Toxicological Sciences最新文献_第9页

A whale of a tale: whale cells evade the driving mechanism for hexavalent chromium-induced chromosome instability. 鲸鱼的故事：鲸鱼细胞逃避六价铬诱导染色体不稳定的驱动机制。

IF 3.4 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae030

Haiyan Lu, Jennifer H Toyoda, Sandra S Wise, Cynthia L Browning, Rachel M Speer, Tayler J Croom-Pérez, Alicia Bolt, Idoia Meaza, John Pierce Wise

{"title":"A whale of a tale: whale cells evade the driving mechanism for hexavalent chromium-induced chromosome instability.","authors":"Haiyan Lu, Jennifer H Toyoda, Sandra S Wise, Cynthia L Browning, Rachel M Speer, Tayler J Croom-Pérez, Alicia Bolt, Idoia Meaza, John Pierce Wise","doi":"10.1093/toxsci/kfae030","DOIUrl":"10.1093/toxsci/kfae030","url":null,"abstract":"Chromosome instability, a hallmark of lung cancer, is a driving mechanism for hexavalent chromium [Cr(VI)] carcinogenesis in humans. Cr(VI) induces structural and numerical chromosome instability in human lung cells by inducing DNA double-strand breaks and inhibiting homologous recombination repair and causing spindle assembly checkpoint (SAC) bypass and centrosome amplification. Great whales are long-lived species with long-term exposures to Cr(VI) and accumulate Cr in their tissue, but exhibit a low incidence of cancer. Data show Cr(VI) induces fewer chromosome aberrations in whale cells after acute Cr(VI) exposure suggesting whale cells can evade Cr(VI)-induced chromosome instability. However, it is unknown if whales can evade Cr(VI)-induced chromosome instability. Thus, we tested the hypothesis that whale cells resist Cr(VI)-induced loss of homologous recombination repair activity and increased SAC bypass and centrosome amplification. We found Cr(VI) induces similar amounts of DNA double-strand breaks after acute (24 h) and prolonged (120 h) exposures in whale lung cells, but does not inhibit homologous recombination repair, SAC bypass, or centrosome amplification, and does not induce chromosome instability. These data indicate whale lung cells resist Cr(VI)-induced chromosome instability, the major driver for Cr(VI) carcinogenesis at a cellular level, consistent with observations that whales are resistant to cancer.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"49-62"},"PeriodicalIF":3.4,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Evaluation of organophosphorus pesticide tyrosine adducts for postmortem change by human serum albumin with liquid chromatography quadrupole Orbitrap mass spectrometry. 用液相色谱四极杆轨道质谱法评估人血清白蛋白中有机磷农药酪氨酸加合物在死后的变化。

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae023

Yoshikazu Yamagishi, Sayaka Nagasawa, Hirotaro Iwase, Yasumitsu Ogra

{"title":"Evaluation of organophosphorus pesticide tyrosine adducts for postmortem change by human serum albumin with liquid chromatography quadrupole Orbitrap mass spectrometry.","authors":"Yoshikazu Yamagishi, Sayaka Nagasawa, Hirotaro Iwase, Yasumitsu Ogra","doi":"10.1093/toxsci/kfae023","DOIUrl":"10.1093/toxsci/kfae023","url":null,"abstract":"Organophosphorus pesticides (OPPs) having a phosphate ester moiety, such as malathion (MA) and methidathion (DMTP), are widely used and have been detected in many fatal cases of accidental exposure or suicide in Japan. In forensic toxicology, the accurate determination of blood OPP concentration is mandatory to prove death by OPP poisoning. However, fatal pesticide concentration in blood at autopsy varies depending on the circumstances surrounding the dead body. In this study, we found that 16 OPPs were degraded by human serum albumin (HSA) in a temperature-dependent fashion. The mechanism underlying MA, DMTP, azinphos-methyl, etrimfos, fenthion (MPP), pirimiphos-methyl, (E)-dimethylvinphos, (Z)-dimethylvinphos, vamidothion, edifenphos (EDDP), fosthiazate, and pyraclofos degradation involves the formation of adducts with tyrosine residues in HSA. The mass spectra obtained by liquid chromatography quadrupole Orbitrap mass spectrometry revealed that phosphate ester amino acid adducts such as Y-adduct1, Y-adduct2, Y-adduct3, Y-adduct4, and Y-adduct5 were formed in HSA solution incubated with OPPs. These results indicate that the 16 OPPs are postmortem changed by HSA. The detection of phosphate ester amino acid adducts such as Y-adduct1, Y-adduct2, Y-adduct3, Y-adduct4, and Y-adduct5, instead of MA, DMTP, azinphos-methyl, etrimfos, MPP, pirimiphos-methyl, (E)-dimethylvinphos, (Z)-dimethylvinphos, vamidothion, EDDP, fosthiazate, and pyraclofos per se, may be used to determine death by these OPPs poisoning.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"40-48"},"PeriodicalIF":3.8,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898284","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

