Toxicology Research最新文献

{"title":"Hormetic association between sodium nitrate and liver enzymes: a study in female and male rats.","authors":"Ramin Zeinodini, Sajad Jeddi, Khosrow Kashfi, Asghar Ghasemi","doi":"10.1093/toxres/tfaf104","DOIUrl":"10.1093/toxres/tfaf104","url":null,"abstract":"<p><p>This study aims to evaluate the long-term dose-dependent effects of sodium nitrate on serum ALT, AST, and ALP in healthy female and male rats. A total of 120 rats (60 females and 60 males) were divided into 6 subgroups (n = 10). In each sex, a control group received regular tap water, while five treatment groups received sodium nitrate in tap water (50, 100, 150, 250, and 500 mg/L). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and nitric oxide (NO) metabolites (NOx) were measured at baseline (month 0) and after 6 mo. Hormetic zones for sodium nitrate in female rats were 10-230 mg/L for ALT, 20-180 mg/L for AST, and 8-270 mg/L for ALP. In males, the zones were 5-190 mg/L for ALT, 7-180 mg/L for AST, and 7-265 mg/L for ALP. Serum NOx levels were negatively correlated with ALT (r = -0.498) and AST (r = -0.320) at moderate doses (100-150 mg/dL) but positively correlated with ALT (r = 0.500) and AST (r = 0.300) at higher doses (250-500 mg/dL (all P < 0.05). Sodium nitrate exhibited a J-shaped dose-response relationship with liver function tests (LFTs) in both female and male rats. Protective effects were observed at moderate doses (100 mg/L for ALT and AST; 150 mg/L for ALP), while low doses (<10 mg/L) were ineffective, and high doses (>200 mg/L for ALT/AST; >250 mg/L for ALP) were toxic. These findings highlight the dual potential of sodium nitrate as both beneficial and harmful, depending on the dosage in healthy state.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf104"},"PeriodicalIF":2.9,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating intracellular calcium dynamics with alkaloids: A novel strategy against oxidative neurodegeneration.","authors":"Serap Niğdelioğlu Dolanbay","doi":"10.1093/toxres/tfaf100","DOIUrl":"10.1093/toxres/tfaf100","url":null,"abstract":"<p><p>Calcium homeostasis plays a pivotal role in neuronal function, and its dysregulation is closely associated with oxidative stress-induced neurotoxicity. This study investigated the protective effects of a methanol alkaloid extract (MAE), rich in allocryptopine, tetrahydropalmatine, and tetrahydroberberine N-oxide, on H₂O₂-induced calcium dysregulation in fPC12 cells. Flow cytometry analysis revealed that MAE pretreatment significantly attenuated intracellular Ca²⁺ accumulation caused by oxidative stress. In line with this, MAE markedly downregulated the mRNA and protein expression levels of CACNA1C (Cav1.2 subunit) and CACNA1D (Cav1.3 subunit), two L-type voltage-gated calcium channels responsible for calcium influx. Furthermore, MAE suppressed the expression of key calcium regulatory proteins, including CALM1, CaMK2A, PMCA (ATP2B1), SERCA (ATP2A1), RyR1, and IP3R (ITPR1), as confirmed by ELISA and Western Blot analysis. Protein-protein interaction (PPI) network analysis demonstrated a highly interconnected and functionally enriched network among these targets, indicating coordinated regulation of calcium signaling pathways. Molecular docking studies supported these findings by showing strong binding affinities of MAE's isoquinoline alkaloids, particularly tetrahydropalmatine, to SERCA (ATP2A1) and IP3R (ITPR1). These interactions suggest a direct modulatory effect on calcium-handling proteins. Overall, this study provides experimental and <i>in silico</i> evidence that MAE exerts multifaceted neuroprotective effects by restoring calcium homeostasis and modulating oxidative stress responses, highlighting its therapeutic potential in calcium-related neurodegenerative conditions.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf100"},"PeriodicalIF":2.1,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish in the spotlight: expanding Frontiers in toxicology and drug discovery.","authors":"Sudharsan Parthasarathy, Shaza H Aly, Siva Vijayakumar Tharumasivam, Durairaj Siva, Gobalan Krishnasamy, Ashajyothi Chavaan, Mohamed El-Shazly","doi":"10.1093/toxres/tfaf095","DOIUrl":"10.1093/toxres/tfaf095","url":null,"abstract":"<p><p>Zebrafish (<i>Danio rerio</i>) has emerged as a valuable model organism in toxicology and drug discovery research. This article provides an overview of the significant contributions of zebrafish to advancing our understanding of toxicology and drug development. Zebrafish offers several advantages, including high fecundity, transparent embryos, and genetic tractability, making it an ideal system for studying drug toxicity and efficacy. The review article highlights key areas where zebrafish has made substantial contributions, such as assessing chemical toxicity, understanding drug metabolism and pharmacokinetics, and identifying novel therapeutic compounds. Furthermore, zebrafish-based assays and screening platforms have been developed to evaluate drug candidates and identify potential toxic effects and researchers have used zebrafish-based tests to study the therapeutic properties of natural compounds. The unique capabilities of zebrafish with its physiological and genetic similarities to humans, have propelled it to the forefront of toxicology and drug discovery, expanding the frontiers of research in these fields.