Pleural translocation and lesions by pulmonary exposed multi-walled carbon nanotubes.
Authors: Wang Q, Wang Q, Zhao Z, Alexander DB, Zhao D, Xu J, Tsuda H Abstract Carbon nanotubes (CNTs) are recently developed tubular nanomaterials, with diameters ranging from a few nanometers to tens of nanometers, and the length reaching up to several micrometers. They can be either single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs). Due to their nano-scaled structure, CNTs have a unique set of mechanical, electrical, and chemical properties that make them useful in information technologies, optoelectronics, energy technologies, material sciences, medical technologies, and other fie...
Source: Journal of Toxicologic Pathology - August 13, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Patient-derived xenograft (PDX) models: characteristics and points to consider for the process of establishment.
Authors: Fujii E, Kato A, Suzuki M Abstract Tumor research has largely relied on xenograft models created by the engraftment of cultured cell lines derived from tumor tissues into immunodeficient mice for in vivo studies. Like in vitro models, such models retain the ability of tumor cells to continuously proliferate, so they have been used to predict the clinical relevance of studies on proliferating cells. However, these models are composed of a limited population of tumor cells, which include only those tumor cells that are able to adapt to culture conditions, and thus they do not reflect the diversity and hetero...
Source: Journal of Toxicologic Pathology - August 13, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Superimposition of hypertension on diabetic peripheral neuropathy affects small unmyelinated sensory nerves in the skin and myelinated tibial and sural nerves in rats with alloxan-induced type 1 diabetes.
In this study, we investigated the effect of hypertension on DPN by investigating the changes in unmyelinated and myelinated nerve fibers in hypertensive rats with alloxan (AL)-induced T1DM. Thirteen-week-old WBN/Kob rats with AL-induced diabetes were allocated to receive tap water only (AL group), tap water containing 0.5% saline (0.5AN group), or tap water containing 0.75% saline (0.75AN group) for 15 weeks. Hyperglycemia was maintained for 15 weeks, and the animals were euthanized at 28 weeks. By 23 weeks of age, the systolic blood pressure was significantly higher in the 0.75AN and 0.5AN groups than in the AL group and...
Source: Journal of Toxicologic Pathology - August 13, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

A spontaneous middle ear adenocarcinoma characterized by abundant eosinophilic matrix in a young male Crl:CD(SD) rat.
Authors: Kokoshima H, Yamada N, Wako Y, Doi T, Tsuchitani M Abstract A mass was detected in the right tympanic cavity of a 15-week-old male Crl:CD(SD) rat. Histological examination revealed papillary or tubular proliferations of epithelial cells including ciliated cells that produce mucus and have an abundant eosinophilic matrix. The malignancy of this tumor was revealed by its destructive proliferation, cellular polymorphism, and high proliferative activity. The tumor was diagnosed as a middle ear adenocarcinoma due to its location and histological characteristics. This is the first report of a middle ear adenocar...
Source: Journal of Toxicologic Pathology - August 13, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Spontaneous membranoproliferative glomerulonephritis in a young Crl:CD-1(ICR) mouse.
Authors: Tochitani T, Kouchi M, Fuji Y, Yoshino Y, Matsumoto I Abstract Here, we reported a spontaneous case of membranoproliferative glomerulonephritis observed in a young ICR mouse. A 5-week-old female mouse was euthanized owing to abdominal swelling and increased body weight. At necropsy, generalized subcutaneous edema, and clear, colorless, non-viscous ascites were observed. Histologically, the kidneys showed diffuse, bilateral glomerular lesions. The lesions were characterized by thickening and double contour of the basement membrane and an increase in mesangial cells and matrix, resulting in the narrowing of ...
Source: Journal of Toxicologic Pathology - August 13, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

A craniopharyngioma in a Wistar rat most likely originated in a Rathke's cleft cyst.
We examined a 110-week-old RccHanTM: WIST Wistar male rat from a carcinogenicity study. No clinical signs were observed, and the rat was sacrificed at the end of the study. Macroscopically, within the midline of the sphenoid bone, was a 10 mm, non-infiltrative, soft, heterogeneous mass. Microscopic evaluation showed an expansile, cystic proliferation, consisting of two patterns of epithelial lining: well-differentiated areas lined by a single layer to a pseudostratified, ciliated-cuboidal epithelia with Goblet cells compatible with Rathke's cleft cyst; and poorly differentiated ones that formed irregular papillary projecti...
