathway by reducing the levels of p-JAK2/JAK2 and p-STAT3/STAT3 proteins. Furthermore, CXCL13 mitigated the suppression of the JAK2/STAT3 signaling pathway and the G0/G1 cell cycle arrest caused by TiO<sub>2</sub> NPs. Taken together, TiO<sub>2</sub> NPs downregulated the expression of CXCL13 to inhibit the activation of downstream JAK2/STAT3 signaling pathway, eventually inducing cell cycle arrest at the G0/G1 phase. These results provide a novel insight for complemented understanding of the mechanisms of TiO<sub>2</sub> NPs–induced cell cycle arrest in GC-1 cells.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"830-840"},"PeriodicalIF":2.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Transgenerational Reproductive and Developmental Toxicity Induced by N-Nitrosodimethylamine and Its Metabolite Formaldehyde in Drosophila melanogaster n -亚硝基二甲胺及其代谢物甲醛对黑腹果蝇的跨代生殖和发育毒性

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-01-07 DOI: 10.1002/jat.4749

Oscar Eduardo Tabares-Mosquera, Javier Andrés Juárez-Díaz, Rafael Camacho-Carranza, Patricia Ramos-Morales

{"title":"Transgenerational Reproductive and Developmental Toxicity Induced by N-Nitrosodimethylamine and Its Metabolite Formaldehyde in Drosophila melanogaster","authors":"Oscar Eduardo Tabares-Mosquera, Javier Andrés Juárez-Díaz, Rafael Camacho-Carranza, Patricia Ramos-Morales","doi":"10.1002/jat.4749","DOIUrl":"10.1002/jat.4749","url":null,"abstract":"<p><i>N</i>-Nitrosodimethylamine (NDMA) is a known water disinfection byproduct (DBP) characterized as a potent hepatotoxin, promutagen, and probable human carcinogen; this is because of the metabolites associated with its biotransformation. The metabolism of NDMA produces formaldehyde, another alkylating agent and DBP. Both compounds are generated from natural and anthropogenic sources, but the safety restrictions applied to NDMA do not extend to the uses of formaldehyde. Hence, potential health and ecological risks are of concern. Due to limited information on the long-term effects of exposure to these compounds at environmentally relevant concentrations, this work aimed to compare the transgenerational reproductive and developmental toxicity of separate exposures to NDMA or its metabolite formaldehyde in <i>Drosophila melanogaster</i> over four generations. The parental flies were fed NDMA or formaldehyde (1.19E−06 to 5 mM) for 48 h during the third larval instar. Subsequent offspring (F1–F3) were grown under compound-free conditions. In the parental generation, both exposures modified the time to emergence and reduced the number of progenies. NDMA, but not formaldehyde, was lethal, affected fertility, and weakly induced malformations. In the next generations, both exposures induced malformed flies and modified the number of offspring. Reproductive toxicity and malformations were maintained for at least three generations, suggesting that detrimental effects could extend to unexposed offspring. This is the first study reporting the associated individual transgenerational effects on reproduction and development between NDMA and its metabolite formaldehyde in <i>D. melanogaster</i>, highlighting the relevance of evaluating multiple generations to accurately determine the health and environmental risks of pollutants.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"841-857"},"PeriodicalIF":2.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jat.4749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Food Safety Evaluation of Recombinant Humanized Type III Collagen Produced by Komagataella phaffii SMD1168-2COL3 法菲Komagataella phaffii SMD1168-2COL3重组人源III型胶原蛋白的食品安全性评价

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-01-02 DOI: 10.1002/jat.4741

Qiu Dai, Shawna Lemke, Yuemei Lu, Steve Taylor, Haihang Li, Shengwei Fu, Xiaowen Wu, Nan Wang, Tian Xue, Xiaoyun He

