Journal of Toxicological Sciences最新文献_第3页

False negatives in the modified ESR-based photosafety test (ESR-PT) caused by ultraviolet-C light. 改良esr光安全试验（ESR-PT）中紫外光引起的假阴性。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.1

Masumi Hinoshita, Yosuke Maeda, Akio Kawai, Masahiro Takeyoshi

{"title":"False negatives in the modified ESR-based photosafety test (ESR-PT) caused by ultraviolet-C light.","authors":"Masumi Hinoshita, Yosuke Maeda, Akio Kawai, Masahiro Takeyoshi","doi":"10.2131/jts.51.1","DOIUrl":"https://doi.org/10.2131/jts.51.1","url":null,"abstract":"The modified electron spin resonance (ESR)-based photosafety test (ESR-PT) is a non-animal prediction test using ESR spectroscopy that is applicable to hydrophobic and colored chemicals and the results show high concordance with existing photosafety reference information. The modified ESR-PT is based on the detection of singlet oxygen and free radical photoproducts generated from chemicals in the presence of 4-hydroxy-2,2,6,6-tetramethyl-piperidine (4-hydroxy-TEMP). We obtained false-negative results caused by signal increment of the control solution, which is used as the denominator of the classifier in the modified ESR-PT, when we used a different type of lighting unit (type I) to the previously used type of lighting unit (type II). Spectral measurement of the irradiated light from the light sources revealed that the type I lighting unit emitted stronger UV-C light than the type II lighting unit. Consequently, as UV-C absorption of 4-hydroxy-TEMP (λmax<210 nm) was confirmed, we repeated the modified ESR-PT using a type I lighting unit equipped with a UV-C cut filter, which led to an apparent decrease of the signal increment in the control solution, and all the false-negative-judged chemicals correctly tested positive but a false positive result was also noted. Therefore, installation of a UV-C cut filter in the lighting unit in modified ESR-PT appears to be a reliable solution for avoiding UV-C light-mediated false-negative results. However, it may also be necessary to reconsider the classifier used in ESR-PT to avoid obtaining false-positive results when using a UV-C cut filter.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 1","pages":"1-6"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ordinal association between cytochrome P450 inhibition and hepatotoxicity severity in rats. 细胞色素P450抑制与大鼠肝毒性程度的有序关系。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.321

Nana Uchida, Minami Shibata, Akira Ooka, Ryota Shizu, Jun-Ichi Takeshita, Kouichi Yoshinari

{"title":"Ordinal association between cytochrome P450 inhibition and hepatotoxicity severity in rats.","authors":"Nana Uchida, Minami Shibata, Akira Ooka, Ryota Shizu, Jun-Ichi Takeshita, Kouichi Yoshinari","doi":"10.2131/jts.51.321","DOIUrl":"https://doi.org/10.2131/jts.51.321","url":null,"abstract":"Cytochrome P450s (P450s) are essential for xenobiotic metabolism, and their inhibition is associated with chemical-induced liver toxicity. While qualitative associations between P450 inhibition and hepatotoxicity have been reported, the quantitative relationship between the degree of inhibition and the severity of hepatotoxicity remains unclear. In this study, we explored the quantitative association between P450 inhibition and hepatotoxicity using lowest observed effect levels (LOELs) from rat repeated-dose toxicity (RDT) studies on 326 chemicals. Inhibitory activities against seven rat P450 isoforms were compared between compounds positive and negative for six liver-related group endpoints (gEPs). The results revealed that inhibitory activity against CYP1A1, CYP2B1, CYP2C6, and CYP3A2 was significantly higher in compounds positive for hepatocellular hypertrophy or dyslipidemia than in negative compounds. Although regression analyses did not show clear linear relationships between P450 inhibition and LOELs, nonparametric trend tests revealed modest monotonic associations, with increased P450 inhibition corresponding to lower LOELs. To identify structural factors influencing inhibition among highly toxic compounds, we compared molecular descriptors between those exhibiting strong or weak P450 inhibition. Descriptors related to aqueous solubility, Verhaar baseline toxicity, and structural complexity were consistently higher in the weak-inhibition group across multiple P450-gEP combinations. These findings suggest that inhibition of CYP1A1, CYP2B1, CYP2C6, and CYP3A2 partly contributes to the severity of hepatocellular hypertrophy and dyslipidemia, whereas highly toxic compounds with low P450 inhibition may exert their toxicity through P450-independent mechanisms.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 5","pages":"321-330"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical features and outcomes of acute paracetamol poisoning in a resource-limited setting: observations from 96 patients in Vietnam. 资源有限地区急性扑热息痛中毒的临床特征和结果：来自越南96例患者的观察

