Toxicology Reports最新文献

{"title":"Toxicological safety profiling of Berberis vulgaris hydroethanolic extract using rodent, zebrafish, and in silico models","authors":"Abanti Goswami ,&nbsp;Vara Prasad Saka ,&nbsp;Mahima Sharma ,&nbsp;Narasimha Kumar G.V. ,&nbsp;Pankaj Gupta ,&nbsp;Digvijay Verma ,&nbsp;Subhash Kaushik","doi":"10.1016/j.toxrep.2025.102195","DOIUrl":"10.1016/j.toxrep.2025.102195","url":null,"abstract":"<div><h3>Background</h3><div>The hydroethanolic extract of <em>Berberis vulgaris</em> root bark (BV) is extensively used in traditional medicine, particularly Homoeopathy, for treating renal and hepatic disorders, yet a systematic safety evaluation remains limited.</div></div><div><h3>Objectives</h3><div>This study aimed to establish a comprehensive preclinical safety profile of BV using <em>in vivo</em> rodent and zebrafish models, alongside <em>in silico</em> toxicity predictions.</div></div><div><h3>Methods</h3><div>Phytochemical profiling was conducted using Liquid Chromatography–Mass Spectrometry (LC–MS). Acute and 28-day repeated-dose oral toxicity studies were performed in Wistar rats following OECD guidelines 423 and 407, respectively. Developmental toxicity was assessed in zebrafish embryos (OECD 236), and <em>in silico</em> toxicity predictions for identified phytoconstituents were generated using ProTox 3.0.</div></div><div><h3>Results</h3><div>LC-MS analysis identified 22 bioactive chemical components. In the acute oral toxicity study, BV administered at 2000 µL/kg caused no mortality or toxicity, indicating an LD₅₀ &gt; 2000 µL/kg. The 28-day repeated-dose study showed no significant alterations in haematological, biochemical, or histological parameters at doses up to 1000 µL/kg/day, establishing a No Observed Adverse Effect Level (NOAEL) of ≥ 1000 µL/kg/day. While lower concentrations were safe in zebrafish, high concentrations (4 µL/2 ml) induced developmental abnormalities such as scoliosis and pericardial edema. Computational analysis predicted low-to-moderate toxicity for the majority of phytoconstituents.</div></div><div><h3>Conclusion</h3><div>BV exhibits a wide safety margin in rodent models and is non-toxic at therapeutically relevant doses. However, observed developmental effects in zebrafish suggest caution at high concentrations, supporting the need for adherence to recommended dosages in traditional therapeutic contexts.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102195"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926067","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":"Lack of genotoxicity and subchronic toxicity in safety assessment studies of a Clostridium beijerinckii formulation","authors":"Esther J. Yu ,&nbsp;John Eid ,&nbsp;Jaime Hernandez-Maldonado ,&nbsp;Andrew Cheng ,&nbsp;Tara Kurihara ,&nbsp;Jason L. Blum ,&nbsp;Denise DiCarlo Emery ,&nbsp;Barry Lynch","doi":"10.1016/j.toxrep.2026.102212","DOIUrl":"10.1016/j.toxrep.2026.102212","url":null,"abstract":"<div><div>A powder formulation of viable <em>Clostridium beijerinckii</em> bacteria (CBEI) was evaluated in a battery of genotoxicity studies and 14-day and 90-day repeat-dose toxicity studies in rats to evaluate CBEI as a food ingredient. All studies followed Organisation for Economic Co-operation and Development (OECD) protocols. CBEI (nonviable) was not mutagenic in an <em>in vitro</em> bacterial reverse mutation assay and was not clastogenic in an <em>in vitro</em> mammalian chromosomal aberration test. Viable CBEI was not genotoxic when evaluated in an <em>in vivo</em> mammalian cell micronucleus assay administered at up to 2.30 × 10¹¹ AFU/kg body weight/day. CBEI was administered to rats via gavage at target doses of 217, 434, and 868 mg/kg body weight/day (equivalent to 4.1 × 10¹⁰, 8.2 × 10¹⁰, and 1.64 × 10¹¹ AFU/kg body weight/day) in a 14-day dose range–finding study and a 90-day repeat-dose study. Target doses were largely achieved based on analyses from 2 independent laboratories. No mortality or treatment-related adverse effects attributed to CBEI consumption were observed in any endpoint. Bacterial translocation from the intestinal tract to the liver, mesenteric lymph nodes and blood was observed, but only one bacterial colony was found to be CBEI. The no-observed-adverse-effect level (NOAEL) was concluded to be the highest dose tested: 868 mg/kg body weight/day (approximately 1.42 × 10¹¹ AFU/kg body weight/day). These results confirm that CBEI was not genotoxic and was not toxic under the conditions of the conducted studies.