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Journal of Toxicologic Pathology

Akane Kashimura, Kouji Tanaka, Hiroko Sato, Hidefumi Kaji, Masaharu Tanaka
To evaluate the usefulness of imaging mass spectrometry (IMS) technology for assessing drug toxicity, we analyzed animal tissues in an amiodarone (AMD)-induced phospholipidosis model by IMS and confirmed the relationship between the distribution of AMD, its metabolites, and representative phospholipids (phosphatidylcholine, PC) and histological changes. AMD was administered to rats for 7 days at 150 mg/kg/day. The lung, spleen, and mesenteric lymph node were histologically examined and analyzed using IMS. The detection intensities of AMD, its metabolites, and typical PCs were higher in regions infiltrated by foamy macrophages compared with normal areas...
July 2018: Journal of Toxicologic Pathology
Masaki Yamazaki, Nami Yabuki, Yasunori Suzuki, Mayumi Ito, Asuka Ikeda, Osamu Natori, Masami Suzuki, Atsuhiko Kato
Assessing how gene expression analysis by RNA sequencing (RNA-Seq) correlates to a unique morphology is increasingly necessary, and laser capture microdissection (LCM) is a critical research tool for discovering the genes responsible in a region of interest (ROI). Because RNA-Seq requires high-quality RNA, a sample preparation procedure that can preserve morphology and give the required quality of RNA is essential. A PAXgene®-fixed paraffin-embedded (XFPE) block can satisfy the need for high-quality RNA, but there are few reports on adapting the method for LCM, such as how small an ROI is analyzable by RNA-Seq...
July 2018: Journal of Toxicologic Pathology
Satoshi Matsuyama, Mohammad Rabiul Karim, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate
Macrophages are required during kidney development and appear in the initiation and propagation of renal injury. To establish baseline data, we analyzed the kinetics of the macrophage with different immunophenotypes in the developing rat kidney (fetus at 18 and 20 days, neonate at 1-21 days, and adult at 7-weeks old). Macrophages reacting to CD68, CD163, and MHC class II were identified in the cortex and medulla of the developing rat kidney. CD68+ macrophages appeared in the fetal kidney as early as fetal day 18, and the number increased gradually in the neonatal kidney, whereas MHC class II+ and CD163+ macrophages first appeared on neonatal days 4 and 8, respectively...
July 2018: Journal of Toxicologic Pathology
Masayo Miki, Norio Ohishi, Eiko Nakamura, Akane Furumi, Fukutaro Mizuhashi
To prevent fixation defects or artifacts in the whole bodies of fish caused by conventional fixatives, such as formalin solution, Bouin's fluid (BF), and Davidson's fluid (DF), the optimal fixatives and fixing method were examined. An improved method of fixing the whole bodies of fish was examined that makes use of a combination of 20% formalin and BF or DF. The fixatives were examined with four representative tissues, i.e., the gill, liver, intestinal tract, and kidney, to evaluate end points including the appearance of degraded tissues and artifacts caused by each fixative, overall morphological clarity of nuclei, staining intensity, and integrity of the other tissues...
July 2018: Journal of Toxicologic Pathology
Vittoria Castiglioni, Enrico Radaelli
Murine hepatoblastoma (HB) is a rare spontaneous tumor with controversial histogenesis. It mainly occurs in aged males, frequently in close association with preexisting hepatocellular neoplasms. The present work describes a spontaneous HB arising within a hepatocellular carcinoma (HCC) in a 22-month-old male C57BL/6J mouse. The mouse also developed pulmonary co-metastases with either tumor components physically associated within the same metastatic foci. Microscopically, the HB consisted of a densely cellular neoplastic growth composed of palisades and perivascular pseudorosettes of poorly differentiated primitive cells, with a scant amount of cytoplasm, elongated hyperchromatic nuclei, and a high mitotic rate, whereas the hepatocellular carcinoma was composed of solid areas of neoplastic hepatocytes...
July 2018: Journal of Toxicologic Pathology
Ayumi Eguchi, Mari Inohana, Misato Nakamura, Rei Nagahara, Megu Itahashi, Kota Nakajima, Toshinori Yoshida, Makoto Shibutani
A 3-year-old female Richardson's ground squirrel developed a subcutaneous mass at the left oral angle. Seven days after removal of the mass, the mass recurred and metastasized to the cervical lymph node. Histologically, the primary mass was subdivided by fibrous trabeculae into various-sized neoplastic cell lobules showing a solid growth pattern with frequent mitoses and sometimes forming intracytoplasmic lumina. Large to medium-sized lobules formed a central cyst plugged by comedo necrosis. Neoplastic cells showed infiltrative subcutaneous growth...
July 2018: Journal of Toxicologic Pathology
Takuma Tsuchiya, Aki Kijima, Yuji Ishii, Shinji Takasu, Yuh Yokoo, Akiyoshi Nishikawa, Tokuma Yanai, Takashi Umemura
Oxidative stress is well known as a key factor of chemical carcinogenesis. However, the actual role of oxidative stress in carcinogenesis, such as oxidative stress-related in vivo mutagenicity, remains unclear. It has been reported that 8-hydroxydeoxyguanosine (8-OHdG), an oxidized DNA lesion, might contribute to chemical carcinogenesis. Potassium bromate (KBrO3 ) and nitrofurantoin (NFT) are known as renal carcinogens in rats. Our previous studies showed an increase in mutant frequencies accompanied by an increased level of 8-OHdG in the kidneys of rodents following KBrO3 or NFT exposure...
