Drug and Chemical Toxicology最新文献

{"title":"The role of lncRNA H19/Hmox1 axis regulating ferroptosis in anthracycline-induced cardiotoxicity.","authors":"Bayan Kadeerbieke, Li Wu, Yuan-Ming Zhang","doi":"10.1080/01480545.2025.2503946","DOIUrl":"https://doi.org/10.1080/01480545.2025.2503946","url":null,"abstract":"<p><p>This study investigates the molecular mechanisms underlying anthracyclines (ANT)-induced cardiotoxicity, with a specific focus on ferroptosis regulated by the long non-coding RNA (lncRNA) H19/heme oxygenase-1 (Hmox1) signaling axis. A retrospective analysis was performed on 50 breast cancer patients who developed ANT-associated cardiac dysfunction. Clinical assessments included measurements of left ventricular ejection fraction (LVEF) and serum markers, such as cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and serum iron levels. Serum analysis revealed a marked downregulation of lncRNA H19 and upregulation of Hmox1, both significantly correlated with impaired cardiac function and disrupted iron homeostasis. To further elucidate the mechanism, an Epirubicin (EPI)-induced injury model in HL-1 cardiomyocytes was established. EPI exposure led to suppression of lncRNA H19, upregulation of Hmox1, and induction of apoptosis and ferroptotic cell death. RNA-seq analysis identified potential downstream targets linking lncRNA H19 to iron metabolism via Hmox1 modulation. Functional assays demonstrated that overexpression of lncRNA H19 mitigated EPI-induced ferroptosis, while enforced expression of Hmox1 reversed these protective effects. Collectively, these findings identify the lncRNA H19/Hmox1 axis as a critical regulator of ferroptosis in ANT-induced cardiotoxicity and suggest it as a potential therapeutic target for mitigating cardiac injury in breast cancer patients undergoing anthracycline chemotherapy.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157420","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}

{"title":"Deferoxamine halt rotenone-induced Parkinson's like symptoms in experimental rats: biochemical, neuroinflammatory, neurotransmitters, and histological evidence.","authors":"Anupam Awasthi, G D Gupta, Shamsher Singh","doi":"10.1080/01480545.2025.2495361","DOIUrl":"https://doi.org/10.1080/01480545.2025.2495361","url":null,"abstract":"<p><p>Rotenone is a pesticide compound that selectively damages dopaminergic neurons in the substantia nigra pars compacta and produces Parkinson's like symptoms in rodents. Deposition of iron and reactive oxygen species (ROS) generation by its oxidation are contributing factors in the etiology of Parkinson's disease. Deferoxamine (DFO) is an iron chelator with high affinity produced by <i>Streptomyces wadayamensis</i>, <i>S. malaysiense</i>, like organisms. The present study provides insight to evaluate the protective effect of DFO in rotenone-induced neurotoxicity in rats. Rotenone (6 μg/2 μl/rat, unilaterally) was injected intranigral on day-1 using a digital stereotaxic apparatus. DFO (50 and 100 mg/kg, intraperitoneally) was given orally daily for 21 days starting from day 8 after the intranigral surgery. On day 28, animals were sacrificed, and the striatum was isolated for oxidative stress parameters (lipid peroxidation, nitrite and reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase), neuroinflammatory cytokines (IL-1β, IL-6, and TNF-α), mitochondrial complexes-I and IV, neurotransmitters (brain catecholamines, gamma-aminobutyric acid, glutamate), and iron level estimation. Unilateral intranigral infusion of rotenone led to significant motor deficits as evidenced by impairments in locomotor activity in open field test, rotarod activity (motor coordination), grip strength, and narrow beam walk performance. DFO administration dose-dependently significantly improved against rotenone-induced behavioral abnormalities in rats, restored the altered level of neurotransmitters in the striatum, and attenuated oxidative stress and inflammatory response in the striatum. These findings indicate that DFO successfully achieved antioxidant and anti-inflammatory properties and protect dopaminergic neurons against rotenone-induced neurotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-16"},"PeriodicalIF":2.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141577","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}

