Toxicology Reports最新文献

{"title":"Multi-endpoint assessment of tunnel wash water and tyre-particle leachate in zebrafish larvae","authors":"Shubham Varshney ,&nbsp;Chinmayi Ramaghatta ,&nbsp;Prabhugouda Siriyappagouder ,&nbsp;Andy M. Booth ,&nbsp;Lisbet Sørensen ,&nbsp;Pål A. Olsvik","doi":"10.1016/j.toxrep.2025.102096","DOIUrl":"10.1016/j.toxrep.2025.102096","url":null,"abstract":"<div><div>Washing of road tunnels is essential for removing accumulated pollutants such as tyre wear particles, brake dust, exhaust residues, and road debris to ensure visibility and safe driving. Tunnel washing generates large volumes of contaminated runoff known as untreated tunnel wash runoff (UTWR). Some countries filter UTWR through a sedimentation process before release to reduce contamination, generating what is known as treated tunnel wash runoff (TWR). This study investigates the potential environmental impact of diluted UTWR (25 %) and TWR (50 %) by evaluating their toxicity in fish and comparing the effect to tyre-particle leachate (TPL, 2 g/L). UTWR was collected during tunnel cleaning, and TWR was collected after 14 days of filtration through sand sediments, from the Bodø tunnel in Norway. Zebrafish larvae, used as a fish model, exposed to contaminated runoff exhibited increased mortality, impaired growth, developmental anomalies, altered swimming behaviour, and changes in gene expression. Both UTWR and TWR exposure induced significant toxicity in zebrafish larvae, though the toxicity caused by TWR was notably lower than that of UTWR. This study shows that current filtration methods of tunnel wash water reduce the levels of most pollutants, however, more research is needed on how tunnel wash-water runoff affect aquatic ecosystems.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102096"},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential protective effect of phycocyanin against gibberellic acid-induced cerebellar toxicity in female rats and their offspring","authors":"Heba Abdelnaser Aboelsoud ,&nbsp;Ebtihal Kamal ,&nbsp;Shaimaa R. Abdelmohsen ,&nbsp;Amany M. Abo-Ouf ,&nbsp;Ayman Geddawy ,&nbsp;Mikail Akbulut ,&nbsp;Shaimaa M. Hafez","doi":"10.1016/j.toxrep.2025.102090","DOIUrl":"10.1016/j.toxrep.2025.102090","url":null,"abstract":"<div><div>Gibberellic acid (GA3), a widely used plant growth regulator, enhances plant size and availability; however, its potential cerebellar toxic effects during pregnancy and lactation remain unclear. The possible neuroprotective role of phycocyanin (PC), a natural antioxidant pigment, against GA3-induced cerebellar toxicity has not been thoroughly investigated, particularly in pregnancy and lactation. Accordingly, the present study aimed to evaluate the protective effect of PC against GA3-induced cerebellar toxicity in mother rats and their offspring. A total of twenty-four pregnant Wistar rats were randomly divided into four groups. Group I (Control) received the vehicle. Group II (PC-treated): received PC (200 mg/kg body weight). Group-III (GA3-treated): received GA3 (55 mg/kg body weight). Group IV (GA3 +PC-treated): received both GA3 (55 mg/kg body weight) and PC (200 mg/kg body weight). All treatments were administered daily via the oral route to the mothers throughout pregnancy and for two weeks after delivery. Light-microscopic and ultrastructural analysis of the cerebellar cortex was performed. The oxidative stress parameters glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation (LPO) in cerebellar tissues were assessed. The data were analyzed using two-way ANOVA (Python and Google CoLab). The results revealed that GA3 administration caused degenerative alterations and damage in the cerebellar cortex, as well as significant oxidative stress, evidenced by increased LPO and decreased GPX and SOD levels in female rats and their offspring. On the other hand, co-administration of PC significantly ameliorated the histological and biochemical alterations induced by GA3 exposure. These findings suggest that PC supplementation may offer a promising protective strategy against GA3-induced cerebellar toxicity in both mother rats and their offspring.