Journal of Applied Toxicology最新文献_第3页

Non-clinical safety evaluation of Yongdamsagan-tang water extract: A 13-week subchronic oral toxicity study in Sprague Dawley rats. 龙胆泻肝汤水提取物的非临床安全性评价：在 Sprague Dawley 大鼠中进行的为期 13 周的亚慢性口服毒性研究。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-10-04 DOI: 10.1002/jat.4703

Woo-Young Jeon, Chang-Seob Seo, Hyekyung Ha, Hyeun-Kyoo Shin, Jae-Woo Cho, Mee-Young Lee

引用次数: 0

Toxic Effects of 4-Bromodiphenyl Ether (BDE-3) on Antioxidant Enzymes, Cell Viability, Histology and Biomolecules in Zebrafish Embryo-Larvae. 4-溴联苯醚（BDE-3）对斑马鱼胚胎-幼鱼抗氧化酶、细胞活力、组织学和生物大分子的毒性影响

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-10-04 DOI: 10.1002/jat.4708

Shiv Kumar, Pooja Chadha

{"title":"Toxic Effects of 4-Bromodiphenyl Ether (BDE-3) on Antioxidant Enzymes, Cell Viability, Histology and Biomolecules in Zebrafish Embryo-Larvae.","authors":"Shiv Kumar, Pooja Chadha","doi":"10.1002/jat.4708","DOIUrl":"https://doi.org/10.1002/jat.4708","url":null,"abstract":"Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants that are being used widely in industrial and consumers products such as plastics, electronics, furniture, textiles and so forth. They can undergo debromination process to form less brominated diphenyl ethers, which are bioaccumulative, more volatile and more toxic in nature. The current study was conducted to reveal the biochemical, apoptotic, histopathological, ultrastructural and biomolecular (ATR-FTIR) toxicity of 4-bromodiphenyl ether (BDE-3) in zebrafish larvae. After the 96-h LC50 determination, the zebrafish embryos were exposed to sublethal concentrations of BDE-3, that is, 0.79 and 1.59 mg/L. The MDA content was found to be significantly increased in BDE-3 exposed larvae whereas the FRAP activity was found to be decreased. The catalase (CAT), glutathione-S-transferase (GST) and acetylcholinesterase (AChE) activity were observed to be significantly increased, and a decreased superoxide dismutase (SOD) activity was reported after the BDE-3 exposure in zebrafish larvae. The cell viability was reported to be decreased in zebrafish larvae after BDE-3 exposure. Histopathological and ultrastructural alterations were also observed in the BDE-3 exposed zebrafish larvae. The changes in the biomolecules such as DNA and protein were also revealed via ATR-FTIR analysis. The present investigation will help to understand the toxic nature of less brominated diphenyl ethers and could be utilised to assess environmental risk.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375460","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

Investigation of oral toxicity of WS₂ nanosheets to mouse intestine: Pathological injury, trace element balance, lipid profile changes, and autophagy. 研究 WS2 纳米片对小鼠肠道的口服毒性：病理损伤、微量元素平衡、脂质变化和自噬。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-09-29 DOI: 10.1002/jat.4701

Zhenghao Zha, Sihuan Luo, Lianghuan Wei, Feixing Li, Youwen Li, Yi Cao

{"title":"Investigation of oral toxicity of WS2 nanosheets to mouse intestine: Pathological injury, trace element balance, lipid profile changes, and autophagy.","authors":"Zhenghao Zha, Sihuan Luo, Lianghuan Wei, Feixing Li, Youwen Li, Yi Cao","doi":"10.1002/jat.4701","DOIUrl":"https://doi.org/10.1002/jat.4701","url":null,"abstract":"The success of graphene oxides has gained extensive research interests in developing novel 2D nanomaterials (NMs). WS2 nanosheets (NSs) are novel transition metal-based 2D NMs, but their toxicity is unclear. In this study, we investigated the oral toxicity of WS2 NSs to mouse intestines. Male mice were administrated with vehicles, 1, 10, or 100 mg/kg NSs via intragastric route, once a day, for 5 days. The results indicate that the NSs did not induce pathological or ultrastructural changes in intestines. There were minimal changes of trace elements that the exposure did not induce W accumulation, and only Co levels were dose-dependently increased. Lipid droplets were observed in all groups of mice, but lipidomics data indicate that WS2 NSs only significantly decreased four lipid species, all belonging to phosphatidylcholine (PC). The levels of proteins regulating autophagic lipolysis, namely, LC3, lysosomal associated membrane protein 2 (LAMP2) and perilipin 2 (PLIN2), were increased, but it was only statistically significantly different for LC3. The results of this study suggest that repeated intragastric exposure to WS2 NSs only induced minimal influences on pathological injury, trace element balance, autophagy, and lipid profiles in mouse intestines, indicating relatively high biocompatibility of WS2 NSs to mouse intestine via oral route.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347374","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