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102212"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173137","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":"The association between organophosphate pesticide residue exposure and non-alcoholic fatty liver disease: A systematic review","authors":"Bahare Mohamadi ,&nbsp;Mohammadreza Tolou Ostadan ,&nbsp;Samira Shokri ,&nbsp;Alireza Bakhtiyari ,&nbsp;Rokhsana Rasooli ,&nbsp;Parisa Sadighara ,&nbsp;Saeed Aghebat-Bekheir","doi":"10.1016/j.toxrep.2026.102216","DOIUrl":"10.1016/j.toxrep.2026.102216","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is a chronic disease that has had a significant prevalence in recent decades. Various factors contribute to the disease, with diet being one of the most important. In recent decades, several studies have reported a correlation between agricultural pesticide residues and NAFLD. This systematic review aimed to discuss scientific findings and analyze evidence of the association between organophosphate pesticide residues and NAFLD. To achieve this, relevant keywords were identified, and a search protocol was established in databases over the past decade to facilitate article retrieval. Finally, a total of 314 articles were identified through the search, of which 21 met the inclusion criteria and were selected for this review. This review identified a diverse range of OPs and their metabolites concerning NAFLD. Glyphosate and its formulations (such as Roundup) were the most studied OPs. The key OPE metabolites most frequently studied were BDCIPP, BCIPHIPP, DPHP, and BCEP. In addition, pesticides such as triphenyl phosphate (TPHP), trichlorofon, tris(1-chloro-2-propyl) phosphate (TCPP), tris(2-chloroethyl) phosphate (TCEP), and tri-ortho-cresyl phosphate (TOCP) were also investigated. The primary method for assessing OPs exposure involved measuring urinary metabolites. We discuss the evidence for the correlation between exposure to OPs and NAFLD, as well as the factors that influence it.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102216"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173138","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":"Concomitant intake of high levels of monosodium glutamate and taurine induces adverse effects in the rat brain","authors":"Yasemin Atici ,&nbsp;Makbule Beyza Sen ,&nbsp;Atakan Saglam ,&nbsp;Gamze Dogan ,&nbsp;Dogan Yucel ,&nbsp;Belma Turan","doi":"10.1016/j.toxrep.2026.102276","DOIUrl":"10.1016/j.toxrep.2026.102276","url":null,"abstract":"<div><div>A common food additive, monosodium glutamate (MSG), is a source of glutamate, the primary excitatory neurotransmitter in the central nervous system, and has been associated with neuronal damage at high levels. Taurine (TAU), a naturally occurring amino acid, is widely used in energy drinks alongside caffeine and sugar. Given the widespread consumption of these products, this study investigated the potential adverse effects of high levels of MSG, TAU, and their combination on systemic and brain oxidative stress/antioxidant balance, as well as cortical histology. Young male Wistar rats (10 weeks old) were randomly assigned to four groups: MSG (1 g/kg/day), TAU (300 mg/kg/day), MSG+TAU (1 g/kg/day + 300 mg/kg/day), and control (CON) group (saline), all administered via oral gavage for 21 days. While serum trace element levels (Cu, Zn, Se) remained unaffected, total oxidant status was significantly higher in the MSG and MSG+TAU groups compared to the TAU and control groups. Oxidative stress markers (8-OHdG and 4-HNE) were elevated in the serum, cortex, and hippocampus of all experimental groups, accompanied by increased total oxidant status and decreased total antioxidant status in these samples. Histological analysis revealed neuronal disorganization and pericapillary edema in the cerebral cortex. These findings indicate that excessive exposure to these compounds may disrupt redox balance and brain tissue integrity to varying degrees, with combined exposure producing more pronounced deleterious effects. Overall, these results suggest that frequent consumption of foods and beverages containing MSG and taurine, particularly at high levels, may pose significant health risks to young individuals.