Quantitation and identification of microplastics accumulation in human placental specimens using pyrolysis gas chromatography mass spectrometry. 利用热解气相色谱质谱法对人体胎盘标本中的微塑料积聚进行定量和鉴定。

IF 3.4 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae021

Marcus A Garcia, Rui Liu, Alex Nihart, Eliane El Hayek, Eliseo Castillo, Enrico R Barrozo, Melissa A Suter, Barry Bleske, Justin Scott, Kyle Forsythe, Jorge Gonzalez-Estrella, Kjersti M Aagaard, Matthew J Campen

{"title":"Quantitation and identification of microplastics accumulation in human placental specimens using pyrolysis gas chromatography mass spectrometry.","authors":"Marcus A Garcia, Rui Liu, Alex Nihart, Eliane El Hayek, Eliseo Castillo, Enrico R Barrozo, Melissa A Suter, Barry Bleske, Justin Scott, Kyle Forsythe, Jorge Gonzalez-Estrella, Kjersti M Aagaard, Matthew J Campen","doi":"10.1093/toxsci/kfae021","DOIUrl":"10.1093/toxsci/kfae021","url":null,"abstract":"The exponential increase in global plastic usage has led to the emergence of nano- and microplastic (NMP) pollution as a pressing environmental issue due to its implications for human and other mammalian health. We have developed methodologies to extract solid materials from human tissue samples by saponification and ultracentrifugation, allowing for highly specific and quantitative analysis of plastics by pyrolysis-gas chromatography and mass spectrometry (Py-GC-MS). As a benchmark, placenta tissue samples were analyzed using fluorescence microscopy and automated particle count, which demonstrated the presence of >1-micron particles and fibers, but not nano-sized plastic particles. Analyses of the samples (n = 10) using attenuated total reflectance-Fourier transform infrared spectroscopy indicated presence of rayon, polystyrene, polyethylene, and unclassified plastic particles. By contrast, among 62 placenta samples, Py-GC-MS revealed that microplastics were present in all participants' placentae, with concentrations ranging widely from 6.5 to 685 µg NMPs per gram of placental tissue, averaging 126.8 ± 147.5 µg/g (mean±SD). Polyethylene was the most prevalent polymer, accounting for 54% of total NMPs and consistently found in nearly all samples (mean 68.8 ± 93.2 µg/g placenta). Polyvinyl chloride and nylon each represented approximately 10% of the NMPs by weight, with the remaining 26% of the composition represented by 9 other polymers. Together, these data demonstrate advancements in the unbiased quantitative resolution of Py-GC-MS applied to the identification and quantification of NMP species at the maternal-fetal interface. This method, paired with clinical metadata, will be pivotal to evaluating potential impacts of NMPs on adverse pregnancy outcomes.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"81-88"},"PeriodicalIF":3.4,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Prenatal prednisone exposure impacts liver development and function in fetal mice and its characteristics. 产前泼尼松暴露影响胎鼠肝脏发育和功能及其特征

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae027

Yongguo Dai, Yu Peng, Zhengjie Lu, Tongyun Mao, Kaiqi Chen, Xiaoqian Lu, Kexin Liu, Xinli Zhou, Wen Hu, Hui Wang

{"title":"Prenatal prednisone exposure impacts liver development and function in fetal mice and its characteristics.","authors":"Yongguo Dai, Yu Peng, Zhengjie Lu, Tongyun Mao, Kaiqi Chen, Xiaoqian Lu, Kexin Liu, Xinli Zhou, Wen Hu, Hui Wang","doi":"10.1093/toxsci/kfae027","DOIUrl":"10.1093/toxsci/kfae027","url":null,"abstract":"Prednisone, a widely used glucocorticoid drug in human and veterinary medicine, has been reported to cause developmental toxicity. However, systematic studies about the effect of prednisone on fetal liver development are still unclear. We investigated the potential effects of maternal exposure to clinically equivalent doses of prednisone during different gestational stages on cell proliferation and apoptosis, cell differentiation, glucose and lipid metabolism, and hematopoiesis in the liver of fetal mice, and explored the potential mechanisms. Results showed that prenatal prednisone exposure (PPE) could suppress cell proliferation, inhibit hepatocyte differentiation, and promote cholangiocyte differentiation in the fetal liver. Meanwhile, PPE could result in the enhancement of glyconeogenesis and bile acid synthesis and the inhibition of fatty acid β-oxidation and hematopoiesis in the fetal liver. Further analysis found that PPE-induced alterations in liver development had obvious stage and sex differences. Overall, the alteration in fetal liver development and function induced by PPE was most pronounced during the whole pregnancy (GD0-18), and the males were relatively more affected than the females. Additionally, fetal hepatic insulin-like growth factor 1 (IGF1) signaling pathway was inhibited by PPE. In conclusion, PPE could impact fetal liver development and multiple functions, and these alterations might be partially related to the inhibition of IGF1 signaling pathway.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"63-80"},"PeriodicalIF":3.8,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029089","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

