Toxicologic Pathology最新文献

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Poster Abstracts of the 20th Congress of the European Society of Toxicologic Pathology (Basel, Switzerland, 26th - 29th of September 2023, Emerging Therapeutic Modalities) 欧洲毒理学病理学会第 20 届大会(瑞士巴塞尔,2023 年 9 月 26-29 日,新兴治疗模式)海报摘要
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2024-03-11 DOI: 10.1177/01926233241236845
{"title":"Poster Abstracts of the 20th Congress of the European Society of Toxicologic Pathology (Basel, Switzerland, 26th - 29th of September 2023, Emerging Therapeutic Modalities)","authors":"","doi":"10.1177/01926233241236845","DOIUrl":"https://doi.org/10.1177/01926233241236845","url":null,"abstract":"","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"27 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140106184","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}
引用次数: 0
Magnitude of Urine Albumin and KIM-1 Changes Can be Used to Differentiate Glomerular Injury From Tubular Injury in Rats. 尿白蛋白和 KIM-1 变化的幅度可用于区分大鼠肾小球损伤和肾小管损伤
IF 1.4 4区 医学
Toxicologic Pathology Pub Date : 2024-02-01 Epub Date: 2024-05-14 DOI: 10.1177/01926233241248656
Yi-Zhong Gu, Erina Paul, Katerina Vlasakova, Sean P Troth, Frank D Sistare, Lila Ramaiah, Oliver Potz, Santosh Sutradhar, Warren E Glaab
{"title":"Magnitude of Urine Albumin and KIM-1 Changes Can be Used to Differentiate Glomerular Injury From Tubular Injury in Rats.","authors":"Yi-Zhong Gu, Erina Paul, Katerina Vlasakova, Sean P Troth, Frank D Sistare, Lila Ramaiah, Oliver Potz, Santosh Sutradhar, Warren E Glaab","doi":"10.1177/01926233241248656","DOIUrl":"10.1177/01926233241248656","url":null,"abstract":"<p><p>Emerging urinary kidney safety biomarkers have been evaluated in recent years and have been shown to be superior to the serum parameters blood urea nitrogen (BUN) and creatinine (sCr) for monitoring kidney injury in the proximal tubule. However, their potential application in differentiating the location of the initial kidney injury (eg, glomerulus vs tubule) has not been fully explored. Here, we assessed the performance of two algorithms that were constructed using either an empirical or a mathematical model to predict the site of kidney injury using a data set consisting of 22 rat kidney toxicity studies with known urine biomarker and histopathologic outcomes. Two kidney safety biomarkers used in both models, kidney injury molecule 1 (KIM-1) and albumin (ALB), were the best performers to differentiate glomerular injury from tubular injury. The performance of algorithms using these two biomarkers against the gold standard of kidney histopathologic examination showed high sensitivity in differentiating the location of the kidney damage to either the glomerulus or the proximal tubules. These data support the exploration of such an approach for use in clinical settings, leveraging urinary biomarker data to aid in the diagnosis of either glomerular or tubular injury where histopathologic assessments are not conducted.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"88-98"},"PeriodicalIF":1.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11283732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923270","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}
引用次数: 0
Complex In Vitro Model Characterization for Context of Use in Toxicologic Pathology: Use Cases by Collaborative Teams of Biologists, Bioengineers, and Pathologists. 复杂体外模型特征描述在毒理病理学中的应用:生物学家、生物工程师和病理学家合作团队的使用案例。
IF 1.4 4区 医学
Toxicologic Pathology Pub Date : 2024-02-01 Epub Date: 2024-06-18 DOI: 10.1177/01926233241253811
Nadine Stokar-Regenscheit, Luisa Bell, Brian Berridge, Daniel Rudmann, Danilo Tagle, Passley Hargrove-Grimes, Dirk Schaudien, Kerstin Hahn, Julia Kühnlenz, Randolph S Ashton, Min Tseng, Mike Reichelt, Steven T Laing, Tomomi Kiyota, Ronnie Chamanza, Radhakrishna Sura, Lindsay Tomlinson
