Toxicological Sciences最新文献

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Acetaminophen should be a critical reference hepatotoxin for evaluating human-relevant in vitro models. 致编辑的信:对乙酰氨基酚应该是评估与人类相关的体外模型的关键参考肝毒素。
IF 3.4 3区 医学
Toxicological Sciences Pub Date : 2025-04-01 DOI: 10.1093/toxsci/kfae163
Hartmut Jaeschke, Anup Ramachandran
{"title":"Acetaminophen should be a critical reference hepatotoxin for evaluating human-relevant in vitro models.","authors":"Hartmut Jaeschke, Anup Ramachandran","doi":"10.1093/toxsci/kfae163","DOIUrl":"10.1093/toxsci/kfae163","url":null,"abstract":"","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"251-252"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898157","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
Regulatory trends of organophosphate and pyrethroid pesticides in cannabis and applications of the Comparative Toxicogenomics Database and Caenorhabditis elegans. 大麻中有机磷和拟除虫菊酯类农药的调控趋势及比较毒物基因组学数据库和秀丽隐杆线虫的应用。
IF 3.4 3区 医学
Toxicological Sciences Pub Date : 2025-04-01 DOI: 10.1093/toxsci/kfaf009
Albert B Rivera, Ariell B Stephens, Kendra D Conrow, Symone T Griffith, Laura E Jameson, Thomas M Cahill, Shreesh R Sammi, Mathew R Swinburne, Jason R Cannon, Maxwell C K Leung
{"title":"Regulatory trends of organophosphate and pyrethroid pesticides in cannabis and applications of the Comparative Toxicogenomics Database and Caenorhabditis elegans.","authors":"Albert B Rivera, Ariell B Stephens, Kendra D Conrow, Symone T Griffith, Laura E Jameson, Thomas M Cahill, Shreesh R Sammi, Mathew R Swinburne, Jason R Cannon, Maxwell C K Leung","doi":"10.1093/toxsci/kfaf009","DOIUrl":"10.1093/toxsci/kfaf009","url":null,"abstract":"<p><p>Organophosphate and pyrethroid pesticides are common contaminants in cannabis. Due to the status of cannabis as an illicit Schedule I substance at the federal level, there are no unified national guidelines in the United States to mitigate the health risk of pesticide exposure in cannabis. Here, we examined the change in the state-level regulations of organophosphate and pyrethroid pesticides in cannabis. The medians of pyrethroid and organophosphate pesticides specified by each state-level jurisdiction increased from zero pesticide in 2019 to 4.5 pyrethroid and 7 organophosphate pesticides in 2023, respectively. Next, we evaluated the potential connections between pyrethroids, organophosphates, cannabinoids, and Parkinson's disease using the Comparative Toxicogenomics Database (CTD). Eleven pyrethroids, 30 organophosphates, and 14 cannabinoids were associated with 95 genes to form 3,237 inferred and curated Chemical-Gene-Phenotype-Disease tetramers. Using a behavioral repulsion assay with the whole organism model Caenorhabditis elegans, we examined the effect of cannabinoids and insecticides on depleting dopamine synthesis. Exposure to chlorpyrifos and permethrin, but not Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), results in dose-dependent effects on 1-nonanol repulsive behaviors in C. elegans, indicating dopaminergic neurotoxicity (P < 0.01). Dose-dependent effects of chlorpyrifos are different in the presence of Δ9-THC and CBD (P < 0.001). As a proof of concept, this study demonstrated how to use new approach methodologies such as C. elegans and the CTD to inform further testing and pesticide regulations in cannabis by chemical class.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"218-227"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012137","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
Transcriptomic analysis in liver spheroids identifies a dog-specific mechanism of hepatotoxicity for amcenestrant. 肝球体的转录组学分析确定了Amcenestrant的狗特异性肝毒性机制。
IF 3.4 3区 医学
Toxicological Sciences Pub Date : 2025-04-01 DOI: 10.1093/toxsci/kfaf012
Piyush Bajaj, Richard J Brennan, Sébastien Laurent, Sylvie Sauzeat, Michael Dufault, Brenda Richards, Karissa Adkins