{"title":"Impact of <i>Bacillus coagulans</i> ATCC7050 supplementation on growth, gut microbiota, and immunity in <i>rainbow trout</i> exposed to pretilachlor.","authors":"Mahdieh Raeeszadeh, Reyhaneh Rezaeishoorijeh, Hamed Ghafarifarsani, Caterina Faggio","doi":"10.1080/01480545.2025.2503942","DOIUrl":"https://doi.org/10.1080/01480545.2025.2503942","url":null,"abstract":"<p><p>This study investigates the effects of <i>Bacillus coagulans</i> ATCC7050 probiotic supplementation on the growth performance, immune function, antioxidant activity, and liver health of rainbow trout (<i>Oncorhynchus mykiss</i>) exposed to the herbicide pretilachlor. Over 30 days, the fish were fed diets supplemented with <i>B. coagulans</i> (1 × 10⁶ or 1 × 10⁸ CFU/g) and/or 12.5% pretilachlor. Probiotic supplementation significantly enhanced growth parameters and reduced the feed conversion ratio, whereas herbicide exposure had the opposite effect (<i>p</i> = 0.000). Immune responses, including lysozyme activity and total immunoglobulin levels, were improved by probiotic treatment but suppressed by pretilachlor exposure (<i>p</i> = 0.001). Additionally, the probiotic increased antioxidant enzyme activity and reduced markers of oxidative stress. Liver function indicators elevated due to herbicide exposure were mitigated by <i>B. coagulans</i> supplementation (<i>p</i> = 0.028). These findings underscore the potential of <i>B. coagulans</i> to counteract herbicide-induced toxicity, supporting fish health and promoting more sustainable aquaculture practices.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":2.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126888","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}

{"title":"Toxicity study of compound honeysuckle moisturizing Chinese herbal extract by oral gavage for 13 weeks in sprague dawley rats.","authors":"Yijun Tian, Jun Li, Kexuan Zhou, Xiaoyu Dai, Lang Yan, Bin Zhang, Lijun Ren, Yun Chen, Jingjing Mao, Jikuai Chen, Quangang Zhu","doi":"10.1080/01480545.2025.2499937","DOIUrl":"https://doi.org/10.1080/01480545.2025.2499937","url":null,"abstract":"<p><p>To assess the safety of oral compound honeysuckle moisturizing Chinese herbal extract for eczema treatment, Sprague-Dawley (SD) rats were oral administered three doses (20.8, 41.6, and 83.3 g/kg, based on raw materials) of the extract daily for 13 consecutive weeks. The study aimed to identify potential toxic reactions, mortality due to accumulation, and recovery after discontinuation. By observing these factors, we sought to determine the target organs of toxicity and establish nontoxic doses for SD rats. The results indicated that during the administration period and subsequent recovery period, there were no significant abnormalities in weight gain, food intake, hematology, blood biochemistry, or urine indicators. Additionally, histopathological analysis of major organs (heart, liver, lungs, kidneys, spleen, and brain) revealed no significant extract-related lesions. Moreover, no significant local toxic lesions were observed in the oral buccal and tongue mucosa. Finally, under the experimental conditions of this study, the preliminary nontoxic response dose of oral gavage compound honeysuckle moisturizing Chinese herbal extract administered to SD rats for 13 weeks was 83.3 g/kg/day (calculated as raw medicine).</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-15"},"PeriodicalIF":2.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964361","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}