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.149

Nguyen Dang Duc

引用次数: 0

Triphenyl phosphate-induced cell injury through endoplasmic reticulum stress in human kidney cells. 磷酸三苯酯通过内质网应激诱导人肾细胞损伤。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.215

Hejun Duan, Liyu Huang, Yixing Feng

{"title":"Triphenyl phosphate-induced cell injury through endoplasmic reticulum stress in human kidney cells.","authors":"Hejun Duan, Liyu Huang, Yixing Feng","doi":"10.2131/jts.51.215","DOIUrl":"10.2131/jts.51.215","url":null,"abstract":"Triphenyl phosphate (TPhP) is a typical organophosphorus flame retardant (OPFR). Due to its high production and widespread use, exposure to TPhP has been shown to induce nephrotoxicity in animal models. Endoplasmic reticulum (ER) stress is found to be correlated with kidney disease caused by exogenous environmental pollutants. Nevertheless, the connection between ER stress and the nephrotoxic effects caused by TPhP is limited. In this study, human renal tubular epithelial cells (HKC) were chosen to explore the effects of TPhP on cell viability, cell apoptosis, and ER stress. Our study indicated that cell viability was dramatically inhibited in a dose-dependent manner. The half lethal concentration (LC50) value of TPhP after 48 hr exposure is 126.4 µM. A concentration-related Caspase-3 activation and apoptosis occurrence were observed in HKC cells following TPhP treatment. Additionally, the induction of ER stress was demonstrated by the up-regulated expression of ER stress-related genes. To elucidate the role of ER stress in cell damage, sodium 4-phenylbutyrate (4-PBA), an ER stress inhibitor, was used in the co-treatment with TPhP. Results revealed that 4-PBA treatment effectively alleviated TPhP-induced ER stress and cytotoxicity in HKC cells. Taken together, these results indicated that ER stress plays a primary role in TPhP-induced nephrocyte damage and 4-PBA could attenuate these effects.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 3","pages":"215-225"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of toxicokinetic interactions mediated by plasma protein binding during amoxapine intoxication. 评估阿莫沙平中毒期间血浆蛋白结合介导的毒性动力学相互作用。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.31

Akifumi Okamoto, Yoshitaka Yamazaki, Natsumi Hattori-Usami, Kenji Momo, Asuka Kaizaki-Mitsumoto, Satoshi Numazawa

