Journal of Toxicologic Pathology最新文献

Metabolism and effects of acetoaceto-o-toluidine in the urinary bladder of humanized-liver mice 乙酰乙酰托烷在人肝小鼠膀胱中的代谢及其影响

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-09-18 DOI: 10.1293/tox.2024-0042

Shugo SUZUKI, Min GI, Yukie YANAGIBA, Nao YONEDA, Shotaro UEHARA, Yuka YOKOTA, Ikue NOURA, Masaki FUJIOKA, Arpamas VACHIRAARUNWONG, Anna KAKEHASHI, Shigeki KODA, Hiroshi SUEMIZU, Hideki WANIBUCHI

{"title":"Metabolism and effects of acetoaceto-o-toluidine in the urinary bladder of humanized-liver mice","authors":"Shugo SUZUKI, Min GI, Yukie YANAGIBA, Nao YONEDA, Shotaro UEHARA, Yuka YOKOTA, Ikue NOURA, Masaki FUJIOKA, Arpamas VACHIRAARUNWONG, Anna KAKEHASHI, Shigeki KODA, Hiroshi SUEMIZU, Hideki WANIBUCHI","doi":"10.1293/tox.2024-0042","DOIUrl":"https://doi.org/10.1293/tox.2024-0042","url":null,"abstract":"Occupational exposure to aromatic amines is a major risk factor for urinary bladder cancer. Our previous studies showed that acetoaceto-o-toluidine, which is produced using o-toluidine as a raw material, promotes urinary bladder carcinogenesis in rats. We also found high concentrations of o-toluidine, a human bladder carcinogen, in the urine of acetoaceto-o-toluidine-treated rats, indicating that urinary o-toluidine derived from acetoaceto-o-toluidine may play an important role in bladder carcinogenesis. However, this has not been investigated in humans. In the present study, we used non-humanized (F1-TKm30 mice) and humanized-liver mice established by human hepatocyte transplantation to compare differences in urinary acetoaceto-o-toluidine metabolites produced by human and mouse liver cells. We also examined the changes in acetoaceto-o-toluidine-induced mRNA expression in the liver and the proliferative effects on the bladder epithelium. Urinary o-toluidine was detected in both non-humanized and humanized mice. Acetoaceto-o-toluidine metabolites in the urine, cell proliferation activities, and DNA damage in the bladder urothelium were similar in non-humanized and humanized-liver mice. RNA expression analysis revealed that CYP1A2 expression increased in the livers of humanized-liver mice, and Cyp2c29 expression (equivalent to human CYP2C9/19) increased in the livers of non-humanized mice. These data suggest that acetoaceto-o-toluidine may be a human carcinogen, as evidenced by the detection of urinary o-toluidine in acetoaceto-o-toluidine-treated humanized-liver mice. This animal model is important for extrapolating toxicity data from animals to humans.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"221 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249051","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

High mobility group box1 as a danger signal inducing the infiltration of neutrophils and macrophages in thioacetamide-induced rat liver injury 高迁移率基团框 1 是硫代乙酰胺诱导的大鼠肝损伤中诱导中性粒细胞和巨噬细胞浸润的危险信号

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-09-16 DOI: 10.1293/tox.2024-0055

Mizuki KURAMOCHI, Mohammad Rabiul KARIM, Takeshi IZAWA, Mitsuru KUWAMURA, Jyoji YAMATE

{"title":"High mobility group box1 as a danger signal inducing the infiltration of neutrophils and macrophages in thioacetamide-induced rat liver injury","authors":"Mizuki KURAMOCHI, Mohammad Rabiul KARIM, Takeshi IZAWA, Mitsuru KUWAMURA, Jyoji YAMATE","doi":"10.1293/tox.2024-0055","DOIUrl":"https://doi.org/10.1293/tox.2024-0055","url":null,"abstract":"The liver, a major organ involved in substance metabolism, is highly susceptible to toxicity induced by chemicals and their metabolites. Although damage-associated molecular patterns (DAMPs) have been implicated in the development of sterile inflammation following cell injury, their involvement in chemically induced hepatocellular injury remains underexplored. This study aimed to determine the role of high-mobility group box 1 (HMGB1), a DAMP, in a rat model of liver injury treated with thioacetamide, a hepatotoxicant. The rats were administered thioacetamide and treated with HMGB1 neutralizing antibody. Histopathological analysis revealed the absence of significant differences between control rats and HMGB1 neutralizing antibody-treated rats. However, HMGB1 neutralizing antibody-treated rats showed a reduction in the hepatic devitalization enzymes, a decrease in the number of anti-inflammatory cluster of differentiation 163+ M2 macrophages and neutrophils in the injured area, and a decrease in cytokine expression. These results suggest that HMGB1 leads to the progression of inflammation after chemically induced hepatocyte injury and may represent a therapeutic target for mitigating such injury.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249050","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