{"title":"Transcriptomic analysis in liver spheroids identifies a dog-specific mechanism of hepatotoxicity for amcenestrant.","authors":"Piyush Bajaj, Richard J Brennan, Sébastien Laurent, Sylvie Sauzeat, Michael Dufault, Brenda Richards, Karissa Adkins","doi":"10.1093/toxsci/kfaf012","DOIUrl":"10.1093/toxsci/kfaf012","url":null,"abstract":"<p><p>Therapeutic drugs can sometimes cause adverse effects in a nonclinical species that do not translate to other species, including human. Species-specific (rat, dog, and human) in vitro liver spheroids were employed to understand the human relevance of cholestatic liver injury observed with a selective estrogen receptor degrader (amcenestrant) in dog, but not in rat, during preclinical development. Amcenestrant showed comparable cytotoxicity in liver spheroids from all 3 species; however, its M5 metabolite (RA15400562) showed dog preferential cytotoxicity after 7 days of treatment. Whole genome transcript profiles generated from liver spheroids revealed downregulation of genes related to bile acid synthesis and transport indicative of strong farnesoid X receptor (FXR) antagonism following treatment with both amcenestrant and its M5 metabolite in the dog but not in rat or human. In human spheroids, upregulation of genes for detoxification enzymes indicative of pregnane X receptor (PXR) agonism was observed following amcenestrant treatment, whereas in the dog these genes were downregulated. The M5 metabolite showed gene dysregulation indicating PXR agonism in both rat and human, and antagonism in dog. Analysis of liver samples from a 3-mo dog toxicity study conducted with amcenestrant showed downregulation of several genes associated with PXR and FXR, corroborating the in vitro results. These results support the hypothesis that dogs are uniquely susceptible to cholestatic hepatotoxicity following administration of amcenestrant due to species-specific antagonism of FXR and highlight the value of in vitro liver spheroids to investigating mechanisms of toxicity and possible species differences.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"228-241"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066654","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
Examining risk assessment implications of genetic and dose-dependent dynamics of lead exposure in breastfeeding using the collaborative cross mouse population. 使用协作杂交小鼠群体研究母乳喂养中铅暴露的遗传和剂量依赖动力学的风险评估含义。
IF 3.4 3区 医学
Toxicological Sciences Pub Date : 2025-04-01 DOI: 10.1093/toxsci/kfaf010
Danila Cuomo, Zhuolin Song, Megan Nitcher, Rachel Lynch, Estefania Barba, Andrew P Feinberg, Ivan Rusyn, Fred A Wright, Weihsueh A Chiu, David W Threadgill
{"title":"Examining risk assessment implications of genetic and dose-dependent dynamics of lead exposure in breastfeeding using the collaborative cross mouse population.","authors":"Danila Cuomo, Zhuolin Song, Megan Nitcher, Rachel Lynch, Estefania Barba, Andrew P Feinberg, Ivan Rusyn, Fred A Wright, Weihsueh A Chiu, David W Threadgill","doi":"10.1093/toxsci/kfaf010","DOIUrl":"10.1093/toxsci/kfaf010","url":null,"abstract":"<p><p>Breastfeeding offers well-documented advantages but may inadvertently introduce lead (Pb) exposure to infants. Scarce data exist on the risks of Pb exposure for breastfed infants, and strategies for risk mitigation are needed, particularly considering the heightened susceptibility of children to adverse effects from Pb exposure. To investigate the potential influence of breastfeeding on blood Pb levels (BLL) in offspring, population variation in BLL between nonparous and parous mouse dams was quantified, as well as in dams exposed to low and high dose while breastfeeding, and their offspring. Female mice from 14 distinct collaborative cross (CC) mouse strains were mated with sires from different CC strains to produce 14 F1 hybrids. Subsequently, dams were administered either low- (100 ppm) or high- (1,000 ppm) dose Pb through ad libitum access drinking water starting the day of delivery for a duration of 4 wk, leading to the subsequent exposure of the offspring via lactation. Genetic background emerged as a predominant factor contributing to variation, with substantial interstrain variability observed in both CC dams and F1 hybrids exposed to low and high doses of Pb. Crucially, the degree of variation in BLL among CC dams exceeded the default variability estimate (geometric SD = 1.6) utilized in regulatory standard settings. These findings underscore the importance of integrating population variability in risk assessment. Ultimately, this study provides critical insights to guide public health decision-making processes concerning Pb exposure through breastfeeding and its potential implications for infants' health.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"242-250"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068317","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
