Journal of Toxicological Sciences最新文献_第2页

The effects of anemia on the timing of pubertal onset in female rats. 贫血对雌性大鼠青春期开始时间的影响。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.83

Mariko Shimada, Yoshinori Hosokawa, Ryo Ihara, Keiko Ogata, Katsumasa Iwashita, Ryoko Matsuyama, Hiroyuki Asano

{"title":"The effects of anemia on the timing of pubertal onset in female rats.","authors":"Mariko Shimada, Yoshinori Hosokawa, Ryo Ihara, Keiko Ogata, Katsumasa Iwashita, Ryoko Matsuyama, Hiroyuki Asano","doi":"10.2131/jts.50.83","DOIUrl":"10.2131/jts.50.83","url":null,"abstract":"Attainment of vaginal patency is an endpoint for the onset of puberty in female animals in toxicity studies. It is widely acknowledged that certain substances with endocrine-modulating effects can influence the timing of puberty in female rats and that factors unrelated to endocrine mechanisms, such as malnutrition and stress, can also affect pubertal onset. Some epidemiological studies have also suggested a link between anemia and delay in pubertal onset in women, however, little is known regarding the relation between hematological changes and female pubertal onset in experimental animals. The purpose of this study was to examine the effects of anemia during the prepubertal period on pubertal onset and reproductive organs in female rats. In this study, anemia was induced by drawing a certain amount of blood from the jugular vein or by intraperitoneal administration of phenylhydrazine, a well-known inducer of hemolytic anemia. As a result, both treatment groups showed a transient anemia characterized by an approximately 20-35% decrease in hemoglobin levels compared to the control group. Anemia in these female rats produced no obvious changes in body weight on each postnatal day and had no effect on the weights and histopathology of reproductive organs after sexual differentiation, but the age at vaginal opening (VO) was delayed and the body weight at VO was higher than the same parameters in the control group. These results suggest that anemia in prepubertal females could cause a delay in pubertal onset.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 2","pages":"83-95"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080638","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

Prolyl hydroxylase domain enzymes (isoforms 1-3, PHD1-3), but not factor-inhibiting HIF-1 (FIH-1), interact with the IKK complex and attenuate LPS-activated NF-kappa-B. 脯氨酸羟化酶结构域酶（异构体1-3，PHD1-3），但不抑制因子HIF-1 (FIH-1)，与IKK复合物相互作用并减弱lps激活的nf - κ b。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.105

Akiyoshi Tamura, Koji Kitayama, Mutsumi Adachi, Kentaro Hashimoto, Ami Oguro, Susumu Imaoka

{"title":"Prolyl hydroxylase domain enzymes (isoforms 1-3, PHD1-3), but not factor-inhibiting HIF-1 (FIH-1), interact with the IKK complex and attenuate LPS-activated NF-kappa-B.","authors":"Akiyoshi Tamura, Koji Kitayama, Mutsumi Adachi, Kentaro Hashimoto, Ami Oguro, Susumu Imaoka","doi":"10.2131/jts.50.105","DOIUrl":"10.2131/jts.50.105","url":null,"abstract":"Hypoxia induces the expression of nuclear factor kappa B (NF-kappa-B). NF-kappa-B functions by forming dimers from five main subunits: p65 (RelA), RelB, p52, p50, and c-Rel. In the classical pathway, NF-kappa-B activity is regulated by the degradation-inducing factor I kappa B kinase (IKK). IKK is composed of an α/β isomer and essential modulator NEMO (γ) subunits in the classical pathway, which may be the major pathway for NF-kappa-B signaling. In the present study, we focused on factor-inhibiting HIF-1 (FIH-1) and Prolyl hydroxylase domain enzyme (PHD), which have been identified as oxygen concentration-dependent regulators of HIF-1α. PHD has three isoforms: PHD1, PHD2, and PHD3, which have different affinities towards HIF-1α. We examined the interactions between IKKα/β and PHD1-3 by immunoprecipitation. PHDs efficiently interacted with IKKα/β. Furthermore, the overexpression of PHDs decreased the mRNA level of IL-1β, a downstream factor of NF-kappa-B activated by LPS. The overexpression of PHD1 and PHD2 markedly reduced IKKα/β protein levels; however, the effects of PHD3 were weaker than those of PHD1 and PHD2. Mutants of the active sites of PHD1 and PHD2 did not decrease IKKα/β protein levels, and a mutation in the active site of PHD3 did not affect IKKα/β protein levels. We also attempted to investigate the interactions of FIH-1 with IKKα/β and IκBα by immunoprecipitation, but found none. Moreover, IKKα/β and p65 protein levels were not affected by the overexpression of FIH-1. Collectively, these results suggest that PHDs directly regulated IKK protein levels, while FIH-1 did not affect the NF-kappa-B classical pathway.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"105-116"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537436","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

