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

Adrenal dysplasia in a young SD rat.
Authors: Kato Y, Kashiwagi E, Asaoka Y, Fujisawa K, Tsuchiya N, Torii M Abstract The present report describes an adrenal dysplasia in which developmental abnormality was observed in the adrenal gland of a six-week-old male Crl:CD(SD) rat. Microscopically, a localized lesion composed of mildly vacuolated adrenal fasciculata cells with a slightly disturbed cord structure and containing areas with high cell density was observed in a unilateral adrenal gland; no macroscopical changes were detected in the organ. The areas with high cell density consisted of two cell types. One type included small cells with a round nucl...
Source: Journal of Toxicologic Pathology - May 17, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Pathological examination of spontaneous vacuolation of pancreatic acinar cells in mice.
Authors: Yasuno K, Igura S, Yamaguchi Y, Imaoka M, Kai K, Mori K Abstract Pancreatic acinar cell vacuolation is spontaneously observed in mice; however, the lesion is rare and has not been well documented. Herein, we present a detailed pathological examination of this lesion. Vacuoles in pancreatic acinar cells were present in 2/15 X gene knockout mice with a C57BL/6J mouse background, 4/298 ICR(CD-1) mice, 1/110 B6C3F1 mice, and 3/399 CByB6F1-Tg(HRAS)2Jic mice. The vacuoles were usually observed in a unit of the acinus, and the lesions were spread throughout the pancreas. These vacuoles contained weakly basophilic...
Source: Journal of Toxicologic Pathology - May 17, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Histopathologic features of melanocytic tumors in Xiphophorus melanoma receptor kinase (xmrk)-transgenic medaka (Oryzias latipes).
Authors: Sugiyama A, Schartl M, Naruse K Abstract Melanocytic tumors in Xiphophorus melanoma receptor kinase (xmrk)-transgenic Carbio and HB11A strains of medaka were examined histopathologically at 7 months post-hatching. Medaka of both strains developed melanocytic tumors with a penetrance of 100%. In both strains, neoplastic cells containing intracytoplasmic melanin pigment granules showed significant invasive growth patterns. In addition, epithelioid neoplastic cells were arranged in solid nests, and spindle neoplastic cells were arranged in interlacing streams and bundles. Nuclear atypia, anisokaryosis, cellul...
Source: Journal of Toxicologic Pathology - May 17, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Establishment of the Global SEND Alliance (G-SEND) in Japan and efficient creation of electronic SEND datasets between CROs.
Authors: Anzai T, Matsuyama T, Wasko M, Hatakeyama H, Horikawa SI, Anzai R, Iwata H, Imai N, Mizuhashi F, Tsuboi M, Okuzono T, Takagi H, Cho H, Rong BTS, Masaki F, Nakae D Abstract The Standard for Exchange of Nonclinical Data (SEND), adopted by the US Food and Drug Administration (FDA), is a set of regulations for digitalization and standardization of nonclinical study data; thus, related organizations have begun implementing processes in support of SEND. The Global Editorial and Steering Committee (GESC), which provides oversight of the International Harmonization of Nomenclature and Diagnostic Criteria (INHAND),...
Source: Journal of Toxicologic Pathology - May 17, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Morphology and physiology of rat placenta for toxicological evaluation.
Authors: Furukawa S, Tsuji N, Sugiyama A Abstract The placenta plays a pivotal role in fetal growth, and placental dysfunction and injury are associated with embryo/fetal toxicity. Histological examination of the rat placenta for safety evaluation provides valuable clues to the mechanisms of this toxicity. However, the placenta has specific and complex biological features unlike those of other organs, and placental structure dramatically changes depending on the time during the gestation period. Thus, time-dependent histopathological examination of the rat placenta should be performed based on the understanding of ...
Source: Journal of Toxicologic Pathology - February 13, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Twist1 was detected in mesenchymal cells of mammary fibroadenoma and invasive components of breast carcinoma in rats.
Authors: Funahashi S, Okazaki Y, Nagai H, Chew SH, Ogawa K, Toyoda T, Cho YM, Toyokuni S Abstract Fibroadenoma (FA) is a common mammary fibroepithelial tumor. The tumor size of the FA is increased by estrogen, progesterone, prolactin, and pregnancy, whereas it decreases after menopause. These observations in humans indicate that FA is hormone dependent. In rats, the most common mammary neoplasm is also FA. Expression levels of Twist1, a transcriptional regulator of epithelial-mesenchymal transition, were examined in paraffin-embedded tissue sections of an experimental rat breast model to find physiological alternat...
Source: Journal of Toxicologic Pathology - February 13, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Effects of aflatoxin B1 on the cell cycle distribution of splenocytes in chickens.
In conclusion, dietary AFB1 could induce cell cycle blockage at G0G1 phase and impair the immune function of the spleen. Cyclin D1/CDK6 complex, which inhibits the activin/nodal signaling pathway, might play a significant role in the cell cycle arrest induced by AFB1. PMID: 30739993 [PubMed] (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - February 13, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

