Neural tissue tolerance to synthetic dural mater graft implantation in a rabbit durotomy model
This study evaluated the safety of ArtiFascia, a synthetic dura mater graft composed of poly(l-lactic-co-caprolactone acid) and poly(d-lactic-co-caprolactone acid), in a rabbit durotomy model. Previously, ArtiFascia demonstrated positive local tolerance and biodegradability in a 12-month preclinical trial. Here, specialized stains were used to evaluate potential brain damage associated with ArtiFascia use. Histochemical and immunohistochemical assessments included Luxol Fast Blue, cresyl Violet, Masson's Trichrome, neuronal nuclei,, Glial Fibrillary Acidic Protein, and ionized calcium-binding adaptor molecule 1 stains. The...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Yuval Ramot Noam Kronfeld Michal Steiner Nora Nseir Manassa Amir Bahar Abraham Nyska Source Type: research

CD44 expression in renal tubular epithelial cells in the kidneys of rats with cyclosporine-induced chronic kidney disease
In this study, we investigated CD44 expression and its role in renal fibrogenesis in a cyclosporine (CyA) rat model of CKD. Seven-week-old male Sprague-Dawley rats fed a low-salt diet were subcutaneously administered CyA (0, 15, or 30 mg/kg) for 28 days. CD44 was expressed in atrophic, dilated, and hypertrophic TECs in the fibrotic lesions of the CyA groups. These TECs were collected by laser microdissection and evaluated by microarray analysis. Gene ontology analysis suggested that these TECs have a mesenchymal phenotype, and pathway analysis identified CD44 as an upstream regulator of fibrosis-related genes, including fi...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Kohei Matsushita Takeshi Toyoda Hirotoshi Akane Tomomi Morikawa Kumiko Ogawa Source Type: research

Induction of lung lesions by bronchial administration using bronchoscope technique in mice
This study aimed to establish an exposure method that can induce homogeneous lesions with minimal inter-individual variability. The distribution of lesions induced by bleomycin (BLM) administration was also analyzed. C57BL mice were intrabronchially administered 20 µL of BLM (3 mg/mL) using a bronchoscope in the left or right bronchus. The mice were sacrificed 14 days after administration, and their lungs were evaluated histopathologically. BLM-induced inflammatory lesions were widely observed in the lungs. In the left bronchus-treated group, lesions were uniformly observed throughout the lobe, and no individual differenc...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Takako Hiyoshi Chiyoko Nishime Eiko Nishinaka Fumiko Seki Kenji Kawai Misa Mochizuki Koji Urano Toshio Imai Taichi Yamamoto Masami Suzuki Source Type: research

Drug review process advancement and required manufacturer and contract research oraganization responses
J Toxicol Pathol. 2024 Apr;37(2):45-53. doi: 10.1293/tox.2023-0106. Epub 2023 Nov 22.ABSTRACTThe United States Senate passed the "FDA Modernization Act 2.0." on September 29, 2022. Although the effectiveness of this Bill, which aims to eliminate the mandatory use of laboratory animals in new drug development, is limited, it represents a significant trend that will change the shape of drug applications in the United States and other countries. However, pharmaceutical companies have not taken major steps towards the complete elimination of animal testing from the standpoint of product safety, where they prioritize patient sa...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Takayuki Anzai Glenn J Myatt Frances Hall Brenda Finney Kenshi Nakagawa Hijiri Iwata Reo Anzai Anne Dickinson Matthew Freer Dai Nakae Hiroshi Onodera Takaaki Matsuyama Source Type: research

Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats
In this study, since the measurement of serum neurofilament light chain could detect changes earlier than pathological examination, it could be useful as a biomarker for peripheral neurotoxicity. Moreover, examination of semi-thin specimens and choline acetyltransferase immunostaining were useful for characterizing morphological neurotoxicity, and image analysis of semi-thin specimens enabled us to objectively show the pathological features.PMID:38584972 | PMC:PMC10995436 | DOI:10.1293/tox.2023-0094 (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Akane Kashimura Satomi Nishikawa Yuhei Ozawa Yui Hibino Takashi Tateoka Mao Mizukawa Hironobu Nishina Tetsuya Sakairi Takanori Shiga Naoyuki Aihara Junichi Kamiie Source Type: research

