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Journal of Toxicologic Pathology

Yoshikazu Yamagishi, Satoshi Furukawa, Ayano Tanaka, Yoshiyuki Kobayashi, Akihiko Sugiyama
In order to clarify the histological localization of cadmium (Cd) in the placenta, we analyzed paraffin sections of placentas from rats with a single Cd exposure on gestation day 18 by the LA-ICP-MS imaging method compared with the histopathological changes. The placentas were sampled at 1 hour, 2 hours, 3 hours, 6 hours, and 24 hours after treatment. Histopathologically, the trophoblasts in the labyrinth zone of the Cd group showed swelling at 1 hour. At 2 and 3 hours, the trophoblasts showed swelling and vacuolar degeneration...
October 2016: Journal of Toxicologic Pathology
Ryo Ando, Shinichiro Ikezaki, Yuko Yamaguchi, Kazutoshi Tamura, Toru Hoshiya
Extraskeletal osteosarcoma is a very rare tumor in humans and animals. This paper describes a case of extraskeletal osteosarcoma observed in the duodenum of a male ICR mouse. Grossly, a solid mass pushing up the tunica serosa was observed in the duodenal wall. Histologically, the tumor was located in the lamina propria mucosae and tela mucosa. Neoplastic cells densely proliferated in these areas, and replaced of the normal tissue components. A small amount of osteoid and a small clump of bone tissue were observed in the area of neoplastic cell proliferation, especially in the lamina propria mucosae...
October 2016: Journal of Toxicologic Pathology
Yohei Sakamoto, Takaharu Nagaoka, Kei Tamura, Hideshi Kaneko
Yolk sac carcinoma is an extremely rare tumor in rats and is usually found in the genital system of aged animals. We encountered a yolk sac carcinoma in the pulmonary artery of an 18-week-old female Sprague-Dawley rat. In a repeated dosing toxicity study (once weekly for 4 weeks, intraperitoneal), this rat was unexpectedly found dead on the 55th day after the final administration of the test article. At necropsy, grayish white nodules were found on the lung surface. Histopathologically, tumor emboli were observed in the trunk and branch of the pulmonary artery...
October 2016: Journal of Toxicologic Pathology
Tomoya Sano, Yuichi Takai, Hisashi Anayama, Takeshi Watanabe, Ryo Fukuda
Mott cells are a variant form of plasma cells in humans and laboratory animals. This report describes the morphological characteristics of Mott cells observed in a 33-week-old female CB6F1-Tg rasH2 mouse. Microscopically, a large number of round cells with abundant eosinophilic globules, which were variable in size, were observed in the spleen and were densely distributed in the red pulp adjacent to the marginal zone. A few similar cells were present in the submandibular lymph node and bone marrow. Neither systemic nor local chronic inflammatory changes were seen in this animal...
October 2016: Journal of Toxicologic Pathology
Lianshan Zhang, Yui Terayama, Taiki Nishimoto, Yasushi Kodama, Kiyokazu Ozaki
Alloxan had been recognized as having a direct nephrotoxic effect different from its diabetogenic action. We encountered previously unreported granulomatous tubulointerstitial nephritis with severe luminal and interstitial mineralization in one diabetic rat after one week of alloxan administration. Histopathologically, many dilated and occluded proximal and distal tubules were segmentally observed in the cortex and outer medulla. The tubular lumen contained minerals and cell debris. Tubular epithelial cells were degenerated and piled up, and they protruded into the lumen, where they enveloped minerals...
October 2016: Journal of Toxicologic Pathology
Hongping Chen, Qinghua Wang, Danni Shi, Dongbo Yao, Lei Zhang, Junping Xiong, Baohua Xu
Numerous pieces of evidence have revealed that oxaliplatin (OXA) evokes mechanical and cold hypersensitivity. However, the mechanism underlying these bothersome side effects needs to be further investigated. It is well known that cyclooxygenase-2 (COX-2) and extracellular signal-regulated kinases (ERK1/2) signaling play crucial roles in several pain states. Our previous data showed that Akt2 in the dorsal root ganglion (DRG) participated in the regulation of OXA-induced neuropathic pain. But it is still unclear whether spinal ERK1/2 signaling is involved in the regulation of OXA-induced hyperalgesia, and the linkage between COX-2 and ERK1/2 signaling in mediating OXA-induced hyperalgesia also remains unclear...
October 2016: Journal of Toxicologic Pathology
Yuan Yuan, Shixun Ma, Yongmei Qi, Xue Wei, Hui Cai, Li Dong, Yufeng Lu, Yupeng Zhang, Qingjin Guo
The objective of the current study was to explore the inhibitory effects of quercetin on cadmium-induced autophagy in mouse kidneys. Mice were intraperitoneally injected with cadmium and quercetin once daily for 3 days. The LC3-II/β-actin ratio was used as the autophagy marker, and autophagy was observed by transmission electron microscopy. Oxidative stress was investigated in terms of reactive oxygen species, total antioxidant capacity, and malondialdehyde. Cadmium significantly induced typical autophagosome formation, increased the LC3-II/β-actin ratio, reactive oxygen species level, and malondialdehyde content, and decreased total antioxidant capacity...