{"title":"Complex In Vitro Model Characterization for Context of Use in Toxicologic Pathology: Use Cases by Collaborative Teams of Biologists, Bioengineers, and Pathologists.","authors":"Nadine Stokar-Regenscheit, Luisa Bell, Brian Berridge, Daniel Rudmann, Danilo Tagle, Passley Hargrove-Grimes, Dirk Schaudien, Kerstin Hahn, Julia Kühnlenz, Randolph S Ashton, Min Tseng, Mike Reichelt, Steven T Laing, Tomomi Kiyota, Ronnie Chamanza, Radhakrishna Sura, Lindsay Tomlinson","doi":"10.1177/01926233241253811","DOIUrl":"10.1177/01926233241253811","url":null,"abstract":"<p><p>Complex in vitro models (CIVMs) offer the potential to increase the clinical relevance of preclinical efficacy and toxicity assessments and reduce the reliance on animals in drug development. The European Society of Toxicologic Pathology (ESTP) and Society for Toxicologic Pathology (STP) are collaborating to highlight the role of pathologists in the development and use of CIVM. Pathologists are trained in comparative animal medicine which enhances their understanding of mechanisms of human and animal diseases, thus allowing them to bridge between animal models and humans. This skill set is important for CIVM development, validation, and data interpretation. Ideally, diverse teams of scientists, including engineers, biologists, pathologists, and others, should collaboratively develop and characterize novel CIVM, and collectively assess their precise use cases (context of use). Implementing a morphological CIVM evaluation should be essential in this process. This requires robust histological technique workflows, image analysis techniques, and needs correlation with translational biomarkers. In this review, we demonstrate how such tissue technologies and analytics support the development and use of CIVM for drug efficacy and safety evaluations. We encourage the scientific community to explore similar options for their projects and to engage with health authorities on the use of CIVM in benefit-risk assessment.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"123-137"},"PeriodicalIF":1.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421105","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}
引用次数: 0
Incidental Gliosis in the Central Nervous System of Control Nonhuman Primates and Rats. 控制非人灵长类动物和大鼠中枢神经系统的意外胶质增生
IF 1.4 4区 医学
Toxicologic Pathology Pub Date : 2024-02-01 Epub Date: 2024-06-03 DOI: 10.1177/01926233241253255
Joy M Gary, Sarah Cramer, Brad Bolon, Alys E Bradley, Mark T Butt
{"title":"Incidental Gliosis in the Central Nervous System of Control Nonhuman Primates and Rats.","authors":"Joy M Gary, Sarah Cramer, Brad Bolon, Alys E Bradley, Mark T Butt","doi":"10.1177/01926233241253255","DOIUrl":"10.1177/01926233241253255","url":null,"abstract":"<p><p>Gliosis, including microgliosis and astrocytosis, can be challenging to interpret in nonclinical studies. Incidences of glial foci in brains and spinal cords of control rats and nonhuman primates (NHPs) were reviewed in the historical control databases from two contract research organizations, including one specializing in neuropathology. In the brain, minimal to mild (grades 1-2) microgliosis was the most common diagnosis, especially in NHPs, although occasional moderate or marked microgliosis (grades 3 and 4) was encountered in both species. Microgliosis was more common in the cerebral cortex, cerebellum, and medulla oblongata in both species and was frequent in the white matter (brain), thalamus, and basal nuclei of NHPs. Gliosis (\"not otherwise specified\") of minimal severity was diagnosed in similar brain sub-sites for both species and was more common in NHPs compared with rats. Astrocytosis was most prominent in the cerebellum (molecular layer) of NHPs but was otherwise uncommon. In the spinal cord, microgliosis was most common in the lateral white matter tracts in rats and NHPs, and in the dorsal white matter tracts in NHPs. These data indicate that low-grade spontaneous glial responses occur with some frequency in control animals of two common nonclinical species.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"114-122"},"PeriodicalIF":1.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200585","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}
引用次数: 0
Scientific and Regulatory Policy Committee Points to Consider: Review of the United States Food and Drug Administration (FDA) Guidance on Pathology Peer Review in Nonclinical Toxicology Studies. 科学与监管政策委员会审议要点:美国食品和药物管理局 (FDA) 非临床毒理学研究病理学同行评审指南评审。
