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Journal of Toxicological Sciences

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https://www.readbyqxmd.com/read/29743446/photodynamic-therapy-using-talaporfin-sodium-induces-heme-oxygenase-1-expression-in-rat-malignant-meningioma-kmy-j-cells
#1
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
https://www.readbyqxmd.com/read/29743445/increased-susceptibility-to-troglitazone-induced-mitochondrial-permeability-transition-in-type-2-diabetes-mellitus-model-rat
#2
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Troglitazone, a member of the thiazolidinedione class of antidiabetic drugs, was withdrawn from the market because it causes severe liver injury.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
https://www.readbyqxmd.com/read/29743444/protective-effects-of-rutin-on-lipopolysaccharide-induced-heart-injury-in-mice
#3
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
https://www.readbyqxmd.com/read/29743443/bisphenol-af-as-an-activator-of-human-estrogen-receptor-%C3%AE-1-er%C3%AE-1-in-breast-cancer-cell-lines
#4
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
https://www.readbyqxmd.com/read/29743442/fluoride-induced-iron-overload-contributes-to-hepatic-oxidative-damage-in-mouse-and-the-protective-role-of-grape-seed-proanthocyanidin-extract
#5
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
https://www.readbyqxmd.com/read/29743441/acidic-conditions-induce-the-suppression-of-cd86-and-cd54-expression-in-thp-1-cells
#6
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
https://www.readbyqxmd.com/read/29743440/hepatic-histopathological-changes-and-dysfunction-in-primates-following-exposure-to-organic-arsenic-diphenylarsinic-acid
#7
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
https://www.readbyqxmd.com/read/29618717/the-profiles-and-networks-of-mirna-lncrna-mrna-and-circrna-in-benzo-a-pyrene-transformed-bronchial-epithelial-cells
#8
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
https://www.readbyqxmd.com/read/29618716/glutathione-has-a-more-important-role-than-metallothionein-i-ii-against-inorganic-mercury-induced-acute-renal-toxicity
#9
Maki Tokumoto, Jin-Yong Lee, Akinori Shimada, Chiharu Tohyama, Masahiko Satoh
Inorganic mercury is a harmful heavy metal that causes severe kidney damage. Glutathione (GSH), a tripeptide comprising L-glutamic acid, glycine and L-cysteine, and metallothionein (MT), a cysteine-rich and metal-binding protein, are biologically important protective factors for renal toxicity by inorganic mercury. However, the relationship between GSH and MT for the prevention of renal toxicity by inorganic mercury is unknown. We examined the sensitivity of the mice depleted in GSH by treatment with L-Buthionine-SR-sulfoximine (L-BSO), and MT-I/II null mice genetically deleted for MT-I and MT-II, to inorganic mercury (HgCl2 )...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29618715/comparing-time-series-of-chemical-concentrations-in-zebrafish-danio-rerio-embryos-larvae-exposed-to-teratogens-with-different-hydrophobicity-caffeine-sodium-valproate-and-diethylstilbestrol
#10
Tasuku Nawaji, Naohiro Mizoguchi, Mika Ono, Takeshi Matuura, Masanori Seki, Hiroki Teraoka
Developmental toxicity is an adverse developmental outcome, i.e., death, malformation, growth retardation, or functional deficiency. Recently, alternative methods of assessing developmental toxicity using zebrafish (Danio rerio) as a preliminary screening have attracted attention because of their low cost and high throughput. However, most toxicity evaluations have been based on a chemical concentration in an aqueous solution, and the chemical concentrations in embryos/larvae and their temporal behavior have in most cases been unclear, regardless of differences of chemical hydrophobicity...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29618714/nicotine-and-methyl-vinyl-ketone-major-components-of-cigarette-smoke-extracts-increase-protective-amyloid-%C3%AE-peptides-in-cells-harboring-amyloid-%C3%AE-precursor-protein
#11
Yoichi Ohshima, Kazumi Iwata, Masakazu Ibi, Misaki Matsumoto, Masato Katsuyama, Chihiro Yabe-Nishimura
