Journal of Xenobiotics最新文献

{"title":"Elemental Composition of <i>Adansonia digitata</i> L. Bark from Two Sudanese Regions: Effects of Sample Preparation and Preliminary Safety Screening.","authors":"Abdelhakam Esmaeil Mohamed Ahmed, Abdaljbbar B A Dawod, Eltayeb Omaima Awad Mustafa, Ismail H Abdi, Elshafia Ali Hamid Mohammed, Béla Kovács","doi":"10.3390/jox16040147","DOIUrl":"10.3390/jox16040147","url":null,"abstract":"<p><p>Growing interest in underutilized plant resources has increased the need for comprehensive characterization of their elemental composition. This study investigated the elemental composition of <i>Adansonia digitata</i> L. bark collected from two ecologically distinct regions of Sudan and compared elemental distributions among three bark sample forms: whole, cryogenically ground bark (Bark-N), mechanically separated powder (Bark-P), and fibre fraction (Bark-F). Following HNO₃-H₂O₂ wet digestion, elemental concentrations were determined by inductively coupled plasma optical emission spectrometry (ICP-OES). Generalized linear mixed-effects models revealed significant differences in regional and bark sample forms for several essential macroelements, essential trace elements, and other naturally occurring elements. Samples from the Blue Nile region contained higher concentrations of K, P, Fe, Cu, Co, and Mo, whereas bark from North Kordofan showed higher Mg, Na, Mn, Zn, Ba, and Sr concentrations. Distinct elemental profiles were also observed among the three bark sample forms. Selected potentially toxic elements (Pb, Cd, Cr, and As) were detected at low concentrations, providing baseline data for preliminary elemental safety screening. In general, this study provides one of the first comprehensive elemental characterizations of Sudanese baobab bark and establishes a reference dataset for future compositional, pharmaceutical, and industrial research.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative In Vitro Response of HaCaT and A375 Melanoma Cells to Zinc Oxide Nanoparticles Synthesized Using Puerarin.","authors":"Sergio Liga, Raluca Vodă, Lavinia Lupa, Raluca Pop, Diana Haj Ali, Iasmina-Alexandra Predescu, Cristina Adriana Dehelean, Francisc Péter","doi":"10.3390/jox16040146","DOIUrl":"10.3390/jox16040146","url":null,"abstract":"<p><p>Zinc oxide nanobiocomposites were successfully synthesized using a green synthesis approach based on the isoflavone Puerarin, resulting in the formation of PUE-ZnO NPs. Building on their previous physicochemical and in ovo characterization, the present study aimed to comparatively evaluate the biological response induced by PUE-ZnO NPs in non-tumorigenic HaCaT keratinocytes and A375 melanoma cells. Cell viability was assessed by MTT assay, and the cellular response was further investigated through bright-field morphological evaluation, Hoechst 33342 nuclear staining, MitoTracker mitochondrial staining, and clonogenic assay. PUE-ZnO NPs showed a favorable cytocompatibility profile in HaCaT cells, with viability remaining above 80% at the highest tested concentration and only moderate impairment of clonogenic capacity at higher concentrations. In contrast, A375 melanoma cells exhibited a stronger response, characterized by reduced viability, marked morphological alterations, nuclear changes, mitochondrial staining disruption, and a pronounced decrease in colony-forming ability. PUE-ZnO NPs may represent a promising phytochemical-assisted ZnO-based nanosystem for further investigation in melanoma-related models.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Bentonite Supplementation Improves Growth Performance of Juvenile <i>Nile tilapia</i> Under Sub-Acute Aflatoxin B₁ Exposure.","authors":"Lane Pineda, May Moh Moh Khin, Saravanan Subramanian, H V L N Swamy, Hoang Nhu Phuc, Tran Huu Loc","doi":"10.3390/jox16040145","DOIUrl":"10.3390/jox16040145","url":null,"abstract":"<p><p>Previous studies evaluating bentonite in <i>Nile tilapia</i> have largely employed high-dose AFB₁ challenge models (≥2 ppm in the diet), whereas information on its efficacy under sub-acute contamination conditions is limited. This study evaluated the effects of a bentonite-based binder on growth performance and selected gross health-related indices in juvenile <i>Nile tilapia</i> exposed to 250 ppb dietary AFB₁. In a 42-day feeding trial, 320 fish were randomly assigned to four treatments: a negative control (NC; no AFB₁ or binder), a positive control (PC; 250 ppb AFB₁), and two AFB₁-contaminated diets supplemented with bentonite at 1 kg/ton (TMX-1) or 2 kg/ton (TMX-2). Dietary AFB₁ exposure to 250 ppb impaired growth and feed intake and increased body-weight variability compared with the NC group (<i>p</i> < 0.01). Bentonite supplementation elicited inclusion-level-dependent responses. Fish fed TMX-2 had higher final body weight (+7.0%) and average daily gain (+7.9%) than those fed the PC diet (<i>p</i> < 0.01), whereas TMX-1 performed similarly to the PC group. Feed conversion ratio differed among treatments, with TMX-2 lower than TMX-1 (<i>p</i> = 0.02) but not significantly different from the NC or PC groups. Mortality, condition factor, body-weight variation and organosomatic indices did not differ among AFB₁-challenged treatments. These findings indicate that dietary bentonite supplementation, particularly at 2 kg/ton, partially alleviated adverse responses associated with sub-acute AFB₁ exposure, primarily through improvements in final body weight and average daily gain, in juvenile <i>Nile tilapia</i> under the conditions of the present study.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fasudil Protects Against Diclofenac-Induced Hepatorenal and Gastric Injury via Modulation of ROCK/TLR4/SIRT1 Signaling and Preservation of Tight Junctions.","authors":"Ali H Al-Baldawi, Mahmoud M Samaha, Marwa S Zaghloul","doi":"10.3390/jox16040144","DOIUrl":"10.3390/jox16040144","url":null,"abstract":"<p><strong>Background: </strong>Diclofenac is a widely consumed non-steroidal anti-inflammatory drug, yet its clinical utility is limited by severe hepatotoxicity, acute kidney injury, and gastric ulceration. While the RhoA/ROCK pathway is implicated in inflammation, its potential as a therapeutic target for multi-organ NSAID toxicity remains unexplored.</p><p><strong>Methods: </strong>This study evaluated the dose-dependent protective effects of the ROCK inhibitor, fasudil, against diclofenac-induced damage and investigated the underlying ROCK2/TLR4/SIRT1 axis. Five separate cohorts were established using thirty male Sprague-Dawley rats. Alongside a normal control and fasudil control group, one experimental group was treated with 100 mg/kg diclofenac. Furthermore, two distinct groups were pretreated with fasudil for seven days before induction, receiving either a 10 mg/kg or a 30 mg/kg dose prior to diclofenac administration.</p><p><strong>Results: </strong>Diclofenac provoked severe hepatic, renal, and gastric injury accompanied by marked oxidative stress. Pretreatment with fasudil markedly reversed these effects and improved hepatic and renal function biomarkers. Mechanistically, fasudil reduced renal and hepatic ROCK2 and TLR4 expression, which consequently suppressed downstream systemic inflammatory markers, including NF-κB and TNF-α. Furthermore, fasudil halted apoptosis by restoring SIRT1 expression and reducing cleaved caspase-3, alongside preserving gastric barrier integrity.</p><p><strong>Conclusions: </strong>Fasudil dose-dependently ameliorates diclofenac-induced hepatic, renal, and gastric injury by silencing the ROCK2/TLR4 inflammatory axis, restoring SIRT1 survival networks, and protecting epithelial tight junctions.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Sustainable Air-Assisted Liquid-Liquid Microextraction Procedure Coupled to Liquid Chromatography-Tandem Mass Spectrometry for the Determination of 11-Nor-9-carboxy-Δ⁹-tetrahydrocannabinol and Hexahydrocannabinol Metabolites in Urine.","authors":"Pamela Cabarcos-Fernández, Sara Odoardi, Serena Mestria, Valeria Valentini, Giulia Biosa, Ana María Bermejo-Barrera, Sabina Strano-Rossi","doi":"10.3390/jox16040143","DOIUrl":"10.3390/jox16040143","url":null,"abstract":"<p><p>Hexahydrocannabinol (HHC) is a semi-synthetic cannabinoid that has recently emerged in the European market, raising concerns regarding its detection in forensic toxicology. Reliable analytical approaches are required for the determination of HHC metabolites together with conventional cannabis biomarkers in biological samples. This study aimed to develop and validate a sample preparation method based on air-assisted liquid-liquid microextraction (AALLME) coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THC-COOH) and HHC metabolites in urine. Urine samples underwent alkaline hydrolysis followed by AALLME using a cyclohexane/ethyl acetate mixture (9:1) prior to LC-MS/MS analysis. Experimental