{"title":"Influence of rapamycin and chloroquine on chemically-induced liver injury in rats.","authors":"Sho Fujiwara, Takeshi Izawa, Mutsuki Mori, Mitsuru Kuwamura","doi":"10.1293/tox.2024-0104","DOIUrl":"10.1293/tox.2024-0104","url":null,"abstract":"<p><p>Drug-induced liver injury is a major reason for the discontinuation of drug development. Autophagy is a self-digestive process in the cell and can suppress cell death by removing damaged organelle from the cell. It is known that autophagy can modify drug-induced liver injury; however, details of the effects of autophagy modulation on chemically-induced hepatotoxicity are unclear. In this study, we investigated the influence of autophagy induction by rapamycin or inhibition by chloroquine on carbon tetrachloride (CCl<sub>4</sub>)- or allyl alcohol (AA)-induced acute liver injury. Ten- to eleven-week-old male F344 rats were administrated with CCl<sub>4</sub> or AA after pretreatment by rapamycin or chloroquine, and were sampled 18 hours after the hepatotoxicant administration. Hepatic expression of the autophagosomal membrane protein LC3-II was significantly suppressed after CCl<sub>4</sub> administration by rapamycin pretreatment, compared with that in vehicle (DMSO) pretreatment. Expression of autophagy cargo protein p62, were significantly decreased after rapamycin treatment with AA administration. Hepatic p62 expression increased by chloroquine pretreatment. Serum AST and ALT were decreased after CCl<sub>4</sub> exposure in both rapamycin- and chloroquine-pretreated rats. On the other hand, regardless of pretreatment, pathological changes were mild in rats with AA exposure. These results showed that pretreatment with rapamycin or chloroquine can attenuate CCl<sub>4</sub>-induced acute liver injury in rats.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 4","pages":"3-14"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052984","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}
Wes Baumgartner, Ute Bach, James Baily, Christine Ruehl-Fehlert, Stacey Fossey, Satoshi Furukawa, Yuki Kato, Victoria Laast, Emily Meseck, Heike Schmidt-Posthaus, Helmut Segner, Shiva Kumar Shanmukhappa, Jan Spitsbergen, Jeffrey Wolf
{"title":"INHAND: Non-proliferative and proliferative lesions of fish - Chapter 12. Fish skeletal and tooth.","authors":"Wes Baumgartner, Ute Bach, James Baily, Christine Ruehl-Fehlert, Stacey Fossey, Satoshi Furukawa, Yuki Kato, Victoria Laast, Emily Meseck, Heike Schmidt-Posthaus, Helmut Segner, Shiva Kumar Shanmukhappa, Jan Spitsbergen, Jeffrey Wolf","doi":"10.1293/tox.2025-0212","DOIUrl":"10.1293/tox.2025-0212","url":null,"abstract":"","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 2 Suppl","pages":"249S-285S"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13340209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405021","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}
Wes Baumgartner, Ute Bach, James Baily, Christine Ruehl-Fehlert, Stacey Fossey, Satoshi Furukawa, Yuki Kato, Victoria Laast, Emily Meseck, Heike Schmidt-Posthaus, Helmut Segner, Shiva Kumar Shanmukhappa, Jan Spitsbergen, Jeffrey Wolf
{"title":"International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Non-proliferative and proliferative lesions of fish - Chapter 1. Introduction.","authors":"Wes Baumgartner, Ute Bach, James Baily, Christine Ruehl-Fehlert, Stacey Fossey, Satoshi Furukawa, Yuki Kato, Victoria Laast, Emily Meseck, Heike Schmidt-Posthaus, Helmut Segner, Shiva Kumar Shanmukhappa, Jan Spitsbergen, Jeffrey Wolf","doi":"10.1293/tox.2025-0191","DOIUrl":"10.1293/tox.2025-0191","url":null,"abstract":"<p><p>The INHAND Project is a joint initiative of the societies of toxicologic pathology from Europe, the United Kingdom, Japan, and North America to standardize diagnostic nomenclature and criteria used in toxicologic studies. The INHAND initiative includes recommended nomenclature for evaluating histologic specimens from nonclinical studies involving laboratory animals including rodents, non-human primates, dogs, minipigs, rabbits, and fish. Specific terminology and criteria are derived from the consensus opinions of senior toxicologic pathologists and subject matter experts who have expertise in the different species of interest. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included government databases, including the Registry of Tumors in Lower Animals (RTLA), academia, and industrial laboratories throughout the world. This introduction provides context for 14 chapters, arranged by organ system, that define the INHAND nomenclature and diagnostic criteria for fish used in nonclinical studies. Additionally, the current introductory chapter describes both general features of INHAND methodology as well as elements characteristic of toxicologic fish studies. The latter includes fish study design and conduct; euthanasia, sampling, the histologic processing of fish tissues, and a general approach to evaluating fish studies.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 2 Suppl","pages":"1S-8S"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13340192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405134","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":"Expression and distribution of tribbles pseudokinase 3 in oxidative stress-mediated acute liver and kidney injury models.","authors":"Yukako Shimotsuma, Takeshi Izawa, Mitsuru Kuwamura","doi":"10.1293/tox.2025-0040","DOIUrl":"10.1293/tox.2025-0040","url":null,"abstract":"<p><p>Tribbles pseudokinase 3 (Trib3) is an inactive protein kinase whose expression increases in response to various stresses. Our previous work showed that Trib3 may play a role in myelin destruction induced by oxidative and endoplasmic reticulum stress in demyelination (<i>dmy</i>) rats. The <i>dmy</i> rat exhibits hind limb ataxia and severe myelin breakdown in the central nervous system. To elucidate how Trib3 contributes to oxidative stress-mediated injury in organs other than the central nervous system, we used two models: an acute liver injury model induced by thioacetamide injection and an acute kidney injury model induced by cisplatin injection. Trib3 mRNA expression increased concurrently with tissue injury and declined during the repair phase. TRIB3 was detected in damaged areas, mainly in degenerated cells and infiltrating macrophages. These results suggest that Trib3 is upregulated in tissues damaged by oxidative stress and may serve as an indicator of tissue injury.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 1","pages":"25-30"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105965","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}
Wes Baumgartner, Ute Bach, James Baily, Christine Ruehl-Fehlert, Stacey Fossey, Satoshi Furukawa, Yuki Kato, Victoria Laast, Emily Meseck, Heike Schmidt-Posthaus, Helmut Segner, Shiva Kumar Shanmukhappa, Jan Spitsbergen, Jeffrey Wolf
{"title":"INHAND: Non-proliferative and proliferative lesions of fish - Chapter 14. Fish special senses.","authors":"Wes Baumgartner, Ute Bach, James Baily, Christine Ruehl-Fehlert, Stacey Fossey, Satoshi Furukawa, Yuki Kato, Victoria Laast, Emily Meseck, Heike Schmidt-Posthaus, Helmut Segner, Shiva Kumar Shanmukhappa, Jan Spitsbergen, Jeffrey Wolf","doi":"10.1293/tox.2025-0214","DOIUrl":"10.1293/tox.2025-0214","url":null,"abstract":"","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 2 Suppl","pages":"306S-327S"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13340148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405056","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}