Toxicology Research最新文献

{"title":"Microsampling in toxicology studies - maximising the scientific, business and 3Rs advantages.","authors":"Helen Prior, Adeyemi O Adedeji, Romalie Allen, Derek Angus, Daniel Baker, Hollie Blunt, David Coleman, Helen-Marie Dunmore, Elisa Passini, Tara Putnam, Marie-Luce Rosseels, Neil Spooner, Jane Stewart, Carol Strepka, Alan Stokes, Tom Verhaeghe, Amanda Wilson, Fiona Sewell","doi":"10.1093/toxres/tfaf045","DOIUrl":"10.1093/toxres/tfaf045","url":null,"abstract":"<p><p>Adoption of a blood microsampling technique can reduce or avoid the use of satellite animals (rodents) for toxicokinetics or other purposes in discovery and toxicology studies and provides refinements applicable for both rodents and larger animals. Microsampling can increase the scientific value of data obtained from rodent studies during drug and (agro)chemical development, enabling multiple endpoints to be investigated and compared in an individual animal in the same way as non-rodents. A cross-sector survey was developed to understand the current use of microsampling in toxicology studies, with the aim of identifying the specific studies in which microsampling was employed and the barriers to wider uptake. A high proportion of the survey responses indicated that microsampling was used, however, the extent varied widely. Some organisations use the technique only in non-GLP studies. Microsampling was used most for pharmacokinetics or toxicokinetics, commonly within small molecule and agrochemical toxicity studies, but less frequently within large molecule, cell/gene therapies or industrial chemical studies. A wide variety of barriers to wider use of microsampling were provided, typically around reticence to change from using larger samples, or not wishing to validate another bioanalytical method given the resources and challenges associated with the validation of a new technology. Despite these barriers, some organisations have adopted microsampling routinely across many/all rodent toxicity studies and there are opportunities to further reduce and refine animal use across all sectors by wider adoption of microsampling.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf045"},"PeriodicalIF":2.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750143","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}

{"title":"Protective effects of corn silk and <i>asparagus Officinalis</i> against formaldehyde-induced reproductive toxicity in male rats via CDK2/Spem1/Fbxo47 and Tet1 pathways.","authors":"Amina Zedan, Mohamed H Abdelfattah, Eman S El-Gezawy, Asmaa M El-Gawish, Amira M El-Moslemany, Neveen M Zeima, Ibrahim Albokhadaim, Sameer Alhojaily, Heba I Ghamry, Badriyah S Alotaibi, Mohamed Marzok, Mustafa Shukry","doi":"10.1093/toxres/tfaf039","DOIUrl":"10.1093/toxres/tfaf039","url":null,"abstract":"<p><p>This study investigated the protective effects of aqueous extracts of <i>Asparagus officinalis</i> and Corn Silk (<i>Stigma maydis</i>) against formaldehyde-induced reproductive toxicity in male albino rats. High-Performance Liquid Chromatography (HPLC) analysis revealed that Gallic acid was the major phenolic component in Corn Silk, while Syringic acid predominated in <i>A. officinalis</i>. Formaldehyde exposure significantly reduced (<i>P</i> < 0.05) body and testicular weights, reproductive hormone levels, sperm count, motility, and normal sperm morphology. It also caused notable histological changes and downregulated fertility-related genes (<i>CDK2, Spem1, Fbxo47,</i> and <i>Tet1</i>). Treatment with the plant extracts, especially at higher concentrations, significantly (<i>P</i> < 0.05) reversed these adverse effects, improved antioxidant status, and reduced tumor necrosis factor-α levels. These findings emphasize the potential applications of <i>A. officinalis</i> and Corn Silk extracts as natural toxicological agents, particularly for mitigating formaldehyde-induced reproductive toxicity. Additionally, their prospective role in fertility treatment underscores their potential to support reproductive health through natural, plant-based interventions.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf039"},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750204","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}