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102090"},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetic exploration of buprenorphine and related metabolites in umbilical cord blood","authors":"Amelia Monfared ,&nbsp;Derek E. Murrell ,&nbsp;Darshan S. Shah ,&nbsp;Melissa Hoang ,&nbsp;Stacy D. Brown ,&nbsp;Sam Harirforoosh","doi":"10.1016/j.toxrep.2025.102093","DOIUrl":"10.1016/j.toxrep.2025.102093","url":null,"abstract":"<div><div>The goal of this study was to explore associations between single-nucleotide polymorphisms (SNPs) and umbilical cord blood concentrations of buprenorphine and its metabolites following maternal administration. This is a sub-study of a prospective observational cohort investigation which included pregnant women receiving buprenorphine for opioid use disorder during pregnancy. Following delivery, umbilical cord blood samples were collected and genotyped using a pharmacogenetic panel. The drug and metabolite concentrations were analyzed through liquid chromatography-mass spectrometry, and genetic association analysis was completed using PLINK software. The included neonates (n = 14) had a mean birth weight of 3.00 ± 0.39 kg and were born to mothers receiving a mean buprenorphine dose of 10.29 ± 6.22 mg. Ten concentration groupings (drug, single metabolite, as well as drug/metabolite(s) combinations) produced 18 unique SNP associations. Two significant associations included variations in CYP3A4 and UGT1A1, which play a role in the metabolism of buprenorphine. These preliminary findings suggest potential pharmacogenetic factors influencing fetal drug exposure, warranting larger studies to validate associations and explore clinical implications for neonatal outcomes.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102093"},"PeriodicalIF":0.0,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coumestrol induces apoptosis and inhibits invasion in human liver cancer cells","authors":"Hoda Abdul-Nabie ,&nbsp;Safia Samir ,&nbsp;Tarek Aboshousha ,&nbsp;Nagui Fares ,&nbsp;Faten Sabra Abo-Zeid","doi":"10.1016/j.toxrep.2025.102091","DOIUrl":"10.1016/j.toxrep.2025.102091","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a major public health problem, with a poor prognosis in patients with advanced disease. We aimed to investigate the cytotoxic activity of coumestrol against human hepatocellular carcinoma HepG2 cells. Crystal violet (CV) assay was performed for cell cytotoxicity assessment on Vero cells (normal Kidney) and HepG2 cells. Apoptosis was analyzed by Annexin V/FITC staining. The relative expression of BAX, bcl-2, NF-Kβ, PCNA, MMP2, Caspase-3, Caspase-9, COX2, and MMP9 was detected using quantitative real-time PCR (qPCR). In addition, immunohistochemical analysis (IHC) of Bax, and PCNA were established. Results indicated that coumestrol induced significant toxicity in HepG2 cells. Annexin V-FITC staining assays revealed that coumestrol-induced cytotoxicity in HepG2 cells was mediated through apoptosis stimulation. The apoptosis in HepG2 cells was mediated through caspase-activation. Cell invasion was inhibited by coumestrol in HepG2 cells via inhibition of MMP-2 and MMP-9 expressions. IHC confirmed the strong expression of Bax and nuclear expression of PCNA in treated cells. To the best of our knowledge, limited studies have investigated the impact of coumestrol. The study showed that coumestrol exhibited cytotoxic and apoptotic effects against HepG2 cells, accompanied by inhibition of invasion-related gene expression.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102091"},"PeriodicalIF":0.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadmium toxicity alleviation in rats using lactobacillus-fermented and unfermented opuntia ficus-indica L. juices","authors":"Nourhan M. Abd El-Aziz ,&nbsp;Ahmed N. Badr ,&nbsp;Ebtehal A. Farrage ,&nbsp;Amira M.G. Darwish ,&nbsp;Mohamed G. Shehata","doi":"10.1016/j.toxrep.2025.102089","DOIUrl":"10.1016/j.toxrep.2025.102089","url":null,"abstract":"<div><div><em>Opuntia ficus-indica L.