A perspective review on factors that influence mutagenicity in medicinal plants and their health implications. 透视药用植物诱变性的影响因素及其对健康的影响。
IF 3.4 3区 医学
Toxicological Sciences Pub Date : 2025-04-01 DOI: 10.1093/toxsci/kfaf004
Victoria Fasiku, Doreen Kyagaba, Atlehang Hlalele, Ayodeji Adegoke, Ochuko L Erukainure, Mamello Sekhoacha
{"title":"A perspective review on factors that influence mutagenicity in medicinal plants and their health implications.","authors":"Victoria Fasiku, Doreen Kyagaba, Atlehang Hlalele, Ayodeji Adegoke, Ochuko L Erukainure, Mamello Sekhoacha","doi":"10.1093/toxsci/kfaf004","DOIUrl":"10.1093/toxsci/kfaf004","url":null,"abstract":"<p><p>Medicinal plants are products from natural sources that have found relevance in medicine for several decades. They are rich in bioactive compounds; thus, they are widely used to treat different ailments globally. Medicinal plants have provided hope for the healthcare industry as most are used to synthesize modern medicines currently used in the treatment of various diseases. However, there are still concerns with respect to the mutagenic properties of medicinal plants. Over the years, researchers have embarked on various studies aimed at investigating the mutagenicity of several medicinal plants found in different regions of the world. In this review, we discussed factors that may influence plant mutagenicity and the findings of in vitro and in vivo mutagenicity studies of several medicinal plants from across the globe. In addition, this review considers the potential health implications of mutagenic medicinal plants and safety measures that can be used to mitigate mutagenesis in medicinal plants. To achieve this, we searched for articles reporting on medicinal plants and mutagenesis on the PubMed, Scopus, and Web of Science databases. Several journal articles reported on the mutagenicity of some medicinal plants; however, it was observed that the majority of the articles reported the nonmutagenicity of medicinal plants. The findings from these studies imply that medicinal plants have good prospects in treating diseases and that they are clinically relevant. However, these reports will require further validation to determine their safety for human use as limited in vivo studies were conducted and there are no clinical safety reports for any of the plants discussed in this review.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"121-142"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971961","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
Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish- and mammalian-based assays. 普遍存在的轮胎防腐剂6PPD和降解物6PPD醌在鱼类和哺乳动物中的生物活性测定。
IF 4.1 3区 医学
Toxicological Sciences Pub Date : 2025-04-01 DOI: 10.1093/toxsci/kfaf008
Mark D Jankowski, Amy F Carpenter, Joshua A Harrill, Felix R Harris, Bridgett Hill, Rochelle Labiosa, Sergei S Makarov, Dalma Martinović-Weigelt, Jo Nyffeler, Stephanie Padilla, Timothy J Shafer, Marci G Smeltz, Daniel L Villeneuve
{"title":"Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish- and mammalian-based assays.","authors":"Mark D Jankowski, Amy F Carpenter, Joshua A Harrill, Felix R Harris, Bridgett Hill, Rochelle Labiosa, Sergei S Makarov, Dalma Martinović-Weigelt, Jo Nyffeler, Stephanie Padilla, Timothy J Shafer, Marci G Smeltz, Daniel L Villeneuve","doi":"10.1093/toxsci/kfaf008","DOIUrl":"10.1093/toxsci/kfaf008","url":null,"abstract":"<p><p>6PPD-quinone (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone), a transformation product of the antiozonant 6PPD (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine) is a likely causative agent of coho salmon (Oncorhynchus kisutch) pre-spawn mortality. Stormwater runoff transports 6PPD-quinone into freshwater streams, rapidly leading to neurobehavioral, respiratory distress, and rapid mortality in laboratory-exposed coho salmon, but causing no mortality in many laboratory-tested species. Given this identified hazard, and potential for environmental exposure, we evaluated a set of U.S. Environmental Protection Agency's high-throughput assays for their capability to detect the large potency difference between 6PPD and 6PPD-quinone observed in coho salmon and screen for bioactivities of concern. Assays included transcriptomics in larval fathead minnow (FHM), developmental and behavioral toxicity in larval zebrafish, phenotypic profiling in a rainbow trout gill cell line, acute and developmental neurotoxicity in mammalian cells, and reporter transcription factor activity in HepG2 cells. 