{"title":"Evaluation of toxicokinetic interactions mediated by plasma protein binding during amoxapine intoxication.","authors":"Akifumi Okamoto, Yoshitaka Yamazaki, Natsumi Hattori-Usami, Kenji Momo, Asuka Kaizaki-Mitsumoto, Satoshi Numazawa","doi":"10.2131/jts.51.31","DOIUrl":"https://doi.org/10.2131/jts.51.31","url":null,"abstract":"Toxicity enhancement mediated by plasma protein binding during intoxication remains poorly understood. It is known that in mice, brain penetration of amoxapine (AMX) increases nonlinearly with increasing doses; therefore, this study investigated its potential to enhance toxicity via plasma protein binding. AMX was added to mouse or human plasma and adjusted to therapeutic, toxic, and lethal concentrations. The plasma protein-binding ratio and free AMX concentration were measured using ultrafiltration and equilibrium dialysis. Furthermore, the binding ratios of varying concentrations of chlorpromazine, which is often co-administered with AMX in cases of overdose, was analyzed in the presence of therapeutic AMX concentrations. The binding ratio of AMX exceeded 90%, thereby demonstrating a high binding rate; however, this ratio was lower in human plasma than in mice. A nonlinear increase in free AMX concentration was observed in mouse plasma, particularly at high concentrations. In contrast, free AMX concentration showed a linear increase in human plasma. Neither the therapeutic nor toxic concentration of chlorpromazine produced any visible effects on the plasma protein binding ratio or the free AMX concentration. These results suggest that protein binding of AMX is more readily saturated in mouse plasma than in human plasma. In addition, chlorpromazine inhibits AMX binding to α1-acid glycoprotein; however, AMX may alternatively binds to albumin, which results in no apparent change in the total binding ratio. Further insights into the toxicokinetic interactions mediated by plasma protein binding are also needed for various toxic substances other than AMX.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 1","pages":"31-44"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal low-dose MeHg exposure leads to proteomic and transcriptomic alterations consistent with neurodegenerative disease in the cerebellum of C57BL/6 mice. 产前低剂量甲基汞暴露导致C57BL/6小鼠小脑中与神经退行性疾病一致的蛋白质组学和转录组学改变。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.89

Allison Loan, Rochelle D'Mello, Yingxi Li, Tuana Nurkan, Zoran Minic, Jing Wang, Hing Man Chan

{"title":"Prenatal low-dose MeHg exposure leads to proteomic and transcriptomic alterations consistent with neurodegenerative disease in the cerebellum of C57BL/6 mice.","authors":"Allison Loan, Rochelle D'Mello, Yingxi Li, Tuana Nurkan, Zoran Minic, Jing Wang, Hing Man Chan","doi":"10.2131/jts.51.89","DOIUrl":"https://doi.org/10.2131/jts.51.89","url":null,"abstract":"Methylmercury (MeHg) is a global pollutant that readily crosses the blood-brain barrier and placenta, posing significant risks to fetal neurodevelopment. While the cerebellum is a recognized target of MeHg toxicity in adults, the effect of fetal exposure remains poorly defined. In this study, we investigated the neurotoxic effects of low-dose MeHg exposure (0.2 ppm via drinking water) on the cerebellums of prenatal C57BL/6 mice using integrated transcriptomic and proteomic analyses. Cerebellar tissues collected from postnatal day 90-120 (P90-120) mice (n = 3/group) were processed for RNA sequencing and proteomics analysis. Differentially expressed genes (DEGs) and proteins (DEPs) revealed significant changes (n = 4/group) in multiple pathways associated with neurodegeneration, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Overlapping transcriptomic and proteomic findings identified potential underlying mechanisms such as chemical carcinogenesis driven by reactive oxygen species and retrograde endocannabinoid signaling, underscoring the central role of oxidative stress in MeHg-induced neurotoxicity. Collectively, these results indicate that prenatal MeHg exposure induces persistent molecular alterations consistent with neurodegenerative processes and synaptic dysfunction, despite the absence of overt behavioral changes at the time of sacrifice. The long-term consequences for delayed symptom onset and the potential contribution of these changes to the etiology of neurodevelopmental disorders warrant further investigation.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 2","pages":"89-100"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Air pollution and COPD: Unveiling the mechanisms through network toxicology and transcriptomics. 空气污染与慢性阻塞性肺病：通过网络毒理学和转录组学揭示机制。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.275

Dong Song, Lin Xie, Xuege Gao, Yushan Chen, Chunjun Zhong, Huicong Li, Shaofeng Zhan, Leshen Lian

