Effective in vitro evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells
In conclusion, an in vitro assay using human and animal MRGPRX2-expressing cells would be an effective platform to investigate the mechanism and predict the human risk of histamine release observed in nonclinical studies.PMID:38556353 | DOI:10.2131/jts.49.163 (Source: Journal of Toxicological Sciences)
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Eri Hamamura-Yasuno Junzo Kinoshita Koichi Goto Kazunori Fujimoto Michael Pignatello Yoshimi Tsuchiya Kazuhiko Mori Source Type: research

Reversible and monitorable nephrotoxicity in rats by the novel potent transcriptional enhanced associate domain (TEAD) inhibitor, K-975
In conclusion, this study revealed that in rats, oral K-975 treatment induced severe proteinuria by podocyte foot process effacement, which was reversible and monitorable by the urinary albumin index, suggesting important information for developing K-975 as an anticancer drug.PMID:38556354 | DOI:10.2131/jts.49.175 (Source: Journal of Toxicological Sciences)
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Hironori Otsuki Takeshi Uemori Yohei Inai Yui Suzuki Tetsuro Araki Ken-Ichiro Nan-Ya Kouichi Yoshinari Source Type: research

Transcriptome analysis of cultured human vascular endothelial cells after γ-ray irradiation and correlation analysis with ATP, ADP, and adenosine as secondary soluble factors
J Toxicol Sci. 2024;49(4):193-208. doi: 10.2131/jts.49.193.ABSTRACTVascular endothelial cells serve as barriers between blood components and subendothelial tissue and regulate the blood coagulation-fibrinolytic system. Ionizing radiation is a common physical stimulant that induces a bystander effect whereby irradiated cells influence neighboring cells through signalings, including purinergic receptor signaling, activated by adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine as secondary soluble factors. Human vascular endothelial EA.hy926 cells were cultured and irradiated with γ-rays or treate...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Tomoya Fujie Miyabi Kobayashi Lihito Ikeuchi Tsuyoshi Nakano Kazuki Kitabatake Yo Shinoda Yasuyuki Fujiwara Chika Yamamoto Mitsutoshi Tsukimoto Toshiyuki Kaji Source Type: research

Octanol/water partition coefficients estimated using retention times in reverse-phase liquid chromatography and calculated in silico as one of the determinant factors for pharmacokinetic parameter estimations of general chemical substances
J Toxicol Sci. 2024;49(4):127-137. doi: 10.2131/jts.49.127.ABSTRACTThe octanol/water partition coefficient P (logP) is a hydrophobicity index and is one of the determining factors for the pharmacokinetics of orally administered substances because it influences membrane permeability. To illustrate the wide-ranging variety of compounds in the chemical space, a two-dimensional data plot consisting of 25 blocks was previously proposed based on a substance's in silico chemical descriptors. The logP values of approximately 200 diverse chemicals (test plus reference compounds covering all 25 blocks of the chemical space) were est...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Koichiro Adachi Makiko Shimizu Fumiaki Shono Kimito Funatsu Hiroshi Yamazaki Source Type: research

Histological differences between the central and peripheral areas of the testes of busulfan-administered mice
In this study, busulfan was intraperitoneally injected at 40 mg/kg body weight into C57BL/6J male mice. After 28 days, in busulfan-treated mice, the diameters of seminiferous tubules were significantly higher in the central than in the peripheral area of the testes. The seminiferous tubular areas also significantly decreased in the peripheral areas compared with the central areas. The number of germ cells per seminiferous tubule was significantly higher in the central than in the peripheral area. Sertoli cell nuclei were detached into the lumen in the peripheral area. The number of Leydig cells was significantly lower in t...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Hidenobu Miyaso Satoshi Yokota Kousuke Suga Yui Hashimoto C éline Kouno Kenta Nagahori Masahiro Itoh Satoshi Kitajima Source Type: research

Comparison of the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin
The objective of this study was to evaluate the effect of AGIQ on the gut microbiota of animals in different dose groups. Male rats and mice received different doses of AGIQ (1.5%, 3%, or 5% w/v) in diet for carcinogenic or chronic toxicity studies (rasH2 mice: 6 months; Sprague-Dawley rats: 12 months). Male minipigs received 100, 300, or 1000 mg/kg/day for 28 days. Fecal samples were collected from the different animal species and analyzed using 16S-rRNA gene sequencing. No significant changes were observed in alpha and beta diversity of the gut microbiota. Characteristic bacteria that responded to AGIQ were identified in...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Hong Liu Ryo Inoue Mihoko Koyanagi Shim-Mo Hayashi Gen Watanabe Kentaro Nagaoka Source Type: research

Effective in vitro evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells
In conclusion, an in vitro assay using human and animal MRGPRX2-expressing cells would be an effective platform to investigate the mechanism and predict the human risk of histamine release observed in nonclinical studies.PMID:38556353 | DOI:10.2131/jts.49.163 (Source: Journal of Toxicological Sciences)
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Eri Hamamura-Yasuno Junzo Kinoshita Koichi Goto Kazunori Fujimoto Michael Pignatello Yoshimi Tsuchiya Kazuhiko Mori Source Type: research

Reversible and monitorable nephrotoxicity in rats by the novel potent transcriptional enhanced associate domain (TEAD) inhibitor, K-975
In conclusion, this study revealed that in rats, oral K-975 treatment induced severe proteinuria by podocyte foot process effacement, which was reversible and monitorable by the urinary albumin index, suggesting important information for developing K-975 as an anticancer drug.PMID:38556354 | DOI:10.2131/jts.49.175 (Source: Journal of Toxicological Sciences)
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Hironori Otsuki Takeshi Uemori Yohei Inai Yui Suzuki Tetsuro Araki Ken-Ichiro Nan-Ya Kouichi Yoshinari Source Type: research