Long-term nanoplastics exposure contributes to impaired steroidogenesis by disrupting the hypothalamic-testis axis: Evidence from integrated transcriptome and metabolome analysis. 长期接触纳米塑料会破坏下丘脑-睾丸轴，导致类固醇生成受损：转录组和代谢组综合分析的证据。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-09-27 DOI: 10.1002/jat.4696

Qian He, Xin Li, Caiyan Xie, Mingzhe Zhang, Zebin Lai, Yan Zhou, Lei Luo, Yunxiao Yang, Mengyuan Qu, Kunming Tian

{"title":"Long-term nanoplastics exposure contributes to impaired steroidogenesis by disrupting the hypothalamic-testis axis: Evidence from integrated transcriptome and metabolome analysis.","authors":"Qian He, Xin Li, Caiyan Xie, Mingzhe Zhang, Zebin Lai, Yan Zhou, Lei Luo, Yunxiao Yang, Mengyuan Qu, Kunming Tian","doi":"10.1002/jat.4696","DOIUrl":"https://doi.org/10.1002/jat.4696","url":null,"abstract":"Cumulative evidence suggested that nanoplastics (NPs) cause male toxicity, but the mechanisms of which are still misty. Steroidogenesis is a key biological event that responsible for maintaining reproductive health. However, whether dysregulated steroidogenesis is involved in NPs-induced impaired male reproductive function and the underlying mechanism remains unclear. In our study, Balb/c mice were continuously exposed to pristine-NPs or NH2-NPs for 12 weeks, spanning the puberty and adult stage. Upon the long-term NPs treatment, the hypothalamus and testis were subjected to transcriptome and metabolome analysis. And the results demonstrated that both primitive-NPs and NH2-NPs resulted in impaired spermatogenesis and steroidogenesis, as evidenced by a significant reduction in sperm quality, testosterone, FSH, and LH. The expression of genes involved in hypothalamic-pituitary-testis (HPT) axis, such as Kiss-1 and Cyp17a1 that encoded the key steroid hormone synthetase, was also diminished. Furthermore, the phosphatidylcholine and pantothenic acid that mainly enriched in glycerophospholipid metabolism were significantly reduced in the testis. Comprehensive analysis of the transcriptome and metabolome indicated that down-regulated Cyp17a1 was associated with decreased metabolites phosphatidylcholine and pantothenic acid. Overall, we speculate that the disturbed HPT axis induced by long-term NPs contributes to disordered glycerophospholipid metabolism and subsequently impaired steroidogenesis. Our findings deepen the understanding of the action of the mechanism responsible for NPs-induced male reproductive toxicology.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347375","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

Nicotine as a female reproductive toxicant-A review. 尼古丁作为一种女性生殖毒物--综述。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2024-09-26 DOI: 10.1002/jat.4702

Jitender Kumar Bhardwaj, Anshu Siwach, Som Nath Sachdeva

{"title":"Nicotine as a female reproductive toxicant-A review.","authors":"Jitender Kumar Bhardwaj, Anshu Siwach, Som Nath Sachdeva","doi":"10.1002/jat.4702","DOIUrl":"https://doi.org/10.1002/jat.4702","url":null,"abstract":"The preceding decades have seen an extensive emergence of the harmful effects of tobacco smoke on systemic health. Among the various compounds of tobacco, nicotine is one of the principal, potentially hazardous, and toxic components which is an oxidant agent that can affect both men's and women's fertility. Nicotine exerts its effect by modulating the expression of transmembrane ligand-gated ion channels called nicotinic acetylcholine receptors. The activities of female reproduction might be disrupted by exposure to nicotine at various sites, such as the ovary or reproductive tract. It's been demonstrated that nicotine might cause oxidative stress, apoptosis, hormonal imbalance, abnormalities in chromosomal segregation, impact oocyte development, and disruption in ovarian morphology and functions. This review paper summarizes the findings and provides an updated overview of the evidence on the harmful effects of nicotine use on women's reproductive health and the resulting detrimental impacts on the body. Additionally, it provides the detailed possible mechanisms involved in impairing reproductive processes like folliculogenesis, oocyte maturation, steroidogenesis, and pregnancy in different animal species.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347376","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