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102276"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158198","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":"Activated carbon from pistachio shells: A promising approach to improve health metrics in mice with zearalenone exposure","authors":"Faezeh Oskoueian ,&nbsp;Kimia Asadi ,&nbsp;Zeinab Javanshir ,&nbsp;Saeed Heidarisani ,&nbsp;Samira Bozorgi Kasgari ,&nbsp;Helia Ghafaripour ,&nbsp;Ehsan Karimi ,&nbsp;Ehsan Oskoueian","doi":"10.1016/j.toxrep.2025.102197","DOIUrl":"10.1016/j.toxrep.2025.102197","url":null,"abstract":"<div><div>Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium species, poses persistent challenges to food and feed safety due to its potent toxicological effects and widespread occurrence in cereal-based products. This study investigated the protective efficacy of activated carbon (AC) derived from pistachio shells, an abundant agricultural by-product against ZEN-induced toxicity in mice. Pistachio shell carbon was prepared through chemical activation and comprehensively characterized using SEM, FTIR spectroscopy, and BET surface area analysis. Activation increased surface area from 4.1 to 275.9 m²/g and enhanced pore volume from 0.009 to 0.26 cm³/g, confirming substantial improvements in adsorptive architecture. Forty BALB/c mice were assigned to four dietary treatments: control, ZEN-contaminated diet, and ZEN diets supplemented with non-activated or activated carbon (0.5 g/kg). ZEN exposure markedly reduced weight gain, feed intake, antioxidant enzyme activity (GPx, SOD, CAT), and jejunal villus morphology, while elevating serum ALT, AST, and ALP activities. Supplementation with activated carbon significantly ameliorated these adverse effects, restoring growth performance, improving antioxidant status, normalizing liver enzymes, and enhancing intestinal integrity. Histopathological observations corroborated reduced mucosal damage in AC-treated mice. These findings demonstrate that pistachio shell–based activated carbon is a potent, sustainable, and low-cost mycotoxin adsorbent capable of mitigating ZEN toxicity. The study highlights a promising strategy for simultaneous agricultural waste valorization and enhancement of food and feed safety systems.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102197"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925977","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":"Prediction of primary human targets and toxicity mechanisms of imidacloprid using integrative In Silico approaches","authors":"Cherdsak Boonyong ,&nbsp;Pannapa Powthong","doi":"10.1016/j.toxrep.2026.102199","DOIUrl":"10.1016/j.toxrep.2026.102199","url":null,"abstract":"<div><div>Imidacloprid is frequently detected as a residue in food commodities, raising concerns about potential human health risks. Previous findings remain fragmented, and no study has systematically elucidated the primary human target organs and underlying mechanisms using an integrative systems toxicology framework. We applied a human-specific network toxicology approach to characterize imidacloprid-induced toxicity comprehensively. By integrating target prediction and ADME/toxicity models (ADMETlab 3.0, admetSAR 3.0, and ProTox 3.0), the study identified three primary human-relevant toxicity endpoints (respiratory toxicity, liver injury, and genotoxicity/carcinogenicity). Protein-protein interaction, GO, and KEGG pathway analyses revealed that MAPK, NF-κB, JAK-STAT, UPR-ER stress, and Wnt signaling networks may be key pathways involved in oxidative stress, inflammatory signaling, cell-cycle dysregulation, and apoptosis. Molecular docking analysis further supported relatively stronger predicted binding of imidacloprid to several upstream regulatory proteins, including PTGS2 (COX-2), NOS3 (eNOS), APC, CDH1 (cadherin-1 or E-cadherin), AR, HSPA5 (GRP78 or BiP), HSP90AA1 (HSP90α), JAK2, and RELA (p65), whereas downstream signaling proteins such as MAPK14 (p38α), MAPK1 (ERK2), MAPK3 (ERK1), NFKB1 (p50/p105), WNT3A (Wnt), TNF (TNF-α), ESR1 (ERα), and BCL2 exhibited moderate predicted binding. Although these findings are derived from computational analyses and do not establish functional disruption, the coordinated involvement of upstream and downstream signaling hubs suggests possible mechanisms through which imidacloprid exposure may influence multiple organ systems. Taken together, this study provides a systems-level, hypothesis-generating framework to support future experimental validation and human health risk assessment.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102199"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925978","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":"Prenatal diazepam exposure impairs maternal caregiving behaviors in rats: Roles of GABAARα1 downregulation, serotonin depletion, and corticosterone dysregulation","authors":"Yasaman Moin ,&nbsp;Samira Khayat ,&nbsp;Hamed Fanaei","doi":"10.1016/j.toxrep.2025.102186","DOIUrl":"10.1016/j.toxrep.2025.102186","url":null,"abstract":"<div><div>This study investigated effects of prenatal exposure to diazepam on maternal and caregiving behaviors in rats postpartum.Twenty-four female rats were randomly divided into two groups: diazepam group and control group. Diazepam was administered during, and maternal