Reported liver toxicity of food chemicals in rats extrapolated to humans using virtual human-to-rat hepatic concentration ratios generated by pharmacokinetic modeling with machine learning-derived parameters. 通过使用机器学习衍生参数的药代动力学建模产生的虚拟人-大鼠肝脏浓度比，将食品化学物质在大鼠中的肝脏毒性外推到人类。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.205

Koichiro Adachi, Manato Hosoi, Yukia Shimura, Makiko Shimizu, Hiroshi Yamazaki

{"title":"Reported liver toxicity of food chemicals in rats extrapolated to humans using virtual human-to-rat hepatic concentration ratios generated by pharmacokinetic modeling with machine learning-derived parameters.","authors":"Koichiro Adachi, Manato Hosoi, Yukia Shimura, Makiko Shimizu, Hiroshi Yamazaki","doi":"10.2131/jts.50.205","DOIUrl":"https://doi.org/10.2131/jts.50.205","url":null,"abstract":"Pharmacokinetic data are not generally available for evaluating the toxicological potential of food chemicals. A simplified physiologically based pharmacokinetic (PBPK) model has been established to evaluate internal exposures to chemicals in rats or humans with no reference to in vitro or in vivo experimental data. In this study, reported liver toxicity levels in rats were extrapolated to humans using virtual hepatic concentration-time curves (AUC) as the interspecies factor. Virtual liver exposures to 27 lipophilic food chemicals (octanol-water partition coefficient logP >1) with reported rat hepatic lowest-observed-effect levels (LOELs) of ≤1000 mg/kg/day were generated using PBPK models with input parameters obtained entirely in silico via machine learning algorithms. The resulting virtual rat and human liver AUCs were correlated (n = 27, r = 0.52, p < 0.01). However, AUCs for the phenolic compounds emodin, isoeugenol, and tert-butylhydroquinone, which have reported rat LOEL values of ≤300 mg/kg/day, were located outside the relatively wide 95% confidence interval, indicating more extensive hepatic elimination in rats than in humans. In vitro depletion of tert-butylhydroquinone in rat liver fractions via sulfation was confirmed to be faster than that in humans. For emodin, isoeugenol, and tert-butylhydroquinone, human-to-rat AUC ratios ranged from 10- to 13-fold; consequently, their extrapolated human hepatic LOEL values were estimated as ≤30 mg/kg/day, i.e., one order of magnitude smaller than the rat LOELs. Despite the small number of lipophilic food chemicals considered here, the PBPK modeling approach using in silico-generated input parameters for rats and humans has the potential to facilitate toxicological studies.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 5","pages":"205-213"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063961","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

Construction and evaluation of an open-source database for inhalation-based physiologically based kinetic modeling of selected categories for industrial chemicals. 基于吸入的基于生理动力学建模的工业化学品选定类别的开源数据库的构建和评估。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.57

Shigechika Yamamoto, Kikuo Yoshida, Mariko Matsumoto, Takashi Yamada

{"title":"Construction and evaluation of an open-source database for inhalation-based physiologically based kinetic modeling of selected categories for industrial chemicals.","authors":"Shigechika Yamamoto, Kikuo Yoshida, Mariko Matsumoto, Takashi Yamada","doi":"10.2131/jts.50.57","DOIUrl":"10.2131/jts.50.57","url":null,"abstract":"A physiologically based kinetic (PBK) model is used for predicting chemical concentrations of toxicological concern in target tissues. Such models are important for understanding toxicokinetics. However, it is challenging to obtain chemical-specific empirical parameter values used for PBK modeling. Thus, developing methods predicting these values is necessary. Herein, we researched PBK models of inhalation exposure to industrial chemicals and developed a database of parameters of approximately 200 chemicals in humans and rodents. Next, the chemicals in the database were classified into three categories (I, IIA, and IIB) based on the intermolecular interactions for humans and rats. Quantitative relationships between blood/air and tissue/blood partition coefficients and physicochemical parameters were derived for the chemicals in each category. Regression analyses of blood/air and fat/blood partition coefficients against Henry's law constant and log D at pH 7.4 for chemicals in category IIA for humans, in which van der Waals and dipole-dipole interactions were involved, yielded 0.88 and 0.54 coefficients of determination, respectively. Moreover, these methods worked for other categories and species. The metabolic parameters maximal velocity (Vmax) and Michaelis-Menten constant (Km) of the chemicals that are primarily metabolized by cytochrome P450 were calculated for humans and rats. Multiple regression analyses of logs Vmax and Km against the occurrence frequency of molecular fragments showed good correlations, respectively. The aforementioned models predicted values close to the reported values for test chemicals within the applicability domains. Our approach could also be applied to other chemicals within the domains that are not included in the database.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 2","pages":"57-68"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080634","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 the barrier function of stratum corneum and viable epidermis and dermis on the skin concentration of topically applied chemicals. 角质层、活表皮和真皮层屏障功能对外敷化学药品皮肤浓度的影响。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.187