{"title":"Air pollution and COPD: Unveiling the mechanisms through network toxicology and transcriptomics.","authors":"Dong Song, Lin Xie, Xuege Gao, Yushan Chen, Chunjun Zhong, Huicong Li, Shaofeng Zhan, Leshen Lian","doi":"10.2131/jts.51.275","DOIUrl":"https://doi.org/10.2131/jts.51.275","url":null,"abstract":"Over the past five decades, air pollution has posed a growing threat to human health, particularly affecting the respiratory system. This study aims to investigate the potential molecular mechanisms underlying the relationship between exposure to air pollutants and the development of COPD and to identify potential gene targets that may play a key role in this process. In this study, researchers used several publicly available databases to obtain target genes related to air pollutants and COPD, determine the overlapping genes between them and performed GO and KEGG enrichment analyses to elucidate the underlying mechanisms. Cross-validation was performed using multiple datasets from the Gene Expression Omnibus (GEO) database to screen out candidate targets, and molecular docking techniques were utilized to investigated molecular interactions between candidate targets and air pollutants. Candidate targets were subsequently validated and analyzed using immune cell infiltration analysis, single-cell transcriptome data, risk prediction model construction and clinical data to further elucidate their relationship with COPD. Findings suggest that HDAC9, DPP9 and KCNN4 are candidate targets of air pollutants that are potentially involved in COPD development. These results offer new insights into the potential molecular mechanisms linking air pollution exposure to COPD and underscore the need for further in-depth research on air pollution issues.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 4","pages":"275-294"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of blood microsampling (50 μL) on toxicological assessment in rats treated with tacrine, a drug known to have adverse effects that increase neutrophils. 血液微采样（50 μL）对大鼠服用他克林毒理学评估的影响，他克林是一种已知有增加中性粒细胞的副作用的药物。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.19

Norimichi Hattori, Yusuke Shibui, Yoichi Tanaka, Yoshiro Saito

{"title":"Effect of blood microsampling (50 μL) on toxicological assessment in rats treated with tacrine, a drug known to have adverse effects that increase neutrophils.","authors":"Norimichi Hattori, Yusuke Shibui, Yoichi Tanaka, Yoshiro Saito","doi":"10.2131/jts.51.19","DOIUrl":"https://doi.org/10.2131/jts.51.19","url":null,"abstract":"To promote the 3Rs in toxicological assessment, the recommendation for blood microsampling in toxicokinetic evaluation is noted in the ICH Harmonized Guideline S3A Q&As. However, there are only a few articles reporting the practical application of microsampling in the toxicological assessment with toxic drugs. In this study, we investigate the effect of microsampling on toxicological assessment in rats treated with tacrine, which is known to have toxic effects that induce an increase in neutrophils and behavioral abnormalities. Thirty female Sprague-Dawley rats were divided into microsampling (MS) and non-microsampling (non-MS) groups, and orally administered tacrine once daily at dose levels of 0 (vehicle only), 3 and 10 mg/kg bw for 28 days (each group: n=5). In the MS group, blood samples (50 μL/time point) were collected at 6 time points on day 1 and 7 time points on day 28 to 29. All the animals underwent necropsy on day 29. By comparing the results of toxicological and toxicokinetic analysis between the MS and non-MS groups, we validated effects of microsampling for toxicological assessment. Although increase in neutrophils and repeated stereotypic behaviors were observed as toxic effects in the rats administered tacrine, we could not find any difference between the MS and non-MS groups, and also found that microsampling did not affect any other data from toxicological and toxicokinetic analysis. In conclusion, blood microsampling appeared to be a feasible technique for the toxicity study of tacrine and was considered to be applicable in the toxicity study of even drugs with toxic effects on hematological parameters, such as an increase in neutrophils.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 1","pages":"19-30"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Considerations for infection risks identified in target safety review. 对目标安全性审查中确定的感染风险的考虑。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.251

