Current Research in Toxicology最新文献

{"title":"Detail study on the interaction between perfluorooctanoic acid (PFOA) with human hemoglobin (Hb)","authors":"N.L. Dilani Perera,&nbsp;Jovany Betancourt,&nbsp;Jaroslava Miksovska,&nbsp;Kevin E. O'Shea","doi":"10.1016/j.crtox.2023.100130","DOIUrl":"10.1016/j.crtox.2023.100130","url":null,"abstract":"<div><p>Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are often referred to as legacy perfluoroalkyl substances (PFAS). Human exposure to PFAS leads to severe negative health impacts including cancers, infertility, and dysfunction in the kidneys. Steady-state absorbance, fluorescence, and circular dichroism (CD) methods were used to study the interactions between PFOA and Hb. The results demonstrate the presence of multiple PFOA binding sites on the Hb protein. The detailed analysis of the ferric hemoglobin protein (met Hb) absorbance data as a function of PFOA concentration indicates the presence of at least two binding sites with equilibrium dissociation constants of 0.8 ± (0.2) × 10⁻⁶ M and 63 ± (15) × 10⁻⁵ M. A competitive binding study with 1,8-ANS showed PFOA can bind to the same binding site as 1,8-ANS on the Hb protein. The titration curve for PFOA binding to Hb in its CO bound form (CO-Hb) yields a single equilibrium dissociation constant of 139 ± (20) × 10⁻⁶ M. PFOA binding at low concentrations occurs at the high-affinity sites leading to the destabilization of the protein structure as reflected by changes in the CD spectrum. PFOA interactions with Hb also interfere with the kinetics of CO association to this protein. The rate for CO association to Hb increases at low PFOA concentrations, whereas at elevated PFOA concentrations, the ligand association is biphasic as a new kinetic process with a different rate constant was observed. Overall, this study provides a detailed explanation of PFOA-induced structural and conformational changes to the Hb protein based on the spectroscopy data.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100130"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8c/0f/main.PMC10563006.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41194504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytanic acid, an inconclusive phytol metabolite: A review","authors":"Muhammad Torequl Islam ,&nbsp;Md. Shimul Bhuia ,&nbsp;João Paulo Martins de Lima ,&nbsp;Francisco Paulo Araujo Maia ,&nbsp;Ana Beatriz Herminia Ducati ,&nbsp;Henrique Douglas Melo Coutinho","doi":"10.1016/j.crtox.2023.100120","DOIUrl":"10.1016/j.crtox.2023.100120","url":null,"abstract":"<div><p>Phytanic acid (PA: 3,7,11,15-tetramethylhexadecanoic acid) is an important biometabolite of the chlorophyll-derived diterpenoid phytol. Its biological sources (occurrence) and ADME (absorption, distribution, metabolism, and elimination) profile are well-discussed in the literature. Cumulative literature suggests that PA has beneficial as well as harmful biological roles in humans and other animals. This study aimed to sketch a brief summary of PA’s beneficial and harmful pharmacological effects in test systems on the basis of existing literature reports. Literature findings propose that PA has anti-inflammatory and immunomodulatory, antidiabetic, anti-obesity, anticancer, and oocyte maturation effects. Although a high plasma PA-level mediated SLS remains controversial, it is evident to link it with Refsum’s disease and other peroxisomal enzyme deficiency diseases in humans, including RCDP and LD; ZHDA and Alzheimer’s disease; progressive ataxia and dysarthria; and an increased risk of some lymphomas such as LBL, FL, and NHL. PA exerts toxic effects on different kinds of cells, including neuronal, cardiac, and renal cells, through diverse pathways such as oxidative stress, mitochondrial disturbance, apoptosis, disruption of Na⁺/K⁺-ATPase activity, Ca²⁺ homeostasis, alteration of AChE and MAO activities, etc. PA is considered a cardiac biomarker in humans. In conclusion, PA may be one of the most important biometabolites in humans.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100120"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/e4/main.PMC10515296.