A critical review of advances in tumor metabolism abnormalities induced by nitrosamine disinfection by-products in drinking water. 关于饮用水中亚硝胺消毒副产物诱发肿瘤代谢异常的研究进展综述。

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae012

Mingjun Sun, Weitao Shen, Xinxin Guo, Yinghao Liao, Yang Huang, Mohan Hu, Ping Ye, Ran Liu

{"title":"A critical review of advances in tumor metabolism abnormalities induced by nitrosamine disinfection by-products in drinking water.","authors":"Mingjun Sun, Weitao Shen, Xinxin Guo, Yinghao Liao, Yang Huang, Mohan Hu, Ping Ye, Ran Liu","doi":"10.1093/toxsci/kfae012","DOIUrl":"10.1093/toxsci/kfae012","url":null,"abstract":"Intensified sanitation practices amid the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak might result in the increased release of chloramine disinfectants into surface water, significantly promoting the formation of nitrosamine disinfection by-products (DBPs) in drinking water. Unfortunately, these nitrosamine DBPs exhibit significant genotoxic, carcinogenic, and mutagenic properties, whereas chlorinating disinfectants remain in global practice. The current review provides valuable insights into the occurrence, identification, contamination status, exposure limits, and toxicity of the new unregulated disinfection by-products (nitrosamine DBPs) in drinking water. As a result, concentrations of nitrosamine DBPs far exceed allowable limits in drinking water, and prolonged exposure has the potential to cause metabolic disorders, a critical step in tumor initiation and progression. Importantly, based on recent research, we have concluded the role of nitrosamines DBPs in different metabolic pathways. Remarkably, nitrosamine DBPs can induce chronic inflammation and initiate tumors by activating sphingolipid and polyunsaturated fatty acid metabolism. Regarding amino acid and nucleotide metabolism, nitrosamine DBPs can inhibit tryptophan metabolism and de novo nucleotide synthesis. Moreover, inhibition of de novo nucleotide synthesis fails to repair DNA damage induced by nitrosamines. Additionally, the accumulation of lactate induced by nitrosamine DBPs may act as a pivotal signaling molecule in communication within the tumor microenvironment. However, with the advancement of tumor metabolomics, understanding the role of nitrosamine DBPs in causing cancer by inducing metabolic abnormalities significantly lags behind, and specific mechanisms of toxic effects are not clearly defined. Urgently, further studies exploring this promising area are needed.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"12-28"},"PeriodicalIF":3.8,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642999","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

Exploring rabbit as a nonrodent species for general toxicology studies. 探索将兔子作为一般毒理学研究的非啮齿动物物种。

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae022

Katie Sokolowski, Patricia V Turner, Elise Lewis, Ronald L Wange, Marie C Fortin

{"title":"Exploring rabbit as a nonrodent species for general toxicology studies.","authors":"Katie Sokolowski, Patricia V Turner, Elise Lewis, Ronald L Wange, Marie C Fortin","doi":"10.1093/toxsci/kfae022","DOIUrl":"10.1093/toxsci/kfae022","url":null,"abstract":"To avoid adverse events in humans, toxicity studies in nonclinical species have been the foundation of safety evaluation in the pharmaceutical industry. However, it is recognized that working with animals in research is a privilege, and conscientious use should always respect the 3Rs: replacement, reduction, and refinement. In the wake of the shortages in routine nonrodent species and considering that nonanimal methods are not yet sufficiently mature, the value of the rabbit as a nonrodent species is worth exploring. Historically used in vaccine, cosmetic, and medical device testing, the rabbit is seldom used today as a second species in pharmaceutical development, except for embryo-fetal development studies, ophthalmic therapeutics, some medical devices and implants, and vaccines. Although several factors affect the decision of species selection, including pharmacological relevance, pharmacokinetics, and ADME considerations, there are no perfect animal models. In this forum article, we bring together experts from veterinary medicine, industry, contract research organizations, and government to explore the pros and cons, residual concerns, and data gaps regarding the use of the rabbit for general toxicity testing.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"29-39"},"PeriodicalIF":3.8,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906473","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

