著者

Hiromitsu WATANABE

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.26, no.2, pp.91-103, 2013 (Released:2013-07-18)

参考文献数

101

被引用文献数

6 24

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This review describes effects of miso with reference to prevention of radiation injury, cancer and hypertension with a twin focus on epidemiological and experimental evidence. Miso with a longer fermentation time increased crypt survival against radiation injury in mice. When evaluating different types of miso provided by different areas in Japan, miso fermented for a longer period increased the number of surviving crypts, and 180 days of fermentation was the most significant. Dietary administration of 180-day fermented miso inhibits the development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and rat colon cancers in F344 rats. Miso was also effective in suppression of lung tumors, breast tumors in rats and liver tumors in mice. The incidence of gastric tumors of groups of rats given NaCl was higher than those of the groups given miso fermented for longer periods. Moreover, the systolic blood pressure of the Dahl male rat on 2.3% NaCl was significantly increased but that of the SD rat was not. However, the blood pressures of the rats on a diet of miso or commercial control diet (MF) did not increase. Even though miso contains 2.3% NaCl, their blood pressures were as stable as those of rats fed commercial diet containing 0.3% salt. So we considered that sodium in miso might behave differently compared with NaCl alone. These biological effects might be caused by longer fermentation periods.

著者

Akane KASHIMURA Kouji TANAKA Hiroko SATO Hidefumi KAJI Masaharu TANAKA

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

pp.2018-0006, (Released:2018-05-03)

被引用文献数

8

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To evaluate the usefulness of imaging mass spectrometry (IMS) technology for assessing drug toxicity, we analyzed animal tissues in an amiodarone (AMD)-induced phospholipidosis model by IMS and confirmed the relationship between the distribution of AMD, its metabolites, and representative phospholipids (phosphatidylcholine, PC) and histological changes. AMD was administered to rats for 7 days at 150 mg/kg/day. The lung, spleen, and mesenteric lymph node were histologically examined and analyzed using IMS. The detection intensities of AMD, its metabolites, and typical PCs were higher in regions infiltrated by foamy macrophages compared with normal areas. This tendency was common in all three organs analyzed in this study. For the spleen, signals for AMD, its metabolites, and typical PCs were significantly more intense in the marginal zone, where foamy macrophages and vacuolated lymphocytes are abundant, than in the other areas. These results indicate that AMD, its metabolites, and PCs accumulate together in foamy or vacuolated cells, which is consistent with the mechanism of AMD-induced phospholipidosis. They also indicate that IMS is a useful technique for evaluating the distribution of drugs and biological components in the elucidation of toxicity mechanisms.

著者

今井 清 吉村 愼介

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.1, no.1, pp.7-12, 1988-05-31 (Released:2009-01-22)

参考文献数

7

被引用文献数

6 6

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The spontaneous tumors in Sprague-Dawley rats were studied in 510 females and 450 males which have been used as control groups of various chronic toxicity tests. The incidence of spontaneous tumor was 86.9% in males and 96.0% in females, respectively. In female rats, the most frequent tumor was pituitary adenoma, and followed by breast tumor, insuloma, and adreno-cortical adenoma. In contrast, pituitary adenoma, insuloma, adrenal pheochromocytoma, and hepatic tumor were common tumors in males. The incidence of pituitary adenoma, mammary tumor, thymoma, and adrenocortical adenoma was higher in females than males. On the other hand, the incidence of lung tumor, hepatocellular carcinoma, follicular cell adenoma of the thyroid, pheochromocytoma, and renal tumor was higher in males. Leukemia was also noted about 2.3% in males and 0.8% in females, and all of them were myelogenic leukemia. Moreover, various other tumors were found in other organs or tissues, but their incidences were low.