Lymphangiomas with the presence of erythrocytes in mesenteric lymph nodes of Wistar Hannover rats Wistar Hannover 大鼠肠系膜淋巴结中存在红细胞的淋巴管瘤

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-09-13 DOI: 10.1293/tox.2024-0007

Yuumi AWAZUHARA, Yuki TOMONARI, Hiroko KOKOSHIMA, Yumi WAKO, Takuya DOI

引用次数: 0

Histopathology of spontaneous lesions in FVB/N mice FVB/N 小鼠自发病变的组织病理学特征

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-09-11 DOI: 10.1293/tox.2024-0027

Atsuko MURAI, Chisato KANEKO, Hisakazu SANADA, Atsuhiko KATO

引用次数: 0

The role of mitochondrial reactive oxygen species in initiating mitochondrial damage and inflammation in wasp-venom-induced acute kidney injury 线粒体活性氧在黄蜂毒素诱导的急性肾损伤中引发线粒体损伤和炎症的作用

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-09-11 DOI: 10.1293/tox.2024-0046

Lingya XIA, Hai YUAN, Zhao GAO, Ying LV, Liang XU, Fengqi HU

{"title":"The role of mitochondrial reactive oxygen species in initiating mitochondrial damage and inflammation in wasp-venom-induced acute kidney injury","authors":"Lingya XIA, Hai YUAN, Zhao GAO, Ying LV, Liang XU, Fengqi HU","doi":"10.1293/tox.2024-0046","DOIUrl":"https://doi.org/10.1293/tox.2024-0046","url":null,"abstract":"Acute kidney injury induced by stings from multiple wasps is a medical emergency and is a driving factor of acute renal dysfunction. Numerous studies have shown that mitochondrial reactive oxygen species (mtROS) play a key role in ischemia-reperfusion injury-, cisplatin-, and sepsis-induced acute kidney injury. However, the role of mtROS and its underlying mechanisms in wasp-venom-induced acute kidney injury remain inconclusive. In this study, we investigated the role and mechanisms of mtROS in mitochondrial damage and inflammation in a mouse model of acute kidney injury induced using wasp venom. Changes in mitochondrial function, transcription factor A (TFAM) expression, and DNA maintenance levels, renal function, stimulator of interferon gene (STING) expression, and inflammatory mediator levels in model mice with or without the mtROS scavenger Mito-Tempo were analyzed in vivo. Downregulation of mtROS levels reversed renal damage and mitochondrial dysfunction, and reduced STING expression and inflammation in the kidneys of model mice. The suppression of mtROS levels also improved the decrease in TFAM levels and mitochondrial DNA copy numbers in the kidneys of the model mice. In summary, the existing evidence in this study shows that mtROS contribute significantly to mitochondrial damage and inflammation in acute kidney injury induced by wasp venom.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"179 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184605","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

The relationship between spontaneous cystic degeneration and pseudocapillarization in sinusoids in the liver of aged Sprague-Dawley rats 老龄 Sprague-Dawley 大鼠肝窦自发性囊变性与假毛细血管化之间的关系

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-09-02 DOI: 10.1293/tox.2024-0034

Atsushi SHIGA, Chinatsu FUJIWARA, Yoshitaka KATOH, Tsuyoshi ITO, Aya OHNUMA-KOYAMA, Naofumi TAKAHASHI, Takanori HARADA