July 2018: Journal of Toxicologic Pathology
Takuma Tsuchiya, Aki Kijima, Yuji Ishii, Shinji Takasu, Yuh Yokoo, Akiyoshi Nishikawa, Tokuma Yanai, Takashi Umemura
Despite its antimicrobial activity, nitrofurantoin (NFT) is a renal carcinogen in rats. Oxidative stress induced by reduction of the nitro group of NFT may contribute to its genotoxicity. This is supported by our recent results indicating that the structure of the nitrofuran plays a key role in NFT-induced genotoxicity, and oxidative DNA damage is involved in renal carcinogenesis. Nuclear factor erythroid 2-related factor 2 (NRF2) regulates cellular responses to oxidative stress. To clarify the role of oxidative stress in the chemical structure-related genotoxic mechanism of NFT, we performed reporter gene mutation assays for NFT and 5-nitro-2-furaldehyde (NFA) using Nrf2 -proficient and Nrf2 -deficient gpt delta mice...
July 2018: Journal of Toxicologic Pathology
Jane Tey Xin Ying, Masanao Yokohira, Yuko Nakano-Narusawa, Keiko Yamakawa, Nozomi Hashimoto, Katsumi Imaida
It is known that γH2AX, which is formed when there is a double-strand break in DNA, can act as a sensitive marker of genomic instability. In this experiment, the time-course manner of the expression of γH2AX in the lung was examined in the early phase after treatment with a lung carcinogen, N-bis (2-hydroxypropyl) nitrosamine (DHPN). The expression of γH2AX is expected to be one of the useful markers for lung carcinogenesis in early stages. Rats were separated into 10 groups of 5 rats. The DHPN groups were administered 0...
July 2018: Journal of Toxicologic Pathology
Robert R Maronpot, Cheryl A Hobbs, Shim-Mo Hayashi
When a comet assay, an increasingly popular in vivo genotoxicity test, shows a positive test result, interpretation of that response requires ruling out any confounding tissue site toxicity. Since the comet assay typically uses only two or three daily doses of test agent, precursor tissue changes indicative of toxicity may be easily overlooked. Using case examples for two flavoring agents, perillaldehyde and 4,5-epoxydec-2( trans )-enal, we highlight the role of pathology peer review in verifying precursor tissue changes indicative of tissue site toxicity, thereby increasing confidence in final interpretation of comet assay results...
July 2018: Journal of Toxicologic Pathology
Munetaka Iwata, Wataru Yamamoto, Takasumi Shimomoto, Yuki Okada, Satomi Oosawa, Daishiro Miura, Yasushi Hara
Growth plates at each end of vertebral bodies play a pivotal role in longitudinal spinal growth. Epiphyseal closures are formed in adult humans. Although monkeys are frequently employed in bone and disc research, the age of epiphyseal closure has not been well documented. In this study, histological analyses of lumbar vertebral end plates and the surrounding tissue were performed in 11 normal cynomolgus monkeys aged approximately 9 to 15 years, and unclosed growth plate cartilage was detected in all the end plates...
April 2018: Journal of Toxicologic Pathology
Norimitsu Shirai, Mark G Evans
The present article describes an occurrence of testicular microlithiasis in a cynomolgus monkey from a routine regulatory toxicology study. The monkey was from a negative control group. Microscopically, the lesion was characterized by multiple extracellular mineralized calculi within seminiferous tubular epithelia of both testes without any tissue reaction or abnormal condition such as cryptorchidism, testicular neoplasm, or hypogonadism. The present case is remarkable in that there is a paucity of reports on spontaneous testicular microlithiasis in nonhuman primates...
April 2018: Journal of Toxicologic Pathology
Tomoharu Naito, Tsuyoshi Saito, Tamami Higuchi, Akira Inomata, Takuo Hayashi, Yasuhiro Shimada, Atsuko Yamauchi-Ohguchi, Sayaka Kenmochi, Chihaya Kakinuma, Takashi Yao
Liposarcoma is a rare neoplasm in rats and is characterized by the presence of lipoblasts containing multiple cytoplasmic vacuoles. We encountered a rare type of liposarcoma in a male SD (Crj:CD(SD)IGS) rat during a long-term study to gather background data. At necropsy at 105 weeks of age, there was a large amount of fatty tissue covering the mesentery, pancreas, and retroperitoneum; a white nodule in the right kidney; and paleness of the liver. Microscopically, the tumor had a well-differentiated component and dedifferentiated high-grade component...