conditions affecting extraction performance were optimized. Method validation was performed according to international guidelines. The method achieved a limit of detection of 2.5 ng/mL and a lower limit of quantification of 5 ng/mL. Precision and accuracy fulfilled the established acceptance criteria across all concentration levels. The applicability of the method was evaluated using eleven authentic THC-COOH-positive routine casework urine samples. THC-COOH was successfully quantified, whereas no HHC metabolites were detected because no urine samples from confirmed HHC users were available. The proposed workflow provides a reduced-solvent sample preparation approach compared with conventional procedures and demonstrated adequate analytical performance for the simultaneous determination of THC-COOH and HHC metabolites in urine.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resorcinol and Related Simple Phenolic Compounds Increase Astrocyte Survival in a Glutamate-Induced Excitotoxicity Model.","authors":"José M Nájera-Maldonado, Paola Molina-Manzano, Eugenia Flores-Alfaro, Mónica Espinoza-Rojo, Isela Parra-Rojas, Patricia Alvarez-Fitz, Mónica Lamas, Ricardo Salazar, Mónica Ramírez","doi":"10.3390/jox16040142","DOIUrl":"10.3390/jox16040142","url":null,"abstract":"<p><p>Simple phenolic compounds can act as antioxidants or prooxidants depending on their structure and environmental conditions. Glutamate-induced excitotoxicity leads to neurodegeneration, astrocyte dysfunction, oxidative stress, and neuroinflammation. This study examined six phenolics: catechol, phloroglucinol, resorcinol, pyrogallol, hydroquinone, and hydroxyquinol, assessing their effects on astrocyte survival in a glutamate-excitotoxic model. Mouse astrocytes (C8-D1A) were exposed to 20 mM glutamate, with phenolics added before, during, or after treatment. Cell viability, morphology, nuclear condensation, ROS levels, and inflammatory cytokines were measured using the MTT assay, microscopy, CellROX, and RT-qPCR. Simultaneously, treatment improved astrocyte survival and preserved morphology, whereas pre- or post-treatment did not confer protection and worsened toxicity at higher doses. Resorcinol showed the strongest protective effect, followed by hydroxyquinol and hydroquinone at lower doses. Resorcinol and hydroxyquinol decreased ROS levels, whereas pyrogallol and hydroquinone increased cell survival without reducing ROS. All four lowered <i>IL-6</i> and <i>TNF-α</i>. These findings demonstrate that the effects of phenolics, whether protective or toxic, depend on concentration, structure, and timing, underscoring their dual role in excitotoxic environments. They also identify resorcinol as a promising candidate for further preclinical study.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Censored-Data-Aware Screening of Hazardous Metal(loid)s in Wild Mushrooms from Urban and Peri-Urban Green Spaces: Multielement Fingerprints and Adult Exposure Assessment.","authors":"Antonio Peña-Fernández, M Carmen Lobo, M Ángeles Peña Fernández, Guillermo Torrado Durán, Mark D Evans, Tiziana Sgamma, Tomás Cámara-Pastor, Gurminderjeet S Jagdev","doi":"10.3390/jox16040141","DOIUrl":"10.3390/jox16040141","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Wild mushrooms collected from urban and peri-urban green spaces may represent environmentally exposed biological matrices for hazardous metal(loid)s, but their interpretation is complicated by taxonomic heterogeneity, tissue partitioning and left-censored analytical data. This study evaluated As, Be, Cd, Co, Cr, Cu, Mn, Ni, Pb, V and Zn in wild mushrooms from Leicester/Leicestershire, UK, using a reconstructed fruiting-body-level dataset designed to avoid double counting paired cap/stem records. The central question was whether taxon- and tissue-aware multielement profiling alters screening-level exposure interpretation compared with a pooled edible-relevant summary. In total, 121 fruiting-body-level units were evaluated on a dry-weight basis. Cu, Mn and Zn were detected in all units, while Cd and Pb were detected in 117/121 and 106/121 units, respectively. V, Cr and Ni were detected in 84/121, 70/121 and 64/121 units, whereas As, Co and Be showed substantial censoring. Be was not interpreted distributionally. Central concentrations selected under the censored-data framework were 1.856 mg kg&lt;sup&gt;-1&lt;/sup&gt; for Cd, 71.142 mg kg&lt;sup&gt;-1&lt;/sup&gt; for