The localization and distribution of cells labeled by a somatic stem cell-recognizing antibody (A3) in rat colon development; possible presence of a new cell type forming the intestinal stem cell niche.
Authors: Nishina H, Katou-Ichikawa C, Kuramochi M, Izawa T, Kuwamura M, Yamate J Abstract A3, generated as a monoclonal antibody against rat malignant fibrous histiocytoma (MFH)-derived cloned cells, recognizes somatic stem cells (bone-marrow/hair follicle stem cells). We investigated the distribution of cells immunoreactive to A3 in the developing rat intestine (particularly, the colon), focusing on the ontogenic kinetics of A3-positive cells. In the rat intestine, A3 labeled spindle-shaped stromal cells localized in the submucosa and labeled endothelial cells of capillaries in the lamina propria forming villi in ...
Source: Journal of Toxicologic Pathology - February 13, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

A histopathological study on adrenal cysts in ferrets.
Authors: Uneyama M, Chambers JK, Miyama K, Miwa Y, Uchida K, Nakayama H Abstract Adrenal disorders are common in ferrets, but there are few studies on cystic lesions of the adrenal gland. The present study describes pathological and immunohistochemical features of adrenal cysts in eleven ferrets and discusses their histogenesis. In nine of eleven cases examined, which included seven, one, and one right, left, and bilateral cases, respectively, cysts were in the adrenal cortex and lined with epithelial cells. These epithelial cells contained an Alcian blue-negative/PAS-positive material and were positive for cytoker...
Source: Journal of Toxicologic Pathology - February 13, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Age-dependent changes in vancomycin-induced nephrotoxicity in mice.
This report is the first to document VCM-induced nephrotoxicity in mice of different ages. Thus, this mouse model could be useful for understanding the mechanisms of VCM-induced nephrotoxicity in the elderly. PMID: 30739996 [PubMed] (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - February 13, 2019 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Characteristics of surfactant proteins in tumorigenic and inflammatory lung lesions in rodents.
In this study, we investigated the expression of SP-A, SP-B, SP-C, and SP-D in neoplastic and inflammatory lung lesions in rodents, as well as their possible application as potential markers for diagnostic purposes. SP-B and SP-C showed strong expression in lung hyperplasia and adenoma, whereas SP-A and SP-D were expressed in the mucus or exudates of inflammatory alveoli. Rodent tumorigenic hyperplasic tissues induced by various carcinogens were positive for napsin A, an aspartic proteinase involved in the maturation of SP-B; this indicated a focal increase in type II pneumocytes in the lungs. Therefore, high expression of...
Source: Journal of Toxicologic Pathology - November 6, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Development of bioresources in Okinawa: understanding the multiple targeted actions of antioxidant phytochemicals.
Authors: Aniya Y Abstract In research to develop healthy foods or preventive medicines from edible and medicinal herbs in Okinawa, we focused on the antioxidant activities of those bioresources. We first confirmed that the herbal antioxidant activities of such herbs increased upon ultraviolet irradiation treatment. This observation explains the high antioxidant activity of Okinawan vegetables, which grow under exposure to stronger ultraviolet light compared with those in other prefectures in Japan. Antidiabetic, hepatoprotective, cancer preventive, and cardioprotective actions were clarified using herbal extracts, ...
Source: Journal of Toxicologic Pathology - November 6, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Effects of the expectorant drug ambroxol hydrochloride on chemically induced lung inflammatory and neoplastic lesions in rodents.
Authors: Yoshida S, Yokohira M, Yamakawa K, Nakano-Narusawa Y, Kanie S, Hashimoto N, Imaida K Abstract Ambroxol hydrochloride (AH) is an expectorant drug used to stimulate pulmonary surfactant and serous airway secretion. Surfactant proteins (SPs) are essential for maintaining respiratory structure and function, although SP expression has also been reported in lung inflammatory and proliferative lesions. To determine whether AH exerts modulatory effects on these lung lesions, we examined its effects on pleural thickening induced by intrathoracic administration of dipotassium titanate (TISMO) in A/JJmsSlc (A/J) mice...
Source: Journal of Toxicologic Pathology - November 6, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Effects of food restriction on the expression of genes related to acetaminophen-induced liver toxicity in rats.
Authors: Tsuchiya Y, Sakai H, Hirata A, Yanai T Abstract It is well known that fasting substantially affects the metabolism of drugs and chemicals. Food restriction also affects drug kinetics, such as absorption, metabolism, and excretion, and therefore, it can potentially modulate the onset of chemical toxicity or drug-induced adverse reactions. In the present study, the expression of drug-metabolizing enzyme genes and total glutathione content in the liver, which are related to toxicity induced by overdose of the hepatotoxic drug acetaminophen (N-acetyl-p-aminophenol; APAP), were examined in rats reared under dif...
Source: Journal of Toxicologic Pathology - November 6, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Brazilian green propolis suppresses acetaminophen-induced hepatocellular necrosis by modulating inflammation-related factors in rats.
