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Journal J Toxicol Sci

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A novel perfusion culture system for screening mitochondrial toxicity in primary mouse hepatocytes.

Chika Yamamoto, Akinori Takemura, Sanae Ishii, Atsushi Doi, Isao Saito, Hideki Yamada, Yoko Sakai, Tamihide Matsunaga, Kousei Ito,

The liver microphysiological system (MPS) model is an in-vitro culture method that mimics physiological blood flow, which enhances basal cellular functions. However, the liver MPS model has not been tested in the preclinical stage because of its obscure utility. It can overcome the major problem of conventional systems-rapid loss of ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2022, 47(1):13-18]

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Development challenges for carcinogenicity risk assessments of topical drugs.

Brett D Hollingshead, Nasir Khan, Maik Schuler, Zaher Radi,

The nonclinical safety package to support development and approval of drugs intended to be administered by topical application generally follows International Council for Harmonisation multidisciplinary 3 (ICH M3) and topic specific safety (ICH S) guidances. However, some aspects of topical drug development may require case-by-case determination of nonclinical safety strategies. ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2022, 47(1):1-11]

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Acyl-CoA:diacylglycerol acyltransferase 1 inhibition in the small intestine increases plasma transaminase activity via the activation of protein kinase C pathway.

Hideaki Yokoyama, Taku Masuyama, Yuki Tanaka, Iori Tsubakihara, Kazuma Kondo, Kouichi Yoshinari,

Acyl-CoAdiacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in the fat absorption step in enterocytes. We previously reported that the pharmacological inhibition of DGAT1 increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in corn oil-loaded rats without any sign of hepatotoxicity. In this study, we investigated this mechanism. ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2022, 47(1):19-30]

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Spatio-temporal distribution of reactive sulfur species during methylmercury exposure in the rat brain.

Takamitsu Unoki, Masahiro Akiyama, Yasuhiro Shinkai, Yoshito Kumagai, Masatake Fujimura,

Brain susceptibility to methylmercury (MeHg) is developmentally and regionally specific in both humans and rodents, but the mechanism is not well clarified. Reactive sulfur species (RSS) with high nucleophilicity can react with MeHg, leading to the formation of a less toxic metabolite bismethylmercury sulfide, thus exerting cytoprotection. In this study, ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2022, 47(1):31-37]

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HepG2-NIAS cells, a new subline of HepG2 cells that can enhance not only CYP3A4 activity but also expression of drug transporters and form bile canaliculus-like networks by the oxygenation culture via a collagen vitrigel membrane.

Toshiaki Takezawa, Miaki Uzu,

We reported the enhanced liver-specific function and structure of HepG2 cells by the oxygenation culture via a collagen vitrigel membrane (CVM). The cells were conditioned in our laboratory for a long period, so their characteristics may change from the original HepG2 cells registered in RIKEN cell bank (RCB) with the ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2022, 47(1):39-50]

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Association between in vitro nuclear receptor-activating profiles of chemical compounds and their in vivo hepatotoxicity in rats.

Susumu Kodama, Nao Yoshii, Akihiro Ota, Jun-Ichi Takeshita, Kouichi Yoshinari, Atsushi Ono,

The liver plays critical roles to maintain homeostasis of living organisms and is also a major target organ of chemical toxicity. Meanwhile, nuclear receptors (NRs) are known to regulate major liver functions and also as a critical target for hepatotoxic compounds. In this study, we established mammalian one-hybrid assay systems ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(12):569-587]

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Constructing a developmental and reproductive toxicity database of chemicals (DART NIHS DB) for integrated approaches to testing and assessment.