IF 1.4 4区 医学
Toxicologic Pathology Pub Date : 2024-02-01 Epub Date: 2024-06-06 DOI: 10.1177/01926233241248654
Kevin S McDorman, Bindu M Bennet, Karyn Colman, James D Fikes, Natalie D Keirstead, Lynda Lanning Retired, Barbara Munch, Annette Romeike, Kenneth A Schafer, Frédéric Schorsch, Michael S Thibodeau, Heath C Thomas, Sean Troth, John L Vahle, Frank J Geoly
{"title":"Scientific and Regulatory Policy Committee Points to Consider: Review of the United States Food and Drug Administration (FDA) Guidance on Pathology Peer Review in Nonclinical Toxicology Studies.","authors":"Kevin S McDorman, Bindu M Bennet, Karyn Colman, James D Fikes, Natalie D Keirstead, Lynda Lanning Retired, Barbara Munch, Annette Romeike, Kenneth A Schafer, Frédéric Schorsch, Michael S Thibodeau, Heath C Thomas, Sean Troth, John L Vahle, Frank J Geoly","doi":"10.1177/01926233241248654","DOIUrl":"10.1177/01926233241248654","url":null,"abstract":"<p><p>In December 2021, the United States Food and Drug Administration (FDA) issued the final guidance for industry titled <i>Pathology Peer Review in Nonclinical Toxicology Studies: Questions and Answers</i>. The stated purpose of the FDA guidance is to provide information to sponsors, applicants, and nonclinical laboratory personnel regarding the management and conduct of histopathology peer review as part of nonclinical toxicology studies conducted in compliance with good laboratory practice (GLP) regulations. On behalf of and in collaboration with global societies of toxicologic pathology and the Society of Quality Assurance, the Scientific and Regulatory Policy Committee (SRPC) of the Society of Toxicologic Pathology (STP) initiated a review of this FDA guidance. The STP has previously published multiple papers related to the scientific conduct of a pathology peer review of nonclinical toxicology studies and appropriate documentation practices. The objectives of this review are to provide an in-depth analysis and summary interpretation of the FDA recommendations and share considerations for the conduct of pathology peer review in nonclinical toxicology studies that claim compliance to GLP regulations. In general, this working group is in agreement with the recommendations from the FDA guidance that has added clear expectations for pathology peer review preparation, conduct, and documentation.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"138-148"},"PeriodicalIF":1.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262945","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}
引用次数: 0
Thank You to Reviewers. 感谢审稿人。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2024-01-21 DOI: 10.1177/01926233241226572
{"title":"Thank You to Reviewers.","authors":"","doi":"10.1177/01926233241226572","DOIUrl":"https://doi.org/10.1177/01926233241226572","url":null,"abstract":"","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233241226572"},"PeriodicalIF":1.5,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513345","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}
引用次数: 0
Adeno-Associated Virus-Mediated Dorsal Root Ganglion Toxicity in the New Zealand White Rabbit. 腺相关病毒介导的新西兰白兔背根神经节毒性
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-02-22 DOI: 10.1177/01926233241229808
Eric Tien, Branka Grubor, Melissa Kirkland, Su Jing Chan, Nick van der Munnik, Wenlong Xu, Kate Henry, Stefan Hamann, Cong Wei, Wan-Hung Lee, Davide Gianni, Ashton Brennecke, Kalyani Nambiar, Jeron Chen, Bin Liu, Shen Shen, Claudine Tremblay, Edward D Plowey, Patrick Trapa, James Fikes, Junghae Suh, Dale Morris