著者

Reem Sabry Jyoji Yamate Laura Favetta Jonathan LaMarre

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.32, no.4, pp.213-221, 2019 (Released:2019-10-22)

参考文献数

78

被引用文献数

9 21

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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 that interference with normal miRNA function leads to infertility and is associated with some reproductive abnormalities. Endocrine disrupting chemicals such as Bisphenol A (BPA) are synthetic hormone mimics that have been found to negatively impact reproductive health. In addition to their direct effects on gene expression, these chemicals are widely implicated in the disruption of epigenetic pathways, including the expression and activity of miRNAs, thereby altering gene expression. In this review, the roles of microRNAs during mammalian oocyte and embryo development are outlined and the different mechanisms by which endocrine disruptors such as BPA interfere with these epigenetic regulators to cause reproductive problems is explored.

著者

Takuma Iguchi Ken Sakurai Satoshi Tamai Kazuhiko Mori

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.31, no.1, pp.3-13, 2018 (Released:2018-01-24)

参考文献数

58

被引用文献数

6

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Circulating microRNAs (miRNAs) can potentially be used as sensitive and specific biomarkers for tissue injury. However, the usefulness of circulating miRNAs as safety biomarkers in nonclinical toxicological studies using nonhuman primates is debatable owing to the limited information on organ-specific miRNAs. Therefore, a systematic investigation was performed to address this point. We identified organ-specific miRNAs from cynomolgus monkeys by next-generation sequencing analysis, which revealed that miR-122 was only abundant in the liver, whereas miR-192 was abundant in the liver, stomach, intestines, and kidney. The sequences of these miRNAs were identical to their human counterparts. Next, the absolute miR-122 and miR-192 levels were qualified by quantitative reverse transcription polymerase chain reaction (RT-qPCR) to determine the circulating levels of the miRNAs. No significant differences in the levels of circulating miRNAs between sexes were noted, and there was greater interindividual variation in miR-122 (20-fold variation) than in miR-192 (8-fold variation), based on their dynamic ranges. Finally, we evaluated the fluctuation in circulating liver-specific miRNAs in a monkey model of acetaminophen-induced hepatotoxicity. Acetaminophen with L-buthionine-(S,R)-sulfoximine induced hepatotoxicity in all the animals, which was characterized histopathologically by centrilobular necrosis and vacuolation of hepatocytes. Circulating miR-122 and miR-192 levels increased more than ALT levels after 24 h, indicating that circulating miR-122 and miR-192 may serve as sensitive biomarkers for the detection of hepatotoxicity in cynomolgus monkeys. This review describes the fundamental profiles of circulating liver-specific miRNAs in cynomolgus monkeys and focusses on their organ specificity, circulating levels, and fluctuations in drug-induced hepatotoxicity.

著者

Yasushi Ohmachi Tomomi Imamura Mizuyo Ikeda Eriko Shishikura Eunjoo Kim Osamu Kurihara Kazuo Sakai

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.28, no.2, pp.65-71, 2015 (Released:2015-05-28)

参考文献数

15

被引用文献数

15 21

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To evaluate the effectiveness of sodium bicarbonate (SB) in removing uranium and protecting animals from uranium toxicity, we intramuscularly administered 1 mg/kg of uranyl nitrate to 8-wk-old male SD rats, and 20 min after administration of uranyl nitrate, the animals were given a single oral administration of SB at 0.1, 0.3 or 1 g/kg. The SB treatment at a dose of 0.3 g/kg or more raised the pH of the rats’ urine until 4 h after treatment, and it significantly reduced the uranium amounts in the kidneys at 1 day after treatment. In another experiment, rats were intramuscularly administered 1 mg/kg of uranyl nitrate, and 20 min later, the animals were treated with sodium bicarbonate (0.1 or 1 g/kg). The rats were autopsied at 1, 3 and 7 days after uranium treatment. High-dose SB resulted in a significant increase in urinary uranium excretion in the first 24 h and a reduction of uranium deposition in the kidneys and femurs, and it also significantly suppressed uranium-induced renal toxicity, as shown by both histopathology and clinical chemistry at 3 days after uranium treatment. Low-dose SB did not show such marked effects. Our findings demonstrated that the uranium decorporation effect of sodium bicarbonate was observed at the dosage showing urine alkalinization in rats and that decorporation effect of sodium bicarbonate might be beneficial if it is administered immediately after incorporation of soluble uranium.