</em> (prickly pear) contains natural compounds with known anti-inflammatory, antioxidant, and neuroprotective effects. This study assessed the ability of normal (NCJ) and Lactobacillus-fermented prickly pear juice (FCJ) to reduce cadmium toxicity in male albino rats. Physical and chemical properties of both juices were analyzed, revealing that fermentation increased total phenolics and flavonoids, boosting antioxidant activity by 48.61 % and extending shelf life by 60 days.To evaluate cadmium detoxification, rats were divided into six groups: Group G1 (saline control), Group G2 (cadmium-intoxicated), Groups G3 and G5 (NCJ and FCJ only), and Groups G4 and G6 (cadmium exposure combined with NCJ or FCJ). After 60 days, the harmful effects of cadmium were assessed by measuring gene expression (TNF-α, P53, BCL-2, IL-1) and examining tissue histology. Both juices reduced cadmium toxicity markers, with FCJ showing superior efficacy. Furthermore, the juice treatments were safe for the rats, as no adverse effects were observed in Groups G3 and G5. These findings suggest that Lactobacillus-fermented juices may be effective in reducing cadmium contamination and promoting detoxification in biological systems.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102089"},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspective on health and ecological risk assessments of potentially toxic metal(loid)s using aquatic biodiversity as biomonitoring indicators","authors":"Lawrence Olusegun Ajala ,&nbsp;Jonathan E.H. Wilson ,&nbsp;Mintesinot Jiru ,&nbsp;Maurice O. Iwunze","doi":"10.1016/j.toxrep.2025.102086","DOIUrl":"10.1016/j.toxrep.2025.102086","url":null,"abstract":"<div><div>The presence of potentially toxic metal(loid)s in the environment is a global concern due to their hazards to humans and ecosystems. This review examines the sources, impacts, and human health and ecological risk assessment of potentially toxic metal(loid)s, focusing on the role of aquatic biodiversity as biomonitoring indicators. Using specific keywords, peer-reviewed studies spanning 2000–2024 were mined and reviewed to identify the trends of potentially toxic metal(loid)s in the marine environment and their resultant human health risks. Accordingly, findings indicated that potentially toxic metal(loid)s found their way into water bodies primarily via mining and smelting, industrial discharge, agricultural practices, stormwater runoff, and indiscriminate waste disposal. In the marine environment, this menace leads to bioaccumulation in aquatic biodiversity, disruption of food chains, reduced or loss of biodiversity, degradation of water quality, and behavioral changes in biodiversity. Through food chain transfer, humans are exposed to health risks such as increased cancer risk, kidney and liver damage, gastrointestinal distress, neurological damage, cardiovascular diseases, bone weakness, and reproductive and developmental defects. The review also revealed a strong correlation between aquatic organisms- like fish, bivalves, invertebrates, and macrophytes- and the accumulation of metal(loid). This highlights their valuable roles in long-term pollution monitoring and their potential as early warning indicators. Applying real-time measurements of concentration levels and associated risks offers a revolutionary approach to ecological and human health risk assessments of potentially toxic metal(loid)s. This will permit the optimal use of predictive modeling, accurate and effective monitoring, and early interventions to guarantee sustainability and prevent environmental and public health. The findings of this study hold great promise for improving the sustainability of ecosystems and human populations.