behaviors were observed and recorded after delivery. Serum corticosterone levels during pregnancy, GABAARα1 expression, and serotonin and BDNF concentrations were measured in hippocampus and prefrontal cortex of the dams. The results showed that mothers exposed to diazepam exhibited a significant reduction in self-grooming (p = 0.0016), nursing (p &lt; 0.0001), and nest-building behaviors (p &lt; 0.0001) compared to the control group. Additionally, diazepam group showed fewer instances of pup retrieval (p = 0.0032) and licking (p = 0.0019). A significant increase in the latency to retrieve pups was observed in the diazepam group (p &lt; 0.0001). The findings demonstrate a significant decrease in GABAARα1 mRNA expression within the prefrontal cortex (P = 0.0023) and hippocampus (P = 0.0138) of diazepam-treated group compared to the control group. Dams in the diazepam group exhibited significantly lower serum corticosterone levels at gestational day 20 (p = 0.0288) and postnatal day 1 (p = 0.0009) compared to the control group. Additionally, serotonin concentration in the prefrontal cortex (p = 0.0036) was significantly reduced in the diazepam group relative to controls.The present study demonstrated that prenatal diazepam exposure significantly impaired maternal caregiving behaviors in rats. These behavioral deficits were associated with disrupted serum corticosterone levels, diminished prefrontal serotonin concentrations, and reduced GABAARα1 mRNA expression in the prefrontal cortex and hippocampus. The findings suggest that diazepam interferes with neurochemical pathways critical for maternal motivation, potentially weakening maternal-infant bonding.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102186"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791814","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":"Investigating the microwave degradation of polypropylene microplastics and their impact on human intestinal cell models","authors":"Raphaela O.G. Ferreira ,&nbsp;Emine Merve Canga ,&nbsp;Aoife Gowen ,&nbsp;Tara McMorrow ,&nbsp;Jun-Li Xu","doi":"10.1016/j.toxrep.2026.102285","DOIUrl":"10.1016/j.toxrep.2026.102285","url":null,"abstract":"<div><div>Humans are inevitably exposed to microplastics (MPs) through various pathways, with ingestion being a primary route. Polypropylene (PP), commonly used for food storage and microwave (MW) heating, has the potential to release MPs when exposed to heat or prolonged use. Despite their detection in human tissues, including the gut, the health impacts of degraded PP particles remain poorly understood. This study investigates the characteristics of MW-treated PP particles and their effects on human intestinal Caco-2 cells, focusing on cell metabolic activity, membrane damage, and oxidative stress. Caco-2 cells were exposed to PP-MPs with a concentration of 200 µg/mL subjected to various MW degradation cycles: 3-minute cycles (repeated 1, 5, and 10 times) and a 30-minute continuous cycle at high power (1000 W), for 24 and 48 h. Surface charge and infrared spectral analyses were employed for chemical characterization of the MPs. Toxicological assays were used to evaluate cell metabolism, membrane integrity, and oxidative stress. Results indicated that prolonged MW exposure led to oxidative degradation in the PP-MPs. After 24 h of exposure to MW-treated PP-MPs, an increase in the metabolic activity of Caco-2 cells ranging from 14% to 35% was observed. However, after 48 h, a statistically significant decrease in metabolic activity, ranging from 10% to 14% was observed for the cells treated with PP-MPs subjected to short MW cycles, while a persistent upregulation was observed for the 30 min continuous MW MPs. No membrane damage was detected in Caco-2 cells under any experimental condition. In contrast, oxidative stress (OS) levels surged by at least 74% in all MW cycle treatments after 24 h exposure and remained elevated compared to untreated controls after 48 h, suggesting OS as a key mechanism influencing cytotoxicity. Cell imaging suggested that MW-degraded PP-MPs induced a ROS-driven intracellular vacuolization consistent with early apoptotic signaling in Caco-2 cells. This study enhances our understanding of the biological effects of PP-MPs exposed to MW degradation, highlighting the need for further research into the broader health implications of plastic usage.