{"title":"A 13-week oral toxicity and toxicokinetic study of cannabidiol in Sprague Dawley rats with a 4-week recovery period.","authors":"Wenhao Xia, Rendy Yanuar, Vivek Mandal, Kasper Renggli, Jenny Ho, Blaine Phillips, Gitte Nykjaer Nikolajsen, Sanne Skov Jensen, Heidi Ziegler Bruun, Julia Hoeng","doi":"10.1080/01480545.2025.2491544","DOIUrl":"https://doi.org/10.1080/01480545.2025.2491544","url":null,"abstract":"<p><p>Cannabidiol (CBD) is widely marketed as a health and wellness product. However, evidence for its effectiveness and safety remains limited. This study assessed the toxicity and toxicokinetic profile of CBD in Sprague Dawley rats over 13 weeks at low (5 mg/kg/day), mid (15 mg/kg/day), and high (150 mg/kg/day) doses, followed by a 4-week recovery period. Toxicokinetic analyses revealed no marked sex differences in systemic exposure to CBD or its metabolite 6-OH-CBD; however, female rats had slightly higher exposure to metabolites 7-OH-CBD and 7-COOH-CBD. Accumulation of CBD and its metabolites was observed following repeated oral administration of CBD. No CBD-related effects on mortality, clinical observations, or ophthalmoscopy were observed during the study. Higher food consumption was observed in rats treated with the high CBD dose group; however, this did not correlate with a statistically significant increase in body weight. A slightly higher fold increase in serum alanine aminotransferase (∼1.4-fold to 1.5-fold) was observed in the CBD high group, which was determined to be reversible. Histopathological analyses showed hepatocyte hypertrophy, but this effect was not accompanied by inflammatory changes or other microscopic lesions and resolved over the recovery period. Hypertrophy of pars distalis cells in pituitary gland and cortical cell vacuolation in adrenal glands were determined to be adaptive changes and reversible during the recovery period. The no-observed effect level was considered to be lower than the lowest tested dose (5 mg/kg/day) and no-observed adverse effect level to be the highest tested dose (150 mg/kg/day).</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962489","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}

{"title":"Arylacetamides exhibit antiproliferative effects on non-transformed mammalian and vegetal cells and toxicity on crustaceans and fish embryos.","authors":"Kátia da Conceição Machado, Jurandy do Nascimento Silva, Débora Caroline do Nascimento Rodrigues, Stefânia Neiva Lavorato, João Marcelo de Castro E Sousa, Ana Amélia de Carvalho Melo-Cavalcante, Patrícia Canteri de Souza, Paulo César Meletti, Diego Sousa Moura, José Roberto de Oliveira Ferreira, Cesar Koppe Grisolia, Ricardo José Alves, Paulo Michel Pinheiro Ferreira","doi":"10.1080/01480545.2025.2492770","DOIUrl":"https://doi.org/10.1080/01480545.2025.2492770","url":null,"abstract":"<p><p>Non-clinical steps for development, validation and biosafety of new medicines and products comprises studies on cells, proteins, and animals. Herein, we evaluated the toxic activity of antitumoral 2-chloro-<i>N</i>-arylacetamides on eukaryotic dividing cells and animal replacement models. Firstly, the cytotoxicity of chloro (compound <b>2</b>), bromo (compound <b>3</b>) and nitro (compound <b>4</b>) acetamides was analyzed by fluorescent assays in fibroblasts. Next, toxicity was evaluated on <i>Allium cepa</i> meristematic cells and 48h-living <i>Artemia salina</i> larvae. Finally, embryos of <i>Danio rerio</i> (zebrafish) were exposed to the compound <b>2</b> (0.14 - 7.2 μg/mL) for 120 h exposure. All arylacetamides were cytotoxic on murine and human fibroblasts, with IC₅₀ values ranging from 1.2 μg/mL (5.6 µM = compound <b>4</b> on L-929) to 4.9 μg/mL (24 µM = compound <b>2</b> on MRC-5 cells), respectively, and inhibited root growth from 10 to 100 µg/mL, corroborated by mitotic index reduction and cell cycle arrest in interphase (<i>p</i> < 0.05) without clastogenic injuries. Compound <b>2</b> showed time- and concentration-dependent killing effects on zebrafish embryos. Its 24 h-acute toxicity at higher concentrations (1.93 and 7.2 μg/mL with 90% and 100% death) corroborated toxicity on aquatic <i>A. salina</i> organisms. After 96 h exposure at 0.52 μg/mL (2.55 µM), almost 100% of the embryos showed more than one lethal/sublethal morphological abnormality (<i>p</i> < 0.05). Then, all arylacetamides showed unspecific toxic effects, mainly the halogenated electrophile chloroacetamide. They present strong antimitotic action on vertebrate and vegetal cells, although such antiproliferative activity does not seem to be directly related to chromosomal damage inductions.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973007","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}