October 2016: Journal of Toxicologic Pathology
Isamu Suzuki, Young-Man Cho, Tadashi Hirata, Takeshi Toyoda, Jun-Ichi Akagi, Yasushi Nakamura, Eun Young Park, Azusa Sasaki, Takako Nakamura, Shigehisa Okamoto, Koji Shirota, Noboru Suetome, Akiyoshi Nishikawa, Kumiko Ogawa
To examine the effects of 4-methylthio-3-butenyl isothiocyanate on esophageal carcinogenesis, male 6-week-old F344 rats were subcutaneously injected with 0.5 mg/kg body weight N-nitrosomethylbenzylamine three times per week for 5 weeks and fed a diet supplemented with 80 ppm 4-methylthio-3-butenyl isothiocyanate, equivalent to 6.05 mg/kg body weight/day for the initiation stage, 4.03 mg/kg body weight/day for the promotion stage, or 4.79 mg/kg body weight/day for all stages. Although the incidence of lesions was not affected by 4-methylthio-3-butenyl isothiocyanate treatment, the multiplicity of squamous cell papilloma in the esophagus was significantly decreased in rats in the 4-methylthio-3-butenyl isothiocyanate initiation stage group (1...
October 2016: Journal of Toxicologic Pathology
Keiko Ogata, Masahiko Kushida, Kaori Miyata, Kayo Sumida, Shuji Takeda, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate
Although 3,3'-iminodipropionitrile (IDPN) is widely used as a neurotoxicant to cause axonopathy due to accumulation of neurofilaments in several rodent models, its mechanism of neurotoxicity has not been fully understood. In particular, no information regarding microRNA (miRNA) alteration associated with IDPN is available. This study was conducted to reveal miRNA alteration related to IDPN-induced neurotoxicity. Rats were administered IDPN (20, 50, or 125 mg/kg/day) orally for 3, 7, and 14 days. Histopathological features were investigated using immunohistochemistry for neurofilaments and glial cells, and miRNA alterations were analyzed by microarray and reverse transcription polymerase chain reaction...
October 2016: Journal of Toxicologic Pathology
Samuel M Cohen, Lora L Arnold
Carcinogenic potential of chemicals is currently evaluated using a two year bioassay in rodents. Numerous difficulties are known for this assay, most notably, the lack of information regarding detailed dose response and human relevance of any positive findings. A screen for carcinogenic activity has been proposed based on a 90 day screening assay. Chemicals are first evaluated for proliferative activity in various tissues. If negative, lack of carcinogenic activity can be concluded. If positive, additional evaluation for DNA reactivity, immunosuppression, and estrogenic activity are evaluated...
October 2016: Journal of Toxicologic Pathology
Samak Sutjarit, Amnart Poapolathep
Fusarenon-X is a non-macrocyclic type B trichothecene mycotoxin. It occurs naturally in agricultural commodities, such as wheat and barley. We investigated fusarenon-X-induced apoptosis in the liver, kidney, and spleen of male and female mice after a single exposure. Thus, mice were orally administered fusarenon-X (4 mg/kg body weight) and were assessed at 0, 3, 9, 18, 24, and 48 hours after treatment. Apoptosis in the liver, kidney, and spleen was determined using hematoxylin and eosin staining, the terminal deoxynucleotidyl transferase dUTP nick end labeling method, immunohistochemistry for proliferating cell nuclear antigen, and electron microscopy...
July 2016: Journal of Toxicologic Pathology
Kaori Isobe, Sydney Mukaratirwa, Claudio Petterino, Alys Bradley
The incidence and range of spontaneous thyroid and parathyroid glands findings were determined in control Han-Wistar and Sprague-Dawley rats, and CD-1 mice from 104-week carcinogenicity studies carried out between 1998 and 2010 at Charles River Edinburgh. In both strains of rats and in CD-1 mice, non-proliferative lesions of the thyroid or parathyroid glands were generally uncommon apart from some findings in CD-1 mice such as ultimobranchial duct/cyst (5.72%), follicular distension/dilatation (3.84%), and cystic follicles (3...
July 2016: Journal of Toxicologic Pathology
Martin Heinrichs, Heinrich Ernst
Craniopharyngiomas are extremely rare epithelial tumors of the sellar region in human beings and domestic and laboratory animals. A craniopharyngioma, 0.6 cm in diameter, was observed grossly in the sellar and parasellar regions of an untreated 23-month-old male Wistar-derived rat sacrificed moribund. The tumor was composed of cords, columns, and nests of neoplastic stratified squamous epithelium with marked hyperkeratosis and parakeratosis. Neoplastic cells formed solid or cystic areas, infiltrating the base of the skull, brain, and pituitary gland...