Source: Journal of Toxicologic Pathology - August 13, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Comparison of longevity and common tumor profiles between Sprague-Dawley and Han Wistar rats.
Authors: Taylor I, Mowat V Abstract The Sprague Dawley (SD) and Han Wistar (HW) are the two most commonly used rat strains in Europe and the US, with the Han Wistar increasing in popularity because of its greater longevity and lower tumor burden. This survey was undertaken at Covance CRS (Huntingdon and Eye) to compare in-house longevity and common spontaneous tumor profiles of the two strains with published data. Data were compiled from 104-week studies started between 2010 and 2017. Mean survival was greater for both sexes of HWs when compared with SDs. Pituitary tumors were the commonest in both strains, with sl...
Source: Journal of Toxicologic Pathology - August 13, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Tissue-specific effects of an anti-desmoglein-3 ADCC antibody due to expression of the target antigen and physiological characteristics of the mouse vagina.
Authors: Fujii E, Funahashi S, Taniguchi K, Kawai S, Nakano K, Kato A, Suzuki M Abstract Desmoglein-3 (DSG3) is a potential target of cytotoxic antibody therapy for squamous cell carcinomas but is also expressed in various normal squamous epithelia. We obtained information about DSG3 distribution in mouse tissues by immunohistochemistry and conducted an intravenous multiple-dose study in mouse to estimate the toxic potential of anti-DSG3 therapy. DSG3 was expressed in the squamous epithelium of several organs including the skin, esophagus, tongue, forestomach, eye, and vagina. It was expressed at all estrous cycles...
Source: Journal of Toxicologic Pathology - May 21, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Impact of altered dietary calcium-phosphorus ratio caused by high-phosphorus diets in a rat chronic kidney disease (CKD) model created by partial ligation of the renal arteries.
This study aimed to establish a rat chronic kidney disease (CKD) model by studying the effects of a high-phosphorus diet in rats that had undergone partial ligation of the renal arteries (RL). Separate groups of 10-week-old male Slc:Sprague-Dawley rats underwent RL and were fed diets with varying phosphorous levels for a period of 48 days. A marked suppression of body weight gain necessitating humane euthanization occurred on day 28 in rats that had undergone RL and were given high-phosphorus feed. By contrast, the group of intact animals on a high-phosphorus feed exhibited a slightly decreased body weight gain from day 21...
Source: Journal of Toxicologic Pathology - May 21, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Minocycline protects against acrylamide-induced neurotoxicity and testicular damage in Sprague-Dawley rats.
In conclusion, minocycline protects against neurotoxic effects of acrylamide and seminiferous tubular damage. Decreasing lipid peroxidation by minocycline might play a role in such protection. PMID: 32425341 [PubMed] (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - May 21, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Effects of 4% paraformaldehyde and modified Davidson's fluid on the morphology and immunohistochemistry of Xiang pig testes.
This study investigated the effects of both mDF and 4% PFA on the morphology and antigen preservation of Xiang pig testes using hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). The stronger testis penetration of mDF compared with that of 4% PFA was primarily manifested as testicular color change and decrease in tissue weight loss. Testes fixed with 4% PFA displayed a severe shrinkage of both the tubular and interstitial compartments and the seminiferous tubule area decreased by 12.02% compared with that in mDF-fixed tissues. In contrast, IHC results showed that 4% PFA fixation achieved better IHC-positive pe...
Source: Journal of Toxicologic Pathology - May 21, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

A histopathological study on spontaneous gastrointestinal epithelial tumors in dogs.
Authors: Saito T, Nibe K, Chambers JK, Uneyama M, Nakashima K, Ohno K, Tsujimoto H, Uchida K, Nakayama H Abstract The present study evaluated the histopathological features, biological nature, anatomical location, sex, age and breeds of dogs affected by spontaneous gastrointestinal epithelial tumor. Biopsy samples of gastrointestinal tumors, from 95 dogs were examined and classified according to the WHO histological classification. A total of 131 samples, including 38 gastric, 13 small intestinal, and 80 large intestinal tumors were examined. The study observed that Jack Russell Terriers and Miniature Dachshunds we...
Source: Journal of Toxicologic Pathology - May 21, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Pathological study of tubular aggregates occurring spontaneously in the skeletal muscles of non-obese diabetic/Cg-PrkdcscidIl2rgtm1sug /ShiJic (NOG) mice.