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102086"},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aflatoxins and fumonisins in nixtamalized corn dough from El Salvador: A two-year survey","authors":"Roberto Hernandez-Rauda ,&nbsp;Oscar Peña-Rodas ,&nbsp;Gissell Arbaiza-Rodríguez ,&nbsp;Marvin Cuadra-Escobar ,&nbsp;Martha Guzman-Rodríguez","doi":"10.1016/j.toxrep.2025.102087","DOIUrl":"10.1016/j.toxrep.2025.102087","url":null,"abstract":"<div><div>Corn is a staple of the Salvadoran diet but is vulnerable to contamination by aflatoxins and fumonisins. While these mycotoxins have been studied in nearby countries, El Salvador lacks similar data, despite over 90 % of its population consuming corn derivatives. This study aimed to monitor aflatoxin and fumonisin levels in nixtamalized corn dough used for making tortillas and assess daily intake for potential exposure. Aflatoxin-positive cases were low at 20 %, with less than 2 % of samples exceeding 10 µg/kg, and none exceeded this limit on average. Fumonisin-positive cases were also low (&lt; 7 %) and only detected in the dry season, with all cases exceeding the maximum limit of 1 mg/kg. The estimated daily intake of aflatoxin exceeded the recommended guidance value of 0 ng/kg body weight per day, varying by locality and season. Moreover, all fumonisin daily intake measurements surpassed the maximum limit of 1 µg/kg body weight per day, showing no seasonal variation. Thus, consuming nixtamalized corn dough contaminated with these mycotoxins poses a potential health risk to Salvadorans.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102087"},"PeriodicalIF":0.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative evaluation of MPTP and rotenone as inducing agents for Parkinson's disease in adult zebrafish: Behavioural and histopathological insights","authors":"Chetan Ashok ,&nbsp;Naveen Kumar Rajasekaran ,&nbsp;Srikanth Jeyabalan ,&nbsp;Gayathri Veeraraghavan ,&nbsp;Subalakshmi Suresh ,&nbsp;Ramya Sugumar ,&nbsp;Sugin Lal Jabaris ,&nbsp;Vetriselvan Subramaniyan ,&nbsp;Ling Shing Wong","doi":"10.1016/j.toxrep.2025.102084","DOIUrl":"10.1016/j.toxrep.2025.102084","url":null,"abstract":"<div><div>Parkinson's disease (PD), a prevalent neurodegenerative disorder, is marked by dopaminergic neuron loss and motor impairments. This study aimed to establish and compare PD models in adult zebrafish using two neurotoxins, MPTP and rotenone, evaluating their impact on behaviour and histopathology. Zebrafish were exposed to MPTP via intraperitoneal injection at two different doses or to rotenone in water for 21 days. Behavioural assessments, including Novel Tank Diving Test, bradykinesia, and C-bend response, revealed progressive motor and anxiety-like impairments, with rotenone exhibiting stronger locomotor effects. Histopathological analyses confirmed dose-dependent neurodegeneration in brain regions, with MPTP showing localized damage and rotenone causing widespread but milder effects. While both neurotoxins induced PD-like phenotypes, rotenone produced more pronounced locomotor deficits, whereas MPTP triggered anxiety-like symptoms. In conclusion, our study demonstrates that MPTP induces significant locomotor dysfunction along with anxiety-like symptoms, while rotenone strongly impacts locomotion with mild anxiety effects. Both neurotoxins exhibited maximum effects at their highest doses and over a similar time frame (Day 14 to Day 22). These findings highlight the distinct neurotoxic mechanisms of MPTP and rotenone and their relevance in modelling PD pathogenesis. The zebrafish model provides a robust platform for studying neurodegenerative diseases and testing therapeutic interventions. Further studies are required to explore the molecular mechanisms underlying their neurotoxic effects and to validate these models for long-term and translational research.