{"title":"Royal jelly and doxorubicin suppressed tumor cells in the xenograft model of lung cancer via the STAT3/FOXM1/ATG7 signaling pathways in athymic nude mice: a biochemical, immunohistochemically and molecular approach.","authors":"Tianying Du, Wanjun Wang, Rui Zhang","doi":"10.1093/toxres/tfaf042","DOIUrl":"10.1093/toxres/tfaf042","url":null,"abstract":"<p><p>Royal Jelly (RJ), a traditional medicinal compound with tumor-suppressive properties, was investigated for its antitumor effects on non-small cell lung cancer (NSCLC) using a mouse xenograft model. Fifty athymic nude mice were divided into five groups: a control group, an untreated NSCLC group, a doxorubicin (DOX)-treated group, an RJ-treated group, and a combined RJ + DOX treatment group. RJ was administered at 200 mg/kg/day by gavage, while DOX was given intraperitoneally at 80 mg/kg on days 10, 20, and 30. Tumor size, volume, and weight were monitored, and Kaplan-Meier analysis assessed survival. Biochemical and histopathological analyses showed that RJ modulated oxidative stress markers, reduced inflammation (IL-6, TNF-α, IL-8, interferon-γ), and inhibited tumor growth. RJ downregulated STAT3/FOXM1/ATG7 signaling pathways involved in tumor cell survival, proliferation, and metastasis. Additionally, RJ promoted mitochondrial apoptosis through increased p53 expression and reduced angiogenesis by suppressing VEGF. Immunohistochemistry revealed decreased Ki-67 expression, indicating reduced tumor cell proliferation. Molecular analyses confirmed RJ's role in modulating key apoptosis and angiogenesis pathways. When combined with DOX, RJ enhanced therapeutic efficacy, suggesting a synergistic effect. These findings highlight RJ's potential as a therapeutic agent targeting STAT3 and related pathways in NSCLC treatment, offering a promising complementary approach to conventional chemotherapy.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf042"},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750210","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}

{"title":"Antioxidant, anti-inflammatory and Uroprotective effects of LAMOTRIGINE Cinnamaldehyde silver complex in cyclophosphamide-induced cystitis.","authors":"Irfan Anjum, Syeda Kainat Zahra, Kashif Barkat, Muhammad Naveed Mushtaq, Mushtaq Ahmad Ansari, Saima Najam, Shah Jahan, Sophia Awais, Kishwar Sultana, Nadia Bibi, Saira Khan, Tariq Nadeem","doi":"10.1093/toxres/tfaf041","DOIUrl":"10.1093/toxres/tfaf041","url":null,"abstract":"<p><p>Cyclophosphamide (CYP)-induced cystitis is a significant clinical challenge in cancer patients, characterized by inflammation, oxidative stress, and muscle dysfunction. This study aimed to investigate the protective effects of lamotrigine cinnamaldehyde silver complex (LCSC) against CYP-induced cystitis. Sprague-Dawley rats were divided into six groups: Control, CYP-induced cystitis (Disease Control), mesna (standard drug), and three LCSC treatment groups (2.5, 5, and 10 mg/kg). Nociception, open-field test, bladder weight, edema, hemorrhage, vascular permeability, histopathological analysis, and the qRT-PCR expression of inflammatory and antioxidant genes were investigated. Molecular docking was performed using AutoDock Tools 1.5.6 software. LCSC treatment significantly reduced nociceptive responses and improved locomotor activity in a dose-dependent manner compared to the diseased control group. LCSC attenuated CYP-induced increases in bladder weight, edema, and hemorrhage. The higher doses of LCSC (5 and 10 mg/kg) were more effective in reducing vascular permeability. In vitro studies revealed that LCSC relaxed the urinary bladder strips in a concentration-dependent manner. LCSC also significantly upregulated the expression of antioxidant genes (catalase and superoxide dismutase) and downregulated inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor-α, and transforming growth factor-β) in a dose-dependent manner. The histopathological evaluation confirmed the preservation of bladder architecture in LCSC-treated rats. LCSC demonstrated strong binding affinities and lower inhibition constants with key inflammatory and muscle protein receptors, including IL-1β, TNF-α, MLCP, and PKC, compared to Mesna. LCSC exhibited potent antioxidant, anti-inflammatory, and uroprotective effects in the CYP-induced rat model of cystitis as a potential therapeutic drug.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf041"},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750189","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}