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf095"},"PeriodicalIF":2.9,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of combined exposure to low levels of aerosolised nickel, copper and arsenic on myocardial injury in rats.","authors":"Xinyue Mu, Shuxia Yu, Yiwen Zhang, Junpu Yu, Tingting Gao, Xin Wang, Li Ma, Ye Ruan, Tian Tian, Rentong Chen","doi":"10.1093/toxres/tfaf101","DOIUrl":"10.1093/toxres/tfaf101","url":null,"abstract":"<p><p>Chronic low-level exposure to nickel (Ni), copper (Cu), and arsenic (As) may contribute to myocardial injury via oxidative stress. This study investigated the effects of these metals in male Sprague-Dawley rats exposed to aerosols of Ni (0.106 mg/m³), Cu (0.048 mg/m³), and As (0.025 mg/m³) at environmental and 10-fold concentrations for 3 mo. Blood metal levels were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS), and oxidative stress and myocardial injury biomarkers were measured with enzyme-linked immunosorbent assay (ELISA). Blood As levels showed a dose-dependent increase in both exposure groups. Myocardial ultrastructural damage, including mitochondrial swelling, disorganized myofibrils, and increased autolysosomes, was observed. Biomarkers of oxidative stress, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), were significantly elevated in both exposure groups, while malondialdehyde (MDA) levels were notably higher in the 10-fold group. Myocardial injury markers (TNNI3, LDHA, and α-HBDH) were elevated in both exposure groups. Significant correlations were found between Cu and As levels and oxidative stress and myocardial injury biomarkers. These findings demonstrate that prolonged low-level exposure to Ni, Cu, and As induces oxidative stress and myocardial injury in rats. The results highlight the potential cardiovascular risks associated with environmental exposure to mixed heavy metals and emphasize the importance of stricter regulatory measures to limit such pollutants.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf101"},"PeriodicalIF":2.9,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorating and therapeutic impact of nano ferrite-chitosan-curcumin nanoparticles against nandrolone decanote induced renal toxicity, inflammation, and oxidative stress in male rats.","authors":"Ehab Tousson, Afaf El Atrash, Somia Zaki, Marwa Negm","doi":"10.1093/toxres/tfaf103","DOIUrl":"10.1093/toxres/tfaf103","url":null,"abstract":"<p><p>The term ``anabolic-androgenic steroids'' (AASs) refers to a class of artificial substances that resemble the natural testosterone. The most often misused androgen, nandrolone decanoate (ND), is regarded as a public health concern that needs immediate action to raise public awareness of toxicology results on AAS usage. This study designed to investigate the therapeutics effect of nano ferrite-chitosan-curcumin nanoparticles (NF-CH-CurNPs) against ND induced renal toxicity, proliferation, inflammation, and oxidative stress in male rats. A total of 48 adult male rats were assigned randomly to 6 groups [1^st group was control; 2^nd group was CurNPs where rats received CurNPs (50 mg/kg BW/2 day) for two wk; 3^rd group was NF-CH-CurNPs where rats received NF-CH-CurNPs (24 mg/Kg BW/2 day) for 2 wk.; 4^th group was ND where rats received ND (25 mg/Kg BW/wk) for four wk; 5th group was ND + CurNPs in which rats received ND for 4 wk then treated with CurNPs for another 2 wk; 6^th group was ND + NF-CH-CurNPs where rats received ND for 4 wk then treated with NF-CH-CurNPs for another 2 wk]. A significant elevation in serum Urea, creatinine, kidney damage, MDA, PCNA, TNFα and a significant depletion in sodium, potassium ions, catalase, SOD, GSH after ND administration as compared to control. On the contrary, treatment of ND with CurNPs or/and NF-CH-CurNPs induced significant enhancements of the studied parameters, kidney structure and functions, oxidative stress, PCNA and TNFα expressions with best results for the treatments with NF-CH-CurNPs that may possibly scavenge free radicals creating valuable effects in contrast to ND.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf103"},"PeriodicalIF":2.