著者

Osamu Katsuta Katsuhiko Shinomiya Takaharu Mochizuki Chinami Kikkawa Miwa Yoshimi Toshimi Ikuse

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.21, no.4, pp.239-241, 2008 (Released:2009-01-14)

参考文献数

9

被引用文献数

2 5

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A unique conjunctive stricture was observed in the eye of a male 17-week-old Japanese White rabbit (Kbl:JW). The conjunctival membrane had proliferated centripetally and covered a large portion of the cornea. However, the membrane did not adhere to the cornea. Histopathologically, the inner epithelium of the conjunctival membrane appeared flattened, while the outer epithelium had become stratified and squamous. Goblet cells were observed on both sides of the epithelium. The lamina propria consisted of well-developed, vascularized collagen fiber. Myxoid change was seen near the tip of the membrane. In animals, these conjunctival membranes have been reported in a few dwarf rabbits, dogs and horses and have had various different terms applied to them due to their unknown etiology. Based on the conventions of human ophthalmology, such lesions should be regarded as pseudopterygia. Therefore, the present case was diagnosed as involving a pseudopterygium. The centripetal proliferation of the conjunctival membrane may be a characteristic finding in animal cases. Our goal is to encourage accumulation of such cases by researchers and practitioners working in the field of toxicology.

著者

Jyoji Yamate Takeshi Izawa Mitsuru Kuwamura

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.36, no.2, pp.51-68, 2023 (Released:2023-04-10)

参考文献数

111

被引用文献数

1

---

The liver is the most important organ that metabolizes and detoxifies chemicals taken into the body. Therefore, there is always a risk of liver damage owing to the toxic effects of chemicals. The mechanisms of hepatotoxicity have been studied extensively and deeply based on toxic effects of chemicals themselves. However, it is important to note that liver damage is variously modified by the patho-biological reactions evoked mainly via macrophages. Macrophages appearing in hepatotoxicity are evaluated by the M1/M2 polarization; M1 macrophages promote tissue injury/inflammation, whereas M2 macrophages show anti-inflammatory action including reparative fibrosis. The “portal vein-liver barrier” regulated by Kupffer cells and dendritic cells in and around the Glisson’s sheath may be related to the initiation of hepatotoxicity. In addition, Kupffer cells exhibit the two-sides of functions (that is, M1 or M2 macrophage-like functions), depending on microenvironmental conditions which may be raised in part by gut microbiota-derived lipopolysaccharide. Furthermore, damage-associated molecular patterns (DAMPs) (in particular, HMGB1) and autophagy (which degrades DAMPs) also play roles in the polarity of M1/M2 macrophages. The mutual relation of “DAMPs (HMGB-1)–autophagy–M1/M2 macrophage polarization” as the patho-biological reaction should be taken into consideration in hepatotoxicity evaluation.

著者

衞藤 光明 加藤 博史 佐々木 次雄 佐々木 裕子 徳永 英博 岩崎 浩子 須田 郁夫

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.6, no.2, pp.233-240, 1993-09-30 (Released:2009-01-22)