Authors: Igura S, Nagatani M, Kasahara K, Andoh R, Fukunaga Y, Hashiguchi O, Okazaki S, Yamaguchi Y Abstract To examine the biological and morphological features of tubular aggregates (TAs) in the skeletal muscles of non-obese diabetic/Cg-PrkdcscidIl2rgtm1Sug /ShiJic (NOG) mice, 73 male and 72 female specific-pathogen-free NOG mice were examined at 7, 18, 22, 26, and 52 weeks of age. TAs were observed as intracytoplasmic eosinophilic materials of the femoral muscles in males at 18, 22, 26, and 52 weeks of age and in females at 52 weeks of age; gender-related differences were noted in the onset time and lesion degre...
Source: Journal of Toxicologic Pathology - May 21, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Hyperglycemia contributes to the development of Leydig cell hyperplasia in male Spontaneously Diabetic Torii rats.
In this study, pathophysiological analyses of the testes were performed on male SDT rats, to understand the effect of insulin treatment on the development of Leydig cell hyperplasia and tumors and the expression of integrins and extracellular matrix proteins. Testicular Leydig cell hyperplasia and tumors were observed in SDT rats at 64 weeks of age but were rarely identified in Sprague-Dawley (SD) rats of the same age. Insulin treatment decreased plasma glucose and HbA1c levels, and interestingly, decreased the number of hyperplastic Leydig cell foci and Leydig cell tumors in treated animals. A similar reduction in the exp...
Source: Journal of Toxicologic Pathology - May 21, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Current status of pathological image analysis technology in pharmaceutical companies: a questionnaire survey of the Japan Pharmaceutical Manufacturers Association.
In conclusion, in this questionnaire survey, TF extracted the current status of image analysis in nonclinical studies performed by pharmaceutical companies and collected opinions on future prospects regarding the development of image analysis software with advanced digital pathology technology. PMID: 32425346 [PubMed] (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - May 21, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Dog-specific hemorrhagic changes induced by liposomal formulations, in the liver and the gallbladder.
Authors: Makita-Suzuki K, Kakinuma C, Inomata A, Shimada Y, Hara T, Yao T Abstract Although several liposomal drugs, including liposomal doxorubicin, have been approved, the etiology of the pathological responses caused by their physicochemical properties remains unknown. Herein, we investigated the pathological changes in the liver and the gallbladder of dogs following a single injection of liposomal doxorubicin (1 or 2.5 mg/kg) or an empty liposomal formulation (i.e., liposomal formulation without doxorubicin, ca. 21 mg/kg as lipid content). Injection of liposomal doxorubicin or the empty liposomal formulation in...
Source: Journal of Toxicologic Pathology - February 15, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Effects of administering different vehicles via single intratracheal instillation on responses in the lung and pleural cavity of Crl:CD(SD) rats.
We examined the toxic effects of pure water, saline, phosphate buffered saline (PBS), 0.5% Kolliphor® P188 (KP188), 0.1% Tween 20 in saline, and 1.0% BSA in PBS. These vehicles were administered to male Crl:CD(SD) rats by a single intratracheal instillation. On day 3, broncho-alveolar lavage fluid (BALF) from the right lung was collected and processed for cell counting and biochemical analysis, while the left lung was used for histopathological examination. Accumulation of alveolar macrophages was observed in all vehicle-treated groups but was minimal in the group administered saline, somewhat higher in the groups admi...
Source: Journal of Toxicologic Pathology - February 15, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Urothelial hyperplasia with calculi (papillomatosis) in the urinary bladder of a male spontaneous diabetic Torii rat.
Authors: Maejima T, Kumagai K, Yabe K, Yasuno K, Ishikawa K, Okado K, Sasaki N, Kai K, Mori K Abstract A 40-week-old male spontaneous diabetic Torii rat, an animal model of type 2 diabetes mellitus, was found to have marked urinary calculi with hematuria in the urinary bladder on necropsy. Histological findings in the urinary bladder included a papillary growth pattern with a fibrovascular stroma without atypia. Fine granular materials in the bladder lumen were positive for Von Kossa staining but negative for periodic acid-Schiff or Gram staining, indicating no apparent bacterial infection in the urinary bladder. S...
Source: Journal of Toxicologic Pathology - February 15, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Subendocardial nodular proliferation of myofibroblasts in a laboratory beagle.
This study describes the morphological characteristics of an endocardial proliferative lesion in the right ventricle of a beagle. PMID: 32051662 [PubMed] (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - February 15, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Angiomatous hyperplasia in the heart of a young rat.