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethnobotanical uses and phytochemical, biological, and toxicological profiles of Datura metel L.: A review","authors":"Tawhida Islam ,&nbsp;Iffat Ara ,&nbsp;Tariqul Islam ,&nbsp;Pankaj Kumar Sah ,&nbsp;Ray Silva de Almeida ,&nbsp;Edinardo Fagner Ferreira Matias ,&nbsp;Cícero Lucas Gomes Ramalho ,&nbsp;Henrique Douglas M. Coutinho ,&nbsp;Muhammad Torequl Islam","doi":"10.1016/j.crtox.2023.100106","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100106","url":null,"abstract":"<div><p>Datura metel L., a recognized poisonous plant in the Solanaceae family, is widely distributed in the world. Traditionally, D. metel is used in many diseases, including neurological and heart diseases; fever; catarrh; pain; diarrhea; skin diseases; chronic bronchitis; asthma; digestive disorders; and so on. It possesses many important phytochemicals that can be used to treat various types of diseases. This review aims at summarizing the traditional uses, phytochemical, biological, and toxicological profiles of D. metel based on the database reports. For this, an up-to-date (till March 20, 2023) search was made in the databases: PubMed, Google Scholar, Science Direct, Scopus, and MedLine, with relevant keywords for the published evidence. Findings suggest that the plant has many traditional uses, such as a cure for madness, epilepsy, psoriasis, heart diseases, diarrhea, mad dog bites, indigestion, etc. It possesses various important phytochemicals, including withanolides, daturaolone, datumetine, daturglycosides, ophiobolin A, baimantuoluoline A, and many others. D. metel has many important biological activities, including antioxidant, anti-inflammatory, anti-microbial, insecticidal, anti-cancer, anti-diabetic, analgesic, anti-pyretic, neurological, contraceptive, and wound healing capacity. In conclusion, the toxic plant, D. metel, can be considered a potential source of phyto-therapeutic lead compounds.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"4 ","pages":"Article 100106"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49777749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chaga mushroom triterpenoids as adjuncts to minimally invasive cancer therapies: A review","authors":"Selina Plehn ,&nbsp;Sajeev Wagle ,&nbsp;H.P. Vasantha Rupasinghe","doi":"10.1016/j.crtox.2023.100137","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100137","url":null,"abstract":"<div><p>Cancer has become the second leading cause of death in the world. Integrative cancer therapy management is continuously evolving to enhance treatment outcomes. Chaga mushroom (<em>Inonotus obliquus</em>) is a parasitic fungus acclaimed to contain pharmaceutical and nutraceutical value in the fight against cancer. In particular, triterpenoid constituents derived from Chaga mushrooms have been recognized for their anti-cancer activity after distinguished cytotoxicity was repeatedly observed in cancer cells treated <em>in vitro</em> with lipophilic fractions of extract compared to aqueous ones. Studies that investigate the anti-cancer activity of Chaga mushroom triterpenoids are reviewed in this article to determine which cancer cell lines demonstrate the greatest susceptibility to them while highlighting the structure–activity relationships that are involved. Triterpenoid supplementation as an adjunct to cancer treatment may be a viable option as inotodiol and 3-β-22 α-dihydroxylanosta-8, 25-diene-24-one have been shown to exhibit anti-cancer activity similar to that of conventional drugs. Advances in addressing bioavailability challenges are also included in this review as studies include <em>in vivo</em> components.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100137"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X2300035X/pdfft?md5=873ac4385989441e838f58e4890cee10&pid=1-s2.0-S2666027X2300035X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136694410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the interferences of systemic azole antifungal drugs with adrenal steroid biosynthesis using H295R cells and enzyme activity assays","authors":"Marie-Christin Jäger,&nbsp;Friedrich L. Joos,&nbsp;Denise V. Winter,&nbsp;Alex Odermatt","doi":"10.1016/j.crtox.2023.100119","DOIUrl":"10.1016/j.crtox.2023.100119","url":null,"abstract":"<div><p>Azole antifungals, designed to inhibit fungal CYP51, have a liability to inhibit human CYP enzymes. Whilst drug-metabolizing CYPs are covered in preclinical safety assessment, those metabolizing endogenous bioactive molecules are usually not. Posaconazole and itraconazole were recently found to cause pseudohyperaldosteronism with hypokalemia and hypertension by inhibiting CYP11B1-dependent adrenal cortisol biosynthesis. Because this was overlooked in preclinical safety assessment, the present study tested whether applying adrenal carcinoma H295R cells could have predicted