Pathogenesis of chemically induced nasal cavity tumors in rodents: contribution to adverse outcome pathway
J Toxicol Pathol. 2024 Jan;37(1):11-27. doi: 10.1293/tox.2023-0098. Epub 2023 Nov 1.ABSTRACTThe pathogenesis of nasal cavity tumors induced in rodents has been critically reviewed. Chemical substances that induce nasal cavity tumors in rats, mice, and hamsters were searched in the National Toxicology Program (NTP), International Agency for Research on Cancer (IARC), and Japan Bioassay Research Center (JBRC) databases, in addition to PubMed. Detailed data such as animal species, administration routes, and histopathological types were extracted for induced nasal cavity tumors. Data on non-neoplastic lesions were also extract...
Source: Journal of Toxicologic Pathology - January 29, 2024 Category: Toxicology Authors: Akiyoshi Nishikawa Kasuke Nagano Hajime Kojima Shoji Fukushima Kumiko Ogawa Source Type: research

Spontaneous mandibular follicular ameloblastoma in a female Sprague-Dawley rat
J Toxicol Pathol. 2024 Jan;37(1):39-43. doi: 10.1293/tox.2023-0072. Epub 2023 Nov 13.ABSTRACTAmeloblastoma is a locally aggressive tumor derived from the odontogenic epithelium of the developing tooth germ. It is rarely reported in experimental Sprague-Dawley (SD) rats. In this 90-day percutaneous repeated-dose toxicity study, mandibular nodules were observed from day 56 to 90. Upon necropsy, a well-demarcated nodule, approximately 1.2×1.0×1.0 cm, was found attached to the mandibular bone, alongside the unerupted left incisor. Histopathologically, the epithelial cells formed islands, nests, or anastomosing strands. The e...
Source: Journal of Toxicologic Pathology - January 29, 2024 Category: Toxicology Authors: Juan Li Guojian Jiang Jie Zhang Zhuolin Ou Xin Wu Yueshu Liu Source Type: research

Molecular autopsy for sudden death in Japan
J Toxicol Pathol. 2024 Jan;37(1):1-10. doi: 10.1293/tox.2023-0080. Epub 2023 Aug 30.ABSTRACTJapan has various death investigation systems; however, external examinations, postmortem computed tomography, macroscopic examinations, and microscopic examinations are performed regardless of the system used. These examinations can reveal morphological abnormalities, whereas the cause of death in cases with non-morphological abnormalities can be detected through additional examinations. Molecular autopsy and postmortem genetic analyses are important additional examinations. They are capable of detecting inherited arrhythmias or in...
Source: Journal of Toxicologic Pathology - January 29, 2024 Category: Toxicology Authors: Takuma Yamamoto Yuko Emoto Takehiko Murase Takahiro Umehara Aya Miura Minori Nishiguchi Kazuya Ikematsu Hajime Nishio Source Type: research

Lobular distribution of enhanced expression levels of heat shock proteins using < em > in-situ < /em > hybridization in the mouse liver treated with a single administration of CCl4
This study was conducted to visualize the lobular distribution of enhanced mRNA expression levels of heat shock proteins (HSPs) in liver samples from carbon tetra chloride (CCl4)-treated mice using in-situ hybridization (ISH). Male BALB/c mice given a single oral administration of CCl4 were euthanized 6 hours or 1 day after the administration (6 h or 1 day). Paraffin-embedded liver samples were obtained, ISH for HSPs was conducted, as well as hematoxylin-eosin staining and immunohistochemistry (IHC). At 6 h, centrilobular hepatocellular vacuolization was observed, and increased signals for Hspa1a, Hspa1b, and Grp78, which ...
Source: Journal of Toxicologic Pathology - January 29, 2024 Category: Toxicology Authors: Hitoshi Kandori Masami Aoki Yumiko Miyamoto Sayuri Nakamura Ryosuke Kobayashi Mitsuharu Matsumoto Kotaro Yokoyama Source Type: research

Pathogenesis of chemically induced nasal cavity tumors in rodents: contribution to adverse outcome pathway
J Toxicol Pathol. 2024 Jan;37(1):11-27. doi: 10.1293/tox.2023-0098. Epub 2023 Nov 1.ABSTRACTThe pathogenesis of nasal cavity tumors induced in rodents has been critically reviewed. Chemical substances that induce nasal cavity tumors in rats, mice, and hamsters were searched in the National Toxicology Program (NTP), International Agency for Research on Cancer (IARC), and Japan Bioassay Research Center (JBRC) databases, in addition to PubMed. Detailed data such as animal species, administration routes, and histopathological types were extracted for induced nasal cavity tumors. Data on non-neoplastic lesions were also extract...
Source: Journal of Toxicologic Pathology - January 29, 2024 Category: Toxicology Authors: Akiyoshi Nishikawa Kasuke Nagano Hajime Kojima Shoji Fukushima Kumiko Ogawa Source Type: research