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manganese exposure: a study on apoptosis and Ferroptosis in mouse Leydig and Sertoli cells.","authors":"Jiaqi He, Tongci Li, Yue Su, Yan Liang, Ying Tian, Renlian Cai, Jidong Zhang, Xiang Lu, Jun Tan","doi":"10.1093/toxres/tfaf098","DOIUrl":"10.1093/toxres/tfaf098","url":null,"abstract":"<p><p>Manganese (Mn), a vital trace element for biological functions, has raised health concerns due to potential toxicity. Excessive Mn impairs male reproduction by reducing testosterone, inducing oxidative stress, and disrupting spermatogenesis. However, its mechanisms targeting Leydig and Sertoli cells remain unclear. This study investigates Mn's reproductive toxicity by utilizing Leydig cell line TM3 and Sertoli cell line TM4, MTT assays revealed median lethal concentrations of 230 μM (TM3) and 170 μM (TM4), with AO/EB/DAPI staining confirming condensed nuclei and enhanced fluorescence. Apoptosis inhibitor Z-VAD-FMK (20 μM) suppressed cell death in both cell lines, whereas ferroptosis inhibitor Ferrostatin-1 (10 μM) specifically attenuated TM4 cell death. Necrosis inhibitor Necrostatin-1 (10 μM) showed no protective effect. Mn triggered ROS elevation in TM4 cells, accompanied by upregulated <i>Caspase 3, Casp8ap2, GPX4, Gtf3c1, Mtfr1, HMOX1, and SLC7A2</i>, while downregulating <i>SLC7A15</i>. These findings reveal Mn activates apoptosis in TM3 cells and concurrent apoptosis/ferroptosis in TM4 cells through ROS-dependent dysregulation of apoptosis- and ferroptosis-related genes. These findings establish distinct toxic mechanisms in TM4 cells and highlight the <i>SLC7A15/HMOX1</i> axis as a therapeutic target to mitigate Mn-induced spermatogenic damage.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf098"},"PeriodicalIF":2.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network toxicology and molecular docking strategy for Analyzing the toxicity and mechanisms of Bisphenol a in hypertension.","authors":"Wenjie Zhang, Yinming Zhang, Jiawei Tang, Ji Wu, Jun Li","doi":"10.1093/toxres/tfaf094","DOIUrl":"10.1093/toxres/tfaf094","url":null,"abstract":"<p><p>Environmental pollution is an important risk factor for hypertension, and bisphenol A (BPA) is a prevalent environmental contaminant. This study aimed to investigate the potential toxicity of BPA and the underlying molecular mechanisms of BPA-induced hypertension through network toxicology and molecular docking. Initially, we predicted that BPA would be cardiotoxic. We subsequently identified 51 potential targets and extracted 14 core targets of the effects of BPA on hypertension. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that these core targets were involved primarily in the estrogen signaling pathway and the calcium signaling pathway. Furthermore, molecular docking confirmed the binding capacity of BPA to these core targets, with <i>ADRB2</i>, <i>ESR1</i>, and <i>MMP9</i> potentially being the key targets through which BPA influences hypertension. Our study elucidates the molecular mechanisms of BPA toxicity and its role in hypertension induction, providing a foundation for the prevention and treatment of hypertension associated with environmental BPA exposure.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf094"},"PeriodicalIF":2.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomics and proteomics reveals the potential mechanisms of hydroquinone-inhibited erythroid differentiation in K562 cells.","authors":"Chunhong Yu, Jiaxi Chen, Zetao Zhao, Xinyue Tan, Xinyu Liu, Zongchun Yi","doi":"10.1093/toxres/tfaf093","DOIUrl":"10.1093/toxres/tfaf093","url":null,"abstract":"<p><p>Hydroquinone (HQ), a key phenolic metabolite of benzene, plays a crucial role in the mechanisms underlying benzene-induced hematotoxicity and carcinogenicity. The mechanism of benzene-induced hematotoxicity hasn't been fully understood yet. The study aimed to elucidate the molecular mechanisms underlying benzene metabolites, HQ-inhibited erythroid differentiation. In this study, K562 cells were exposed to 40 μM HQ for 72 h, followed by induction with 40 μM Hemin for 48 h. Cell proliferation, hemoglobin synthesis, and gene and protein expression were assessed using trypan blue, benzidine staining, RT-PCR, RNA-seq, label-free proteomic analysis, and parallel reaction monitoring (PRM). The results demonstrated that HQ significantly inhibited erythroid differentiation in Hemin-induced K562 cells, downregulating key erythroid differentiation genes. HQ-induced differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were involved in oxidative stress, apoptosis, and erythroid differentiation-related GO terms, as well as metabolic, ferroptosis, biosynthesis of amino acids-related pathways. Network analysis identified five key hub proteins (MYB, ALAS1, ALAS2, FECH, and STAT5B) with the highest interaction scores, among which ALAS2 emerged as a potential major regulator in HQ-exposed K562 cells based on its role in erythroid differentiation. These findings provide novel insights into the molecular mechanisms underlying HQ-induced hematotoxicity and highlight potential therapeutic targets for mitigating the adverse effects of benzene exposure.