参考文献数

38

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Thimerosal (ethylmercuric thiosalicylic acid, sodium salt) in an organic mercury compound which has been used as a preservative in some vaccines and human immunoglobulin products for intramuscular use. This study was designed to examine the safety of thimerosal for mice. Thimerosal solutions of 0.2 ml at 0.01% (the concentration used in vaccines) or at 0.1% were injected twice a week into the intraperitoneal (IP) cavity or subcutaneous (SC) tissue of BALB/c mice. Clinical signs and symptoms such as crossing hind legs were observed in animals injected more than 17 times with the 0.1% thimerosal solution (total thimerosal dose; 70μg Hg/g body weight) into the IP cavity. But the IP administrations of 0.01% thimerosal did not effect the animals even after 35 injections, nor the SC administrations at any dose. At autopsy, nervous system, kidney, liver, heart, lung, spleen, intestine, and skin were examined under light-microscopy with hematoxylin and eosin stain and mercury-histochemistry by photoemulsion method. Peritonitis was observed in all animals that received IP injections with 0.1% thimerosal. Mercury granules were present in the kidney and spleen of the animals receiving IP injections of 7μg Hg/g body weight. Histochemically, mildly positive reaction to mercury was detected in the brain and the liver in the same group of mice. No peritonitis was found in this group of mice. The positive results observed in this series of experiments were obtained only with multiple injections of the high dose thimerosal solution. No toxic effects were found with the 0.01% dosis, which is the same concentration used in commercial vaccines. Thimerosal administered in mice was biotransformed into inorganic mercury, and it was readily degradated into inorganic mercury by four well-known reactive oxygen-producing systems, and the amounts of inorganic mercury produced from thimerosal were the same as those from ethyl mercury and were higher than those from methyl mercury.

著者

Naofumi Takahashi Satoru Yamaguchi Ryouichi Ohtsuka Makio Takeda Toshinori Yoshida Tadashi Kosaka Takanori Harada

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.36, no.1, pp.31-43, 2023 (Released:2023-01-13)

参考文献数

51

被引用文献数

1

---

Our previous 4-week repeated dose toxicity study showed that wood preservative chromated copper arsenate (CCA) induced hepatocellular hypertrophy accompanied by biochemical hepatic dysfunction and an increase in oxidative stress marker, 8-hydroxydeoxyguanosine, in female rats. To further explore the molecular mechanisms of CCA hepatotoxicity, we analyzed 10%-buffered formalin-fixed liver samples from female rats for cell proliferation, apoptosis, and protein glutathionylation and conducted microarray analysis on frozen liver samples from female rats treated with 0 or 80 mg/kg/day of CCA. Chemical analysis revealed that dimethylated arsenical was the major metabolite in liver tissues of male and female rats. CCA increase labeling indices of proliferating cell nuclear antigen and decrease terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling accompanied with increased expression of protein glutathionylation, indicating a decrease in glutathione (GSH) in hepatocytes of female rats. Microarray analysis revealed that CCA altered gene expression of antioxidants, glutathione-S-transferase (GST), heat shock proteins and ubiquitin-proteasome pathway, cell proliferation, apoptosis, DNA methylation, cytochrome P450, and glucose and lipid metabolism in female rats. Increased expression of GSTs, including Gsta2, Gsta3, Mgst1, and Cdkn1b (p27), and decreased expression of the antioxidant Mt1, and DNA methylation Dnmt1, Dnmt3a, and Ctcf were confirmed in the liver of female rats in a dose-dependent manner. Methylation status of the promoter region of the Mt1 was not evidently changed between control and treatment groups. The results suggested that CCA decreased GSH and altered the expression of several genes, including antioxidants, GST, and DNA methylation, followed by impaired cell proliferation in the liver of female rats.

著者

Sabina Šturm Tanja Švara Ellinor Spörndly-Nees Vesna Cerkvenik-Flajs Mitja Gombač Anna-Luisa Weber Klaus Weber

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.34, no.4, pp.331-338, 2021 (Released:2021-10-01)

参考文献数

34

被引用文献数

2

---

Testicular histopathology is considered the most sensitive and reliable method to detect the effects of chemicals on sperm production. To carry out a sensitive examination of testicular histopathology and interpret the changes require knowledge of spermatogenic stages. Spermatogenic staging based on acrosome development during spermiogenesis is conventionally performed in animal species routinely used for research and toxicity testing. In contrast, small ruminants, such as sheep and goats, are rarely used as animal models to evaluate toxicity in male reproductive organs. To the best of our knowledge, a comparable spermatogenic staging system in rams has not yet been fully characterised. Hence, this study aimed to adapt the existing spermatogenic staging based on acrosome development in bull testes to fit the seminiferous epithelium cycle of ram testes. The results show that spermatogenic staging based on acrosome development in bull testes can, with slight modifications, be efficiently used for the staging of ram testes.