Authors: Piccicuto V, Dincer Z, Walker S, Gray C Abstract This case report describes angiomatous hyperplasia in the heart which is an unusual location in a young male Sprague-Dawley rat in a short-term toxicity study. Histologically, the lesion was characterized by blood-filled vascular channels of variable diameter lined by a thin wall and surrounded by a thin fibrous stroma and minimal lympho-plasmacytic and neutrophilic infiltrate in the apex of the heart. Immunohistopathology using CD31 confirmed the blood vessel origin, and using Ki67 confirmed low cell-proliferative activity in the vascular endothelial cells....
Source: Journal of Toxicologic Pathology - February 15, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

A case of hepatic leiomyosarcoma with osteosarcomatous differentiation (malignant mesenchymoma) in a dog.
Authors: Takai Y, Sano T, Watanabe T Abstract A rare spontaneous hepatic leiomyosarcoma with osteosarcomatous differentiation was observed in a female beagle dog and its morphological and immunohistochemical characteristics were examined. Upon necropsy, an endoceliac mass originating from the liver was detected, which was composed of hematoid fluid-filled cysts and white to grayish solid tissue. There were no macroscopic findings in other organ systems. Histopathologically, the hepatic mass consisted of two different mesenchymal components. One form was spindle cells arranged in interlacing fascicles immunohistoche...
Source: Journal of Toxicologic Pathology - February 15, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Histopathological evaluation of crypt fission during intestinal development in neonatal mice.
Authors: Yamazaki M, Fujii E, Watanabe T, Kato A, Suzuki M Abstract Pathological evaluation of juvenile toxicity studies requires the understanding of normal tissue development at different ages. Here, we report the morphological features of the neonatal mouse intestine, focusing on crypt fission. Postnatal day (PND) 7 and 14 mice showed fewer crypts and less mature epithelial morphology compared to PND 21 and 28. Crypt fission occurred in three stages: 1) flattening of the crypt base into a skirt shape, 2) penetration of myofibroblasts into the crypt base center, and 3) complete separation of a single crypt into t...
Source: Journal of Toxicologic Pathology - February 15, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

A histopathological analysis of spontaneous neoplastic and non-neoplastic lesions in aged male RccHan:WIST rats.
In this study, we describe spontaneous lesions found in 39 male RccHan:WIST rats used as a control in a carcinogenicity study. Neoplastic lesions were frequently seen in the endocrine system, such as pituitary adenomas in the pars distalis. This strain exhibited a high incidence of thymoma (10.3%), compared to other strains. We encountered an oligodendroglioma, a pituitary adenoma of the pars intermedia, and a prostate adenocarcinoma, which are comparatively rare in rats. While the variety and incidence of non-neoplastic lesions were similar to those in other strains, several interesting lesions occurred with relatively hi...
Source: Journal of Toxicologic Pathology - February 15, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Contemporary activities of Toxicologic Pathology Societies.
Authors: Maronpot RR, Dagli MLZ Abstract Educational activities and training opportunities in toxicologic pathology are major goals of 9 formally established Toxicologic Pathology Societies and the International Academy of Toxicologic Pathology. Some Toxicologic Pathology Societies have examination-based certification programs while others accept certification or registration by veterinary pathology organizations including the American College of Veterinary Pathologists, the European College of Veterinary Pathologists. We summarize here the membership numbers and current activities of formally established Toxicolog...
Source: Journal of Toxicologic Pathology - February 15, 2020 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

MicroRNAs: potential targets and agents of endocrine disruption in female reproduction.
Authors: Sabry R, Yamate J, Favetta L, LaMarre J Abstract MicroRNAs are short non-coding RNAs that have been widely recognized as key mediators in the epigenetic control of gene expression and which are present in virtually all cells and tissues studied. These regulatory molecules are generated in multiple steps in a process called microRNA biogenesis. Distinct microRNA expression patterns during the different stages of oocyte and embryo development suggest important regulatory roles for these small RNAs. Moreover, studies antagonizing specific microRNAs and enzymes in microRNA biogenesis pathways have demonstrated...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Proteomics approach to investigate dynamic protein profile involved in high fat diet-induced fatty liver disease in rats.