{"title":"Adeno-Associated Virus-Mediated Dorsal Root Ganglion Toxicity in the New Zealand White Rabbit.","authors":"Eric Tien, Branka Grubor, Melissa Kirkland, Su Jing Chan, Nick van der Munnik, Wenlong Xu, Kate Henry, Stefan Hamann, Cong Wei, Wan-Hung Lee, Davide Gianni, Ashton Brennecke, Kalyani Nambiar, Jeron Chen, Bin Liu, Shen Shen, Claudine Tremblay, Edward D Plowey, Patrick Trapa, James Fikes, Junghae Suh, Dale Morris","doi":"10.1177/01926233241229808","DOIUrl":"10.1177/01926233241229808","url":null,"abstract":"<p><p>Recombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) has been observed in non-human primates (NHPs) following intravenous (IV) and intrathecal (IT) delivery. Administration of recombinant AAV encoding a human protein transgene via a single intra-cisterna magna (ICM) injection in New Zealand white rabbits resulted in histopathology changes very similar to NHPs: mononuclear cell infiltration, degeneration/necrosis of sensory neurons, and nerve fiber degeneration of sensory tracts in the spinal cord and of multiple nerves. AAV-associated clinical signs and incidence/severity of histologic findings indicated that rabbits were equally or more sensitive than NHPs to sensory neuron damage. Another study using human and rabbit transgene constructs of the same protein demonstrated comparable changes suggesting that the effects are not an immune response to the non-self protein transgene. Rabbit has not been characterized as a species for general toxicity testing of AAV gene therapies, but these studies suggest that it may be an alternative model to investigate mechanisms of AAV-mediated neurotoxicity and test novel AAV designs mitigating these adverse effects.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"35-54"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139933025","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}
引用次数: 0
Guide for Combining Primary Tumors for Statistical Analysis in Rodent Carcinogenicity Studies. 啮齿动物致癌性研究统计分析原发肿瘤组合指南》。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-03-06 DOI: 10.1177/01926233241230553
Charlotte Keenan, Muthafar Al-Haddawi, Jean-Guy Bienvenu, Alys Elizabeth Bradley, Paul Brown, Hepei Chen, Karyn Colman, Michael Elwell, Nicholas Gatto, Dawn Goodman, Binod Jacob, Lynda Lanning, LuAnn McKinney, Erin Muhlbradt, Rick Perry, Alessandro Piaia, Daniel Potenta, Karen S Regan, Benjamin Sefing, Michael Thibodeau, Erin Tibbs-Slone, Jochen Woicke, Craig M Zwickl
{"title":"Guide for Combining Primary Tumors for Statistical Analysis in Rodent Carcinogenicity Studies.","authors":"Charlotte Keenan, Muthafar Al-Haddawi, Jean-Guy Bienvenu, Alys Elizabeth Bradley, Paul Brown, Hepei Chen, Karyn Colman, Michael Elwell, Nicholas Gatto, Dawn Goodman, Binod Jacob, Lynda Lanning, LuAnn McKinney, Erin Muhlbradt, Rick Perry, Alessandro Piaia, Daniel Potenta, Karen S Regan, Benjamin Sefing, Michael Thibodeau, Erin Tibbs-Slone, Jochen Woicke, Craig M Zwickl","doi":"10.1177/01926233241230553","DOIUrl":"10.1177/01926233241230553","url":null,"abstract":"<p><p>The Tumor Combination Guide was created at the request of the U. S. Food and Drug Administration (FDA) by a Working Group of biopharmaceutical experts from international societies of toxicologic pathology, the Food and Drug Administration (FDA), and members of the Standard for Exchange of Nonclinical Data (SEND) initiative, to assist pharmacology/toxicology reviewers and biostatisticians in statistical analysis of nonclinical tumor data. The guide will also be useful to study and peer review pathologists in interpreting the tumor data. This guide provides a higher-level hierarchy of tumor types or categories correlating the tumor names from the International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) publications with those available in the NEOPLASM controlled terminology (CT) code list in SEND. The version of CT used in a study should be referenced in the nonclinical study data reviewer's guide (SDRG) (section 3.1) of electronic submissions to the FDA. The tumor combination guide instructions and examples are in a tabular format to make informed decisions for combining tumor data for statistical analysis. The strategy for combining tumor types for statistical analysis is based on scientific criteria gleaned from the current scientific literature; as SEND and INHAND terminology and information evolve, this guide will be updated.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"13-20"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040389","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}
引用次数: 0
Deep Learning-Based Spermatogenic Staging in Tissue Sections of Cynomolgus Macaque Testes. 基于深度学习的猕猴睾丸组织切片生精分期。
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-03-11 DOI: 10.1177/01926233241234059