this liability and whether other systemic triazole antifungals interfere with adrenal steroidogenesis. Forskolin-stimulated H295R cells were exposed to systemic triazole antifungals that are currently used, and key adrenal steroids were quantified by UHPLC-MS/MS. To support the findings from the H295R model, activity assays for steroidogenic enzymes were performed. The analysis of the steroid profiles and product/substrate ratios predicted the CYP11B1 and CYP11B2 inhibition by posaconazole and itraconazole. Comparison of their steroid profiles allowed distinguishing their effects and suggested inhibition of adrenal androgen synthesis by posaconazole but not itraconazole, which was confirmed by CYP17A1 17,20-lyase activity measurements. In line with clinical observations, there was no evidence from these experiments for an inhibition of either CYP11B1/2 or CYP17A1 by voriconazole, fluconazole or isavuconazole. However, itraconazole and isavuconazole exerted an overall inhibition of steroidogenesis by a mechanism warranting further investigations. In conclusion, analyses of steroid profiles from the H295R assay and product/substrate ratios provide important information on the interference of a chemical with adrenal steroidogenesis and the underlying mechanism. This approach facilitates prioritization of further investigations, including enzyme expression and activity studies.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100119"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10483343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilot testing and optimization of a larval fathead minnow high throughput transcriptomics assay","authors":"Daniel L. Villeneuve ,&nbsp;Michelle Le ,&nbsp;Monique Hazemi ,&nbsp;Adam Biales ,&nbsp;David C. Bencic ,&nbsp;Kendra Bush ,&nbsp;Robert Flick ,&nbsp;John Martinson ,&nbsp;Mackenzie Morshead ,&nbsp;Kelvin Santana Rodriguez ,&nbsp;Kelsey Vitense ,&nbsp;Kevin Flynn","doi":"10.1016/j.crtox.2022.100099","DOIUrl":"10.1016/j.crtox.2022.100099","url":null,"abstract":"<div><p>Concentrations at which global gene expression profiles in cells or animals exposed to a test substance start to differ significantly from those of controls have been proposed as an alternative point of departure for use in screening level hazard assessment. The present study describes pilot testing of a high throughput compatible transcriptomics assay with larval fathead minnows. One day post hatch fathead minnows were exposed to eleven different concentrations of three metals, three selective serotonin reuptake inhibitors, and four neonicotinoid-like compounds for 24 h and concentration response modeling was applied to whole body gene expression data. Transcriptomics-based points of departure (tPODs) were consistently lower than effect concentrations reported in apical endpoint studies in fish. However, larval fathead minnow-based tPODs were not always lower than concentrations reported to elicit apical toxicity in other aquatic organisms like crustaceans or insects. Random <em>in silico</em> subsampling of data from the pilot assays was used to evaluate various assay design and acceptance considerations such as transcriptome coverage, number of replicate individuals to sequence per treatment, and minimum number of differentially expressed genes to produce a reliable tPOD estimate. Results showed a strong association between the total number of genes for which a concentration response relationship could be derived and the overall variability in the resulting tPOD estimates. We conclude that, for our current assay design and analysis pipeline, tPODs based on fewer than 15 differentially expressed genes are likely to be unreliable for screening and that interindividual variability in gene expression profiles appears to be a more significant driver of tPOD variability than sample size alone. Results represent initial steps toward developing high throughput transcriptomics assays for use in ecological hazard screening.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"4 ","pages":"Article 100099"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/08/main.PMC9816907.