In this study, fluorescence difference gel electrophoresis (DIGE) combined with mass spectrometry was performed to profile the intracellular processes in the rat liver at the proteome level when rats were fed a high-fat diet for 8 weeks. Dynamic changes of 27 protein spots were observed. Among them, upregulation of 14 spots and downregulation of 13 spots were observed during the eight weeks of the high fat diet-induction period. These spots were analyzed by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF), and ultimately 24 proteins were identified with more than 95% confi...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Brain findings associated with risperidone in rhesus monkeys: magnetic resonance imaging and pathology perspectives.
This study characterized brain changes associated with risperidone in nonhuman primates. Rhesus monkeys were orally administered risperidone in a dose-escalation paradigm up to a maximum tolerated dose of 0.5 mg/kg/day for 3 weeks, or 3 months followed by a 3-month recovery period. Transient and fully reversible neurological signs consistent with risperidone pharmacology were observed. The results of a magnetic resonance imaging evaluation after 3 months of treatment and at the end of the 3-month recovery period showed no meaningful changes in the brain. There were no risperidone-related brain weight changes or gross findi...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Overexpression of interleukin-20 receptor subunit beta (IL20RB) correlates with cell proliferation, invasion and migration enhancement and poor prognosis in papillary renal cell carcinoma.
Authors: Cui XF, Cui XG, Leng N Abstract Papillary renal cell carcinoma (PRCC) accounts for about 10 percent of all renal cell carcinomas, and the prognosis is poor for people with advanced disease. Interleukin-20 receptor subunit beta (IL20RB) is a single-pass type I membrane protein of the type II cytokine receptor family and is related to the pathogenesis of chronic inflammation and autoimmune diseases, including psoriasis, glaucoma, vitiligo, rheumatoid arthritis, and inflammatory bowel disease. However, little has been reported on IL20RB with respect to cancer, especially in PRCC. Thus, we performed this study...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Location and dynamic changes of inflammation, fibrosis, and expression levels of related genes in SiO2-induced pulmonary fibrosis in rats in vivo.
In this study, silicosis models of rat were established by a one-time dusting method, and the rats were sacrificed after 30, 60, and 120 days (herein referred to as the 30, 60, and 120 days groups, respectively). The rats without dust exposure were used as the control. The lungs were removed to observe pathological changes using hematoxylin and eosin and Masson's trichrome staining and transmission electron microscopy, and the degree of collagen type I and III deposition in the lung was evaluated by enzyme-linked immunosorbent assay. The levels of malondialdehyde and superoxide dismutase were measured by spectrophotometry,...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Differential responses on energy metabolic pathway reprogramming between genotoxic and non-genotoxic hepatocarcinogens in rat liver cells.
Authors: Ito Y, Nakajima K, Masubuchi Y, Kikuchi S, Saito F, Akahori Y, Jin M, Yoshida T, Shibutani M Abstract To clarify difference in the responses on the reprogramming of metabolism toward carcinogenesis between genotoxic and non-genotoxic hepatocarcinogens in the liver, rats were repeatedly administered genotoxic hepatocarcinogens (N-nitrosodiethylamine, aflatoxin B1, N-nitrosopyrrolidine, or carbadox) or non-genotoxic hepatocarcinogens (carbon tetrachloride, thioacetamide, or methapyrilene hydrochloride) for 28, 84, or 90 days. Non-genotoxic hepatocarcinogens revealed transcript expression changes suggestive o...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

The effects of β-naphthoflavone on rat placental development.
The effects of β-naphthoflavone on rat placental development. J Toxicol Pathol. 2019 Oct;32(4):275-282 Authors: Furukawa S, Tsuji N, Hayashi S, Kuroda Y, Kimura M, Hayakawa C, Takeuchi K, Sugiyama A Abstract The morphological effects of β-naphthoflavone (β-NF) on placental development in pregnant rats were examined. β-NF, administered to pregnant rats intraperitoneally at 15 mg/kg bw from gestation day (GD) 9 to GD 14, had no effect on maternal body weight gain, mortality, or clinical sign. In the β-NF-exposed rats, intrauterine growth retardation (IUGR) rates increased on GDs ...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Spontaneous abdominal hemangiosarcoma in a ferret.
Authors: Nakamura SI, Tsukahara T Abstract Herein, we describe the case of a 6-year-old female ferret that died within a few days of the onset of anorexia and reduced spontaneous locomotor activity. Necropsy revealed a dark red abdominal mass of unknown origin between the right lobes of the pancreas and the proximal jejunum, with massive blood retention in the peritoneal cavity. Histopathologically, spindle-shaped or sometimes polygonal tumor cells were proliferating with irregularly shaped vascular spaces containing blood components and surrounding-tissue infiltration. In some areas, tumor cells formed distinctly ...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Spontaneous hemangioendothelial cell hyperplasia of the heart in a young ICR mouse.