July 2016: Journal of Toxicologic Pathology
Tetsuya Ide, Akiko Moriyama, Kazuyuki Uchida, James K Chambers, Takanobu Okazaki, Kinji Kobayashi, Shunji Nakatsuji, Masahiro Matsumoto
A male cynomolgus monkey (Macaca fascicularis) of 5 years and 11 months of age from the vehicle control group of a 4-week repeated oral dose toxicity study had a spontaneously occurring mass lesion directly attached to the proximal part of the left trigeminal nerve. Histologically, the mass was characterized by a multifocal nodular appearance. Nodular zones showed low to moderate cellularity and were composed of small round cells exhibiting nuclear uniformity. On the other hand, inter-nodular zones were composed of nerve fiber containing septa and closely aggregated highly pleomorphic cells...
July 2016: Journal of Toxicologic Pathology
Akira Inomata, Kazuhiro Hayakawa, Toyohiko Aoki, Satoru Hosokawa
Carcinosarcoma is a rare neoplasm composed of malignant epithelial and stromal elements, and, for rats, carcinosarcomas in the kidney have not been reported. In a long-term study to gather background data, we encountered a spontaneous carcinosarcoma originating from the renal pelvis with metastasis to the lung. At necropsy, a mass was observed in the abdominal cavity, and white nodules were scattered in lung lobes. Microscopically, there was polypoid hyperplasia of the urothelium accompanied by hyperplasia of spindle stromal cells in the pelvis...
July 2016: Journal of Toxicologic Pathology
Yoshika Yamakawa, Tetsuya Ide, Hikaru Mitori, Yuji Oishi, Masahiro Matsumoto
Accumulation of macrophages containing brown pigments in the lungs is a well-known spontaneous lesion found in cynomolgus monkey. However, its pathogenesis has not been clearly described. In our survey, brown pigment-laden macrophages were found in the lungs of 4 out of 43 cases. Brown pigments were mostly found in the macrophages of the perivascular interstitium, which proved to be hemosiderin. Some small- to medium-sized vessels that exhibited prominent accumulation of brown pigment-laden macrophages showed degeneration and necrosis of the smooth muscle cells of tunica media...
July 2016: Journal of Toxicologic Pathology
Cheng Zhe Zu, Masato Kuroki, Ayano Hirako, Takashi Takeuchi, Satoshi Furukawa, Akihiko Sugiyama
Pregnant rats were treated intraperitoneally with a single dose of methotrexate (MTX) 90 mg/kg on gestation day (GD) 13, and fetal eyeballs were examined time-dependently from GD 13.5 to 15.5. Throughout the experimental period, the inner plate of the ocular cup in the MTX group was significantly thinner than that in the control group. In the inner plate of the ocular cup on GD 15 and 15.5, whereas a developed ganglion cell layer was observed in the control group, the ganglion cell layer in the MTX group was undeveloped and indistinguishable...
July 2016: Journal of Toxicologic Pathology
Ryota Tochinai, Yuriko Nagata, Minoru Ando, Chie Hata, Tomo Suzuki, Naoyuki Asakawa, Kazuhiko Yoshizawa, Kazumi Uchida, Shoichi Kado, Toshihide Kobayashi, Kimiyuki Kaneko, Masayoshi Kuwahara
Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs)...
July 2016: Journal of Toxicologic Pathology
Junko Sato, Masahiro Nasu, Minoru Tsuchitani
Accurate analysis of female reproductive toxicity requires a thorough understanding the differences in and specifics of estrous or menstrual cycles between laboratory animals. There are some species differences such as the time of sex maturation, the length of the estrous or menstrual cycle, the length of the luteal phase, the number of dominant follicles or corpora lutea, the size of follicles, processes of luteinization, and hormonal changes during the estrous or menstrual cycle. Rodents have a short estrous cycle, and their ovarian cycling features are the same in both ovaries, which contain a large number of follicles and corpora lutea...
July 2016: Journal of Toxicologic Pathology
Minoru Tsuchitani, Junko Sato, Hiroko Kokoshima
As basic knowledge for evaluation of pancreatic toxicity, anatomical structures were compared among experimental animal species, including rats, dogs, monkeys, and minipigs. In terms of gross anatomy, the pancreases of dogs, monkeys, and minipigs are compact and similar to that of humans. The rat pancreas is relatively compact at the splenic segment, but the duodenal segment is dispersed within the mesentery. In terms of histology, the islet of each animal is characterized by a topographic distribution pattern of α- versus β-cells...
July 2016: Journal of Toxicologic Pathology
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