6PPD was more consistently bioactive across assays, with distinct activity in the developmental neurotoxicity assay (mean 50th centile activity concentration = 0.91 µM). Although 6PPD-quinone was less potent in FHM and zebrafish, and displayed minimal neurotoxic activity in mammalian cells, it was highly potent in altering organelle morphology in RTgill-W1 cells (phenotype-altering concentration = 0.024 µM compared with 0.96 µM for 6PPD). Although in vitro sensitivity of RTgill-W1 cells may not be as sensitive as intact Coho salmon, the assay may be a promising approach to test chemicals for 6PPD-quinone-like activities. The other assays each identified unique bioactivities of 6PPD, with neurobehavioral and developmental neurotoxicity being most affected, indicating a need for further assessment of this chemical. Our results demonstrate that the common tire additive, 6PPD, is bioactive in a broader set of assays than the environmental transformation product 6PPD-quinone and that it may be a developmental neurotoxicant in mammals, whereas 6PPD-quinone was much more potent than 6PPD in altering the intracellular phenotype of rainbow trout gill cells. Application of the set of high-throughput and high-content bioassays to test the bioactivity of this emerging pollutant has provided data to inform both ecological and human health assessments.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"198-217"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024818","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
Comparative analysis of Caco-2 cells and human jejunal and duodenal enteroid-derived cells in gel- and membrane-based barrier models of intestinal permeability. Caco-2细胞与人空肠和十二指肠肠源性细胞在肠通透性凝胶和膜屏障模型中的比较分析。
IF 3.4 3区 医学
Toxicological Sciences Pub Date : 2025-04-01 DOI: 10.1093/toxsci/kfaf011
Haley L Moyer, Leoncio Vergara, Clifford Stephan, Courtney Sakolish, Lucie C Ford, Han-Hsuan D Tsai, Hsing-Chieh Lin, Weihsueh A Chiu, Remi Villenave, Philip Hewitt, Stephen S Ferguson, Ivan Rusyn
{"title":"Comparative analysis of Caco-2 cells and human jejunal and duodenal enteroid-derived cells in gel- and membrane-based barrier models of intestinal permeability.","authors":"Haley L Moyer, Leoncio Vergara, Clifford Stephan, Courtney Sakolish, Lucie C Ford, Han-Hsuan D Tsai, Hsing-Chieh Lin, Weihsueh A Chiu, Remi Villenave, Philip Hewitt, Stephen S Ferguson, Ivan Rusyn","doi":"10.1093/toxsci/kfaf011","DOIUrl":"10.1093/toxsci/kfaf011","url":null,"abstract":"<p><p>Intestinal absorption is a key toxicokinetics parameter. Although the colon carcinoma cell line Caco-2 is the most used in vitro model to estimate human drug absorption, models representing other intestinal segments are available. We characterized the morphology, tissue-specific markers, and functionality of 3 human intestinal cell types: Caco-2, primary human enteroid-derived cells from jejunum (J2), and duodenum (D109) when cultured in the OrganoPlate 3-lane 40 microphysiological system (MPS) or static 24-well Transwells. In both conditions, J2 and D109 formed dome-like structures; Caco-2 formed uniform monolayers. In MPS, only Caco-2 formed tubules. Cells grown on Transwells formed a thicker monolayer. All cells and conditions exhibited expression of ZO-1 (tight junctions). Polarization markers Ezrin and Villin were highest in J2 and D109 in MPS, highest expression of Mucin was observed with J2. However, J2 and D109 exhibited poor barrier (70 kDa TRITC-dextran) in MPS, whereas robust barrier was recorded in Transwells. Barrier function and drug transport were evaluated using caffeine, indomethacin, and propranolol. The gel lane in MPS acted as a blockade; only a small fraction crossed, even without cells. The permeability ratios were used to parameterize the probabilistic compartmental absorption model to determine whether in vitro data could reduce uncertainty. The most accurate prediction of the fraction absorbed was achieved with Transwell-derived data from Caco-2, combined with the experimentally derived segment-specific absorption ratios. The impact of this study includes demonstration that enteroid-derived cells cultured in MPS show most physiological morphology, but that studies of drug permeability in this MPS are challenging.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"181-197"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068206","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