{"title":"Deciphering the genotoxic and cytotoxic properties of teicoplanin: a combined laboratory and computational investigation.","authors":"Ahmet Ali Berber, Işıl Deniz Aliravci, Nihan Akinci Kenanoğlu, Şefika Nur Demir","doi":"10.1080/01480545.2025.2502446","DOIUrl":"https://doi.org/10.1080/01480545.2025.2502446","url":null,"abstract":"<p><p>In this study, the mutagenicity and carcinogenicity of the teicoplanin antibiotic were first investigated using the Vega Hub and Toxtree software through <i>in silico</i> prediction. The cytotoxic and genotoxic effects were evaluated using <i>in vitro</i> assays, including the mitotic index (MI), micronucleus (MN), nuclear division index (NDI), and Comet Assay (CA) in human lymphocytes. In the <i>in vitro</i> studies, both 24-hour and 48-hour exposures were conducted for MI, and teicoplanin significantly decreased MI compared to the control at all concentrations. In addition, a significant increase was detected in the MN frequency compared to the negative control at all concentrations. In the Comet assay, tail length significantly increased compared to the control at all concentrations except for 5.6 µg/mL, while tail moment and comet tail intensity significantly increased at all concentrations compared to the control. In conclusion, within the concentration range used in this study, teicoplanin was found to have cytotoxic and genotoxic effects.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-10"},"PeriodicalIF":2.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988361","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}

{"title":"Silymarin attenuates cobalt chloride-induced redox imbalance and cardio-renal dysfunctions in rats.","authors":"Temitayo Olabisi Ajibade, Okezi Michael Ohore, Oluwaseun Olarenwaju Esan, Bisi Olajumoke Adeoye, Ayodele Stephen Ake, Moses Olusola Adetona, Omolola Victoria Awoyomi, Olumayowa Olawumi Igado, Taiwo Olaide Oyagbemi, Adewunmi Victoria Adeogun, Ademola Adetokunbo Oyagbemi, Temidayo Olutayo Omobowale, Oluwafemi Omoniyi Oguntibeju, Evaristus Nwulia, Momoh Audu Yakubu","doi":"10.1080/01480545.2025.2499540","DOIUrl":"https://doi.org/10.1080/01480545.2025.2499540","url":null,"abstract":"<p><p>Silymarin is an extract of <i>Silybum marianum</i> that is used traditionally for the treatment of several diseases. This study sought to evaluate the protective effects of silymarin on cobalt chloride (CoCl₂)-induced cardio-renal toxicities in rats. Forty rats were randomly divided into four groups of 10 rats each: control; 300 mg/kg CoCl₂; CoCl₂ + 100 mg/kg silymarin; and 100 mg/kg silymarin only. All administrations were done orally. At the end of the experimental period (seven days), blood pressure parameters, markers of oxidative stress, antioxidant defense status, renal function test, histopathology and immunohistochemical expressions were evaluated on the heart and kidney tissues. Silymarin significantly (<i>p</i> < 0.05) altered CoCl₂-induced alterations in blood pressure parameters, antioxidants and markers of oxidative stress, blood urea nitrogen and creatinine. Histopathological evaluation revealed area of infiltration of the myocardium by inflammatory cells and hemorrhages in the kidney of rats exposed to CoCl₂ without silymarin treatment, but these lesions were absent in the control and silymarin groups. Increased immunohistochemical expression of cardiac troponin I and matrix metalloproteinase-2 (MMP-2) was observed in the cardiac tissues of rats exposed to CoCl₂ without silymarin treatment. The immunohistochemical expression of cystatin C was heightened, while that of angiotensin-converting enzyme 2 (ACE2) was attenuated in the CoCl₂ untreated group compared with the control and silymarin groups. In conclusion, silymarin effectively mitigated the toxic effects of CoCl₂ on the heart and kidney tissues of rats due to its ability to positively modulate the activities of endogenous antioxidants and neutralize reactive oxygen species in cardiac and renal systems.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973447","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}