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10508170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zn and Se abrogate heavy metal mixture induced ovarian and thyroid oxido-inflammatory effects mediated by activation of NRF2-HMOX-1 in female albino rats","authors":"Boma F. Eddie-Amadi ,&nbsp;Anthonet N. Ezejiofor ,&nbsp;Chinna N. Orish ,&nbsp;Orish E. Orisakwe","doi":"10.1016/j.crtox.2022.100098","DOIUrl":"10.1016/j.crtox.2022.100098","url":null,"abstract":"<div><p>The thyroid is vital for the proper functioning of the female reproductive system since it regulates the metabolism and development of ovary. This is an evaluation of the essential trace elements ETE on the heavy metals mixture HMM mediated oxido-inflammatory effects in the ovary and thyroid of female albino rats. Five groups (5 female rats /group) were treated as follows for 60 days: Group 1: Deionized water only; Group 2: (Pb, Hg, Mn and Al); Group 3: HMM + ZnCl₂, 0.80 mg/kg; Group 4: HMM + Na₂SeO₃, 1.50 mg/kg; Group 5: HMM + ZnCl₂, 0.80 mg/kg and Na₂SeO₃, 1.50 mg/kg combined. On day 60 animals were euthanized, ovary and thyroid were harvested and used for, MDA, NO, antioxidants, TNF-α, IL-6, HMOX-1, Caspase-3, NF-KB, NRF2, HM and histopathology. There was significant bioaccumulation of Pb, Al, Hg and MN; elevated IL-6 and TNF-α, MDA and NO, caspase-3 and NRF2, NFKB and HMOX-1 with significant decrease in antioxidants in the HMM only group in comparison to the control. Co-treatment with ETE reversed most of these effects.</p><p>ETE may ameliorate HMM -induced ovarian and thyrotoxicity in female albino rats by blunting oxido-inflammatory activities.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"4 ","pages":"Article 100098"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9823124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the sensitivity and specificity of phosphatidylethanol (PEth) cutoffs to identify alcohol exposed pregnancies","authors":"Julie M. Hasken ,&nbsp;Anna-Susan Marais ,&nbsp;Marlene M. de Vries ,&nbsp;Wendy O. Kalberg ,&nbsp;David Buckley ,&nbsp;Charles D.H. Parry ,&nbsp;Soraya Seedat ,&nbsp;Philip A. May","doi":"10.1016/j.crtox.2023.100105","DOIUrl":"10.1016/j.crtox.2023.100105","url":null,"abstract":"<div><p>In the literature on alcohol use biomarkers, there has been debate as to what a valid and/or utilitarian cut off level should be for various research applications. In this manuscript, we assessed the sensitivity and specificity of multiple cutoff values for phosphatidylethanol (PEth) from bloodspots relative to self-report, the Alcohol Use Disorder Identification Test (AUDIT) scores, and another alcohol use biomarker ethyl glucuronide (EtG) from fingernails in a sample of 222 pregnant women in the Western Cape Province of South Africa. Receiver operating characteristic (ROC) curves were used to assess the area under the curve (AUC) and assess PEth cutoff values of ≥2, ≥4, ≥8, ≥14, and ≥20 nanograms per milliliter (ng/ml). The highest AUC value was attained when PEth was compared to an AUDIT score of 1 or more. Depending on the cutoff used to determine alcohol consumption, PEth identified 47%–70% of the individuals as alcohol-consuming while 62.6%–75.2% were identified by self-reported measures, and 35.6% were identified by EtG. In this sample, sensitivity and accuracy were highest at less stringent PEth cutoffs when compared to self-report, AUDIT score of 1 or more, 5 or more, 8 or more, and EtG ≥ 8 picograms per milligram (pg/mg). For research purposes, less stringent cutoffs, such as PEth ≥ 8 ng/ml, may be considered a valid, positive cutoff for identifying women who consume alcohol during pregnancy in this population. A cutoff of PEth ≥ 20 ng/ml may miss individuals who reported consuming alcohol (false negatives).</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"4 ","pages":"Article 100105"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123138/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9414263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of wheatgrass (Triticum aestivum Linn) toxicity against breast cancer cell lines by simulated microgravity","authors":"Wajdy Al-Awaida ,&nbsp;Hamzeh J. Al-Ameer ,&nbsp;Ahmad Sharab ,&nbsp;Rand T. Akasheh","doi":"10.1016/j.crtox.2023.100127","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100127","url":null,"abstract":"<div><p>This study scrutinizes the effects of simulated microgravity on the antioxidant and cytotoxic potential, along with the phytochemical content of wheatgrass (<em>Triticum aestivum Linn</em>). To imitate microgravity, wheatgrass seeds were germinated in a 3D-clinostat at different rotations per minute (5, 10, 15, and 20 rpm), together with terrestrial gravity control, over 10 days. After germination, the methanolic extracts were analyzed using UPLC-Triple Quad LCMS for their phytochemical composition and tested for their hydrogen peroxide, nitric