Yuichiro Amano, Yoshitaka Inui, Satoko Yoshioka, Jodi Goodwin

{"title":"Considerations for infection risks identified in target safety review.","authors":"Yuichiro Amano, Yoshitaka Inui, Satoko Yoshioka, Jodi Goodwin","doi":"10.2131/jts.51.251","DOIUrl":"https://doi.org/10.2131/jts.51.251","url":null,"abstract":"Target Safety Review (TSR) is a document that triggers the Target Safety Assessment and is designed to predict and identify on-target safety risks. However, with regard to the anticipated on-target risks extracted by TSR, nonclinical toxicity studies sometimes have limitations in predicting clinical safety risks. In this study, we investigated whether nonclinical toxicity studies could predict clinical infection risks expected in TSR. Using the OFF-X database, we identified 942 targets and 1323 drugs associated with infection risks. Through successive filters, i.e., applying \"drug alert\", \"on-target\", \"causality with severity\", \"class score\", and \"evidence levels\", biologics became the focus, resulting in six targets and 17 drugs approved by PMDA. From PMDA reports, package inserts, and interview forms, we extracted immune-related findings in nonclinical toxicity studies and infection risks in clinical settings to analyze predictivity by target. Our survey shows clear immune-related toxicity in nonclinical studies of CD20 inhibitors (obinutuzumab, ofatumumab, rituximab), TNF-alpha inhibitors (adalimumab, golimumab), and IL-6R antagonists (sarilumab, tocilizumab). Indicators included B cell depletion, thymus atrophy, and decreased neutrophils. For IL-17, IL-23, and IL-1beta inhibitors, nonclinical studies did not always predict the infection risks observed in clinical settings. Although nonclinical toxicity studies sometimes provided insights into potential infection risks which can be anticipated by its target, their predictive power for specific mechanism of actions and infections appeared limited. Understanding the MOAs and biological background of the drug through the TSR and identifying and mitigating risks early in the project are essential for the safe development of new therapeutic agents.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 4","pages":"251-258"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hydrogen sulfide donor GYY4137 attenuates RANKL-induced osteoclast differentiation and multi-nucleation. 硫化氢供体GYY4137减弱rankl诱导的破骨细胞分化和多核。

IF 1.5 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.267

Tomohiro Takagi, Hirofumi Inoue, Hiromu Morimoto, Nobuyuki Takahashi, Mariko Uehara

{"title":"Hydrogen sulfide donor GYY4137 attenuates RANKL-induced osteoclast differentiation and multi-nucleation.","authors":"Tomohiro Takagi, Hirofumi Inoue, Hiromu Morimoto, Nobuyuki Takahashi, Mariko Uehara","doi":"10.2131/jts.51.267","DOIUrl":"https://doi.org/10.2131/jts.51.267","url":null,"abstract":"Hydrogen sulfide (H2S) is a novel gasotransmitter produced in mammalian cells and is known to various regulate physiological functions. Previous study reported that an imbalance in H2S metabolism is associated with defective bone homeostasis. However, the detailed mechanism of how H2S affect osteoclast differentiation remains unclear. In the present study, we demonstrated that the effect of H2S donor GYY4137 on osteoclast differentiation and multi-nucleation. Treatment of GYY4137 significantly decreased the number of receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive cells and inhibited the expression of osteoclast-related genes, nuclear factor of activated T-cells 1 (NFATc1) and Cathepsin K(Ctsk). Additionally, the increased gene expression of dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast stimulatory transmembrane protein (OC-STAMP), and v-ATPase V0 subunit d2 (Atp6v0d2), which are cell-cell fusion-related molecules by RANKL treatment, was attenuated by GYY4137. Furthermore, GYY4137 suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK1/2, and p38MAPK, compared to RANKL-treated cells. Thus, our data suggested that H2S donor GYY4137 as a novel osteoclast genesis inhibitor, significantly decreases osteoclast differentiation and multi-nucleation by inhibiting the expression of the cell-cell fusion molecules.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 4","pages":"267-274"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0