{"title":"Effects and regulatory mechanisms of bisphenol a on the increases apoptosis and decreases differentiation potential in mouse embryonic stem cells.","authors":"Cheng-Kai Lee, Fu-Ting Wang, Chien-Hsun Huang, Hsin-Ju Lin, Wen-Hsiung Chan","doi":"10.1093/toxres/tfaf043","DOIUrl":"10.1093/toxres/tfaf043","url":null,"abstract":"<p><p>Bisphenol A has deleterious effects on reproductive, developmental, cell biological, and physiological functions. Here, we investigated the dosage effects of bisphenol A on the differentiation potential and apoptosis of mouse embryonic stem cells, and assessed some relevant regulatory mechanisms. Our results showed that bisphenol A at doses of 1-2 μmol/L triggers apoptotic processes without necrotic cell death in the ESC-B5 mouse embryonic stem cell line. No death effect was seen at treatment dosages of 0.5 μmol/L or less. Mechanistically, the application of 1-2 μmol/L bisphenol A directly increased the intracellular oxidative stress levels, significantly increased the cytoplasmic calcium and nitric oxide contents, decreased the mitochondrial membrane potential, activated caspases-9 and -3, and triggered programmed cell death. Interestingly, embryoid body formation assays showed that 0.5 μmol/L bisphenol A decreased the differentiation potential of ESC-B5 cells without inducing apoptotic processes. Together, our results indicate that treatment with 1-2 μmol/L bisphenol A induces apoptosis and triggers hazardous effects on the differentiation and developmental potential of mouse embryonic stem cells in vitro<i>.</i> These results provide important evidence that bisphenol A should be considered a potent cytotoxin that has dose-dependent impacts on differentiation and apoptosis in a mouse embryonic stem cell line.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf043"},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750139","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}

{"title":"Toxicity Profiling of a Polyherbal formulation for hepatic health: acute and subacute evaluation.","authors":"Kalyani A Autade, Ramdas B Pandhare","doi":"10.1093/toxres/tfaf040","DOIUrl":"10.1093/toxres/tfaf040","url":null,"abstract":"<p><p>All-natural products must be examined for any potential risks before being placed on the market. In this work, a polyherbal formulation with hepatoprotective properties was evaluated for acute, subacute, and subchronic toxicity. To examine the polyherbal syrup's toxicological profile in Wistar Albino rats. In compliance with OECD recommendations 423 and 407, acute and repeated dosage toxicity tests were carried out. A single oral dose of 2000 mg/kg was used to assess acute toxicity in vivo for 14 days, and repeated doses of 50, 100, and 200 mg/kg were applied for 28 days to examine sub-acute toxicity. According to the results of an acute toxicity investigation, rats given up to 2000 mg/kg did not exhibit any toxic symptoms, behavioral abnormalities, or death. Consequently, the oral hazardous dose's LD50 needs to be more than 2000 mg/mL. The safety of PHF was further validated by sub-acute toxicity experiments, which revealed no biochemical, haematological, or histological differences between rats administered with 50, 100, or 200 mg/kg and the control group (<i>P</i> < 0.05). The investigation reached its conclusion that histopathological examinations show no substantial weight changes and normal architectural changes in vital organs such the heart, brain, kidneys, liver, lungs, and spleen, indicating that the PHS is not linked to major organ degenerative potential. There were no discernible changes in the groups treated with polyherbal syrup in terms of AST or ALT, two markers of hepatocellular injury. Lipid markers such total cholesterol, HDL, LDL, VLDL, and TGL did not show any appreciable alterations.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf040"},"PeriodicalIF":2.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727201","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}