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102084"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute toxicological evaluation of bone-targeted parathyroid hormone-related peptide (PTHrP) antagonist to inhibit breast cancer metastases to bone","authors":"Tulasi Ponnapakkam ,&nbsp;Muralidharan Anbalagan ,&nbsp;Robert E. Stratford Jr. ,&nbsp;Binghao Zou ,&nbsp;Robert Blair ,&nbsp;Brian G. Rowan ,&nbsp;Robert Gensure","doi":"10.1016/j.toxrep.2025.102085","DOIUrl":"10.1016/j.toxrep.2025.102085","url":null,"abstract":"<div><div>The present study evaluates the <em>in vivo</em> acute toxicological profile and drug distribution of a novel bone-targeted parathyroid hormone-related peptide (PTHrP) antagonist for bone metastatic breast cancer. [W2]PTH(1−33)-CBD was created by fusing PTHrP antagonist peptide to the bacterial collagen-binding domain (CBD) of ColG collagenase from Clostridium histolyticum to target the drug to type 1 collagen in bone. Acting as an inverse agonist at the PTH/PTHrP receptor, [W2]PTH(1−33)-CBD induced apoptosis in breast cancer cells and reduced tumor burden in mouse tibia. Female C57BL/6 mice were injected with vehicle, 320 µg/kg, or 1000 µg/kg [W2]PTH(1−33)-CBD as a single injection. Animal behavior, body weight, mortality, and biochemical and organ toxicity assays showed no significant changes during 28-day study period. [W2]PTH(1−33)-CBD distribution assessed by immunohistochemistry confirmed localization to bone, skin, and kidney. No significant changes in liver enzymes or serum protein were observed. Treatment reduced serum calcium and increased creatinine, but kidney histology showed no toxicity. Histological analysis of the kidneys showed no alterations, indicating no toxicity. Histological analysis of spleen, lungs, skin, and bone showed no pathological changes. Pharmacokinetic analysis was done after a single injection of 1000 µg/kg dose (via subcutaneous and intravenous) to female Sprague Dawley rats to determine how the body metabolizes [W2]PTH(1−33)-CBD. Serum was collected at various time points, and drug analysis was performed. Exposure from both routes was similar, indicating complete absorption of [W2]PTH(1−33)-CBD following SC. No clinically significant biochemical or histopathological changes were observed at these doses, thus establishing a safety profile for treatment with novel [W2]PTH(1−33)-CBD.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102085"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of the effects of a cholesterol-supplemented high-fat diet by aryl hydrocarbon receptor (AHR) activation and/or tryptophan reduction in male mice","authors":"Avinash Bathina ,&nbsp;Janne Hakanen ,&nbsp;Atso Raasmaja ,&nbsp;Jere Lindén ,&nbsp;Laura Mairinoja ,&nbsp;Suraj Unniappan ,&nbsp;Lars Pettersson ,&nbsp;Raimo Pohjanvirta","doi":"10.1016/j.toxrep.2025.102083","DOIUrl":"10.1016/j.toxrep.2025.102083","url":null,"abstract":"<div><div>Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor whose role in energy metabolism is obscure. Most of its physiological ligands are derived from tryptophan (TRP). Here, fifty male C57BL/6JRccHsd mice were assigned to one of five feeding groups, control diet (CD), high-fat diet (HFD; 45 % of energy from fat), HFD with only 70 % of the regular TRP concentration (HFDtrp), HFD supplemented with a weakly toxic AHR agonist C2 (HFDc2), or HFDtrp with C2 (HFDtrp-c2). All diets contained 2 % cholesterol and were fed for 18 weeks. On weeks 14–16, the mice were tested for gas exchange and locomotor activity, and on weeks 15–17 for glucose tolerance (GTT) and insulin sensitivity (ITT). At termination, tissue samples were collected for biochemical and AI-assisted histological analyses. Body weight gain (BWG) was only 28–38 % higher in the HFD groups than in the CD group, but the HFD-fed mice accumulated 43–61 % more fat. Calorie intake was greater in the two low-TRP groups than in the two other HFD groups, while BWG remained similar. C2 induced <em>Cyp1a1</em> expression (an index of AHR activity) in all tissues examined and increased the ratio of micro-/macrosteatosis in the liver. The HFDs tended to reduce insulin sensitivity, CO₂ production, and the ability to respond appropriately to a low-temperature challenge. These findings suggest that the effects of AHR activity modulation on energy balance are strongly context-dependent. A sensitive response to long-term AHR activation appears to be elevated micro-/macrosteatosis ratio in the liver when exposed to HFD.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102083"},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}