Authors: Tomikawa E, Asaoka Y, Togashi Y, Mutsuga M, Imura N, Oshida K Abstract Spontaneous nonneoplastic proliferative lesions of the cardiac hemangioendothelium are extremely rare in humans and animals. Here, we describe a spontaneous hemangioendothelial cell hyperplasia in the heart of a 9-week-old male ICR mouse. The lesion was observed focally in the interventricular septum, with no compression of the surrounding tissues. In the lesion, a single layer of hemangioendothelial cells that had a polygonal shape with enlarged nuclei and plump cytoplasm closely lined surrounding widened capillary vascular spaces and ...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Segmental aplasia of a uterine horn in two RccHan:WIST rats.
Authors: Shimotsuma Y, Takeda S, Ogata K, Miyata K Abstract Aplasia of the uterine horn caused by developmental defects has been reported in several species but has not been reported in RccHan:WIST rats. We encountered spontaneous segmental aplasia of a right uterine horn in two RccHan:WIST rats and detailed its pathological characteristics. The right uterine horn of both rats had similar gross and histological appearances. At necropsy, there was segmental loss of the tissues corresponding to normal right uterine horn, which consisted of a fibrous band connected to the uterine cervix. A cystic structure with clear ...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Renal lesions in leptin receptor-deficient medaka (Oryzias latipes).
Authors: Chisada S, Sugiyama A Abstract The aim of this study was to elucidate the renal lesions of leptin receptor-deficient medaka showing hyperglycemia and hypoinsulinemia and to evaluate the usefulness of the medaka as a model of diabetic nephropathy. Leptin receptor-deficient medaka at 20 and 30 weeks of age showed hyperglycemia and hypoinsulinemia; they also showed a higher level of plasma creatinine than the control medaka. Histopathologically, dilation of glomerular capillary lumina and of afferent/efferent arterioles was observed in leptin receptor-deficient medaka at 20 weeks of age, and then glomerular e...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Increased circulating peroxiredoxin-4 in sepsis model rats involves secretion from hepatocytes and is mitigated by GYY4137.
Authors: Unuma K, Yoshikawa A, Aki T, Uemura K Abstract Circulating peroxiredoxin-4 (Prx4) is suggested as a prognosis marker as well as a regulator of many diseases. We aimed to examine 1) whether Prx4 is secreted from the liver in an animal model of sepsis and 2) effects of GYY4137, a hydrogen sulfide donor molecule, on septic liver injury as well as the hepatic secretion of Prx4. Rats (Wistar, male, 6 weeks old) were administered lipopolysaccharide (LPS, 15 mg/kg body weight, i.p.) with or without pre-administration of GYY4137 (50 mg/kg body weight, i.p.) and sacrificed 24 h after LPS administration. Hematoxylin...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Immunohistochemical characterization of oxidative stress in the lungs of rats exposed to the humidifier disinfectant polyhexamethylene guanidine hydrochloride.
Authors: Lee YH, Seo DS, Lee MJ, Cha HG Abstract Polyhexamethylene guanidine hydrochloride (PHMG-HCl), an antimicrobial additive in humidifier disinfectants, was associated with the pulmonary disease outbreak in South Korea. However, PHMG-mediated oxidative stress has only been studied in vitro. Here, we evaluated PHMG-induced oxidative stress in the lungs of rats exposed to PHMG-HCl. Male F344 rats were exposed to different concentrations of PHMG-HCl for 13-weeks via whole-body inhalation. Histopathological examination of the exposed rats showed the presence of lung lesions, including alveolar/interstitial fibrosi...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Quantification of histopathological findings using a novel image analysis platform.
In this study, we used HALO to quantify various histopathological changes and findings that were difficult to analyze using conventional image processing software. Using the tissue classifier module, the morphological features of degeneration/necrosis of the hepatocytes and muscle fibers, bile duct in the liver, basophilic tubules and hyaline casts in the kidney, cortex in the thymus, and red pulp, white pulp, and marginal zone in the spleen were learned and separated, and areas of interest were quantified. Furthermore, using the cytonuclear module and vacuole module in combination with the tissue classifier module, the nu...
Source: Journal of Toxicologic Pathology - November 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Effects of astragalus injection on different stages of early hepatocarcinogenesis in a two-stage hepatocarcinogenesis model using rats.