Adolescent exposure to Δ9-tetrahydrocannabinol (THC) impairs testicular function in young adult male mice. 青少年接触Δ9-tetrahydrocannabinol (THC)会损害年轻成年雄性小鼠的睾丸功能。
IF 3.4 3区 医学
Toxicological Sciences Pub Date : 2025-03-24 DOI: 10.1093/toxsci/kfaf035
Jinhwan Lim, Caitlin Quach, Julie Nguyen, Andrew Rizk, Samantha Getze, Kwang-Mook Jung, Stephen V Mahler, Daniele Piomelli, Ulrike Luderer
{"title":"Adolescent exposure to Δ9-tetrahydrocannabinol (THC) impairs testicular function in young adult male mice.","authors":"Jinhwan Lim, Caitlin Quach, Julie Nguyen, Andrew Rizk, Samantha Getze, Kwang-Mook Jung, Stephen V Mahler, Daniele Piomelli, Ulrike Luderer","doi":"10.1093/toxsci/kfaf035","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf035","url":null,"abstract":"<p><p>Cannabis use typically starts in early to mid-adolescence. Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, targets cannabinoid receptors (CBRs) to exert its pharmacological effects. Expression of CBRs has been observed in human and rodent testes, but their potential role in the control of reproductive function remains unclear. We aimed to elucidate how THC exposure during adolescence or young adulthood affects the reproductive health of males. C57BL/6N male mice were given THC (5 mg/kg) or vehicle, once daily by intraperitoneal (ip) injection from postnatal day (PND) 30 to PND 43 (adolescent exposure) or PND 70 to PND 83 (adult exposure), and testes were harvested at PND 70 and PND 110, respectively. Results showed that CBRs (CB1R and CB2R) and enzymes that biosynthesize or inactivate the endocannabinoid anandamide (AEA) -N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) or fatty acid amide hydrolase (FAAH), respectively-are expressed in the mouse testis. THC exposure in adolescence decreased sperm numbers and increased seminiferous tubule degeneration in young adult testes, while adult exposure did not affect spermatogenesis and seminiferous tubule morphology. Both adolescent and adult THC exposure resulted in decreased plasma testosterone levels; however, only mice with adolescent THC exposure showed impaired steroidogenesis with dysregulated expression of steroidogenic acute regulatory protein (StAR) and steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1). Our results support that adolescent THC exposure may cause testicular toxicity through direct and aberrant activation of CBRs in the testis. These studies show that the adolescent testis is more sensitive than the adult testis to THC-induced disruption of spermatogenesis.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701344","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
Distribution of polybrominated diphenyl ethers (PBDEs) in placental tissues of maternal and fetal origin in exposed Wistar rats and associations with thyroid hormone levels. 多溴联苯醚(PBDEs)在Wistar大鼠胎盘组织中的分布及其与甲状腺激素水平的关系
IF 3.4 3区 医学
Toxicological Sciences Pub Date : 2025-03-01 DOI: 10.1093/toxsci/kfae151
Shaza Gaballah, Brian Hormon, Genavieve St Armour Mason Nelson, Jinyan Cao, Kate Hoffman, Heather B Patisaul, Heather M Stapleton
{"title":"Distribution of polybrominated diphenyl ethers (PBDEs) in placental tissues of maternal and fetal origin in exposed Wistar rats and associations with thyroid hormone levels.","authors":"Shaza Gaballah, Brian Hormon, Genavieve St Armour Mason Nelson, Jinyan Cao, Kate Hoffman, Heather B Patisaul, Heather M Stapleton","doi":"10.1093/toxsci/kfae151","DOIUrl":"10.1093/toxsci/kfae151","url":null,"abstract":"<p><p>In utero exposure to polybrominated diphenyl ethers (PBDEs) is linked to adverse pregnancy and fetal health outcomes, including altered thyroid hormone (TH) levels. Despite their phase-out, PBDEs are still commonly detected in newborn cord blood. While PBDEs can cross the placenta, few studies have separately assessed