{"title":"Magnesium isoglycyrrhizinate prevented the liver injury of acetaminophen by promoting mitochondrial biogenesis.","authors":"Shuang Xia, Zhi-Yu Hu, Rong Cao, Lin Guo, Jia-Ting Ma, Ming-Xuan Xiao, Jiayi Liu, Bo-Wen Zhai, Rao Fu, Zhi-Chao Jiang, Hui Gong, Miao Yan","doi":"10.1093/toxres/tfaf024","DOIUrl":"10.1093/toxres/tfaf024","url":null,"abstract":"<p><p>Acetaminophen (N-acetyl-para-aminophenol, APAP) is the most widely used antipyretic and anti-inflammatory drug in the world. It is reported that APAP-induced liver damage accounts for about half of all liver failure patients in Europe and the United States. Magnesium isoglycyrrhizinate (MI) is the fourth-generation glycyrrhizic acid preparation developed in China. It has anti-inflammatory, hepatocyte membrane protection, and liver function recovery effects. This study aimed to investigate the effect of MI on alleviating APAP-induced liver injury and explore potential mechanisms. C57 BL/6 J mice were used to assess the efficacy of liver protection, by detecting ALT, AST, H&E and TUNEL staining. Liver samples from saline, APAP, APAP combined with MI group were selected for the transcriptomics analysis. MI significantly prevented the elevation of ALT, and AST. Hepatocyte necrosis was alleviated when MI was co-treated with APAP in TUNEL assay. There were no differences in total GSH levels or GSH/GSSG ration between APAP and MI group. Western Blot MI showed MI didn't affect the protein levels of CYP2E1 expression, mitochondrial p-JNK and cytosolic Endo G. GO analysis showed that mitochondria were the main target of MI in reducing APAP-induced liver injury. MI also significantly upregulated the expression of TFAM, NRF-1, PGC-1β and Sirt1. MI restored mRNA levels of oxidative phosphorylation genes and recovered mitochondrial membrane potential that fell after APAP administration. In conclusion, MI alleviated APAP-induced liver injury by promoting mitochondrial biogenesis.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf024"},"PeriodicalIF":2.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727197","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}

{"title":"Metabolomic profiling of adenine-induced CKD: pathway interconnections and kidney injury.","authors":"Ai-Ping Li, Xing-Xing Zhang, Qing-Yu Zhang, Meng-Jiao Wang, Zheng Ju, Xiao-Yu Zhang, Xue-Mei Qin, Guang-Zhen Liu","doi":"10.1093/toxres/tfaf035","DOIUrl":"10.1093/toxres/tfaf035","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is acknowledged as one of the largest public health problems in the world, characterized by a complex and diverse pathogenesis. Adenine-induced CKD, a classical model with multiple injury mechanisms, has been extensively employed in CKD research. However, the complete elucidation of the mechanisms underlying adenine-induced CKD remains elusive. In this study, the impacts of adenine (200 mg/kg/day) intake on the urine metabolome of rats were initially investigated using non-targeted metabolomics, and then targeted metabolomics was used to quantitatively verify key metabolites on crucial metabolic pathways. Interestingly, the interconnectedness of two significant pathways was discovered and validated through molecular biology techniques. The results found that adenine can cause significant perturbations in purine metabolism and the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan. Subsequent targeted metabolomic analysis revealed a significant reduction in amino acid and hypoxanthine and creatinine levels in the kidneys of CKD rats, accompanied by an increase in xanthine level. Further analysis found that purine pathway can increase ROS production and affect the level of aromatic amino acid transporter SLC7A5, thus influencing the biosynthesis pathway of phenylalanine, tyrosine and tryptophan, ultimately contributing to kidney injury. This discovery provides offers novel insights into the underlying pathological mechanism of adenine-induced CKD. The development of chronic kidney disease is induced by multiple pathways of aromatic amino acid metabolism and purine metabolism.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf035"},"PeriodicalIF":2.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707788","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}