Reference gene considerations for toxicological assessment of the flame retardant triphenyl phosphate in an in vitro fish embryonic model. 在体外鱼类胚胎模型中对阻燃剂磷酸三苯酯进行毒理学评估时的参考基因考虑。

IF 3.3 4区医学

Journal of Applied Toxicology Pub Date : 2024-09-18 DOI: 10.1002/jat.4698

Logan Germain,Delaine Pereira,Louise M Winn

{"title":"Reference gene considerations for toxicological assessment of the flame retardant triphenyl phosphate in an in vitro fish embryonic model.","authors":"Logan Germain,Delaine Pereira,Louise M Winn","doi":"10.1002/jat.4698","DOIUrl":"https://doi.org/10.1002/jat.4698","url":null,"abstract":"The reliability of relative quantification RT-qPCR depends upon the gene of interest being normalized to one or more reference genes, with the assumption that the chosen reference genes do not experience altered expression with experimental conditions. The correct choice of stable reference genes is critical when investigating alterations to gene transcript levels following exposure to endocrine and metabolic disrupting chemicals, such as the flame retardant triphenyl phosphate (TPhP). This study assessed the stability of eight reference genes following TPhP exposure in embryonic cells derived from rainbow trout (Oncorhynchus mykiss). The genes β-actin (actb) and 18s rRNA (18s) were stable, while glyceraldehyde-3-phosphate dehydrogenase (gapdh) relative expression was found to be increased. gapdh is a popular reference gene and has been previously used in the literature for investigating TPhP exposure in teleost fish models. We discuss the implications of gapdh upregulation in the context of TPhP as a metabolic disrupting chemical. Furthermore, we quantified the expression of the tumor suppressor gene p53 following TPhP exposure in relation to different reference genes to use as an example to report on how discrepancies in findings might arise depending on the stability of the chosen reference gene.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"5 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261859","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

Flame retardant, hexabromocyclododecane, increases production of pro‐inflammatory cytokines, interleukin 1‐beta and interleukin 6, in human immune cells 阻燃剂六溴环十二烷会增加人体免疫细胞中促炎细胞因子（白细胞介素 1-beta 和白细胞介素 6）的产生

IF 3.3 4区医学

Journal of Applied Toxicology Pub Date : 2024-09-17 DOI: 10.1002/jat.4700

April Falconer‐Turner, Kameron Brooks, Eseoghene Ogaga, Margaret M. Whalen

{"title":"Flame retardant, hexabromocyclododecane, increases production of pro‐inflammatory cytokines, interleukin 1‐beta and interleukin 6, in human immune cells","authors":"April Falconer‐Turner, Kameron Brooks, Eseoghene Ogaga, Margaret M. Whalen","doi":"10.1002/jat.4700","DOIUrl":"https://doi.org/10.1002/jat.4700","url":null,"abstract":"Hexabromocyclododecane (HBCD) is an environmental contaminant due to its use as a flame retardant in a variety of applications ranging from building insulation, furniture upholstery, and housing for appliances and electronics. HBCD is found in wildlife, human breastmilk, and serum. Interleukin 1‐beta (IL‐1β) and interleukin 6 (IL‐6) are pro‐inflammatory cytokines, whose dysregulation is associated with chronic inflammation and the pathologies that result, such as tumor growth, rheumatoid arthritis, Crohn's disease, and multiple sclerosis. HBCD has been shown to increase the secretion of both IL‐1β and IL‐6 from human immune cells. However, it is not clear if these increases are due solely to HBCD effects on the secretory process or whether it is stimulating cellular production of IL‐1β and IL‐6. This study examines if HBCD can increase the production of IL‐1β and IL‐6 by immune cells by simultaneously assessing secreted levels and cellular levels of these cytokines. Additionally, the mechanisms for any observed changes in production are investigated. Peripheral blood mononuclear cells were exposed to HBCD over a range of concentrations and lengths of exposure. HBCD was found to stimulate IL‐1β and IL‐6 production after 6 hrs. of exposure and production was sustained and intensified at 24 hrs. This increase in IL‐1β and IL‐6 production appears to, in part, be a result of increased mRNA expression. Additionally, the MAPK pathways, specifically the p38 and p44/42 pathways, appear to be required for HBCD‐induced increases in IL‐1β and IL‐6 production.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"30 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261547","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

Nebivolol hydrochloride and its impurities induce pseudo‐allergic reactions via mast cell activation 盐酸奈必洛尔及其杂质通过激活肥大细胞诱发假性过敏反应