{"title":"Food Safety Evaluation of Recombinant Humanized Type III Collagen Produced by Komagataella phaffii SMD1168-2COL3","authors":"Qiu Dai, Shawna Lemke, Yuemei Lu, Steve Taylor, Haihang Li, Shengwei Fu, Xiaowen Wu, Nan Wang, Tian Xue, Xiaoyun He","doi":"10.1002/jat.4741","DOIUrl":"10.1002/jat.4741","url":null,"abstract":"<div>\u0000 \u0000 <p>Collagens are biofunctional proteins that have been widely used in many fields, including biomedical, cosmetics, and skin care for their value in maintaining the integrity of cellular membranes. Collagens are also commonly consumed in foods and provide a source of protein and amino acids. As part of the safety assessment for this particular recombinant humanized type III (RHTypeIII) collagen produced by <i>Komagataella phaffii</i> SMD1168-2COL3, a series of toxicological tests were conducted. This collagen has ≥ 90% amino acid sequence homology to bovine and porcine collagen. The RHTypeIII collagen showed no evidence of genotoxic potential in a battery of tests. It was not toxic in an acute oral study, with no effects at 10 g/kg BW. The RHTypeIII collagen was not developmentally toxic in Sprague Dawley (SD) rat, and the NOAEL was 4.5 g/kg BW/day. In a 90-day oral gavage study in rats, there were no adverse findings observed; therefore, the high dose level (4.5 g/kg BW/day) was considered the NOAEL. The protein sequence was subjected to homology searches against the AllergenOnline database (sliding 80–amino acid windows and full sequence searches). From the 80-amino acid alignment searches, 23 significant matches were identified (> 35% identity and <i>E</i> value < 1 × 10<sup>−7</sup>) to allergens of bovine, fish, anisakis, feverfew pollen, ragweed pollen, and wheat origin. Although matches were identified, further assessment of the in silico results combined with a literature review demonstrates that the risk of allergenic cross-reactivity for this collagen is low. These results demonstrate RHTypeIII collagen is not toxic and unlikely to present a risk of allergy when used as a food ingredient.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"808-829"},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

6-Chloronicotinic Acid Induces Toxicity in Mouse Neural Stem Cells via the C3ar1 Signaling 6-氯烟酸通过C3ar1信号诱导小鼠神经干细胞毒性

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-12-29 DOI: 10.1002/jat.4746

Min He, Yahang Lin, Xiaojing Zhang, Siyi Wang, Xinyu Yang, Fengzhen Cui, Xia Sheng

{"title":"6-Chloronicotinic Acid Induces Toxicity in Mouse Neural Stem Cells via the C3ar1 Signaling","authors":"Min He, Yahang Lin, Xiaojing Zhang, Siyi Wang, Xinyu Yang, Fengzhen Cui, Xia Sheng","doi":"10.1002/jat.4746","DOIUrl":"https://doi.org/10.1002/jat.4746","url":null,"abstract":"<div>\u0000 \u0000 <p>Neural stem cells (NSCs) are essential for brain development due to their ability to proliferate and differentiate into various neural cell types. Neonicotinoid insecticides (NNIs), which have replaced traditional pesticides, are now widely used and frequently detected in environmental and biological samples. Prenatal exposure to NNIs has been associated with an increased risk of neurodevelopmental disorders in offspring, yet the causal relationship and the underpinning mechanism remain to be clarified. As one of the primary metabolites of chloropyridinyl neonicotinoids, 6-chloronicotinic acid (6-ClNA) has been identified as a potential neurotoxin, though its effects on NSCs have not been fully explored. Here, we demonstrate that 6-ClNA exposure significantly disrupted NSC proliferation and differentiation in vitro. Transcriptomic analyses revealed that 6-ClNA altered the expression of pathways related to proliferation, apoptosis, and inflammation, with notable activation of the C3ar1/C1qa signaling axis. Genetic ablation of <i>C3ar1</i> using siRNA markedly restored NSC proliferation and neurosphere formation, as well as reduced apoptosis, suggesting a central role of C3ar1/C1qa in mediating 6-ClNA's neurotoxic effects. These findings imply that early-life exposure to NNIs may affect the fitness and function of NSCs, wherein the <i>C3ar1</i> pathway plays an indispensable role.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"783-794"},"PeriodicalIF":2.7,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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