著者

Shojiro Ichimata Yukiko Hata Kojiro Hirota Naoki Nishida

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.35, no.3, pp.255-262, 2022 (Released:2022-07-02)

参考文献数

19

被引用文献数

1

---

A 32-year-old woman attempted suicide by ingesting Gloriosa bulbs and died approximately 2 days later. Toxicological examination revealed a potentially fatal blood concentration of colchicine (0.096 mg/L). In addition to the increased mitotic figures in the gastrointestinal mucosa, a unique finding for acute colchicine intoxication, pathological examination showed microvesicular lipid droplets in the liver, kidney, heart, and conduction system. Furthermore, central chromatolysis of neurons was observed in the pontine nucleus, medial accessory olivary nucleus, nucleus of the solitary tract, and nucleus ambiguus. Grumose degeneration of the cerebellar dentate nucleus was also evident. These pathological findings may help identify colchicine intoxication, even in the absence of evidence suggesting ingestion during autopsy. Moreover, pathological changes in the heart and central nervous system may be associated with the development of serious complications of acute colchicine intoxication.

著者

Sarawoot PALIPOCH Chuchard PUNSAWAD

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.26, no.3, pp.293-299, 2013 (Released:2013-10-15)

参考文献数

21

被引用文献数

56 76

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Cisplatin is a chemotherapeutic agent widely used in treatment of several cancers. It is documented as a major cause of clinical nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the involvement of oxidative stress in the pathogenesis of cisplatin-induced liver and kidney injury. Wistar rats were divided into four groups. Group 1 (control) was intraperitoneally (IP) injected with a single dose of 0.85% normal saline. Groups 2, 3 and 4 were IP injected with single doses of cisplatin at 10, 25 and 50 mg/kg body weight (BW), respectively. At 24, 48, 72, 96 and 120 h after injection, BW, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and activity of superoxide dismutase (SOD) and histology of the liver and kidney were evaluated. Cisplatin caused a reduction in BW of rats in groups 2, 3 and 4 at all post injection intervals. The levels of serum ALT, AST, BUN and creatinine and MDA of the kidney and liver were markedly increased especially at 48 and 72 h, whereas the activity of SOD was decreased after cisplatin injection. Liver sections revealed moderate to severe congestion with dilation of the hepatic artery, portal vein and bile duct and disorganization of hepatic cords at 50 mg/kg of cisplatin. Kidney sections illustrated mild to moderate tubular necrosis at 25 and 50 mg/kg of cisplatin. Therefore, oxidative stress was implicated in the pathogenesis of liver and kidney injury causing biochemical and histological alterations.

著者

Toshinori Yoshida Mio Kobayashi Suzuka Uomoto Kanami Ohshima Emika Hara Yoshitaka Katoh Naofumi Takahashi Takanori Harada Tatsuya Usui Mohamed Elbadawy Makoto Shibutani

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.35, no.3, pp.225-235, 2022 (Released:2022-07-02)

参考文献数

66

被引用文献数

4

---

The development of in vitro toxicity assessment methods using cultured cells has gained popularity for promoting animal welfare in animal experiments. Herein, we briefly discuss the current status of hepatoxicity assessment using human- and rat-derived hepatocytes; we focus on the liver organoid method, which has been extensively studied in recent years, and discuss how toxicologic pathologists can use their knowledge and experience to contribute to the development of in vitro chemical hepatotoxicity assessment methods for drugs, pesticides, and chemicals. We also propose how toxicological pathologists should assess toxicity regarding the putative distribution of undifferentiated and differentiated cells in the organoid when liver organoids are observed in hematoxylin and eosin–stained specimens. This was done while considering the usefulness and limitations of in vitro studies for toxicologic pathology assessment.