Takashi Yamada, Minoru Miura, Tomoko Kawamura, Kazuo Ushida, Kaoru Inoue, Makiko Kuwagata, Naruo Katsutani, Akihiko Hirose,

Developmental and reproductive toxicity (DART) is an important endpoint, and databases (DBs) are essential for evaluating the risk of untested substances using alternative methods. We have constructed a reliable and transparent DART DB, which we named DART NIHS DB, using the publicly available datasets of DART studies of industrial chemicals ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(11):531-538]

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A rapid screening assay for L452R and T478K spike mutations in SARS-CoV-2 Delta variant using high-resolution melting analysis.

Akira Aoki, Hirokazu Adachi, Yoko Mori, Miyabi Ito, Katsuhiko Sato, Kenji Okuda, Toru Sakakibara, Yoshinori Okamoto, Hideto Jinno,

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been reported worldwide and novel SARS-CoV-2 variants continue to emerge. A novel SARS-CoV-2 strain, the Delta variant (B.1.617.2), is spreading worldwide. The Delta variant has reportedly high infectivity and immune evasion potency. In June 2021, the World Health Organization categorized it ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(10):471-476]

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Resveratrol reverses the programmed high-susceptibility to non-alcoholic fatty liver disease by targeting the hepatic SIRT1-SREBP1c pathway in prenatal ethanol-exposed rat offspring.

Lang Shen, Lijia Xie, Li Chen, Li Liu, Xiao Shi, Xiaocong Wang, Donghong Chen, Hui Wang, Song Quan, Zhijian Wang,

An increased susceptibility to non-alcoholic fatty liver disease (NAFLD) in female rat offspring that experienced prenatal ethanol exposure (PEE) has been previously demonstrated. The present study further investigated the potential mechanism. Based on the results from both fetal and adult studies of offspring rats that experienced PEE (4 g/kg/day), the ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(9):413-423]

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Metabolic activation and deactivation of dietary-derived coumarin mediated by cytochrome P450 enzymes in rat and human liver preparations.

Norie Murayama, Hiroshi Yamazaki,

Dietary-derived coumarin is of clinical interest for its potential hepatotoxicity in humans because such toxicity is especially evident in rats. In this study, the oxidative metabolism of coumarin to active coumarin 3,4-epoxide (as judged by the formation rates of o-hydroxyphenylacetic acid) and excretable 7-hydroxycoumarin was investigated in liver fractions from ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(8):371-378]

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Pharmacokinetics of primary oxidative metabolites of thalidomide in rats and in chimeric mice humanized with different human hepatocytes.

Tomonori Miura, Shotaro Uehara, Makiko Shimizu, Hiroshi Suemizu, Hiroshi Yamazaki,

The approved drug thalidomide is teratogenic in humans, nonhuman primates, and rabbits but not in rodents. The extensive biotransformation of 5'-hydroxythalidomide after oral administration of thalidomide (250 mg/kg) in rats was investigated in detail using liquid chromatography-tandem mass spectrometry. Probable metabolites 5'-hydroxythalidomide sulfate and glucuronide were extensively formed, with approximately ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(7):311-317]

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Hypoalgesia and recovery in methylmercury-exposed rats.

Yo Shinoda, Yuta Yamada, Eiko Yoshida, Tsutomu Takahashi, Yayoi Tsuneoka, Komyo Eto, Toshiyuki Kaji, Yasuyuki Fujiwara,

Methylmercury (MeHg), the causal substrate in Minamata disease, can lead to severe and chronic neurological disorders. The main symptom of Minamata disease is sensory impairment in the four extremities; however, the sensitivity of individual sensory modalities to MeHg has not been investigated extensively. In the present study, we performed stimulus-response ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(6):303-309]

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Fasudil alleviates acetaminophen-induced liver injury via targeting Rhoa/ROCK signal pathway.

Xiwen Ren, Tong Meng, Xingbin Ren, Xiaoyu Li, Lin Lu,

Fasudil is an inhibitor of Rhoa/ROCK signaling, which is involved in anti-inflammatory and anti-injury effects. The purpose of this study was to explore the effects of Fasudil on acetaminophen (APAP)-induced liver injury and reveal its potential molecular mechanism. In this study, C57BL/6 J mice were divided into different groups and ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(6):255-262]

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Curcumin promotes cholesterol efflux by regulating ABCA1 expression through miR-125a-5p/SIRT6 axis in THP-1 macrophage to prevent atherosclerosis.