Hiroaki Todo, Takeshi Oshizaka, Syuuhei Komatsu, Kenji Sugibayashi

{"title":"Effect of the barrier function of stratum corneum and viable epidermis and dermis on the skin concentration of topically applied chemicals.","authors":"Hiroaki Todo, Takeshi Oshizaka, Syuuhei Komatsu, Kenji Sugibayashi","doi":"10.2131/jts.50.187","DOIUrl":"10.2131/jts.50.187","url":null,"abstract":"Three-dimensional cultured skin (3D skin) models have been utilized for in vitro skin permeation tests to evaluate the skin permeation rate and local effects (efficacy and toxicity) of applied chemicals, particularly from the perspective of the 3Rs (reduction, replacement, refinement) approach. The steady-state concentration of applied chemicals at different depths in the viable epidermis and dermis (VED) is affected by their skin permeation parameters, such as permeability coefficient (Kp) and partition coefficient (K) from the donor solution to the skin of the chemicals. In the present study, the steady-state concentration of chemicals in the VED of EpiDerm 606X (EpiDerm) as representative of a 3D skin model were compared with hairless rat skin. The VED concentrations of chemicals in EpiDerm were higher than those in hairless rat skin when a model hydrophilic compound, antipyrine, and a model lipophilic compound, flurbiprofen, were applied, suggesting that the barrier functions of the VED against the whole skin were higher in EpiDerm than in hairless rat skin. When an ester compound, ethyl nicotinate, was applied, the VED concentration of nicotinic acid, a metabolite of ethyl nicotinate, was lower in EpiDerm than in hairless rat skin. These differences in the VED concentrations of applied chemicals might be related to false-positives and -negatives of topical effects evaluated with 3D skin models. It is important to pay particular attention to differences in VED concentration in 3D skin models and real skin when evaluating local efficacy and toxicity using 3D skin models.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 4","pages":"187-198"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772432","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

Determination of putrefactive amine and ammonia concentrations around decomposed corpses. 腐尸周围腐胺和氨浓度的测定。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.75

Hiroaki Sato, Takahiro Umehara, Satoshi Kimura, Toshiko Tanaka, Sang-Eun Kim

{"title":"Determination of putrefactive amine and ammonia concentrations around decomposed corpses.","authors":"Hiroaki Sato, Takahiro Umehara, Satoshi Kimura, Toshiko Tanaka, Sang-Eun Kim","doi":"10.2131/jts.50.75","DOIUrl":"10.2131/jts.50.75","url":null,"abstract":"The surface of a rotting corpse is covered with liquid decomposition products that have flowed out of the body that include putrefactive amines produced via putrefaction and decarboxylation reactions of proteins. Ammonia generated by deamination is also present around the corpse as a liquid or gas. As these putrefactive substances are toxic to humans, we attempted to measure the concentration of putrefactive substances in decomposed corpses in this study. Liquid putrefaction products were collected from the surface of a corpse, and the concentrations of putrefactive amines such as histamine, tyramine, phenethylamine, and tryptamine were analyzed by LC-MS/MS. Ammonia in the liquid and air around the corpse was also measured. Putrefactive amines and ammonia were present on all corpse surfaces. The highest concentrations and postmortem days in parentheses were as follows: histamine 2.26 mg/g (15 days), tyramine 1.77 mg/g (16 days), phenethylamine 4.90 mg/g (24 days), tryptamine 1.58 mg/g (17 days) and ammonia 25.6 mg/g (24 days postmortem). The highest concentration of ammonia in the air was 1310 ppm at 24 days postmortem. The ammonia level in the air around a corpse is toxic to humans. Inhalation of putrefactive amines and ammonia can cause chemical irritation to the respiratory tract and the skin and damage the mucous membrane of the eye. Oral ingestion can also cause poisoning symptoms such as blood pressure changes and headaches. Adequate protection against putrefactive substances is required when in contact with decaying corpses.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 2","pages":"75-81"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080635","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

