Journal of Xenobiotics最新文献

{"title":"A Comparative Multi-Bioassay Assessment of Tetracycline Mixture Toxicity in Water and Soil Using Harmonized Dose-Response Modeling.","authors":"Chrysi A Papadimitriou, Christina Emmanouil, Amalia Moriki, Vasileios Bartzis","doi":"10.3390/jox16040122","DOIUrl":"10.3390/jox16040122","url":null,"abstract":"<p><p>Tetracyclines (TCs) are antibiotics widely used in human and veterinary medicine as well as in agricultural practices. They may be retained in soil or drift into freshwater, thereby exerting effects on non-target organisms and deteriorating ecological quality. In this study, tetracycline (T), oxytetracycline (OT), chlortetracycline (CT), and their binary and ternary mixtures were evaluated using a battery of bioassays including terrestrial plants, aquatic crustaceans, a ciliate protist and a bacterial species. Results showed a concentration-dependent effect for parameter immobilization in <i>Daphnia magna</i> and <i>Artemia salina</i>, seed germination in the terrestrial plants, and bioluminescence inhibition and growth inhibition in <i>Aliivibrio fischeri</i> and <i>Tetrahymena thermophila</i>, respectively. For <i>A. fischeri</i>, statistically significant interactions were observed between dose and exposure time. <i>A. salina</i> demonstrated greater sensitivity than <i>D. magna</i> in all cases. Both <i>A. salina</i> and <i>A. fischeri</i> showed increased toxicity to OT and the ternary mixture. Dicots presented greater sensitivity than the monocot species in all cases. In the combined exposures, there was a deviation from the concentration addition (CA) model, with possible synergism for CT + T and the ternary mixture for <i>A. fischeri</i>. The concurrent environmental exposure of non-target organisms to TCs should be investigated further.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580492","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":"Methylsulfonylmethane Attenuates Dexamethasone-Induced Hepatic Insulin Resistance in Rats: Associations with SGK1, p-AMPK/mTOR, Inflammatory and Angiogenic Markers.","authors":"Ahmad A Alresheedi, Omnia A Nour, Dalia H El-Kashef, Manar A Nader","doi":"10.3390/jox16040121","DOIUrl":"10.3390/jox16040121","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Glucocorticoid therapy remains clinically indispensable, yet its long-term use is profoundly constrained by insulin resistance (IR), hepatic steatosis, and progressive metabolic dysfunction. Methylsulfonylmethane (MSM), a naturally occurring sulfur-containing nutraceutical with established antioxidant and anti-inflammatory activities, has emerged as a promising metabolic modulator; however, its therapeutic relevance in glucocorticoid-induced hepatic IR has not previously been explored. <b>Methods:</b> Male Wistar rats received MSM (200 or 400 mg/kg/day, p.o.) for 14 days, while dexamethasone (DEX) (8 mg/kg/day, i.p.) was administered during the final 7 days to induce severe metabolic dysfunction. <b>Results:</b> DEX provoked profound IR, dyslipidemia, oxidative stress, hepatocellular injury, and steatotic degeneration accompanied by marked ultrastructural abnormalities. Remarkably, MSM conferred dose-dependent metabolic and hepatoprotective effects, significantly restoring glucose homeostasis, insulin responsiveness, lipid metabolism, and hepatic structural integrity. Mechanistically, MSM exerted a pleiotropic regulatory effect through suppression of the glucocorticoid-responsive kinase SGK1, restoration of AMPK/mTOR signaling balance, and normalization of insulin signaling pathways and metabolic transcriptional regulators. Furthermore, MSM effectively attenuated oxidative stress and inflammatory amplification consistent with modulation of the NLRP3/NF-κB/IL-6 axis. Importantly, the current work identifies angiogenic remodeling demonstrated by DEX-induced upregulation of VEGF and CD34, both of which were substantially suppressed by MSM treatment. <b>Conclusions:</b> This study provides novel evidence that MSM mitigates glucocorticoid-induced hepatic IR through coordinated modulation of glucocorticoid-responsive kinases, metabolic signaling networks, redox-inflammatory cascades, and pathological angiogenesis. Consequently, MSM may represent a promising candidate for further preclinical and clinical evaluation regarding its capacity to limit glucocorticoid-associated metabolic burdens.