Chao Tan, Lan Zhou, Weinong Wen, Nan Xiao,

<h4>Objective</h4>To seek out the effect of curcumin on cholesterol efflux in THP-1 macrophages and clarify its specific mechanism.<h4>Methods</h4>THP-1 macrophages were cultured with curcumin at different concentrations, followed by detection of the toxicity of curcumin to cells utilizing CCK-8 assay. Following culturing with serum-free ox-LDL, THP-1 macrophages were transfected with mi-miR-125a-5p, ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(5):209-222]

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Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury.

Yuki Shimizu, Takamitsu Sasaki, Eri Yonekawa, Hirokazu Yamazaki, Rui Ogura, Michiko Watanabe, Takuomi Hosaka, Ryota Shizu, Jun-Ichi Takeshita, Kouichi Yoshinari,

Drug-induced liver injury (DILI) is one of the major causes for the discontinuation of drug development and withdrawal of drugs from the market. Since it is known that reactive metabolite formation and being substrates or inhibitors of cytochrome P450s (P450s) are associated with DILI, we systematically investigated the association between ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(4):167-176]

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Human ES and iPS cells display less drug resistance than differentiated cells, and naïve-state induction further decreases drug resistance.

Yulia Panina, Junko Yamane, Kenta Kobayashi, Hideko Sone, Wataru Fujibuchi,

Pluripotent stem cells (PSCs) possess unique characteristics that distinguish them from other cell types. Human embryonic stem (ES) cells are recently gaining attention as a powerful tool for human toxicity assessment without the use of experimental animals, and an embryonic stem cell test (EST) was introduced for this purpose. However, ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(3):131-142]

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Development challenges associated with rAAV-based gene therapies.

Michael W Bolt, Joseph T Brady, Lawrence O Whiteley, K Nasir Khan,

The number of gene therapies in development continues to increase, as they represent a novel method to treat, and potentially cure, many diseases. Gene therapies can be conducted with an in vivo or ex vivo approach, to cause gene augmentation, gene suppression, or genomic editing. Adeno-associated viruses are commonly used ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(2):57-68]

Cited: 2 times

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Effects of fenofibrate and its combination with lovastatin on the expression of genes involved in skeletal muscle atrophy, including FoxO1 and its targets.

Haruka Ajima, Yuko Kai, Junya Fujimaki, Shiori Akashi, Akihito Morita, Osamu Ezaki, Yasutomi Kamei, Shinji Miura,

Fibrates and statins have been widely used to reduce triglyceride and cholesterol levels, respectively. Besides its lipid-lowering effect, the side effect of muscle atrophy after fibrate administration to humans has been demonstrated in some studies. Combination therapy with fibrates and statins also increases the risk of rhabdomyolysis. FoxO1, a member ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(1):11-24]

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Corneal lesions related to an anesthetic mixture of medetomidine, midazolam, and butorphanol treatment in rats.

Kyohei Kamio, Junya Morita, Yutaka Nakanishi, Minoru Sasaki, Masaki Wakamatsu,

An anesthetic mixture of medetomidine, midazolam and butorphanol (MMB) has been recently used in laboratory animals. We observed corneal opacity in nephrectomized rats that had undergone two operations under MMB anesthesia at 4 and 5 weeks of age. To evaluate the features of this corneal opacity, ophthalmic examinations were conducted ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(12):561-568]

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Roles of human cytochrome P450 1A2 in coumarin 3,4-epoxidation mediated by untreated hepatocytes and by those metabolically inactivated with furafylline in previously transplanted chimeric mice.