{"title":"Thymoquinone loaded zinc oxide Nanoformulations synthesis, characterization and evaluation of their efficacy against carbon tetrachloride induced Hepatorenal toxicity in rats.","authors":"Mariam Hashim, Sumaira Anjum, Huma Mujahid, Khalid S Alotaibi, Shatha B Albattal, Heba I Ghamry, Mohamed Mohamed Soliman","doi":"10.1093/toxres/tfaf037","DOIUrl":"10.1093/toxres/tfaf037","url":null,"abstract":"<p><p>Thymoquinone (THQ), a strong antioxidant and anti-inflammatory bioactive compound has been reported in numerous studies to prevent the hepatorenal toxicity caused by various xenobiotics. Similarly, the zinc oxide nanoparticles (ZnONPs) have been used to protect against the hepatorenal damages caused by oxidative stress due to their potent antioxidant properties. The aim of this study was to synthesize and investigate the possible protective effects of THQ, ZnONPs and THQ-loaded ZnONPs against CCl₄ induced hepatorenal toxicity in albino rats. ZnONPs and THQ-loaded ZnONPs were synthesized and characterized by various techniques. For the in-vivo study, thirty albino rats were randomly divided into five groups of six rats each. The control group received normal saline and 2^nd group (injury group) received CCl₄ only. The 3^rd group (T1-group) received CCl₄ + ZnONPs, the 4^th group (T2-group) received CCl₄ + THQ, and the 5^th group (T3-group) received CCl₄ + THQ-loaded ZnONPs. Renal and hepatic biomarkers (total bilirubin, AST, ALT, ALP, blood urea nitrogen and creatinine), lipid profiles, antioxidant levels and histopathological studies were investigated. The synthesized NPs showed a spherical shape with an average size of 16-30 nm and exhibited hexagonal structures. Results showed that THQ-loaded ZnONPs resulted in a decrease in liver and kidney biomarkers as well as a reduction in TC, TG, and LDL levels compared to groups received ZnONPs and THQ alone. CAT, SOD, GR and DPPH-radical scavenging ability were maintained at normal levels in group T3, which received THQ-loaded ZnONPs compared to T1 and T2 groups. Hepatic histopathological analysis revealed a reduction in hydropic degeneration and hepatocyte congestion in the central veins, alongside a decrease in tubular cell swelling and normalization of renal histology in the THQ-loaded ZnONPs groups. In conclusion, results of this investigation demonstrate that THQ-loaded ZnONPs can act as an efficient protectant and antioxidant against oxidative stress and hepatorenal toxicity caused by various xenobiotics.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf037"},"PeriodicalIF":2.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655691","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}

{"title":"Sensitivity and stability of Balb/c, C57BL/6J, and ICR mice to the acute liver injury induced by concanavalin A.","authors":"Mingjie Song, Xuan Gao, Ruirui Kou, Na Liu, Xiaomin Ma, Tao Zeng, Cuili Zhang","doi":"10.1093/toxres/tfaf036","DOIUrl":"10.1093/toxres/tfaf036","url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) is an autoimmune disease mediated by abnormal autoimmune. The pathogenesis and pathological manifestation of immune-mediated liver injury, induced by concanavalin A (ConA) in mice, closely parallel those observed in human AIH. However, the sensitivity and stability of mice to ConA vary depending on the strain and sex of the mice. Therefore, this study aimed to compare the sensitivity and stability of Balb/c, C57BL/6J, and ICR mice to ConA-induced acute liver injury. In this study, the mice in ConA group were injected with ConA (15 mg/kg·bw) via tail vein. After 8 h, the blood, liver, and spleen were collected for subsequent analysis. The liver index of Balb/c mice was increased (<i>P</i> < 0.05). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels of male C57BL/6J mice in ConA-treated group were the highest among the three strains of mice, followed by female Balb/c mice (<i>P</i> < 0.05). After ConA challenge, ICR, Balb/c, and C57BL/6J mice (both male and female) appeared markedly inflammatory cell infiltration and hepatocyte necrosis. Furthermore, hemorrhagic necrosis is more severe in females than in males. Lastly, male C57BL/6J and female Balb/c mice had the lowest coefficient of variation in serum ALT, AST, and LDH activities, while female Balb/c mice had the minimum coefficient of variation of the liver index, suggesting that they have good stability to ConA. Altogether, our study found that Balb/c female and C57BL/6J male mice have high sensitivity and good stability to ConA challenge, which were suitable for mimicking the pathology of AIH in humans.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf036"},"PeriodicalIF":2.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655690","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}