Lars Mecklenburg, C Marc Luetjens, Annette Romeike, Rohit Garg, Pranab Samanta, Amogh Mohanty, Tijo Thomas, Gerhard Weinbauer
{"title":"Deep Learning-Based Spermatogenic Staging in Tissue Sections of Cynomolgus Macaque Testes.","authors":"Lars Mecklenburg, C Marc Luetjens, Annette Romeike, Rohit Garg, Pranab Samanta, Amogh Mohanty, Tijo Thomas, Gerhard Weinbauer","doi":"10.1177/01926233241234059","DOIUrl":"10.1177/01926233241234059","url":null,"abstract":"<p><p>The indirect assessment of adverse effects on fertility in cynomolgus monkeys requires that tissue sections of the testis be microscopically evaluated with awareness of the stage of spermatogenesis that a particular cross-section of a seminiferous tubule is in. This difficult and subjective task could very much benefit from automation. Using digital whole slide images (WSIs) from tissue sections of testis, we have developed a deep learning model that can annotate the stage of each tubule with high sensitivity, precision, and accuracy. The model was validated on six WSI using a six-stage spermatogenic classification system. Whole slide images contained an average number of 4938 seminiferous tubule cross-sections. On average, 78% of these tubules were staged with 29% in stage I-IV, 12% in stage V-VI, 4% in stage VII, 19% in stage VIII-IX, 18% in stage X-XI, and 17% in stage XII. The deep learning model supports pathologists in conducting a stage-aware evaluation of the testis. It also allows derivation of a stage-frequency map. The diagnostic value of this stage-frequency map is still unclear, as further data on its variability and relevance need to be generated for testes with spermatogenic disturbances.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"4-12"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094624","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}
引用次数: 0
Difference in the Mechanism of Iron Overload-Enhanced Acute Hepatotoxicity Induced by Thioacetamide and Carbon Tetrachloride in Rats. 硫代乙酰胺和四氯化碳诱导大鼠铁超载增强急性肝中毒机制的差异
IF 1.5 4区 医学
Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-03-25 DOI: 10.1177/01926233241235623
Yohei Inai, Takeshi Izawa, Tomomi Kamei, Sho Fujiwara, Miyuu Tanaka, Jyoji Yamate, Mitsuru Kuwamura
{"title":"Difference in the Mechanism of Iron Overload-Enhanced Acute Hepatotoxicity Induced by Thioacetamide and Carbon Tetrachloride in Rats.","authors":"Yohei Inai, Takeshi Izawa, Tomomi Kamei, Sho Fujiwara, Miyuu Tanaka, Jyoji Yamate, Mitsuru Kuwamura","doi":"10.1177/01926233241235623","DOIUrl":"10.1177/01926233241235623","url":null,"abstract":"<p><p>Iron overload has been recognized as a risk factor for liver disease; however, little is known about its pathological role in the modification of liver injury. The purpose of this study is to investigate the influence of iron overload on liver injury induced by two hepatotoxicants with different pathogenesis in rats. Rats were fed a control (Cont), 0.8% high-iron (0.8% Fe), or 1% high-iron diet (1% Fe) for 4 weeks and were then administered with saline, thioacetamide (TAA), or carbon tetrachloride (CCl<sub>4</sub>). Hepatic and systemic iron overload were seen in the 0.8% and 1% Fe groups. Twenty-four hours after administration, hepatocellular necrosis induced by TAA and hepatocellular necrosis, degeneration, and vacuolation induced by CCl<sub>4</sub>, as well as serum transaminase values, were exacerbated in the 0.8% and 1% Fe groups compared to the Cont group. On the other hand, microvesicular vacuolation induced by CCl<sub>4</sub> was decreased in 0.8% and 1% Fe groups. Hepatocellular DNA damage was increased by iron overload in both models, whereas a synergistic effect of oxidative stress by excess iron and hepatotoxicant was only present in the CCl<sub>4</sub> model. The data showed that dietary iron overload exacerbates TAA- and CCl<sub>4</sub>-induced acute liver injury with different mechanisms.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"55-66"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289046","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}
引用次数: 0
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