著者

Young-Man Cho Yasuko Mizuta Jun-ichi Akagi Takeshi Toyoda Mizuki Sone Kumiko Ogawa

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.31, no.1, pp.73-80, 2018 (Released:2018-01-24)

参考文献数

26

被引用文献数

68 112

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In this study, we aimed to evaluate changes in the acute toxicity of intraperitoneally administered silver nanoparticles (AgNPs) of varying sizes in BALB/c mice. Seven-week-old female BALB/c mice were intraperitoneally administered AgNPs measuring 10, 60, or 100 nm in diameter (0.2 mg/mouse) and then sacrificed 1, 3, or 6 h after treatment. In mice administered 10 nm AgNPs, reduced activity and piloerection were observed at 5 h post administration, and lowered body temperature was observed at 6 h post administration, with histopathological changes of congestion, vacuolation, single cell necrosis, and focal necrosis in the liver; congestion in the spleen; and apoptosis in the thymus cortex. These histopathological changes were not evident following administration of either 60 or 100 nm AgNPs. These results suggested that smaller AgNPs, e.g., those measuring 10 nm in diameter, had higher acute toxicity in mice.

著者

Taishi SHIMAZAKI Ameya DESHPANDE Anindya HAJRA Tijo THOMAS Kyotaka MUTA Naohito YAMADA Yuzo YASUI Toshiyuki SHODA

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

pp.2021-0053, (Released:2021-11-27)

被引用文献数

1

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Artificial intelligence (AI)-based image analysis is increasingly being used for preclinical safety-assessment studies in the pharmaceutical industry. In this paper, we present an AI-based solution for preclinical toxicology studies. We trained a set of algorithms to learn and quantify multiple typical histopathological findings in whole slide images (WSIs) of the livers of young Sprague Dawley rats by using a U-Net-based deep learning network. The trained algorithms were validated using 255 liver WSIs to detect, classify, and quantify seven types of histopathological findings (including vacuolation, bile duct hyperplasia, and single-cell necrosis) in the liver. The algorithms showed consistently good performance in detecting abnormal areas. Approximately 75% of all specimens could be classified as true positive or true negative. In general, findings with clear boundaries with the surrounding normal structures, such as vacuolation and single-cell necrosis, were accurately detected with high statistical scores. The results of quantitative analyses and classification of the diagnosis based on the threshold values between “no findings” and “abnormal findings” correlated well with diagnoses made by professional pathologists. However, the scores for findings ambiguous boundaries, such as hepatocellular hypertrophy, were poor. These results suggest that deep learning-based algorithms can detect, classify, and quantify multiple findings simultaneously on rat liver WSIs. Thus, it can be a useful supportive tool for a histopathological evaluation, especially for primary screening in rat toxicity studies.

著者

福島 昭治 今井田 克己 萩原 昭裕 香川 雅孝 荒井 昌之

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.1, no.1, pp.25-32, 1988-05-31 (Released:2009-01-22)

参考文献数

23

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Dose-response studies on early lesions and carcinogenesis of urinary bladder were carried out in male rats treated with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). In experiment 1, BBN was given in 6 different concentrations as solutions in drinking water to examine early lesions of the urinary bladder to F344, 6-week-old rats for up to 12 weeks. Doses of more than 0.01% BBN induced histologically simple hyperplasia and papillary or nodular hyperplasia, and scanning electron microscopically pleomorphic microvilli, short, uniform microvilli, and ropy or leafy microridges. 0.005% BBN treatment also induced ropy or leafy microridges. In experiment 2, BBN was given in 3 different doses to Wistar, 8-week-old rats for up to 82 weeks. The highest dose, 0.005% induced urinary bladder carcinoma and the lowest dose, 0.0005% did not develop any changes of the urinary bladder.