Transcriptome analysis of cultured human vascular endothelial cells after γ-ray irradiation and correlation analysis with ATP, ADP, and adenosine as secondary soluble factors
J Toxicol Sci. 2024;49(4):193-208. doi: 10.2131/jts.49.193.ABSTRACTVascular endothelial cells serve as barriers between blood components and subendothelial tissue and regulate the blood coagulation-fibrinolytic system. Ionizing radiation is a common physical stimulant that induces a bystander effect whereby irradiated cells influence neighboring cells through signalings, including purinergic receptor signaling, activated by adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine as secondary soluble factors. Human vascular endothelial EA.hy926 cells were cultured and irradiated with γ-rays or treate...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Tomoya Fujie Miyabi Kobayashi Lihito Ikeuchi Tsuyoshi Nakano Kazuki Kitabatake Yo Shinoda Yasuyuki Fujiwara Chika Yamamoto Mitsutoshi Tsukimoto Toshiyuki Kaji Source Type: research

Octanol/water partition coefficients estimated using retention times in reverse-phase liquid chromatography and calculated in silico as one of the determinant factors for pharmacokinetic parameter estimations of general chemical substances
J Toxicol Sci. 2024;49(4):127-137. doi: 10.2131/jts.49.127.ABSTRACTThe octanol/water partition coefficient P (logP) is a hydrophobicity index and is one of the determining factors for the pharmacokinetics of orally administered substances because it influences membrane permeability. To illustrate the wide-ranging variety of compounds in the chemical space, a two-dimensional data plot consisting of 25 blocks was previously proposed based on a substance's in silico chemical descriptors. The logP values of approximately 200 diverse chemicals (test plus reference compounds covering all 25 blocks of the chemical space) were est...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Koichiro Adachi Makiko Shimizu Fumiaki Shono Kimito Funatsu Hiroshi Yamazaki Source Type: research

Histological differences between the central and peripheral areas of the testes of busulfan-administered mice
In this study, busulfan was intraperitoneally injected at 40 mg/kg body weight into C57BL/6J male mice. After 28 days, in busulfan-treated mice, the diameters of seminiferous tubules were significantly higher in the central than in the peripheral area of the testes. The seminiferous tubular areas also significantly decreased in the peripheral areas compared with the central areas. The number of germ cells per seminiferous tubule was significantly higher in the central than in the peripheral area. Sertoli cell nuclei were detached into the lumen in the peripheral area. The number of Leydig cells was significantly lower in t...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Hidenobu Miyaso Satoshi Yokota Kousuke Suga Yui Hashimoto C éline Kouno Kenta Nagahori Masahiro Itoh Satoshi Kitajima Source Type: research

Comparison of the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin
The objective of this study was to evaluate the effect of AGIQ on the gut microbiota of animals in different dose groups. Male rats and mice received different doses of AGIQ (1.5%, 3%, or 5% w/v) in diet for carcinogenic or chronic toxicity studies (rasH2 mice: 6 months; Sprague-Dawley rats: 12 months). Male minipigs received 100, 300, or 1000 mg/kg/day for 28 days. Fecal samples were collected from the different animal species and analyzed using 16S-rRNA gene sequencing. No significant changes were observed in alpha and beta diversity of the gut microbiota. Characteristic bacteria that responded to AGIQ were identified in...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Hong Liu Ryo Inoue Mihoko Koyanagi Shim-Mo Hayashi Gen Watanabe Kentaro Nagaoka Source Type: research

Effective in vitro evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells
In conclusion, an in vitro assay using human and animal MRGPRX2-expressing cells would be an effective platform to investigate the mechanism and predict the human risk of histamine release observed in nonclinical studies.PMID:38556353 | DOI:10.2131/jts.49.163 (Source: Journal of Toxicological Sciences)
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Eri Hamamura-Yasuno Junzo Kinoshita Koichi Goto Kazunori Fujimoto Michael Pignatello Yoshimi Tsuchiya Kazuhiko Mori Source Type: research

Reversible and monitorable nephrotoxicity in rats by the novel potent transcriptional enhanced associate domain (TEAD) inhibitor, K-975
In conclusion, this study revealed that in rats, oral K-975 treatment induced severe proteinuria by podocyte foot process effacement, which was reversible and monitorable by the urinary albumin index, suggesting important information for developing K-975 as an anticancer drug.PMID:38556354 | DOI:10.2131/jts.49.175 (Source: Journal of Toxicological Sciences)
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Hironori Otsuki Takeshi Uemori Yohei Inai Yui Suzuki Tetsuro Araki Ken-Ichiro Nan-Ya Kouichi Yoshinari Source Type: research

Transcriptome analysis of cultured human vascular endothelial cells after γ-ray irradiation and correlation analysis with ATP, ADP, and adenosine as secondary soluble factors
J Toxicol Sci. 2024;49(4):193-208. doi: 10.2131/jts.49.193.ABSTRACTVascular endothelial cells serve as barriers between blood components and subendothelial tissue and regulate the blood coagulation-fibrinolytic system. Ionizing radiation is a common physical stimulant that induces a bystander effect whereby irradiated cells influence neighboring cells through signalings, including purinergic receptor signaling, activated by adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine as secondary soluble factors. Human vascular endothelial EA.hy926 cells were cultured and irradiated with γ-rays or treate...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Tomoya Fujie Miyabi Kobayashi Lihito Ikeuchi Tsuyoshi Nakano Kazuki Kitabatake Yo Shinoda Yasuyuki Fujiwara Chika Yamamoto Mitsutoshi Tsukimoto Toshiyuki Kaji Source Type: research