PBDEs or THs in the maternal and fetal placental tissues. Additionally, no studies have separately assessed THs in these tissues across mid- and late gestation, during the onset of fetal TH synthesis. To address these gaps, we conducted a study with Wistar rats and examined PBDE accumulation in the maternal and fetal placenta. Pregnant dams were exposed daily to sesame oil vehicle, a low dose, or high dose PBDE mixture. At GD15 and 20, dams were sacrificed and placental tissues were collected. Tissues were analyzed for PBDEs, T3, rT3, and T4 using mass spectrometry. BDE-47, -99, -100, and -209 were frequently detected in both the fetal and maternal placenta. At GD15, higher concentrations of BDE-99, -100, and -209 were measured in the fetal placenta; however, this trend reversed by GD20, with higher maternal placental concentrations. Placental T3 and T4 were significantly impacted by exposure, tissue, and exposure × tissue at GD15, with significant reductions in both THs following low-dose exposure in the maternal placenta. By GD20, maternal placental T3 was only significantly reduced in the high exposure groups and there was no effect on placental T4. Overall, these results highlight the rapid developmental changes that occur throughout gestation between the maternal and fetal placenta, and the differential impacts of gestational PBDE exposure on placental T3 and T4 across mid- and late gestation.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"20-30"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772596","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
Haloacetamides exacerbate non-alcoholic fatty liver disease induced by a high-fat diet in C57BL/6J mice. 卤代乙酰胺加重C57BL/6J小鼠高脂饮食诱导的非酒精性脂肪性肝病
IF 3.4 3区 医学
Toxicological Sciences Pub Date : 2025-03-01 DOI: 10.1093/toxsci/kfae160
Zhiqiang Jiang, Lili Yang, Qinxin Liu, Meiyue Qiu, Yu Chen, Mengying Teng, Yubin Zhang, Xing Liu, Zhonghua Zhao, Yuxin Zheng, Melvin Andersen, Weidong Qu
{"title":"Haloacetamides exacerbate non-alcoholic fatty liver disease induced by a high-fat diet in C57BL/6J mice.","authors":"Zhiqiang Jiang, Lili Yang, Qinxin Liu, Meiyue Qiu, Yu Chen, Mengying Teng, Yubin Zhang, Xing Liu, Zhonghua Zhao, Yuxin Zheng, Melvin Andersen, Weidong Qu","doi":"10.1093/toxsci/kfae160","DOIUrl":"10.1093/toxsci/kfae160","url":null,"abstract":"<p><p>Obesity, a significant global health issue, heightens the risk of non-alcoholic fatty liver disease (NAFLD). Its interaction with environmental pollutants might exacerbate NAFLD's severity. Haloacetamides (HAcAms), a group of emerging nitrogenous disinfection byproducts (DBPs) and potent oxidative stressors, are found in chlorinated drinking water. Since oxidative stress is associated with HAcAms-DBP cytotoxicity and a key factor in NAFLD pathogenesis, we hypothesize that HAcAms-DBPs could exacerbate liver injury and NAFLD, particularly with high-fat diets. This study examined HAcAms-DBPs' impact on liver lipid metabolism in mice treated with 1 to 100 times the background drinking water level (13.05 µg/L) for up to 16 weeks of oral administration. Compared to a high-fat-only group, mice co-exposed to a high-fat diet and HAcAms-DBPs for 16 weeks had elevated serum alanine transaminase, aspartate transaminase, triglyceride, hepatic lipid aggregation, and inflammation response. Under high-fat conditions, background drinking water levels of HAcAms significantly upregulated liver Acetyl-CoA carboxylase 1, fatty acid synthase, peroxisome proliferator-activated receptor gamma (PPARγ), PPARγ coactivator-1α, glucose transporter 1 and 4 protein expression in C57BL/6J mice; 10 times background significantly increased expression of inflammatory marker tumor necrosis factor and liver fibrosis marker protein alpha-smooth muscle actin; 100 times further increased both liver damage and markers of early non-alcoholic steatohepatitis phenotypes like steatosis and lobular inflammation. HAcAms-DBPs plus high-fat conditions worsened liver damage. The possible health risks of NAFLD induced by HAcAms in obese individuals deserve further study.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"57-69"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847430","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}
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