April 2018: Journal of Toxicologic Pathology
Yoshitaka Katoh, Tsuyoshi Ito, Yuko Shimada, Aya Ohnuma-Koyama, Naofumi Takahashi, Yoshimasa Okazaki, Atsushi Shiga, Maki Kuwahara, Toshinori Yoshida, Takanori Harada
A whitish mass approximately 30 mm in diameter was noted in the anterior mediastinum of a 67-week-old female Fischer 344 rat. Histopathologically, two types of tumor cells were identified on the basis of morphologic features: epithelial tumor cells with a tubular or cord-like growth pattern and rhabdomyosarcomatous tumor cells characterized by the presence of cross-striations. Immunohistochemically, the epithelial tumor cells reacted positively for cytokeratin AE1/AE3, and some reacted positively for p63, which is expressed in normal thymic epithelial cells...
April 2018: Journal of Toxicologic Pathology
Kiyokazu Ozaki, Yui Terayama, Tetsuro Matsuura, Isao Narama
Clinical and experimental research have suggested that dyslipidemia aggravates diabetic peripheral neuropathy (DPN). However, whether dyslipidemia is a risk factor for DPN remains unclear. To investigate the effect of dyslipidemia on DPN, morphological features of peripheral nerves were analyzed in diabetic rats treated with a high-fat diet (HFD). Male rats were divided into four groups: nondiabetic rats (N), alloxan-induced diabetic rats (AL), diabetic rats treated with an HFD (AH), and nondiabetic rats treated with an HFD (HF)...
April 2018: Journal of Toxicologic Pathology
Yusuke Kemmochi, Takeshi Ohta, Yu Motohashi, Akihiro Kaneshige, Sohei Katsumi, Kochi Kakimoto, Yuzo Yasui, Akiko Anagawa-Nakamura, Kaoru Toyoda, Eriko Taniai-Riya, Akemi Takahashi, Toshiyuki Shoda, Takahisa Yamada
Sarcopenia is the age-related decrease of muscle mass and function. Diabetes and obesity are known to be risk factors that exacerbate sarcopenia, but the underlying mechanism of diabetes-related sarcopenia is still unknown. Obese type 2 diabetes SDT fatty rats show early onset of severe diabetes and there have been no reports on the characteristics of their skeletal muscle. Therefore, pathophysiological analyses were performed for the skeletal muscle in these rats. Diabetic male SDT fatty rats were sacrificed at 8, 16, 24, 32 and 40 weeks of age...
April 2018: Journal of Toxicologic Pathology
Akihiko Yamamoto, Satomi Harano, Noriko Shinya, Ayataka Nagano, Yoshinobu Miyatsu, Kyouko Sawabe, Takayuki Matsumura, Manabu Ato, Motohide Takahashi, Hisashi Taki, Toru Hifumi
The redback spider ( Latrodectus hasseltii ) is nonindigenous to Japan but has now spread throughout the country. Bites to humans are rare but can be fatal. We prepared freeze-dried redback spider antivenom for therapeutic use against bites in Japan by immunization of horse plasma. This study included two nonclinical tests of the antivenom: a local irritation study involving a single intramuscular administration to rabbits (with injections of physiological saline and an existing freeze-dried diphtheria antitoxin as control and comparison substances, respectively) and a 2-week repeated intermittent intravenous-dose toxicity study in rats...
April 2018: Journal of Toxicologic Pathology
Shino Kumabe, Junko Sato, Yuki Tomonari, Miwa Takahashi, Kaoru Inoue, Midori Yoshida, Takuya Doi, Yumi Wako, Minoru Tsuchitani
To clarify the histopathological characteristics of rat endometrial stromal sarcoma (ESS), we morphologically reviewed 12 malignant uterine tumors protruding into the lumen in previous rat carcinogenicity studies. The 12 cases were classified into the following 6 types based on their morphological features: spindle cell and collagen rich type, pleomorphic/spindle cell and compact type, decidual alteration type, histiocytic and multinucleated giant cell mixture type, Antoni A-type schwannoma type, and Antoni B-type schwannoma type...
April 2018: Journal of Toxicologic Pathology
Daichi Harata, Yuya Tsuchiya, Tomoyuki Miyoshi, Tokuma Yanai, Kazuhiko Suzuki, Tomoaki Murakami
In the several types of amyloidoses, participation of oxidative stresses in the pathogenesis and the effect of antioxidants on amyloidosis have been reported. Meanwhile, the relationship between oxidative stresses and pathogenesis of amyloid A (AA) amyloidosis is still unclear. In this study, we used an antioxidant, Brazilian propolis, to investigate the inhibitory effects on AA amyloidosis. The results showed that AA deposition was inhibited by administration of propolis. Increased expression of antioxidant markers was detected in molecular biological examinations of mice treated with propolis...
April 2018: Journal of Toxicologic Pathology
Meg Ferrell Ramos, Julia Baker, Elke-Astrid Atzpodien, Ute Bach, Jacqueline Brassard, James Cartwright, Cynthia Farman, Cindy Fishman, Matt Jacobsen, Ursula Junker-Walker, Frieke Kuper, Maria Cecilia Rey Moreno, Susanne Rittinghausen, Ken Schafer, Kohji Tanaka, Leandro Teixeira, Katsuhiko Yoshizawa, Hui Zhang
No abstract text is available yet for this article.
2018: Journal of Toxicologic Pathology
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