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Journal of Toxicological Sciences

Shigeo Suzuki, Yumie Morimoto-Kobayashi, Chika Takahashi, Yoshimasa Taniguchi, Mikio Katayama
It has been demonstrated that successive ingestion of matured hop extract (MHE), produced by extraction from heat-treated hops, results in body fat reduction in animals and humans; however, preclinical safety studies have not been reported. In this study, we conducted in vitro and in vivo safety studies for MHE. Genotoxicity was evaluated using the Ames test, in vitro chromosomal aberration test, and in vivo micronucleus test. To assess acute safety, a single, oral administration of MHE to rats was monitored...
2018: Journal of Toxicological Sciences
Changhua He, Koji Arizono, Hezhe Ji, Yuka Yakushiji, Daizhou Zhang, Kuangwei Huang, Yasuhiro Ishibashi
Total mercury (THg) and methylmercury (MeHg) bioaccumulation was explored in the Bimastus parvus species of earthworm (B. parvus) native to the leachate-contaminated forest soils around a Hg-polluted traditional landfill in Japan. General soil properties and concentrations of THg and MeHg in forest soils and in B. parvus were determined. The results indicated that the average THg concentrations in B. parvus and in forest soils in the leachate-contaminated sites were 10.21 and 14.90 times higher than those in the reference sites, respectively, whereas similar average MeHg concentrations were observed in forest soils (< 0...
2018: Journal of Toxicological Sciences
Atsushi Fujiwara, Miki Shimosawa, Masahiko Iino, Mikio Sasaki, Shin-Ichi Sato, Akihito Shimoi
The purpose of this study was to investigate the discriminative stimulus properties of morphine and codeine using different administration routes to that used at drug discrimination training. Rats were trained to discriminate morphine at 3 mg/kg from saline by the intraperitoneal route in a standard two-lever drug discrimination paradigm. Generalization of morphine by the subcutaneous and the oral routes, and codeine by the intraperitoneal and the oral routes to the discriminative stimulus properties of the morphine training dose were investigated...
2018: Journal of Toxicological Sciences
Shohei Yoshimaru, Ryota Shizu, Satoshi Tsuruta, Yuto Amaike, Makoto Kano, Takuomi Hosaka, Takamitsu Sasaki, Kouichi Yoshinari
The nuclear receptor pregnane X receptor (PXR) plays a major role in the xenobiotic-induced expression of drug-metabolizing enzymes. PXR activation is also associated with several adverse events in the liver. Especially, the receptor enhances hepatocyte proliferation mediated by chemical liver tumor promoters, suggesting that exposure to PXR activators increases the risk of liver cancer. In this study, we have investigated the influences of food additives on PXR to understand their potential adverse effects when they are taken in combination with other chemical compounds...
2018: Journal of Toxicological Sciences
Atsushi Watanabe, Kazuyuki Tsurui, Shigeki Yoneyama, Hijiri Iwata, Takayuki Anzai, Christopher Jerome, Dai Nakae
Teriparatide, a drug used in the treatment of osteoporosis, was administered to rats subcutaneously for the duration of 3 months, at a frequency of either once weekly or once daily to demonstrate the varying levels of anabolic action the drug can have on bone depending on the dosing frequency. The levels of biomarkers in the blood were compared and found to vary in osteocalcin (OC), a biomarker of bone formation, and cross-linked N-telopeptide of type 1 collagen (NTx), a biomarker of bone resorption, according to the dosing frequency...
2018: Journal of Toxicological Sciences
Takeshi Toyoda, Young-Man Cho, Jun-Ichi Akagi, Yasuko Mizuta, Kohei Matsushita, Akiyoshi Nishikawa, Katsumi Imaida, Kumiko Ogawa
Although obesity is increasing worldwide, experimental studies examining the possible association between obesity and susceptibility to chemical toxicity are limited. In the present study, we performed a 13-week toxicity study for acetaminophen (APAP), a well-known drug that exhibits hepatotoxicity as an adverse effect, using an obese rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 80, 253, 800, 2,530, or 8,000 ppm APAP in the diet for 13 weeks...
2018: Journal of Toxicological Sciences
Takayuki Abo, Takuo Yuki, Rui Xu, Daisuke Araki, Yutaka Takahashi, Hitoshi Sakaguchi, Hiroshi Itagaki
The Short Time Exposure (STE) test method is an in vitro method for assessing the eye irritation potential of chemicals and is used to classify the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Category 1 and No Category (NC). The method has been adopted by the Organisation for Economic Co-operation and Development (OECD) as test guideline (TG) 491 since 2015. While this method can be used to classify GHS NC, it is not suitable for testing highly volatile substances and solids other than surfactants...