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102285"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167655","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":"The toxicology of orally administered Δ9-tetrahydrocannabinol in sheep","authors":"Sarah A. Stevens ,&nbsp;Scott H. Edwards ,&nbsp;Glenys K. Noble ,&nbsp;Colin J. Scrivener ,&nbsp;Christopher E. Petzel ,&nbsp;Christopher D. May ,&nbsp;Zi Xuan Tai ,&nbsp;Bronwyn L. Blake ,&nbsp;Kenneth C. Dods ,&nbsp;Leon N. Warne ,&nbsp;Gaye L. Krebs","doi":"10.1016/j.toxrep.2026.102221","DOIUrl":"10.1016/j.toxrep.2026.102221","url":null,"abstract":"<div><h3>Introduction</h3><div>As part of a larger study to assess the potential value of industrial hemp biomass (the low Δ⁹-tetrahydrocannabinol (Δ⁹-THC) variety of <em>Cannabis sativa</em> L.) as a feed for ruminants, a pharmacokinetics study of Δ⁹-THC, one of the main cannabinoids of interest, was undertaken. In undertaking this study, the toxicology of orally administered Δ⁹-THC was incidentally investigated and was discussed in the current paper.</div></div><div><h3>Methods</h3><div>Eight Merino ewes were administered with two <em>per os</em> (PO) doses of 88.5 mg Δ⁹-THC/kg bodyweight (BW) 12 h apart. Blood samples were taken periodically to determine the pharmacokinetics of Δ⁹-THC but also to check blood troponin I concentrations post dose administration as in the pharmacokinetics study there were adverse effects to the heart following intravenous administration of Δ⁹-THC.</div></div><div><h3>Results</h3><div>Following the PO dose of Δ⁹-THC, the pharmacokinetics were able to be determined (and were published separately); however, significant adverse clinical signs were observed in the sheep. Clinical signs included ataxia (stumbling, swaying), abnormal posture (head held low, head resting on the wall of the pen, back legs crossed over), somnolence, wool pulling, increased salivation, a prolonged reduction in feed intake and consequent decrease in BW. Plasma troponin I concentrations were elevated in three of the eight sheep following the PO dose of Δ⁹-THC.</div></div><div><h3>Conclusions</h3><div>The adverse clinical signs noted have implications for iHemp biomass as a potential feed for ruminants due to both animal health and production effects. Further research is required to investigate appropriate feeding strategies for iHemp biomass to be utilised as a feed for ruminants.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102221"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173134","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":"Azilsartan as a novel anti-ferriptotic agent via the upregulation of the Nrf2/HO-1/SLC7A11/GPX4 axis and downregulation of inflammatory pathways in folic acid-induced acute kidney injury in male mice","authors":"Elaf Mahmood Shihab ,&nbsp;Saba Naseer Abbas ,&nbsp;Saja Majeed Shareef ,&nbsp;Rana Jawad Hasan ,&nbsp;Khulood Majid Alsaraf ,&nbsp;Hayder Adnan Fawzi","doi":"10.1016/j.toxrep.2026.102204","DOIUrl":"10.1016/j.toxrep.2026.102204","url":null,"abstract":"<div><h3>Purpose</h3><div>Azilsartan, a unique angiotensin II receptor blocker (ARB) with an oxo-oxadiazole ring, exhibits antioxidant and anti-inflammatory properties, but its role in ferroptosis-mediated AKI remains unexplored. This study investigates whether azilsartan protects against FA-induced AKI in male mice by attenuating ferroptosis, modulating iron metabolism, and suppressing inflammatory signaling.</div></div><div><h3>Methods</h3><div>42 male C57BL/6 J mice were randomized into six groups: control, FA-induced AKI, three azilsartan doses (1, 3, 5 mg/kg), and ferrostatin-1 (Fer-1) as a positive control. Azilsartan or Fer-1 was administered for 7 days before FA injection (250 mg/kg, i.p.) and continued for 3 days post-induction. Renal function (serum urea, creatinine), ferroptosis markers (GPX4, MDA, Nrf2, SLC7A11, HO-1), iron-handling proteins (ferritin, TfR1), inflammatory mediators (TNF-α, NF-κB p65), and histopathology were assessed.</div></div><div><h3>Results</h3><div>FA-AKI caused marked renal dysfunction, elevated KIM-1, lipid peroxidation, depletion of GPX4, downregulation of Nrf2/HO-1/SLC7A11 and TfR1, reduction of transferrin levels, and inflammatory activation. Azilsartan improved renal function and histology in a dose-dependent manner, restored GPX4, reduced MDA, upregulated Nrf2/HO-1/SLC7A11 and TfR1, increased ferritin levels, and suppressed TNF-α/NF-κB. High-dose azilsartan achieved effects comparable to those of Fer-1.</div></div><div><h3>Conclusion</h3><div>Azilsartan confers potent protection against FA-induced AKI by activating the Nrf2/HO-1/SLC7A11/GPX4 axis, reducing lipid peroxidation, normalizing iron metabolism, and attenuating inflammation. These findings support azilsartan’s potential as a repurposed therapy for ferroptosis-driven renal injury.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102204"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977345","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}