Induction of systemic inflammation by welding fume exposure in office workers as well as welders in welding factories. 办公室工作人员和焊接工厂的焊工接触焊接烟雾引起全身炎症。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.215

Mayumi Tsuji, Chihaya Koriyama, Tatsuto Nakane, Susumu Ueno, Yasuhiro Ishihara

{"title":"Induction of systemic inflammation by welding fume exposure in office workers as well as welders in welding factories.","authors":"Mayumi Tsuji, Chihaya Koriyama, Tatsuto Nakane, Susumu Ueno, Yasuhiro Ishihara","doi":"10.2131/jts.50.215","DOIUrl":"https://doi.org/10.2131/jts.50.215","url":null,"abstract":"Welding fumes are metal particles of 1 µm or less generated during welding. Welding fumes generated in welding factories spread throughout the workplace. However, the effects of exposure have been measured primarily in welding workers, and no research has been conducted on the effects of fumes on workplace office workers. In this study, we recruited welding and office workers who worked in the same factories at ten workplaces in Japan, mainly in the Kyushu and Kanto regions, and separated their serum after blood sampling. We also obtained serum from the general subjects of Minami-Kagoshima City, which is located far from the welding factory. Cytokines and chemokines were quantified in the serum samples, and the concentration of interleukin (IL)-1β was significantly increased in office workers and welders compared with general subjects. Importantly, the serum concentrations of IL-12p70, IL-17A, IL-33, tumor necrosis factor α, and C-C motif chemokine ligand 3 in office workers were significantly higher than those in the general subjects, and there was no significant difference in the levels of these inflammatory molecules between welders and general subjects. This study suggests that office workers exposed to high fume concentrations exhibit increased systemic inflammation. Exposure assessments should be conducted not only for welders but also for office workers to reduce exposure risks.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 5","pages":"215-221"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007435","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

Potential of connexin 32 as a predictive marker for drug-induced cholestatic liver injury in a collagen vitrigel-culture model of HepG2-NIAS cells, a new subline of HepG2 cells, with bile canaliculus-like structures. 连接蛋白32在HepG2- nias细胞（一种具有胆管样结构的HepG2细胞亚系）胶原培养模型中作为药物性胆汁淤积性肝损伤预测标志物的潜力

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.135

Miaki Uzu, Toshiaki Takezawa

{"title":"Potential of connexin 32 as a predictive marker for drug-induced cholestatic liver injury in a collagen vitrigel-culture model of HepG2-NIAS cells, a new subline of HepG2 cells, with bile canaliculus-like structures.","authors":"Miaki Uzu, Toshiaki Takezawa","doi":"10.2131/jts.50.135","DOIUrl":"10.2131/jts.50.135","url":null,"abstract":"Cholestatic drug-induced liver injury (DILI) is caused by the aberrant excretion of bile acids (BAs) from hepatocytes via bile canaliculus-like structures (BCLSs) into the bile ducts. The precise in vitro evaluation method for cholestatic DILI has not been established due to a lack of specific markers and cell resources. We previously reported that HepG2-NIAS cells cultured on a collagen vitrigel (CV) membrane formed BCLSs with high protein expression of transporters involved in the excretion of BAs, including bile salt export pump (BSEP). In this study, the potential of connexin (Cx) 32, a component of gap junction, as a predictive marker for cholestatic DILI was investigated using a CV-culture model of HepG2-NIAS cells. The cells were treated with 7 drugs with different DILI-risk levels, and cell toxicity and Cx32 expression were evaluated. Cell toxicity was significantly increased not only by high DILI-risk drugs (troglitazone and cyclosporine A) but also by chlorpromazine with low DILI-risk. Furthermore, cell toxicity of troglitazone was not enhanced by a co-treatment with taurocholate, suggesting the low involvement of inhibition of BA excretion via BSEP in cholestatic DILI. In contrast, the total protein expression of Cx32 and co-localization of Cx32 and F-actin, which is composed of BCLSs, were significantly increased only by high DILI-risk drugs. Treatment with high DILI-risk drugs also induced the increased protein expression of zonula occludens (ZO)-1, which supports BCLSs concerted with Cx32. These results suggest that Cx32 expression in the CV-culture model of HepG2-NIAS cells may be a prominent predictive marker for cholestatic DILI.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"135-145"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537434","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