Cu, 14.318 mg kg&lt;sup&gt;-1&lt;/sup&gt; for Mn, 3.874 mg kg&lt;sup&gt;-1&lt;/sup&gt; for Ni, 2.171 mg kg&lt;sup&gt;-1&lt;/sup&gt; for Pb, 0.104 mg kg&lt;sup&gt;-1&lt;/sup&gt; for V and 97.506 mg kg&lt;sup&gt;-1&lt;/sup&gt; for Zn. Taxon-level profiles showed marked heterogeneity, and paired tissue analysis in &lt;i&gt;Agaricus bitorquis&lt;/i&gt; showed higher cap than stem concentrations for Cd, Cu, Pb and Zn. The primary PCA was restricted to well-detected elements (Cd, Cu, Mn, Pb, V and Zn), explaining 73.92% of total variance across the first three components. Sensitivity analyses showed that the overall PCA configuration remained stable across alternative treatments of censored observations and after exclusion of flagged extreme records, although some loading magnitudes showed moderate variation. Under the 300 g fresh-weight week&lt;sup&gt;-1&lt;/sup&gt; scenario, Cd represented 47.3% of the EFSA tolerable weekly intake of 2.5 µg kg&lt;sup&gt;-1&lt;/sup&gt; bw week&lt;sup&gt;-1&lt;/sup&gt; in the pooled edible-relevant population (&lt;i&gt;N&lt;/i&gt; = 43) and 50.9% in &lt;i&gt;Agaricus bitorquis&lt;/i&gt;; however, taxon-specific screening changed both the magnitude and ranking of the principal threshold-based drivers, with Cu becoming the leading driver for &lt;i&gt;Coprinopsis atramentaria&lt;/i&gt; and &lt;i&gt;Marasmius oreades&lt;/i&gt;. None of the primary or exploratory park-level soil-mushroom associations remained statistically significant after false-discovery-rate correction in the harmonised eight-park analysis. Overall, the findings partially support the working hypothesis: taxon- and tissue-aware profiling improved screening-level interpretation, whereas park-level soil context did not provide robust evidence of prediction or transfer. The fruiting-body-level, censored-data-aware framework provides a transparent basis for exposure screening, although uncertainties related to speciation, bioaccessibility, moisture assumptions and anal","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zirconium, Hafnium and Tellurium Signatures in Wild Mushrooms from Leicester and Leicestershire, England.","authors":"Antonio Peña-Fernández, Tomás Cámara-Pastor, M Ángeles Peña Fernández, M Carmen Lobo-Bedmar","doi":"10.3390/jox16040139","DOIUrl":"10.3390/jox16040139","url":null,"abstract":"<p><p>Zirconium (Zr), hafnium (Hf) and tellurium (Te) are environmentally and technologically relevant elements whose occurrence in wild macrofungi remains insufficiently characterised. This study investigated their concentrations, distribution and multielement relationships in wild mushroom fruiting bodies collected from urban and peri-urban green spaces in Leicester and Leicestershire, England, together with contextual topsoil geochemistry. Acid-recoverable concentrations were determined through inductively coupled plasma mass spectrometry in 121 fruiting-body-level mushroom units and 26 independent site-level composite topsoils. Zr and Hf were detected above their respective working limits of detection in all mushroom units and topsoil composites, whereas Te was detected in 118/121 mushroom units but remained below the working limit of detection in all topsoil composites. Median mushroom concentrations were 170 ng g^-1 dry weight for Zr, 270 ng g^-1 for Hf and 110 ng g^-1 for Te. Comparatively elevated concentrations were observed in <i>Panaeolina foenisecii</i> collected from Abbey and Braunstone Parks and in <i>Mycena citrinomarginata</i> from Victoria Park, while <i>Agaricus bitorquis</i> from St Augustine Road showed lower and less variable concentrations. Park-level concentrations were strongly correlated across the three elements (Spearman's <i>ρ</i> = 0.819-0.885; all BH-adjusted <i>q</i> < 0.001), and the first principal component accounted for 93.4% of the total variance, consistent with the strong inter-element correlations. However, contextual soil-mushroom comparisons for Zr and Hf were inconclusive because of limited site overlap and spatial mismatch, and no direct inference regarding environmental source or soil-to-mushroom transfer was supported. These findings establish an exploratory baseline for Zr, Hf and Te in wild mushrooms and demonstrate the value of taxon- and site-resolved fungal biomonitoring for under-characterised environmental elements.