The increased ratio of longer amyloid-β (Aβ1-42)/shorter amyloid-β (Aβ1-40) peptides, generated from amyloid precursor protein (APP), is known to promote the development of Alzheimer's disease (AD). To investigate the role of smoking in Aβ production, we determined the production of Aβ species in the presence of nicotine or methyl vinyl ketone (MVK), major components of cigarette smoke extracts, in Flp-In™ T-REx™ -293 (T-REx293) cells harboring a single copy of human APP. While treatment with nicotine or MVK did not affect the amount of APP, the levels of Aβ1-40 in the culture media were significantly increased...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29618713/development-of-an-in-vitro-photosafety-evaluation-method-utilizing-intracellular-ros-production-in-thp-1-cells
#12
Akemi Toyoda, Hiroshi Itagaki
Photoreactive compounds that may experience exposure to ultraviolet (UV) radiation can lead to the intracellular production of reactive oxygen species (ROS), which may cause phototoxic and photoallergenic responses. Here, we developed a novel in vitro photosafety assay and investigated whether it could be used to predict phototoxicity and photosensitivity by measuring changes in intracellular ROS production. THP-1 cells that had previously taken up 5-(and-6)-carboxy-2',7'-difluorodihydrofluorescein diacetate (carboxy-H2 DFFDA), a ROS-sensitive fluorescent reagent, were exposed to photoreactive substances such as phototoxic and photoallergenic materials and then subjected to with UV-A irradiation (5 J/cm2 )...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29618712/cytochrome-p450-dependent-drug-oxidation-activities-in-commercially-available-hepatocytes-derived-from-human-induced-pluripotent-stem-cells-cultured-for-3-weeks
#13
Norie Murayama, Hiroshi Yamazaki
Hepatocyte-like cells differentiated from human induced pluripotent stem (iPS) cells are of great interest for applications in pharmacological research. For drug metabolism testing, commercially available hepatocytes derived from human iPS cells are generally recommended to be used 1 week after seeding on plates. In this study, however, after 3-4 weeks of culture according to the manufacturer's instructions, human cytochrome P450 (P450) 2C9- and 2C19-dependent diclofenac 4'-hydroxylation and omeprazole 5-hydroxylation activities of the iPS-derived hepatocytes had significantly increased above the activities at 1 week and had reached levels similar to those in HepaRG cells, a human hepatocyte-like cell line...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29540657/improvement-of-human-cell-line-activation-test-h-clat-using-short-time-exposure-methods-for-prevention-of-false-negative-results
#14
Kazuto Narita, Yuuki Ishii, Phuc Thi Hong Vo, Fumiko Nakagawa, Shinichi Ogata, Kunihiko Yamashita, Hajime Kojima, Hiroshi Itagaki
Recently, animal testing has been affected by increasing ethical, social, and political concerns regarding animal welfare. Several in vitro safety tests for evaluating skin sensitization, such as the human cell line activation test (h-CLAT), have been proposed. However, similar to other tests, the h-CLAT has produced false-negative results, including in tests for acid anhydride and water-insoluble chemicals. In a previous study, we demonstrated that the cause of false-negative results from phthalic anhydride was hydrolysis by an aqueous vehicle, with IL-8 release from THP-1 cells, and that short-time exposure to liquid paraffin (LP) dispersion medium could reduce false-negative results from acid anhydrides...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29540656/zonation-of-the-drug-metabolizing-enzyme-cytochrome-p450-3a-in-infant-mice-begins-in-pre-weaning-period
#15
Satoshi Kitaoka, Jo Hatogai, Wataru Ochiai, Kiyoshi Sugiyama
The drug-metabolizing enzyme CYP3A is a heterogeneous enzyme found in the liver that displays local characteristics referred to as "zonation." Zonation contributes to improved energy efficiency in metabolism. The objective of this study was to determine a scientific basis for the safety of fetuses and nursing infants in cases in which the use of pharmaceuticals by pregnant and nursing mothers is unavoidable. In addition, we analyzed CYP3A zonation in the liver using mice from the fetus stage to the nursing stage...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29540655/radical-scavenging-effects-of-1-naphthol-2-naphthol-and-their-sulfate-conjugates
#16