{"title":"The relationship between spontaneous cystic degeneration and pseudocapillarization in sinusoids in the liver of aged Sprague-Dawley rats","authors":"Atsushi SHIGA, Chinatsu FUJIWARA, Yoshitaka KATOH, Tsuyoshi ITO, Aya OHNUMA-KOYAMA, Naofumi TAKAHASHI, Takanori HARADA","doi":"10.1293/tox.2024-0034","DOIUrl":"https://doi.org/10.1293/tox.2024-0034","url":null,"abstract":"Cystic degeneration (CD) in the liver is a cyst-like lesion composed of one or more pseudocysts lacking lining cells, occurring spontaneously in rats older than 12 months, with a male predilection. In this study, 32 CDs were identified in 23 out of 104 non-treated, control male Sprague-Dawley rats from two combined chronic toxicity and carcinogenicity studies with agrochemicals. They were examined histologically, histochemically, and immunohistochemically to assess the pathogenesis and pathological significance of CD, focusing on pseudocapillarization in aged rat liver. Pseudocapillarization refers to age-related capillarization of hepatic sinusoids and is distinct from sinusoidal capillarization observed in hepatic cirrhosis. Both CD and pseudocapillarization, characterized by factor VIII-related antigen expression, were primarily noted in the periportal regions of the rat liver. CD areas exhibited enhanced vimentin expression in a diffuse linear pattern in their septa with occasional focal linear α-smooth muscle actin expression and the fluid containing hyaluronic acid accumulated in their lumen that are thought to be formed by hepatocellular apoptosis. These findings suggest a series of reactive changes associated with hepatocellular apoptosis due to pseudocapillarization in the sinusoids. In conclusion, spontaneous CD in rat liver is not a degenerative lesion or cystic enlargement of stellate cells, but a structural abnormality in pre-existing liver tissue resulting from aging-related changes in sinusoidal endothelial cells and hepatocytes. Pseudocapillarization of sinusoids is considered a precursor lesion of CD in the rat liver.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"22 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184607","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

Effects of letrozole on rat placental development 来曲唑对大鼠胎盘发育的影响

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-07-31 DOI: 10.1293/tox.2024-0025

Satoshi FURUKAWA, Naho TSUJI, Kazuya TAKEUCHI

{"title":"Effects of letrozole on rat placental development","authors":"Satoshi FURUKAWA, Naho TSUJI, Kazuya TAKEUCHI","doi":"10.1293/tox.2024-0025","DOIUrl":"https://doi.org/10.1293/tox.2024-0025","url":null,"abstract":"We examined the morphological effects of letrozole on placental development in pregnant rats. Letrozole was orally administered at a repeat dose to pregnant rats at 0 mg/kg (control group) and 0.04 mg/kg (letrozole group) from gestation day (GD) 6 to GD 20. In the letrozole group, fetal mortality and placental weight increased from GD 15 onwards and GD 13 onwards, respectively. Fetal weights increased on GDs 15 and 17 but decreased on GD 21. Histopathologically, letrozole treatment induced multiple cysts lined with undifferentiated syncytiotrophoblasts in the trophoblastic septa on GD 13. These cysts then develop into dilated maternal sinusoids with congestive hyperemia, resulting in an enlarged placenta. In the metrial gland, there was a dilated lumen of the spiral artery and interstitial edema throughout the experimental period, resulting in thickened metrial gland. These changes are considered to be due to maternal blood circulation stagnation in the metrial gland, which is associated with dilated maternal sinusoids in the labyrinth zone. Thus, although letrozole induces an enlarged placenta due to congestive hyperemia of the labyrinth zone and transient increases in fetal weight, these placentas are thought to decline in function as the pregnancy progresses, leading to intrauterine growth restriction at the end of pregnancy.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"86 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867466","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

Immunohistochemical characteristics of cytokeratin expression in epithelial type thymoma and thymic epithelial hyperplasia in F344 rats F344 大鼠上皮型胸腺瘤和胸腺上皮增生中细胞角蛋白表达的免疫组化特征

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-07-25 DOI: 10.1293/tox.2024-0045

Yuki TOMONARI, Junko SATO, Mitsutoshi UCHIDA, Takeshi KANNO, Takuya DOI, Yoshiyasu KOBAYASHI

{"title":"Immunohistochemical characteristics of cytokeratin expression in epithelial type thymoma and thymic epithelial hyperplasia in F344 rats","authors":"Yuki TOMONARI, Junko SATO, Mitsutoshi UCHIDA, Takeshi KANNO, Takuya DOI, Yoshiyasu KOBAYASHI","doi":"10.1293/tox.2024-0045","DOIUrl":"https://doi.org/10.1293/tox.2024-0045","url":null,"abstract":"We have previously reported on thymomas in Wistar Hannover rats with medullary differentiation and revealed that two different cytokeratin (CK) immunohistochemical types of thymic epithelia (TE), CK18 and CK14, lead to the formation of cortical-medullary structures. In aged F344 rats, epithelial type thymoma rarely occurs, and thymic epithelial hyperplasia is common. However, CK expression in these F344 rat lesions is unknown. We investigated three hyperplasia and four thymomas in F344 for histopathological features and CK18 and CK14 expression. Hyperplasia was characterized by an increase in tubular structures in the medulla. Thymomas were nodular in shape, with tubular structures similar to those observed in hyperplasia, along with irregular structures such as cord, papillary, and spindloid. Immunohistochemical analysis revealed that the tubular structures consisted of two layers: inner cuboidal-to-columnar TE and outer round-to-oval TE, positive for CK18 and CK14, respectively. The two-layer pattern was maintained to some extent in the irregular structures.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"47 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141785980","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