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148832513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The JAK1 Inhibitor Upadacitinib Curbs Acute Liver Failure via Suppressing IFN-γ/JAK1/STAT1 and TNF-α/NF-κB/MAPK Pathways and Modulating Bax/Bcl-2 Ratio.","authors":"Abdulaziz F Alhussaini, Sara H Hazem, Eman A Saad, Mahmoud Elshal","doi":"10.3390/jox16040140","DOIUrl":"10.3390/jox16040140","url":null,"abstract":"<p><p>Acute liver failure (ALF) is a fulminant hepatic syndrome characterized by rapid hepatocellular destruction, severe impairment of liver function, and high mortality. Effective pharmacological interventions capable of limiting early hepatic injury remain lacking. Upadacitinib (UPA), a selective inhibitor for Janus kinase 1 (JAK1) with established anti-inflammatory activity, has not previously been investigated in experimental ALF. Consequently, the current study examined the hepatoprotective potential and underlying mechanisms of UPA in a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALF murine model. Mice were pretreated with UPA (10 or 20 mg/kg) prior to LPS/D-GalN challenge. UPA significantly attenuated liver injury, as demonstrated by marked reductions in serum ALT, AST, ALP, and γ-GT levels, together with substantial improvement in hepatic histopathology, attenuation of necroinflammation, and reduction in neutrophil accumulation. UPA also restored hepatic redox balance through reduction in lipid peroxidation and nitrosative stress, alongside enhancement of antioxidant capacity. Mechanistically, UPA suppressed IFN-γ/JAK1/STAT1 signaling and downregulated NF-κB p65 and inducible nitric oxide synthase (iNOS) expression, with subsequent reduction in hepatic TNF-α production. In parallel, UPA inhibited MAPK pathway activation, including ERK1/2, JNK, and p38 signaling. Moreover, UPA attenuated hepatocellular apoptosis through suppression of active caspase-3 and Bax expression with restoration of Bcl-2 levels. The 20 mg/kg dose consistently produced greater biochemical, molecular, and histopathological protection than the lower dose. In conclusion, UPA confers significant protection against LPS/D-GalN-induced ALF through coordinated suppression of oxidative stress, inflammatory signaling, and apoptosis, primarily associated with inhibition of the IFN-γ/JAK1/STAT1 and TNF-α/NF-κB/MAPK pathways and modulation of the Bax/Bcl-2 ratio, underscoring its viability as a promising therapeutic candidate for ALF.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oridonin Ameliorates Concanavalin A-Elicited Hepatitis in Mice: Insight into Suppressing TLR7/PKM2/NLRP3-Driven Inflammation and M1/M2 Polarization.","authors":"Saif Dhahir, Fatma M Amin, Manar A Nader","doi":"10.3390/jox16040138","DOIUrl":"10.3390/jox16040138","url":null,"abstract":"<p><p><b>Background:</b> Autoimmune hepatitis (AIH) represents a clinically challenging immune-mediated liver disease, owing to its complex pathogenesis and limited targeted therapeutic options. Growing evidence highlights the key role of lymphocyte-mediated hepatic inflammation, dysregulated cytokine milieu, and oxidative stress in AIH progression. Oridonin (ORI), a bioactive diterpenoid with well-established antioxidant, anti-inflammatory, and immunoregulatory effects, remains unexplored in AIH. The present work aims to survey the potential impacts of ORI in Concanavalin A (Con A)-prompted AIH in mice, with particular emphasis on TLR7/PKM2/NLRP3 inflammatory signaling and macrophage polarization. <b>Methods:</b> Male BALB/c mice (<i>n</i> = 30) were allocated into five groups: CTR group, ORI-CTR group, Con A group, ORI (5 mg/kg) + Con A group, and ORI (10 mg/kg) + Con A group. ORI was administered i.p. for 4 days before a single Con A injection (15 mg/kg i.v.). Serum liver enzymes, hepatic pathological changes, oxidative milieu, and varied immunological factors were assessed. <b>Results:</b> ORI markedly attenuated Con A-induced hepatic injury, as evidenced by the reduced liver transaminases, preserved hepatic architecture, and restored oxidative milieu. Moreover, ORI suppressed T-cell activation, modulated M1/M2 polarization, and reduced pro-inflammatory cytokines. These effects were accompanied by the suppression of TLR7/PKM2/NLRP3 inflammatory signaling. <b>Conclusions:</b> ORI exhibits hepatoprotective effects against Con A-induced AIH and these effects are associated with the modulation of inflammatory and immunometabolic responses as well as downregulating TLR7/PKM2/NLRP3 signaling.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}