Spontaneous mandibular follicular ameloblastoma in a female Sprague-Dawley rat
J Toxicol Pathol. 2024 Jan;37(1):39-43. doi: 10.1293/tox.2023-0072. Epub 2023 Nov 13.ABSTRACTAmeloblastoma is a locally aggressive tumor derived from the odontogenic epithelium of the developing tooth germ. It is rarely reported in experimental Sprague-Dawley (SD) rats. In this 90-day percutaneous repeated-dose toxicity study, mandibular nodules were observed from day 56 to 90. Upon necropsy, a well-demarcated nodule, approximately 1.2×1.0×1.0 cm, was found attached to the mandibular bone, alongside the unerupted left incisor. Histopathologically, the epithelial cells formed islands, nests, or anastomosing strands. The e...
Source: Journal of Toxicologic Pathology - January 29, 2024 Category: Toxicology Authors: Juan Li Guojian Jiang Jie Zhang Zhuolin Ou Xin Wu Yueshu Liu Source Type: research

Molecular autopsy for sudden death in Japan
J Toxicol Pathol. 2024 Jan;37(1):1-10. doi: 10.1293/tox.2023-0080. Epub 2023 Aug 30.ABSTRACTJapan has various death investigation systems; however, external examinations, postmortem computed tomography, macroscopic examinations, and microscopic examinations are performed regardless of the system used. These examinations can reveal morphological abnormalities, whereas the cause of death in cases with non-morphological abnormalities can be detected through additional examinations. Molecular autopsy and postmortem genetic analyses are important additional examinations. They are capable of detecting inherited arrhythmias or in...
Source: Journal of Toxicologic Pathology - January 29, 2024 Category: Toxicology Authors: Takuma Yamamoto Yuko Emoto Takehiko Murase Takahiro Umehara Aya Miura Minori Nishiguchi Kazuya Ikematsu Hajime Nishio Source Type: research

Lobular distribution of enhanced expression levels of heat shock proteins using < em > in-situ < /em > hybridization in the mouse liver treated with a single administration of CCl4
This study was conducted to visualize the lobular distribution of enhanced mRNA expression levels of heat shock proteins (HSPs) in liver samples from carbon tetra chloride (CCl4)-treated mice using in-situ hybridization (ISH). Male BALB/c mice given a single oral administration of CCl4 were euthanized 6 hours or 1 day after the administration (6 h or 1 day). Paraffin-embedded liver samples were obtained, ISH for HSPs was conducted, as well as hematoxylin-eosin staining and immunohistochemistry (IHC). At 6 h, centrilobular hepatocellular vacuolization was observed, and increased signals for Hspa1a, Hspa1b, and Grp78, which ...
Source: Journal of Toxicologic Pathology - January 29, 2024 Category: Toxicology Authors: Hitoshi Kandori Masami Aoki Yumiko Miyamoto Sayuri Nakamura Ryosuke Kobayashi Mitsuharu Matsumoto Kotaro Yokoyama Source Type: research

Pathogenesis of chemically induced nasal cavity tumors in rodents: contribution to adverse outcome pathway
J Toxicol Pathol. 2024 Jan;37(1):11-27. doi: 10.1293/tox.2023-0098. Epub 2023 Nov 1.ABSTRACTThe pathogenesis of nasal cavity tumors induced in rodents has been critically reviewed. Chemical substances that induce nasal cavity tumors in rats, mice, and hamsters were searched in the National Toxicology Program (NTP), International Agency for Research on Cancer (IARC), and Japan Bioassay Research Center (JBRC) databases, in addition to PubMed. Detailed data such as animal species, administration routes, and histopathological types were extracted for induced nasal cavity tumors. Data on non-neoplastic lesions were also extract...
Source: Journal of Toxicologic Pathology - January 29, 2024 Category: Toxicology Authors: Akiyoshi Nishikawa Kasuke Nagano Hajime Kojima Shoji Fukushima Kumiko Ogawa Source Type: research

Spontaneous mandibular follicular ameloblastoma in a female Sprague-Dawley rat
J Toxicol Pathol. 2024 Jan;37(1):39-43. doi: 10.1293/tox.2023-0072. Epub 2023 Nov 13.ABSTRACTAmeloblastoma is a locally aggressive tumor derived from the odontogenic epithelium of the developing tooth germ. It is rarely reported in experimental Sprague-Dawley (SD) rats. In this 90-day percutaneous repeated-dose toxicity study, mandibular nodules were observed from day 56 to 90. Upon necropsy, a well-demarcated nodule, approximately 1.2×1.0×1.0 cm, was found attached to the mandibular bone, alongside the unerupted left incisor. Histopathologically, the epithelial cells formed islands, nests, or anastomosing strands. The e...
Source: Journal of Toxicologic Pathology - January 29, 2024 Category: Toxicology Authors: Juan Li Guojian Jiang Jie Zhang Zhuolin Ou Xin Wu Yueshu Liu Source Type: research