Perfluorooctane sulfonate induces hepatotoxicity through promoting inflammation, cell death and autophagy in a rat model. 在大鼠模型中，全氟辛烷磺酸通过促进炎症、细胞死亡和自噬诱导肝毒性。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.45

Leilei Tang, Jianjun Zhu, Sheng Zhuge, Jiawen Yu, Guojun Jiang

{"title":"Perfluorooctane sulfonate induces hepatotoxicity through promoting inflammation, cell death and autophagy in a rat model.","authors":"Leilei Tang, Jianjun Zhu, Sheng Zhuge, Jiawen Yu, Guojun Jiang","doi":"10.2131/jts.50.45","DOIUrl":"10.2131/jts.50.45","url":null,"abstract":"Perfluorooctane sulfonate (PFOS) is reported to cause hepatotoxicity in animals and humans. However, the underlying mechanism by which it affects organelle toxicity in the liver are not well elucidated yet. This study aimed to investigate the mechanisms underlying PFOS-induced hepatic toxicity, focusing on inflammation, cell death, and autophagy. We established a PFOS-exposed Sprague-Dawley (SD) rat liver injury model by intraperitoneal injection of PFOS (1 mg/kg and 10 mg/kg body weight) every alternate day for 15 days. Our findings indicated that PFOS increased liver weight, caused lipid disorder and hepatic steatosis in rats. Meanwhile, PFOS disrupted the structure of mitochondria, increased accumulation of reactive oxygen species (ROS), repressed superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels, and elevated malondialdehyde (MDA) and nitric oxide synthase (NOS) amounts. We found PFOS induced inflammation as evidenced by activation of NOD-like receptor protein 3 (NLRP3), Cleaved cysteine-aspartic acid protease (caspase)1, tumor necrosis factor (TNF)α and interleukin (IL)-1β levels. Moreover, PFOS exposure significantly decreased B-cell lymphoma2 (Bcl2)/Bcl2 associated X (Bax) ratio and increased the protein expression of Cleaved caspase-3. Compared with the control group, PFOS upregulated the protein expression of necroptotic markers and autophagy-related proteins. In conclusion, PFOS induced inflammation, cell death, and autophagy through oxidative stress by ROS overload, thereby providing a mechanistic explanation for PFOS-induced hepatotoxicity.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 2","pages":"45-55"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080637","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

The Journal of Toxicological Sciences and Fundamental Toxicological Sciences to become open access journals. 《毒理学科学杂志》和《基础毒理学科学》成为开放获取期刊。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.R1

Toshiyuki Kaji, Akira Naganuma

{"title":"The Journal of Toxicological Sciences and Fundamental Toxicological Sciences to become open access journals.","authors":"Toshiyuki Kaji, Akira Naganuma","doi":"10.2131/jts.50.R1","DOIUrl":"https://doi.org/10.2131/jts.50.R1","url":null,"abstract":"We would like to express our gratitude for your contributions to our official scientific journals, The Journal of Toxicological Sciences and Fundamental Toxicological Sciences.We have decided to make both journals open access in order to internationalize them and expand their reach to a broader audience. Articles will be published under the Creative Commons license with the highest degree of freedom, CC BY (4.0). As a result of this change, article copyright will belong to the authors, and secondary use, including copying, distribution, display, storage, modification, and commercial use, can be carried out without the relevant society's permission.The new Instructions for Authors will be published on the journal websites in advance. These new submission guidelines \u2028will apply to papers submitted on or after June 1, 2025 (Japan time). Please note that the previous Instructions for Authors will apply to papers submitted until May 31, 2025 (Japan time).We hope that this change will encourage you to submit more of your excellent papers to The Journal of Toxicological Sciences and Fundamental Toxicological Sciences.Toshiyuki Kaji, Ph.D.Editor-in-ChiefThe Journal of Toxicological SciencesAkira Naganuma, Ph.D.Editor-in-ChiefFundamental Toxicological Sciences.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 5","pages":"R1"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971045","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