Optimal testing time for cerebral heterotopia formation in the rat comparative thyroid assay, a downstream indicator for perinatal thyroid hormone insufficiency 大鼠比较甲状腺测定中脑异位形成的最佳测试时间--围产期甲状腺激素不足的下游指标

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-07-16 DOI: 10.1293/tox.2024-0004

Keiko OGATA, Hidenori SUTO, Akira SATO, Keiko MAEDA, Kenta MINAMI, Naruto TOMIYAMA, Tadashi KOSAKA, Hitoshi HOJO, Naofumi TAKAHASHI, Hiroaki AOYAMA, Tomoya YAMADA

{"title":"Optimal testing time for cerebral heterotopia formation in the rat comparative thyroid assay, a downstream indicator for perinatal thyroid hormone insufficiency","authors":"Keiko OGATA, Hidenori SUTO, Akira SATO, Keiko MAEDA, Kenta MINAMI, Naruto TOMIYAMA, Tadashi KOSAKA, Hitoshi HOJO, Naofumi TAKAHASHI, Hiroaki AOYAMA, Tomoya YAMADA","doi":"10.1293/tox.2024-0004","DOIUrl":"https://doi.org/10.1293/tox.2024-0004","url":null,"abstract":"In a past study, we proposed a modified Comparative Thyroid Assay (CTA) with additional examinations of brain thyroid hormone (TH) concentrations and brain histopathology but with smaller group sizes. The results showed that the modified CTA in Sprague Dawley rats detected 10 ppm 6-propylthiouracil (6-PTU)-induced significant suppressions of serum/brain TH concentrations in offspring. To confirm the reliability of qualitative brain histopathology and identify the optimal testing time for heterotopia (a cluster of ectopic neurons) in the modified CTA, brain histopathology together with serum/brain TH concentrations were assessed in GD20 fetuses and PND2, 4, 21, and 28 pups using a similar study protocol but with a smaller number of animals (N=3–6/group/time). Significant hypothyroidism was observed and brain histopathology revealed cerebral heterotopia formation in PND21 and PND28 pups, with likely precursor findings in PND2 and PND4 pups but not in GD20 fetuses. This study confirmed that the optimal testing time for cerebral heterotopia in rat CTA was PND21 and thereafter. These findings suggest that cerebral heterotopia assessment at appropriate times may be a useful alternative to the original CTA design. \u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"31 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141721041","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

Spontaneous B-cell lymphoma in the cranial mediastinal lymph node of an aged male C57BL/6J mouse 一只老年雄性 C57BL/6J 小鼠头颅纵隔淋巴结中的自发性 B 细胞淋巴瘤

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-07-03 DOI: 10.1293/tox.2023-0130

Shoko SUZUKI, Mao MIZUKAWA, Akane KASHIMURA, Hironobu NISHINA, Tetsuya SAKAIRI, Satomi NISHIKAWA

{"title":"Spontaneous B-cell lymphoma in the cranial mediastinal lymph node of an aged male C57BL/6J mouse","authors":"Shoko SUZUKI, Mao MIZUKAWA, Akane KASHIMURA, Hironobu NISHINA, Tetsuya SAKAIRI, Satomi NISHIKAWA","doi":"10.1293/tox.2023-0130","DOIUrl":"https://doi.org/10.1293/tox.2023-0130","url":null,"abstract":"B-cell lymphoma is generally observed in the spleen, mesenteric lymph nodes, and Peyer’s patches in aged mice and rarely appears in other organs. Herein, we report a case of spontaneous B-cell lymphoma originating from the cranial mediastinal lymph node in a male 75-week-old C57BL/6J mouse. Macroscopically, a white mass was found at the base of the heart with no connection to the thymus. Microscopic examination revealed a solid proliferation of tumor cells with large nuclei at the center of the mass. Some macrophages, normal-sized lymphocytes, and lymphatic sinuses were found in both central and peripheral areas. Immunohistochemical analysis showed positive staining for cluster of differentiation 19, paired box protein 5, immunoglobulin M, and Ki-67 but not for cytokeratin AE1/AE3. These findings were not completely consistent with the established mouse lymphoma classification, leading to a diagnosis of B-cell lymphoma originating from the cranial mediastinal lymph node. This case report is the first to document a B-cell lymphoma in the cranial mediastinal lymph nodes in an aged C57BL/6J mouse model.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"16 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521262","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