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf093"},"PeriodicalIF":2.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doxorubicin chitosan-coated ferrite nanoparticles ameliorate hepatic toxicity in Ehrlich solid tumor bearing mice.","authors":"Maha Elkholy, Osama A Sweef, Ehab Tousson, Afaf El-Atrash, Aliaa M Radwan","doi":"10.1093/toxres/tfaf099","DOIUrl":"10.1093/toxres/tfaf099","url":null,"abstract":"<p><p>Malignant tumors, particularly breast malignancies, are leading causes of mortality worldwide due to abnormal cell growth and apoptosis dysregulation, with Ehrlich solid tumors being the most prevalent. This study was designated to study the curative role of load the anticancer drug Doxorubicin (DOX) into chitosan-coated ferrite nanoparticles (CT-MNPs) to form Ferrite/CT/DOX Nano-system against Ehrlich solid tumor (EST) induced hepatotoxicity. A total of 80 female mice were randomly and equally divided into 8 groups (Control; Free Dox; CT-MNPs; DOX-CT-MNPs; EST; EST + Free Dox; EST + CT-MNPs; EST + Dox-CT-MNPs). Current results revealed that EST mice showed a significant elevation in the liver enzyme activities by 200%, thiobarbituric acid (TBAR), proliferating cell nuclear antigen (PCNA) and caspase 3 immunoreactivities. In contrast, total protein, reduced glutathione level (GSH), catalase (CAT) and super oxide dismutase (SOD) activities were markedly reduced by 16.4%, 25.2%, 72.7%, 49%, and 53.15% respectively compared to control mice. Treatment with DOX in free form significantly raises liver oxidative damage, and apoptosis compared to EST untreated mice. Additionally, the treatment with DOX-CT- MNPs improves biochemical and histopathological alterations and decreases apoptosis by 32% compared to free DOX. In conclusion, the loading and encapsulation of DOX into chitosan-coated ferrite nanoparticles ameliorate and minimize the liver toxicity and damage caused by DOX as free form.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf099"},"PeriodicalIF":2.9,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of wasabi (<i>Wasabia japonica</i>) rhizome and its main bioactive compound, allyl isothiocyanate, on the early stages of fibrosis-associated hepatocarcinogenesis.","authors":"Taís Carolina Paes Bronzato, Letícia Cardoso Valente, Agnes Suemy Varicoda, Matheus Antônio Filiol Belin, Núbia Alves Grandini, Taynara Aparecida Vieira, Jordanna Cruzeiro, Camila Renata Correa Camacho, Luís Fernando Barbisan, Guilherme Ribeiro Romualdo","doi":"10.1093/toxres/tfaf092","DOIUrl":"10.1093/toxres/tfaf092","url":null,"abstract":"<p><p>The poor prognosis of fibrosis-associated hepatocellular carcinoma (HCC) encourages preventive strategies. The wasabi rhizome (<i>Wasabia japonica)</i> - of the Brassicaceae family - is widely used as an ingredient in culinary, and is rich in bioactive compounds, including the abundant allyl isothiocyanate (AITC). Although other wasabi isothiocyanates showed beneficial effects on HCC in vitro, the implications of this <i>in natura</i> food in in vivo models are unknown. Thus, we evaluated whether wasabi rhizome or AITC attenuates the early stages of fibrosis-associated hepatocarcinogenesis. Male C57BL6/J mice were submitted to a chemically induced hepatocarcinogenesis model, receiving diethylnitrosamine (DEN) carcinogen, and multiple fibrogenic thioacetamide (TAA) cycles. Concomitantly to TAA (6 wk), the animals received by intragastric administration (5×/wk) daily prepared wasabi rhizome extract (0.5 or 1.0 g/kg body weight [bw]) or AITC (2 mg/kg bw, in 0.2% wasabi rhizome proportion). Both wasabi and AITC did not modify the alterations in body and organ weights, and serum biomarkers (ALT, AST, and urea) induced by DEN/TAA regimen used. The DEN/TAA-mediated increase in liver inflammation/fibrosis (collagen area, scores, p65 protein) and liver preneoplastic foci burden remained unaltered after wasabi/AITC interventions. In addition, AITC had minor effects on attenuating the DEN/TAA-mediated effects in pro-inflammatory CD68+ cells and antioxidant capacity in the liver. In vitro, AITC reduced the viability of collagen-producing hepatic stellate cells, while no major effects were observed in vivo. In summary, wasabi and AITC exert minor effect on the early stages of fibrosis-associated hepatocarcinogenesis, while it seemed to be safe food ingredients in doses tested herein.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf092"},"PeriodicalIF":2.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}