oxide, and DPPH scavenging activities. The cytotoxic effects of these extracts were evaluated against normal skin fibroblasts, normal breast cells (MCF-10), and breast cancer cells (MCF-7 and MDA-231). The findings showed an extended root growth in wheatgrass germinated under microgravity (WGM) compared to under gravity (WGG). Additionally, WGM extracts demonstrated increased H2O2–, NO–, and DPPH-scavenging activities and a higher content of polyphenols and flavonoids than WGG extracts. These effects were amplified with an increase in clinostat rotations. Moreover, WGM extracts were found to contain a unique set of bioactive compounds (compounds that were detected in the microgravity-germinated wheatgrass but were either absent or present in lower concentrations in wheatgrass germinated under standard gravity conditions.), including pyridoxine, apigenin, and tocopherol, among others, which were absent in WGG. The UPLC-Triple Quad LCMS analysis revealed these unique bioactive compounds in WGM. Notably, WGM extracts showed enhanced cytotoxic effects against normal skin fibroblasts, normal MCF-10, MCF-7, and breast cancer MDA-231 cell lines, with increased cytotoxicity correlating with the number of clinostat rotations. Particularly, WGM extract (at 20 rpm) demonstrated significantly stronger cytotoxicity against MCF-7 breast cancer cells. Further in-depth gene expression analysis of MCF-7 cells exposed to WGM revealed a significant downregulation of genes integral to breast cancer pathways, tyrosine kinase signaling, and DNA repair, complemented by upregulation of certain cell survival and cytotoxic genes. These alterations in genetic pathways associated with cell survival, hormone responses, and cancer progression may elucidate the enhanced cytotoxicity observed in WGM extracts. Our findings underscore the potential of microgravity as a tool to enhance the cytotoxic capabilities of wheatgrass against cancer cell lines, presenting a promising direction for future research in the field of space biology and its implications for terrestrial health.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100127"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49772587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluorene-9-bisphenol affects the terminal differentiation of mouse embryonic bodies","authors":"Aidan J. McLaughlin ,&nbsp;Anthony I. Kaniski ,&nbsp;Darena I. Matti ,&nbsp;Nicodemus C. Monear ,&nbsp;Jessica L. Tischler ,&nbsp;Besa Xhabija","doi":"10.1016/j.crtox.2023.100133","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100133","url":null,"abstract":"<div><p>Fluorene-9-bisphenol (BHPF) has recently attracted interest as it is increasingly used in industrial settings as a substitute for Bisphenol A (BPA). However, the effects of BHPF exposure on embryonic stem cell (ESC) self-renewal, pluripotency, and differentiation remain poorly understood. This study investigates the impacts of BHPF on mouse embryonic stem cells (mESCs) and embryonic bodies (EBs). Our results reveal that BHPF exposure leads to a morphological shift in mESCs, reducing the percentage of dome-shaped colonies and indicating loss of self-renewal and pluripotency. BHPF exposure also appeared to affect the early stages of EB formation and their growth dynamics, with a reduction in EB numbers and an increase in their size. Subsequent gene expression analysis revealed that BHPF exposure led to increased expression of the inflammatory gene Il6, indicating a potential stress response.</p><p>Furthermore, BHPF affected the terminal differentiation pathway, modulating the expression of 16 genes associated with distinct cell types, including lymphatic endothelium, keratinocyte epithelium, pancreatic beta cells, macrophages, monocytes, T-cells, neurons, retinal ganglion cells, nephrons proximal tubule cells, and cardiomyocytes. These findings offer insights into the impact of BHPF on ESC biology and suggest potential implications for developmental and neurodegenerative disorders. Future work should focus on elucidating the underlying mechanisms of BHPF-mediated effects on stem cell function. This may offer new perspectives for understanding the health impacts of environmental exposure to BHPF.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100133"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X23000312/pdfft?md5=b38e261825fe611e9869dd083e87cd6f&pid=1-s2.0-S2666027X23000312-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92099019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}