Tomonori Miura, Shotaro Uehara, Makiko Shimizu, Norie Murayama, Hiroshi Suemizu, Hiroshi Yamazaki,

Coumarin is a naturally occurring component of food products but is of clinical interest for its potential hepatotoxicity in humans. In the current study, the pharmacokinetics of coumarin in humanized-liver mice after oral and intravenous administrations (30 mg/kg) were investigated for its transformations to metabolically active coumarin 3,4-epoxide (as estimated ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(11):525-530]

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Data on long-term survival of the NOD/Shi-scid IL-2Rγnull (NOG) mouse in two facilities.

Yuji Yamashita, Tamio Sato, Kaori Noishiki, Kinji Kobayashi, Asako Uchiyama, Hiroyuki Izumi, Takashi Tamura, Masayuki Shikamura, Yu Oinishi, Miho Saito, Shin Kawamata,

The objective of this study was to investigate an appropriate observation period for an evaluation of tumorigenicity in NOD/Shi-scid IL-2 Rγ<sup>null</sup> (NOG) mice. At SNBL, 19 male and 19 female NOG mice were observed the general condition from 7 weeks old up to 68 weeks old and at FBRI, 7 ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(10):453-469]

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Mercury, cadmium, and lead in cigarettes from international markets: concentrations, distributions and absorption ability of filters.

Quang Phan Dinh, Randy Novirsa, Huiho Jeong, Willy Cahya Nugraha, Sylvester Addai-Arhin, Pham Hung Viet, Nobuaki Tominaga, Yasuhiro Ishibashi, Koji Arizono,

Mercury (Hg), cadmium (Cd), and lead (Pb) concentrations in marketed cigarettes from South Korea, Vietnam, Japan, Indonesia, Taiwan, Thailand, the United Kingdom (UK), Belgium, Italy, Finland, and France were investigated. The cigarettes from Vietnam and Thailand had the highest trend of Hg. Meanwhile, Cd was found higher in cigarettes from ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(9):401-411]

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Chronic cardiotoxicity assessment of BMS-986094, a guanosine nucleotide analogue, using human iPS cell-derived cardiomyocytes.

Shota Yanagida, Ayano Satsuka, Sayo Hayashi, Atsushi Ono, Yasunari Kanda,

Predicting drug-induced side effects in the cardiovascular system is very important because it can lead to the discontinuation of new drugs/candidates or the withdrawal of marketed drugs. Although chronic assessment of cardiac contractility is an important issue in safety pharmacology, an in vitro evaluation system has not been fully developed. ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(8):359-369]

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Central inhibition prevents the in vivo acute toxicity of harmine in mice.

Yang Lv, Hongyu Liang, Jun Li, Xiuxiu Li, Xiaohui Tang, Songyu Gao, Hao Zou, Jing Zhang, Mei Wang, Liang Xiao,

<h4>Background</h4>Harmine is a β-carboline alkaloid that displays antidepressant, antitumor and other pharmacological effects. However, the strong toxic effects limit its clinical application, and should be first considered.<h4>Purpose</h4>To evaluate the in vivo toxicity of harmine and explore intervention strategies against its toxicity.<h4>Methods</h4>The in vivo toxicity of harmine was assessed from the ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(6):289-301]

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Salvianolic acid B attenuated cisplatin-induced cardiac injury and oxidative stress via modulating Nrf2 signal pathway.

Zhenjian Lin, Yuyan Bao, Bing Hong, Yangyang Wang, Xiaomin Zhang, Yaping Wu,

Cardiovascular complications have been well documented as the downside to conventional cancer chemotherapy. As a notable side effect of cisplatin (CDDP), cardiotoxicity represents a major obstacle to the successful treatment of cancer. It has been reported that Salvianolic acid B (SalB) possesses cardioprotective quality. However, the effect of SalB on ... Read more >>

J Toxicol Sci (The Journal of toxicological sciences)
[2021, 46(5):199-207]

Cited: 1 time

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