著者

阿部 敏男 宮嶌 宏彰

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.3, no.2, pp.245-256, 1990-11-30 (Released:2009-02-12)

参考文献数

34

被引用文献数

3 3

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The basic structure of rat incisors and the process of enamel formation are reviewed, and the drug-induced lesions of rat incisors are discribed. The rodent incisors grow, calcify and erupt continuously throughout the life of the animal, and show in one longitudinal section the complete life cycle of tooth development from inception to maturity. Therefore it is a valuable biologic indicator which reflects and records, during its development, the metabolic status of the animal. Drug-induced lesions in developing enamel of incisors are white discoloration of enamel surface, degeneration, necrosis, and atrophy of ameloblasts and/or papillary cells, disturbance of pigmentation, and hypocalcification of enamel. These changes correlate with the stage of enamel formation. The advantage of using rat incisors for toxicity studies is stressed.

著者

Yuval RAMOT Michal STEINER Netanel AMOUYAL Yossi LAVIE Guy KLAIMAN Abraham J. DOMB Abraham NYSKA Tal HAGIGIT

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

pp.2020-0041, (Released:2020-08-31)

被引用文献数

3

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Fracture-related infections remain a leading cause of morbidity and mortality. We aimed to establish a simple contaminated radial osteotomy model to assess the efficacy of a biodegradable polymer poly(sebacic-co-ricinoleic acid) [p(SA-RA)] containing 20% w/w gentamicin. A unilateral transverse osteotomy was induced in Sprague-Dawley (SD) rats, followed by application of Staphylococcus aureus suspension over the fracture. After successfully establishing the contaminated open fracture model, we treated the rats either systemically (intraperitoneal cefuroxime), locally with p(SA-RA) containing gentamicin, or both. Control groups included non-contaminated group and contaminated groups that were either untreated or treated with the polymer alone. After 4 weeks, the bones were subjected to micro-CT scanning and microbiological and histopathology evaluations. Micro-CT analysis revealed similar changes in the group subjected to both local and systemic treatment as in the non-contaminated control group. Lack of detectable bacterial growth was noted in most animals of the group subjected to both local and systemic treatment, and all samples were negative for S. aureus. Histopathological evaluation revealed that all treatment modalities containing antibiotics were highly effective in reducing infection and promoting callus repair, resulting in early bone healing. While p(SA-RA) containing gentamicin treatment showed better results than cefuroxime, the combination of local and systemic treatment displayed the highest therapeutic potential in this model.

著者

Keiko Makita-Suzuki Chihaya Kakinuma Akira Inomata Yasuhiro Shimada Takefumi Hara Takashi Yao

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.33, no.1, pp.1-9, 2020 (Released:2020-01-24)

参考文献数

40

被引用文献数

2

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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 induced hemorrhagic changes in the liver and the gallbladder. These changes were accompanied by minimal cellular infiltration with no obvious changes in the blood vessels. As there were no differences in the incidence and severity of hemorrhage between the groups administered comparable amounts of total lipid, the physicochemical properties of the liposomal formulation rather than an active pharmacological ingredient, doxorubicin, were associated with the hemorrhagic changes. Furthermore, decreased cytoplasmic granules with low electron density in mast cells beneath the endothelium of the hepatic vein were observed in the liver of dogs treated with liposomal doxorubicin or empty liposomal formulation. Injection of compound 48/80, a histamine releaser induced comparable hemorrhage in dogs, implying that hemorrhage caused by injection of liposomal doxorubicin or the empty liposomal formulation could be attributed to the histamine released from mast cells. The absence of similar hemorrhagic lesions in other species commonly used in toxicology studies (i.e., rats and monkeys), as well as humans, is due to the lack of mast cells beneath the endothelium of the hepatic vein in these species.