Technical evaluation and standardization of the human thyroid microtissue assay. 人类甲状腺微组织测定的技术评估和标准化。

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae014

Briana Foley, Kristen Hopperstad, John Gamble, Scott G Lynn, Russell S Thomas, Chad Deisenroth

{"title":"Technical evaluation and standardization of the human thyroid microtissue assay.","authors":"Briana Foley, Kristen Hopperstad, John Gamble, Scott G Lynn, Russell S Thomas, Chad Deisenroth","doi":"10.1093/toxsci/kfae014","DOIUrl":"10.1093/toxsci/kfae014","url":null,"abstract":"The success and sustainability of U.S. EPA efforts to reduce, refine, and replace in vivo animal testing depends on the ability to translate toxicokinetic and toxicodynamic data from in vitro and in silico new approach methods (NAMs) to human-relevant exposures and health outcomes. Organotypic culture models employing primary human cells enable consideration of human health effects and inter-individual variability but present significant challenges for test method standardization, transferability, and validation. Increasing confidence in the information provided by these in vitro NAMs requires setting appropriate performance standards and benchmarks, defined by the context of use, to consider human biology and mechanistic relevance without animal data. The human thyroid microtissue (hTMT) assay utilizes primary human thyrocytes to reproduce structural and functional features of the thyroid gland that enable testing for potential thyroid-disrupting chemicals. As a variable-donor assay platform, conventional principles for assay performance standardization need to be balanced with the ability to predict a range of human responses. The objectives of this study were to (1) define the technical parameters for optimal donor procurement, primary thyrocyte qualification, and performance in the hTMT assay, and (2) set benchmark ranges for reference chemical responses. Thyrocytes derived from a cohort of 32 demographically diverse euthyroid donors were characterized across a battery of endpoints to evaluate morphological and functional variability. Reference chemical responses were profiled to evaluate the range and chemical-specific variability of donor-dependent effects within the cohort. The data-informed minimum acceptance criteria for donor qualification and set benchmark parameters for method transfer proficiency testing and validation of assay performance.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"89-107"},"PeriodicalIF":3.8,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681592","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

Carbamazepine transmits immune effect by activation of gut-liver axis and TLR signaling pathway from parental zebrafish to offspring. 卡马西平通过激活亲代斑马鱼的肠肝轴和 TLR 信号通路向子代斑马鱼传递免疫效应。

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae026

Xuan Liu, Fan Liu, Li Liu, You Song, Hongling Liu

{"title":"Carbamazepine transmits immune effect by activation of gut-liver axis and TLR signaling pathway from parental zebrafish to offspring.","authors":"Xuan Liu, Fan Liu, Li Liu, You Song, Hongling Liu","doi":"10.1093/toxsci/kfae026","DOIUrl":"10.1093/toxsci/kfae026","url":null,"abstract":"Carbamazepine (CBZ) has been identified in the aquatic environment as an emerging contaminant. Its immune effect across generations at environmentally relevant concentrations is little known. We aim to elucidate the effects of CBZ on the immune system in zebrafish (Danio rerio), hypothesizing the effects caused by CBZ exposure in the parental generation can be passed on to its offspring, leading to impairment of innate immune function and defense against pathogen weakened. A suite of bioassays (including a test with added lipopolysaccharide) was used to measure the effects of environmentally relevant levels of CBZ (1, 10, and 100 μg/l) on zebrafish at multiple biological levels, and across 2 successive generations (21 days exposure for F0; 5 and 21 days exposure or nonexposure for F1). The results showed that CBZ affected homeostasis in the immune system, caused liver vacuolization, increased the inflammation-related microbiota proportion in gut, and decreased reproduction, by induction of oxidative stress and modulation of Toll-like receptors (TLR) signaling pathway on gut-liver axis. The effects of exposure to CBZ over 21 days in F0 could be passed to the next generation. Intergenerational effects on TLR and antioxidant defense system were also observed in nonexposed F1 at 5 days post-fertilization (5 dpf), but diminished at 21 dpf. The finding provided evidence to unravel immune response by gut-liver axis mediated and oxidative stress under 4 test conditions. The study has raised a potential concern about the multigenerational immune effects of environmental pollutants and calls for a focus on the risk of synergetic pathogen infection.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"108-119"},"PeriodicalIF":3.8,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040393","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