2018: Journal of Toxicological Sciences
Keisuke Goda, Kosuke Saito, Kyotaka Muta, Akio Kobayashi, Yoshiro Saito, Shoichiro Sugai
Valproic acid (VPA) is known to induce hepatic steatosis due to mitochondrial toxicity in rodents and humans. In the present study, we administered VPA to SD rats for 3 or 14 days at 250 and 500 mg/kg and then performed lipidomics analysis to reveal VPA-induced alteration of the hepatic lipid profile and its association with the plasma lipid profile. VPA induced hepatic steatosis at the high dose level without any degenerative changes in the liver on day 4 (after 3 days dosing) and at the low dose level on day 15 (after 14 days dosing)...
2018: Journal of Toxicological Sciences
Makiko Shimizu, Hiroshi Suemizu, Sawa Mizuno, Takashi Kusama, Tomonori Miura, Shotaro Uehara, Hiroshi Yamazaki
Medicinal carnitine-derived and dietary-derived malodorous trimethylamine and its non-malodorous metabolite trimethylamine N-oxide were historically regarded as nontoxic. Clinical and toxicological interest has recently arisen because of their potential association with atherosclerosis. We previously reported a human physiologically based pharmacokinetic (PBPK) model for trimethylamine and its primary metabolite, trimethylamine N-oxide, based on reported rat trimethylamine pharmacokinetics. However, rats are poor metabolizers with respect to trimethylamine N-oxygenation, and this species difference was investigated in vitro using substrate depletion rates in rat and human liver microsomes...
2018: Journal of Toxicological Sciences
Weiwei Huang, Juan Chang, Ping Wang, Chaoqi Liu, Qingqiang Yin, Qun Zhu, Fushan Lu, Tianzeng Gao
Aflatoxin B1 (AFB1 ) and zearalenone (ZEA) are the secondary toxic metabolites of fungi which contaminate a wide range of food and feedstuffs. Limiting exposure of humans and livestock to them is very essential. Among numerous methods of mycotoxin-degradation, biodegradation by microorganisms and enzymes is an effective and promising approach to eliminate their hazards. The present study aims to optimize the proportion of different species of beneficial microbes by means of response surface methodology (RSM) and its combination with mycotoxin-degradation enzymes...
2018: Journal of Toxicological Sciences
Norie Murayama, Hiroshi Suemizu, Shotaro Uehara, Takashi Kusama, Marina Mitsui, Yusuke Kamiya, Makiko Shimizu, F Peter Guengerich, Hiroshi Yamazaki
Lenalidomide has been shown to be potentially teratogenic in thalidomide-sensitive animal species. Screening for thalidomide analogs devoid of teratogenicity/toxicity-attributable to drug metabolism and disposition, but having immunomodulatory properties-is a strategic pathway towards development of new anticancer drugs. Plasma concentrations of lenalidomide were investigated in immunodeficient control and humanized-liver mice following oral administration of lenalidomide (50 mg/kg). Plasma concentrations of lenalidomide (1-2 hr after administration) were slightly but significantly higher in humanized-liver mice than in control mice (p < 0...
2018: Journal of Toxicological Sciences
Shugo Suzuki, Hiroyuki Kato, Satoshi Fuji, Taku Naiki, Aya Naiki-Ito, Yoriko Yamashita, Satoru Takahashi
Screening prostatic carcinogens is time-consuming due to the time needed to induce preneoplastic and neoplastic lesions. To overcome this, we investigated alternative molecular markers for detection of prostatic carcinogens in a short period in rats. After treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), expression of high-mobility group protein B2 (HMGB2) was up-regulated in rat ventral prostate. To evaluate the applicability of HMGB2 in the early detection of carcinogenicity of chemicals using animal models, we examined HMGB2 expression in prostate of rats...
2018: Journal of Toxicological Sciences
Tsutomu Takahashi, Saki Suzuki, Suzuka Misawa, Jiro Akimoto, Yo Shinoda, Yasuyuki Fujiwara
Photodynamic therapy (PDT) using talaporfin sodium (TS) is tumor cell-selective less invasive therapy for the treatment of malignant glioma. We previously demonstrated that PDT using TS (TS-PDT) treatment exhibits anti-tumor activity against not only glioblastoma cells but also malignant meningioma cells. In general, various stress response proteins have been reported to affect the sensitivity determination for anticancer agents against tumor cells. However, the relationship between the therapeutic effect of TS-PDT and stress response systems in tumor cells is not adequately investigated...
2018: Journal of Toxicological Sciences
Masahiro Segawa, Shuichi Sekine, Tomoyuki Sato, Kousei Ito
Troglitazone, a member of the thiazolidinedione class of antidiabetic drugs, was withdrawn from the market because it causes severe liver injury. One of the mechanisms for this adverse effect is thought to be mitochondrial toxicity. To investigate the characteristics of troglitazone-induced liver toxicity in more depth, the toxicological effects of troglitazone on hepatocytes and liver mitochondria were investigated using a rat model of type 2 diabetes mellitus (T2DM). Troglitazone was found to increase mitochondrial permeability transition (MPT) in the liver mitochondria of diabetic rats to a greater extent than in control rats, whereas mitochondrial membrane potential and oxidative phosphorylation were not affected...