Authors: Tang Q, Zhang M, Hong Z, Chen Y, Wang P, Wang J, Wang Z, Fang R, Jin M Abstract To clarify the suppressive effects of astragalus injection (AI) on different stages of early hepatocarcinogenesis induced by weak promotion, SD rats initiated with a single intraperitoneal (i.p.) injection of N-diethylnitrosamine (DEN) at 200 mg/kg body weight and promoted with 0.5% piperonyl butoxide (PBO) in diet were repeatedly administered AI at 5 ml/kg body weight/day in the early postinitiation (EPI) or late postinitiation (LPI) period for 2 or 8 weeks, respectively. The number and area of glutathione S-transferase placen...
Source: Journal of Toxicologic Pathology - August 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

A 13-week subchronic toxicity study of hexyl acetate in SD rats.
Authors: Toyoda T, Cho YM, Matsushita K, Tachibana S, Senuma M, Akagi JI, Ogawa K Abstract Hexyl acetate (CAS No. 142-92-7) is a naturally occurring ester compound that has a fruity odor. Despite its frequent use as a nature-identical flavoring agent, there are limited repeated dose toxicity data for hexyl acetate. Here we performed a 13-week subchronic toxicity study of hexyl acetate in male and female Crl:CD(SD) rats under GLP regulations. Hexyl acetate was given orally by gavage at doses of 0, 100, 300, or 1,000 mg/kg/day using corn oil as the vehicle. No significant toxicological changes in general condition, b...
Source: Journal of Toxicologic Pathology - August 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Increased susceptibility to mammary carcinogenesis and an opposite trend in endometrium in Trp53 heterozygous knockout female mice by backcrossing the BALB/c strain onto the background C3H strain.
Authors: Machida Y, Sudo Y, Uchiya N, Imai T Abstract Patients with dominantly inherited Li-Fraumeni syndrome have a loss-of-function mutation in TP53 and develop diverse mesenchymal and epithelial neoplasms at multiple sites. Trp53 +/- female mice with the BALB/c background provide unique characteristics for the study of breast cancer in Li-Fraumeni syndrome; however, we previously found that female C3H-Trp53+/ - mice did not spontaneously develop mammary tumors. Therefore, we obtained F1 and N2-N4 female mice by backcrossing the BALB/c strain and examined the incidence of mammary and other tumors in lifetime stud...
Source: Journal of Toxicologic Pathology - August 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Spontaneous globule leukocyte tumor accompanied by inflammatory cells in a Wistar Hannover rat.
Authors: Sato J, Tomonari Y, Doi T, Tsuchitani M Abstract We encountered hematolymphoid neoplastic lesions in the form of many nodules in the spleen and liver in a 110-week-old male Wistar Hannover rat (Crl:WI (Han)). The lesions contained atypical proliferative cells, eosinophils, lymphocytes, and macrophages. The proliferative cells comprised various atypical cell types with or without cytoplasmic eosinophilic granules. The granules were positively stained using periodic acid-Schiff and elastase stains, were bluish purple using phosphotungstic acid and hematoxylin, and showed no metachromasia using toluidine blue...
Source: Journal of Toxicologic Pathology - August 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

An extraskeletal osteosarcoma in the auricle of a Wistar Hannover rat.
Authors: Shiga A, Katoh Y, Ito T, Ohnuma-Koyama A, Takahashi N, Okazaki Y, Harada T Abstract An extraskeletal osteosarcoma was detected in the auricle of a 110-week-old female Wistar Hannover rat. Grossly, the tumor, measuring 15 mm in size, was observed in the subcutis as a solid and hard mass. Histologically, the majority of the mass comprised mature, compact bone. It was surrounded by neoplastic cells showing a variety of histologies, such as sarcoma, not otherwise specified, and myxosarcoma away from the bone-forming region. However, these different histological regions were considered to be components of a sin...
Source: Journal of Toxicologic Pathology - August 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

A chronic toxicity study of diphenylarsinic acid in the drinking water of C57BL/6J mice for 52 weeks.
Authors: Yamaguchi T, Gi M, Fujioka M, Tago Y, Kakehashi A, Wanibuchi H Abstract Diphenylarsinic acid (DPAA), a neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping. The purpose of the present study was to evaluate the potential toxicity of DPAA when administered to mice in their drinking water for 52 weeks. DPAA was administered to mice at concentrations of 0, 6.25, 12.5, and 25 ppm in their drinking water for 52 weeks. There were no significant differences in final body weights between the control groups and the DPAA treatment groups in male or femal...