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580638","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":"Safranal Enhances the Efficacy of Praziquantel Against <i>Schistosoma mansoni</i> Infection and Alleviates Liver Fibrosis, Inflammation and Oxidative Stress in Mice.","authors":"Azza Fahmy, Amany Mohammed Mohmmed Hegab, Hanan S Mossalem, Samah Sulaiman Abuzahrah, Saud Omar Alafghani, Alaaeldin Ahmed Hamza, Nouf Juaid, Amr Amin","doi":"10.3390/jox16040120","DOIUrl":"10.3390/jox16040120","url":null,"abstract":"<p><p>Although praziquantel (PZQ) is the main antischistosomal drug currently in use, concerns remain regarding incomplete reversal of schistosomiasis-induced pathology and the emergence of drug resistance. This study evaluates the combined effect of PZQ with safranal, a bioactive saffron constituent, on <i>Schistosoma mansoni</i>-induced pathology in mice. Male CD1 Swiss albino mice were exposed to 60 <i>S. mansoni</i> cercariae and, at week 9 post-infection, were treated with PZQ (500 mg/kg orally for two consecutive days), safranal (50 mg/kg/day), or both, for three weeks. The animals were sacrificed at week 11 post-infection. Worm and egg burdens, liver histopathology, fibrotic markers, oxidative stress, and inflammatory cytokines were assessed. Combined PZQ + safranal therapy significantly reduced adult worm counts and hepatic and intestinal egg loads compared to PZQ alone. All treatments decreased liver index (hepatomegaly), with the combination treatment providing the best intervention. Histological analyses revealed significantly reduced granuloma size and hepatic necrosis post-treatment, particularly in the combination group. The levels of proinflammatory cytokines (TNF-α, IL-1β) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10) were significantly lowered in treated mice, most notably with the combination treatment. Oxidative stress was also markedly attenuated, and infected mice exhibited elevated malondialdehyde and depleted antioxidant enzymes (SOD, CAT, GSH). Interestingly, PZQ and/or safranal restored antioxidant status and reduced lipid peroxidation, with the combination being most effective. Furthermore, collagen deposition and expression of hepatic fibrotic markers α-smooth muscle actin (α-SMA), TGF-β1, and matrix metalloproteinase-9 were most effectively suppressed by combined therapy. To conclude, safranal enhances PZQ's antischistosomal efficacy and confers additive protection against <i>Schistosoma</i>-induced liver fibrosis.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580591","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":"Xenobiotic Hazards in Aircraft Cabin Air.","authors":"Jeremy J Ramsden","doi":"10.3390/jox16040119","DOIUrl":"10.3390/jox16040119","url":null,"abstract":"<p><p>Most airline passengers and crew assume that the air in the cabin is free from harmful or hazardous substances, as is mandated by airworthiness regulations. While fresh air entering the cabin is sterile (and if recirculated is usually efficiently filtered to remove microorganisms), if the fresh air is bled off the turbine compressors (as is the case in about 95% of airliners currently in service), it may be contaminated with traces of engine oil and ultrafine particles abraded from the turbine blades, and possibly traces of hydraulic fluid leaking from servo systems. Engine oil contains tricresyl phosphate (TCP) as an essential antiwear agent, but it is also a well-known neurotoxin, and it has been suggested that there may be no safe lower limit of exposure, not least because of considerable variation among individuals in sensitivity to tri-<i>ortho</i>-cresyl phosphate (T<i>o</i>CP) and other isomers with at least one <i>ortho</i> constituent. This paper reviews current knowledge about these hazards and discusses the medical and economic motivations for diminishing them. A calculation based on maintaining the life quality index shows that eliminating xenobiotic hazards in aircraft cabin air is likely to be affordable.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580639","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":"Preventing Pesticide Toxicity Risk Through Self-Reported Practices in Children of Farming Communities: A Social Practice Theory Perspective.","authors":"Nuraeni Nuraeni, Herdis Herdiansyah, Fatmah Fatmah, Haruki Agustina, Rully Yusuf","doi":"10.3390/jox16030117","DOIUrl":"10.3390/jox16030117","url":null,"abstract":"<p><p>This study analyzes the determinants of self-reported behaviours and perceptions associated with pesticide toxicity risk in children using the Social Practice Theory framework, linking individual factors and agricultural practices to understand vulnerability and prevention opportunities. This research was conducted in Pattapang Village, Tinggimoncong District, Gowa Regency, South Sulawesi Province, Indonesia. To examine the relationship between pesticide use patterns, social norms, competence, material, and individual aspects and the risk of sensitive toxicity in children, data were analyzed using structural equation modeling-partial least squares (SEM-PLS) with bootstrapping resampling. Pesticide use patterns had a significant negative effect on toxicity risk. Competence was the strongest predictor of pesticide use patterns, followed by materials and short-term goals. Personal values dominate personal norms and long-term goals, while social norms only influence personal norms. Self-efficacy, personal norms, and long-term goals showed no significant effects. The novelty of this research lies in the integration of a socio-ecological approach with individual psychological factors in a comprehensive structural model that explains the complex mechanisms of children's protective behavior formation from pesticide toxicity, identifying that personal values-not personal norms or self-efficacy-are the most effective leverage points for farmer behavior change interventions.