Parenteral nutrition-associated liver injury: clinical relevance and mechanistic insights. 肠外营养相关肝损伤：临床意义和机理认识。

IF 3.4 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae020

Milos Mihajlovic, Zenzi Rosseel, Elisabeth De Waele, Mathieu Vinken

{"title":"Parenteral nutrition-associated liver injury: clinical relevance and mechanistic insights.","authors":"Milos Mihajlovic, Zenzi Rosseel, Elisabeth De Waele, Mathieu Vinken","doi":"10.1093/toxsci/kfae020","DOIUrl":"10.1093/toxsci/kfae020","url":null,"abstract":"Intestinal failure-associated liver disease (IFALD) is a relatively common complication in individuals receiving parenteral nutrition (PN). IFALD can be manifested as different types of liver injury, including steatosis, cholestasis, and fibrosis, and could result in liver failure in some cases. The onset and progression of IFALD are highly dependent on various patient and PN-related risk factors. Despite still being under investigation, several mechanisms have been proposed. Liver injury can originate due to caloric overload, nutrient deficiency, and toxicity, as well as phytosterol content, and omega-6 to omega-3 fatty acids ratio contained in lipid emulsions. Additional mechanisms include immature or defective bile acid metabolism, acute heart failure, infections, and sepsis exerting negative effects via Toll-like receptor 4 and nuclear factor κB inflammatory signaling. Furthermore, lack of enteral feeding, gut dysbiosis, and altered enterohepatic circulation that affect the farnesoid x receptor-fibroblast growth factor 19 axis can also contribute to IFALD. Various best practices can be adopted to minimize the risk of developing IFALD, such as prevention and management of central line infections and sepsis, preservation of intestine's length, a switch to oral and enteral feeding, cyclic PN, avoidance of overfeeding and soybean oil-based lipid formulations, and avoiding hepatotoxic substances. The present review thus provides a comprehensive overview of all relevant aspects inherent to IFALD. Further research focused on clinical observations, translational models, and advanced toxicological knowledge frameworks is needed to gain more insight into the molecular pathogenesis of hepatotoxicity, reduce IFALD incidence, and encourage the safe use of PN.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"1-11"},"PeriodicalIF":3.4,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932974","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

Single pulmonary nanopolystyrene exposure in late-stage pregnancy dysregulates maternal and fetal cardiovascular function. 妊娠晚期单次肺部接触纳米聚苯乙烯会导致母体和胎儿心血管功能失调。

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae019

C M Cary, S B Fournier, S Adams, X Wang, E J Yurkow, P A Stapleton

{"title":"Single pulmonary nanopolystyrene exposure in late-stage pregnancy dysregulates maternal and fetal cardiovascular function.","authors":"C M Cary, S B Fournier, S Adams, X Wang, E J Yurkow, P A Stapleton","doi":"10.1093/toxsci/kfae019","DOIUrl":"10.1093/toxsci/kfae019","url":null,"abstract":"Large-scale production and waste of plastic materials have resulted in widespread environmental contamination by the breakdown product of bulk plastic materials to micro- and nanoplastics (MNPs). The small size of these particles enables their suspension in the air, making pulmonary exposure inevitable. Previous work has demonstrated that xenobiotic pulmonary exposure to nanoparticles during gestation leads to maternal vascular impairments, as well as cardiovascular dysfunction within the fetus. Few studies have assessed the toxicological consequences of maternal nanoplastic (NP) exposure; therefore, the objective of this study was to assess maternal and fetal health after a single maternal pulmonary exposure to polystyrene NP in late gestation. We hypothesized that this acute exposure would impair maternal and fetal cardiovascular function. Pregnant rats were exposed to nanopolystyrene on gestational day 19 via intratracheal instillation. 24 h later, maternal and fetal health outcomes were evaluated. Cardiovascular function was assessed in dams using vascular myography ex vivo and in fetuses in vivo function was measured via ultrasound. Both fetal and placental weight were reduced after maternal exposure to nanopolystyrene. Increased heart weight and vascular dysfunction in the aorta were evident in exposed dams. Maternal exposure led to vascular dysfunction in the radial artery of the uterus, a resistance vessel that controls blood flow to the fetoplacental compartment. Function of the fetal heart, fetal aorta, and umbilical artery after gestational exposure was dysregulated. Taken together, these data suggest that exposure to NPs negatively impacts maternal and fetal health, highlighting the concern of MNPs exposure on pregnancy and fetal development.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"149-159"},"PeriodicalIF":3.8,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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