Shintaro Sugahara, Kumiko Fukuhara, Yuki Tokunaga, Shuhei Tsutsumi, Yuto Ueda, Masateru Ono, Katsuhisa Kurogi, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu, Shin Yasuda
1-Naphthol (1-Nap) and 2-naphthol (2-Nap) are phenolic isomers that may be subjected to sulfate conjugation in vivo. Phase-II sulfate conjugation of phenolic compounds is generally thought to result in their inactivation. This study aimed to investigate the antioxidative effects of 1-NapS and 2-NapS, in comparison with their unsulfated counterparts, using established free radical scavenging assays. Based on the calculated EC50 values, 1-NapS resulted in 5.60 to 7.35-times lower antioxidative activity than 1-Nap...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29540654/a-reaction-mechanism-based-prediction-of-mutagenicity-%C3%AE-halo-carbonyl-compounds-adduct-with-dna-by-s-n-2-reaction
#17
Yu Haranosono, Hiroki Ueoka, Gakushi Kito, Shingo Nemoto, Masaaki Kurata, Hideyuki Sakaki
Most of the α-halo carbonyl (AHC) compounds tend to be predicted as mutagenic by structure-activity relationship based on structural category only, because they have an alkyl halide structure as a structural alert of mutagenicity. However, some AHC compounds are not mutagenic. We hypothesized that AHC reacts with DNA by SN 2 reaction, and the reactivity relates to mutagenicity. As an index of SN 2 reactivity, we focused on molecular orbitals (MOs), as the direction and position of two molecules in collision are important in the SN 2 reaction...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29540653/necrosis-in-human-neuronal-cells-exposed-to-paraquat
#18
Naho Hirayama, Toshihiko Aki, Takeshi Funakoshi, Kanako Noritake, Kana Unuma, Koichi Uemura
Paraquat (PQ) is an herbicide that was once used worldwide, but is now prohibited in many nations due to its high toxicity to humans. However, there are still rare cases of the fetal intoxication of PQ, which was purchased prior to the prohibition in Japan. In this study, several cell death pathways, the mitochondrial stress response, and autophagy were examined in SH-SY5Y cells exposed to PQ. The results reveal the decrease of a mitochondrial stress sensitive-BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) protein, the suppression of autophagic flux, and the lack of apoptosis as well as other regulated forms of necrosis, such as necroptosis and ferroptosis...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29540652/comparison-of-electropharmacological-effects-between-terfenadine-and-its-active-derivative-fexofenadine-using-a-cross-over-study-in-halothane-anesthetized-dogs-to-analyze-variability-of-pharmacodynamic-and-pharmacokinetic-profiles-of-terfenadine-and-torsadogenic
#19
Kentaro Ando, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Hiroyuki Harada, Hiroyoshi Miyamoto, Naoki Inamura, Kan Takagi, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Hiroko Izumi-Nakaseko, Atsuhiko T Naito, Atsushi Sugiyama
In order to better understand the variability of pharmacodynamic and pharmacokinetic profiles of terfenadine between the previous studies as well as to qualitatively and quantitatively examine the proarrhythmic potential of its major active metabolite fexofenadine in comparison with that of terfenadine, we directly compared their electropharmacological effects with halothane-anesthetized dogs (n = 3). For this purpose, we adopted a cross-over design, which can directly compare the effects of terfenadine and fexofenadine under the identical metabolic condition...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29540651/the-involvement-of-nox4-in-fine-particulate-matter-exposure-induced-cardiac-injury-in-mice
#20
Fan Wu, Jinying Zhang
Epidemiological studies have confirmed that ambient fine particulate matter (PM2.5 ) exposure is associated with cardiovascular disease (CVD). However, the underlying mechanisms in PM2.5 exposure-induced heart injury are largely unknown. It has been acknowledged that NADPH oxidase (Nox) 4 plays a critical role in CVD development. To investigate the acute effects of PM2.5 on the mouse heart and the role of Nox4 in PM2.5 exposure-induced cardiac injury, C57BL/6J mice were instilled with saline or 1.5, 3.0, 6...
2018: Journal of Toxicological Sciences
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