{"title":"Protective effects of curcumin against valproic acid induced brain kidney and liver damage in rats.","authors":"Kübra Asena Terim Kapakin, İsmail Bolat, Hatice İskender, Eda Dokumacioğlu, Esra Manavoğlu Kirman, Merve Bolat, Mevlana Gül","doi":"10.1080/01480545.2024.2391868","DOIUrl":"10.1080/01480545.2024.2391868","url":null,"abstract":"<p><p>Valproic acid (VPA) is a broad-spectrum drug that is now widely used as an antiepileptic. Although VPA has positive therapeutic effects, it also causes various toxic effects in tissues. Curcumin, a natural antioxidant found in ginger, has antibacterial and antiinflammatory activity. In this study, the toxic effects of VPA on brain, kidney, and liver tissues and the protective activity of curcumin against these effects were investigated. In this study, male Wistar-Albino rats were used. Rats were divided into 4 groups control, VPA, CUR, and CUR + VPA. Rats were administered intraperitoneal VPA and CUR intragastrically. In the study, MDA, SOD, IL-6, and IL-18 levels were measured by the ELISA method in rats. It was observed that VPA triggered oxidative stress and inflammation in tissues, while CUR administration positively regulated these parameters. Studies also showed that VPA increased the expressions of TNF-α and NF-kB in tissues, but CUR administration downregulated these expressions The findings revealed that CUR protects by preventing the oxidative stress and inflammation caused by VPA in the tissues and may be an important agent in reducing the side effects of this drug used as an antiepileptic.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"644-659"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105420","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}

{"title":"Human quad liver-on-chip system as a tool toward bridging the gap between animals and humans regarding toxicology and pharmacology of a cannabidiol-rich cannabis extract.","authors":"Laura E Ewing, Charles M Skinner, Mitchell R McGill, Stefanie Kennon-McGill, Kirsten Clement, Charles M Quick, Eric U Yee, D Keith Williams, Larry A Walker, Mahmoud A ElSohly, Bill J Gurley, Igor Koturbash","doi":"10.1080/01480545.2024.2388292","DOIUrl":"10.1080/01480545.2024.2388292","url":null,"abstract":"<p><p>Cannabidiol (CBD) is a major phytocannabinoid from <i>Cannabis sativa</i>. It is currently widely available and widely used in the USA, but despite its rapid progress to market, the pharmacology and toxicology of both CBD and cannabidiol-rich cannabis extracts (CRCE) remain largely unknown. The goals of this study were to investigate the potential of a novel human microphysiological system to emulate CRCE-induced hepatotoxicity and pharmacological properties demonstrated in animal models. For this purpose, C57BL6/J male mice were subjected to dosing with either 0, 61.5, 184.5, or 615 mg/kg of CRCE for 10 days. The liver-on-chip system, incorporating human primary hepatocytes, sinusoidal endothelial cells, as well as Kupffer and stellate cells was subjected to 0, 300, 1,200, or 4,400 ng/mL of CRCE (8 h exposure followed by 16 h washout) for 5 days. Administration of CRCE in mice resulted in nearly 4-fold elevations of plasma ALT at 615 mg/kg (<i>p</i> < 0.01) and a dose-dependent decrease in intrahepatic miR-122. Elevated levels of ALT, paralleled by decreased intrahepatic and increased effluent levels of miR-122, were also observed in the liver-on-chip, although these results were not statistically significant. Exposure to CRCE resulted in a robust and dose-dependent induction of key cytochrome P450 enzymes, namely <i>Cyp1a2</i>, <i>Cyp2b6</i> (<i>CYP2B10</i>), <i>Cyp2e1</i>, and <i>Cyp2c9</i> (<i>CYP2C19</i>) in both mouse livers and liver-on-chip. The results of this study demonstrate the congruence between the responses observed in mouse and human liver-on-chip experimental systems and provide evidence of the potential microphysiological systems hold for translating animal data into clinical practice.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"578-585"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}