IF 3.3 4区医学

Journal of Applied Toxicology Pub Date : 2024-09-17 DOI: 10.1002/jat.4699

Liju Yu, Yi Shan, Jiayu Lu, Huaizhen He

引用次数: 0

Nuciferine protects hyperandrogen‐injured ovarian granulosa cells by inhibiting ferroptosis via SOX2‐mediated activation of the SLC7A11/GPX4 axis 核iferine 通过 SOX2 介导的 SLC7A11/GPX4 轴活化抑制铁突变，从而保护高雄激素损伤的卵巢颗粒细胞

IF 3.3 4区医学

Journal of Applied Toxicology Pub Date : 2024-09-17 DOI: 10.1002/jat.4697

Hongyu Yang, Shichao Chen, Shanshan Yin, Qi Ding

{"title":"Nuciferine protects hyperandrogen‐injured ovarian granulosa cells by inhibiting ferroptosis via SOX2‐mediated activation of the SLC7A11/GPX4 axis","authors":"Hongyu Yang, Shichao Chen, Shanshan Yin, Qi Ding","doi":"10.1002/jat.4697","DOIUrl":"https://doi.org/10.1002/jat.4697","url":null,"abstract":"Polycystic ovary syndrome (PCOS) is a common endocrine disorder that can cause menstrual irregularities, infertility, polycystic ovaries, and metabolic abnormalities. Female reproductive health and quality of life are significantly affected by PCOS, which has recently been associated with ferroptosis in granulosa cells (GCs). Nuciferine (NF) is a naturally extracted substance with multiple pharmacological activities, which is reported with anti‐ferroptosis function. Herein, the influence of NF for androgen‐induced ferroptosis in GCs was investigated to explore the potential value of NF on treating PCOS. 10 μM NF and 20 μM NF were employed for treating KGN cells according to cell viability results. KGN cells were treated with 10 μM dehydroepiandrosterone (DHEA) for 1 day, followed by introducing 10 μM NF and 20 μM NF for 24 h. Strikingly reduced cell viability, increased lactate dehydrogenase release and reactive oxygen species (ROS) production, enhanced apoptosis, upregulated Bax, downregulated Bcl‐2, restrained malondialdehyde contents, and declined superoxide dismutase activity were observed in DHEA‐treated KGN cells, which were significantly reversed by NF. Significantly repressed GPX4, SLC7A11, and SOX2 levels, as well as increased ACSL4 levels and Fe2+ levels in DHEA‐treated KGN cells, were notably rescued by NF. Furthermore, the inhibitory effect of NF on ROS production and ferroptosis in DHEA‐treated KGN cells was partially abrogated by silencing SOX2. Collectively, NF protected DHEA‐injured ovarian GCs by inhibiting ferroptosis via upregulating SOX2.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"88 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261861","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 ameliorative potential of metformin against aluminum‐induced neurotoxicity: Insights from in vitro studies 二甲双胍对铝诱导的神经毒性的改善潜力：体外研究的启示

IF 3.3 4区医学

Journal of Applied Toxicology Pub Date : 2024-09-14 DOI: 10.1002/jat.4695

Sonia Sanajou, Anil Yirün, Göksun Demirel, Pinar Erkekoğlu, Gönül Şahin, Terken Baydar

{"title":"The ameliorative potential of metformin against aluminum‐induced neurotoxicity: Insights from in vitro studies","authors":"Sonia Sanajou, Anil Yirün, Göksun Demirel, Pinar Erkekoğlu, Gönül Şahin, Terken Baydar","doi":"10.1002/jat.4695","DOIUrl":"https://doi.org/10.1002/jat.4695","url":null,"abstract":"Alzheimer's disease (AD) is increasingly recognized as a metabolic disorder, often referred to as type 3 diabetes, due to its strong association with insulin resistance. Chronic exposure to aluminum, a known neurotoxin, has been identified as a significant risk factor in the development and progression of AD. This study explores the potential of metformin, a common anti‐diabetic drug, to mitigate aluminum‐induced neurotoxicity in an in vitro model of AD. Our findings reveal that metformin significantly reduces oxidative stress markers such as malonaldehyde, carbonyl groups, and reactive oxygen species while enhancing antioxidant defenses. Metformin modulates critical signaling pathways, including glycogen synthase kinase 3 beta (GSK3‐β)/RAC‐alpha serine/threonine protein kinase (RAC‐alpha serine/threonine protein kinase (Akt1)/protein phosphatase 2A (PP2A) and Wnt/β‐catenin, decreasing Tau protein levels and promoting neurogenesis. These results suggest that metformin may offer a novel therapeutic approach for AD, particularly in cases where aluminum exposure is a contributing factor.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"30 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261862","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