Authors: Tsuchiya Y, Sakai H, Hirata A, Yanai T Abstract Propolis is a resin-like material produced by honey bees from bud exudates and sap of plants and their own secretions. An ethanol extract of Brazilian green propolis (EEBGP) contains prenylated phenylpropanoids and flavonoids and has antioxidative and anti-inflammatory effects. Acetaminophen (N-acetyl-p-aminophenol; APAP) is a typical hepatotoxic drug, and APAP-treated rats are widely used as a model of drug-induced liver injury. Oxidative stress and inflammatory reactions cause APAP-induced hepatocellular necrosis and are also related to expansion of the les...
Source: Journal of Toxicologic Pathology - November 6, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Hepatic lesions induced by feeding Western diets to Zucker fatty rats, an insulin-resistant model.
In conclusion, hepatic lesions, such as inflammation, fibrosis, and necrosis, were observed in the ZF-WD rats. The sucrose/fat/cholesterol-enriched diet induced significant lipotoxicity in the livers of animals in this insulin-resistant model. PMID: 30393432 [PubMed] (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - November 6, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Difference in morphology and interactome profiles between orthotopic and subcutaneous gastric cancer xenograft models.
In conclusion, pathological analysis and CASTIN analysis revealed that ORT models of OE19 cells have a more invasive character and enhanced interaction with stromal cells compared with SC models. PMID: 30393433 [PubMed] (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - November 6, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Gene expression profile in retinal excitotoxicity induced by L-glutamate in neonatal rats.
Authors: Mitori H, Izawa T, Kuwamura M, Matsumoto M, Yamate J Abstract In neonatal rats, glutamate could induce retinal thinning depending on the development stage, and the severity peaked at treatment on postnatal day (PND) 8. To elucidate the molecular mechanism of retinal thinning induced by L-glutamate in neonatal rats, we investigated the time-course gene expression profile in the developing retina in addition to initial histopathological changes. Histopathologically, apoptotic cells in the inner retina were observed at 6 hours after treatment on PNDs 4, 6 and 8, and inflammatory cell infiltration was noted at...
Source: Journal of Toxicologic Pathology - November 6, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Histopathological and functional changes in a single-dose model of combretastatin A4 disodium phosphate-induced myocardial damage in rats.
In conclusion, myocardial injury, bradycardia, and depressed cardiac function were induced in rats by a single-dose of CA4DP. The lesion distribution and electrocardiographic features suggested that myocardial injury was induced by ischemia. These findings are similar to MDA-induced cardiotoxicity in humans, and this rat model will prove useful in studies of the cardiotoxicity in humans. PMID: 30393435 [PubMed] (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - November 6, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Utilizing novel telepathology system in preclinical studies and peer review.
Authors: Siegel G, Regelman D, Maronpot R, Rosenstock M, Hayashi SM, Nyska A Abstract The demand for board certified toxicologic pathologists and expansion of IT capabilities has resulted in an increase of "virtual" and "distance" pathology (telepathology), and a need for greater flexibility in real time consultations. Newly developed microscope-integrated telepathology systems enable geographically remote stakeholders to view the live histopathology slide as seen by the microscope user. Simultaneous online viewing, annotation, and dialog between pathologists and study experts facilitates good s...
Source: Journal of Toxicologic Pathology - November 6, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Nonproliferative and Proliferative Lesions of the Rat and Mouse Endocrine System.
Authors: Brändli-Baiocco A, Balme E, Bruder M, Chandra S, Hellmann J, Hoenerhoff MJ, Kambara T, Landes C, Lenz B, Mense M, Rittinghausen S, Satoh H, Schorsch F, Seeliger F, Tanaka T, Tsuchitani M, Wojcinski Z, Rosol TJ Abstract The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative among the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative les...
Source: Journal of Toxicologic Pathology - August 31, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Nonproliferative and Proliferative Lesions of the Ratand Mouse Special Sense Organs(Ocular [eye and glands], Olfactory and Otic).
Authors: Ramos MF, Baker J, Atzpodien EA, Bach U, Brassard J, Cartwright J, Farman C, Fishman C, Jacobsen M, Junker-Walker U, Kuper F, Moreno MCR, Rittinghausen S, Schafer K, Tanaka K, Teixeira L, Yoshizawa K, Zhang H PMID: 30158741 [PubMed] (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - August 31, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

Role of pathology peer review in interpretation of the comet assay.
Authors: Maronpot RR, Hobbs CA, Hayashi SM Abstract 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 i...
Source: Journal of Toxicologic Pathology - August 11, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research

γH2AX is immunohistochemically detectable until 7 days after exposure of N-bis (2-hydroxypropyl) nitrosamine (DHPN) in rat lung carcinogenesis.
γH2AX is immunohistochemically detectable until 7 days after exposure of N-bis (2-hydroxypropyl) nitrosamine (DHPN) in rat lung carcinogenesis. J Toxicol Pathol. 2018 Jul;31(3):163-168 Authors: Ying JTX, Yokohira M, Nakano-Narusawa Y, Yamakawa K, Hashimoto N, Imaida K Abstract 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-hydroxypropy...
Source: Journal of Toxicologic Pathology - August 11, 2018 Category: Toxicology Tags: J Toxicol Pathol Source Type: research