Source: Journal of Toxicologic Pathology - August 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Strain differences in histopathological features of lymphoid tissues of SD and F344 rats in a T cell-dependent antibody response assay of cyclophosphamide.
Authors: Ogawa B, Nakanishi Y, Koyama T, Arima K, Sasaki M Abstract When conducting histopathological evaluation of lymphoid tissues, it is necessary to know the variability and strain differences in histological features of different sites of lymphoid tissues. To investigate in detail the variability of lymphoid tissues and strain differences of control rats as well as those of immune reactivity and sensitivity to immunosuppression, we performed a histopathological analysis of various lymphoid tissues in conjunction with the evaluation of immune function in a T cell-dependent antibody response (TDAR) assay with cy...
Source: Journal of Toxicologic Pathology - August 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Evaluation of a biomarker for the diagnosis of pancreas cancer using an animal model.
In this study, we found that LRG-1 was overexpressed in rat PDC compared with normal pancreas tissue of the control rats. Serum levels of LRG-1 were also significantly higher in rats bearing PDC than in controls. Importantly, chronic pancreatitis in male Wistar Bonn/Kobori rats, which is a widely accepted as a model of chronic pancreatitis, did not cause serum levels of LRG-1 to become elevated. These results strongly support serum LRG-1 as a candidate biomarker for noninvasive diagnosis of PDC. Our models of pancreas cancer provide a useful strategy for evaluation of candidate markers applicable to human cancer. PMID:...
Source: Journal of Toxicologic Pathology - August 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Lack of preventive effect of maternal exposure to α-glycosyl isoquercitrin and α-lipoic acid on developmental hypothyroidism-induced aberrations of hippocampal neurogenesis in rat offspring.
Lack of preventive effect of maternal exposure to α-glycosyl isoquercitrin and α-lipoic acid on developmental hypothyroidism-induced aberrations of hippocampal neurogenesis in rat offspring. J Toxicol Pathol. 2019 Jul;32(3):165-180 Authors: Masubuchi Y, Tanaka T, Okada R, Ito Y, Nakahara J, Kikuchi S, Watanabe Y, Yoshida T, Maronpot RR, Koyanagi M, Hayashi SM, Shibutani M Abstract Hypothyroidism during the developmental stage induces disruption of hippocampal neurogenesis in later life, as well as inducing oxidative stress in the brain. The present study investigated the preventive effect o...
Source: Journal of Toxicologic Pathology - August 15, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Dimethylarsinic acid may promote prostate carcinogenesis in rats.
In this study, six-week-old male F344 rats were orally treated with a total of six chemicals (2-acetylaminofluorene (2-AAF), p-cresidine, dimethylarsinic acid (DMA), glycidol, N-nitrosodiethylamine and acrylamide) for four weeks. Animals were sacrificed at the end of the study, and HMGB2 and Ki-67 immunohistochemistry was performed. The numbers of HMGB2- and Ki-67- positive cells in all prostate lobes were significantly increased by DMA, one of the arsenicals, compared with the controls. Meanwhile, the number of Ki-67-positive cells in lateral and dorsal prostate lobes was significantly decreased by 2-AAF with the reductio...
Source: Journal of Toxicologic Pathology - May 17, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Dimethyl fumarate ameliorates cisplatin-induced renal tubulointerstitial lesions.
In this study, we investigated whether the DMF-mediated antioxidative mechanism activated by Nrf2 can ameliorate CIS-induced renal tubulointerstitial lesions in rats. In Experiments 1 and 2, 25 five-week-old male Wistar rats were divided into five groups: control, CIS, and 3 CIS+DMF groups (300, 1,500, and 7,500 ppm in Experiment 1; 2,000, 4,000, and 6,000 ppm in Experiment 2). Rats were fed their respective DMF-containing diet for 5 weeks. CIS was injected 1 week after starting DMF administration, and the same volume of saline was injected into the control group. CIS-induced severe tubular injury, such as necrosis and deg...
Source: Journal of Toxicologic Pathology - May 17, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Short-term detection of gastric genotoxicity using the DNA double-strand break marker γ-H2AX.
In conclusion, γ-H2AX in combination with other gene expression analyses could be a useful biomarker in a short-term experiment on gastric chemical genotoxicity. PMID: 31092975 [PubMed] (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - May 17, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research