2018: Journal of Toxicological Sciences
Liu Xianchu, Zheng Lan, Liu Ming, Mo Yanzhi
Rutin has a wide range of beneficial health properties in the amelioration of multi-organ injury owing to its various biological effects. The aim of this study was to investigate the effects of rutin on lipopolysaccharide (LPS)-induced heart injury and clarify its potential cardioprotective mechanism. The mouse model of heart injury was intraperitoneal infection with LPS, and rutin was orally administered for 8 consecutive days. One day after LPS injection, heart histopathology, cardiac marker enzymes and cardiac fibrosis related genes were determined to evaluate the cardioprotective effects of rutin...
2018: Journal of Toxicological Sciences
Hiroyuki Okazaki, Masayo Hirao-Suzuki, Shuso Takeda, Yukimi Takemoto, Ramu Mizunoe, Koichi Haraguchi, Kazuhito Watanabe, Masufumi Takiguchi, Hironori Aramaki
Bisphenol AF (BPAF) is now recognized as one of the replacements for bisphenol A (BPA). Although considerable experimental evidence suggests that BPA is an endocrine-disrupting chemical, the toxicological profile of BPAF has been investigated in less detail than that of BPA, even at the in vitro level. BPAF has been established as an activator of estrogen receptor α (ERα) in many cell lines; however, controversy surrounds its effects on the other isoform, ERβ (i.e., whether it functions as a stimulator)...
2018: Journal of Toxicological Sciences
Qiang Niu, Ping He, Shangzhi Xu, Ruling Ma, Yusong Ding, Lati Mu, Shugang Li
Emerging evidence has demonstrated that iron overload plays an important role in oxidative stress in the liver. This study aimed to explore whether fluoride-induced hepatic oxidative stress is associated with iron overload and whether grape seed proanthocyanidin extract (GSPE) alleviates oxidative stress by reducing iron overload. Forty Kunming male mice were randomly divided into 4 groups and treated for 5 weeks with distilled water (control), sodium fluoride (NaF) (100 mg/L), GSPE (400 mg/kg bw), or NaF (100 mg/L) + GSPE (400 mg/kg bw)...
2018: Journal of Toxicological Sciences
Takafumi Mitachi, Minori Mezaki, Kunihiko Yamashita, Hiroshi Itagaki
To evaluate the sensitization potential of chemicals in cosmetics, using non-animal methods, a number of in vitro safety tests have been designed. Current assays are based on the expression of cell surface markers, such as CD86 and CD54, which are associated with the activation of dendritic cells, in skin sensitization tests. However, these markers are influenced by culture conditions through activating danger signals. In this study, we investigated the relationship between extracellular pH and the expression of the skin sensitization test human cell line activation test (h-CLAT) markers CD86 and CD54...
2018: Journal of Toxicological Sciences
Tomoyuki Masuda, Kazuhiro Ishii, Yukio Morishita, Nobuaki Iwasaki, Yasuyuki Shibata, Akira Tamaoka
Organic arsenic diphenylarsinic acid (DPAA[V]) accumulates at high concentrations in the liver of primates after its subchronic administration. However, no studies on the hepatic effects of organic arsenic compounds, including DPAA(V), on primates have been reported to date. To clarify the toxicokinetics of DPAA(V) in the liver of primates, hepatic tissue specimens were collected from cynomolgus monkeys (n = 32) at 5, 29, 170, and 339 days after repeated administration of DPAA(V) for 28 days. Four histopathological changes in the specimens were observed and pathologically evaluated...
2018: Journal of Toxicological Sciences
Xinhang Jiang, Xiaoying Wu, Feiyu Chen, Wei He, Xintong Chen, Linhua Liu, Huanwen Tang
Our aim was to demonstrate the significance of miRNA, lncRNA, and circRNA in the transformation of human bronchial epithelial cells induced by benzo(a)pyrene (BaP), and to investigate their regulatory networks. Hierarchical clustering, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and network regulation analysis were used to analyze the high-throughput sequencing results of human bronchial epithelial cell line BEAS-2B and BaP-transformed BEAS-2B cells (BEAS-2B-T). 76,191,786 and 3,431differentially-expressed miRNA, lncRNA, mRNA and circRNA were detected, respectively; 43 miRNA, 48 lncRNA, 438 mRNA and 2,079 circRNA were up-regulated; 33 miRNA, 143 lncRNA, 348 mRNA and 1,352 circRNA were down-regulated...
2018: Journal of Toxicological Sciences
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