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13302243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319674","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 Multidisciplinary Review of Phytoremediation Strategies for Heavy Metal-Contaminated African Soils: From Geochemical Assessment to Genetic Enhancement.","authors":"Fatouma Mohamed Abdoul-Latif, Rohit Kumar, Talal Mohamed, Ali Merito, N Chinmaya Kumar, Ibrahim Houmed Aboubaker, Pannaga Pavan Jutur","doi":"10.3390/jox16030118","DOIUrl":"10.3390/jox16030118","url":null,"abstract":"<p><p>African soils face increasing levels of metal pollution due to industrialization, artisanal mining activities, improper waste management, and enhanced agricultural productivity. However, unlike many organic pollutants, heavy metals do not degrade naturally and therefore persist in environmental systems for prolonged periods. Heavy metals accumulate over many decades in the soil and bioaccumulate through the food chain causing severe health complications such as cancer, kidney problems, and neurological impairment. This paper reviews the current literature on the origin, prevalence, and behavior of the main pollutants Pb, Cd, Cr, As, Hg, and Cu. The major phytoremediation methods including phytoextraction, rhizofiltration, phytostabilization, and phytovolatilization are highlighted alongside in planta screening methods for hyperaccumulating plants including <i>Berkheya coddii</i> (Ni) and <i>Haumaniastrum robertii</i> (Co). The paper evaluates various enhancement techniques such as the use of chelators, Rhizobium inoculations, and genetic modifications. The significance of these approaches in tropical and subtropical climates is discussed. The paper suggests a holistic framework involving empirical kinetic modeling, geospatial machine learning (random forest, kriging), and molecular omics in prediction modeling. Major hurdles in such predictions include lack of field-based verification of the models, biotechnology safety of genetically modified (GM) organisms, and inadequate regulations. Future perspectives emphasize community-driven phytomining, biomass recycling, and resilient phytoremediation solutions.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13302604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319804","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":"Atmospheric Washout Dynamics of Organic Micropollutants: A Study of PAH, PAE, and BTEX Concentrations in Rainwater Across Northern Serbia.","authors":"Brankica Kartalović, Rastko Tomanović, Kristina Habschied, Alma Mikuška, Mirta Sudarić Bogojević, Antonije Žunić, Dora Bjedov","doi":"10.3390/jox16030116","DOIUrl":"10.3390/jox16030116","url":null,"abstract":"<p><p>Atmospheric wet deposition represents a major pathway for the transfer of organic micropollutants into terrestrial and aquatic ecosystems. This study investigates the occurrence and spatial distribution of polycyclic aromatic hydrocarbons (PAHs), phthalate esters (PAEs), and BTEX compounds in rainwater across Northern Serbia (Vojvodina region). Rainwater samples were collected during the 2025-2026 heating season at three locations: a petrochemical site in Kikinda, a traffic- and residentially influenced site in Sremska Mitrovica, and an urban background site in Sombor. Total concentrations showed pronounced spatial variability, with the highest ΣBTEX and ΣPAE levels recorded in Kikinda (∑BTEX = 2.818 μg L^∑1; ∑PAE = 0.930 μg L^∑1). Diagnostic ratios identified a dominant petrogenic signature in Kikinda (LMW/HMW > 1), while pyrogenic sources prevailed in Sremska Mitrovica and Sombor ((Fla/Fla + Pyr) > 0.5). BTEX profiles across all sites were characterised by the absence of benzene and elevated toluene and xylene levels (B/T ≈ 0; T/X > 1). Health risk assessment indicated an acceptable but non-negligible carcinogenic risk from PAHs, particularly for children in industrial areas. These findings highlight the role of precipitation as an efficient scavenger of organic pollutants and emphasise the need for integrated atmospheric-hydrological monitoring frameworks in industrialised regions.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13301899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319832","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 Network Toxicology Framework for Identification of Immune System Disruption by Per- and Polyfluoroalkyl Substance (PFAS) Mixture: In Silico Analysis.","authors":"Katarina Baralić, Katarina Vidić, Đurđica Marić, Jovana Živanović, Aleksandra Buha Djordjevic, Marijana Ćurčić, Zorica Bulat, Biljana Antonijević, Danijela Đukić-Ćosić","doi":"10.3390/jox16030115","DOIUrl":"10.3390/jox16030115","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are persistent, chemically stable compounds widely used in daily life. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS) were identified as the most relevant PFAS due to their prevalence and toxicity. This study aimed to investigate the immunotoxic mechanisms of a mixture of these PFAS using an in silico approach. Comparative Toxicogenomic Database (CTD), GeneMANIA, CytoHubba (Cytoscape), ToppGene Suite, and Metascape were used for the analysis. A total of 65 immune-related genes were identified as common to all four PFAS, with <i>IFNG</i>, <i>TNF</i>, <i>IL1B</i>, <i>IL6</i>, <i>TYK2</i>, <i>CD3E</i>, <i>CASP8</i>, <i>VAV1</i>, <i>ARHGAP4</i>, and <i>CARD11</i> emerging as key hub genes. CTD phenotype analysis indicated immune dysregulation, with decreased humoral and adaptive immune responses in humans and tissue-specific modulation of B- and T-cell activity in mice, while no immune-related phenotypes were observed for PFNA. Network analysis identified functional modules associated with apoptotic and immune signaling, endothelial cell migration and angiogenesis, and shared inflammatory and viral response pathways. Disease enrichment analysis associated PFAS with autoimmune disorders (rheumatoid arthritis, asthma), metabolic conditions, and cardiovascular diseases (experimental diabetes, hypertensive disease). These results highlight PFAS involvement in immune modulation, cytokine signaling, and disease susceptibility.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13302081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319810","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":"Mortality Burden and Years of Life Lost Attributable to Air Pollution in Liguria, Italy: A Health Impact Assessment.","authors":"Sebastiano La Maestra, Francesco D'Agostini, Linda Ferrea","doi":"10.3390/jox16030114","DOIUrl":"10.3390/jox16030114","url":null,"abstract":"<p><p>Air pollution is a major environmental determinant of premature mortality and population health burden. Liguria represents a vulnerable Mediterranean region due to intense urbanisation, port-related emissions, complex topography and an ageing population. This study quantified the mortality burden and Years of Life Lost (YLL) attributable to long-term exposure to PM_2.5, NO₂ and O₃ in Liguria (Italy), and estimated the potentially avoidable burden under WHO guideline scenarios. A Health Impact Assessment (HIA) was conducted using ARPAL air quality data and ISTAT mortality data for the population aged ≥30 years during 2022-2024. Relative risks were derived from the European ELAPSE project and WHO meta-analyses. Attributable mortality was estimated using a log-linear Health Impact Function, while YLL were calculated using regional life tables and normalised per 100,000 inhabitants. PM_2.5 was the main contributor to air pollution-related mortality, accounting for 1333 attributable deaths in 2022. Corresponding YLL ranged from 755 to 1012 per 100,000 inhabitants over the study period. NO₂ showed a relevant but secondary contribution, while O₃ effects were smaller and more uncertain. WHO guideline scenarios indicated a substantial potentially avoidable burden of deaths and YLL. These findings support targeted environmental and public health interventions in highly urbanised coastal regions.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13301063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319961","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":"Neurobehavioural Effects of the Methylimidazolium Ionic Liquid M8OI in Rats.","authors":"Tarek M Abdelghany, Alaa A Budastour, Ahmed S Kamel, Sherehan M Ibrahim, Alex Charlton, Simon Wilkinson, Catherine Arden, Noha F Abdelkader, Matthew C Wright","doi":"10.3390/jox16030113","DOIUrl":"10.3390/jox16030113","url":null,"abstract":"<p><p>M8OI is a cytotoxic methylimidazolium ionic liquid solvent through its binding to the ubiquinone binding site on complex I of the mitochondrial electron transport chain. Given the overlap in terms of toxic mechanism of action with the pesticide rotenone, the potential neurotoxic effects of M8OI were examined. In vitro, cytotoxicity and mitochondrial function were assessed in SH-SY5Y cells by measuring MTT reduction and oxygen consumption/extracellular acidification using a Seahorse analyser. SH-SY5Y cells were sensitised to M8OI toxicity by replacing medium glucose with galactose. Glucose protected the cells from M8OI toxicity, whereas galactose showed no clear dose-response protection. M8OI induced a dose-dependent reduction in oxygen consumption rate with a compensatory increase in extracellular acidification rate, consistent with inhibition of mitochondrial oxidative phosphorylation and a shift toward glycolysis. In vivo, rats were orally exposed via drinking water for 20 weeks and assessed using behavioural tests. In addition, the concentrations of M8OI and its metabolites were quantified by LC-MS in rat brain and other tissues. In rats, M8OI concentrations were ~30-fold higher in kidney than brain, and brain levels were at least 100-fold lower than the concentrations that affected SH-SY5Y cell viability in vitro. However, based on open field tests, M8OI exposure suppressed motor activity without any anxious behaviours. The cytotoxicity of M8OI in SH-SY5Y neuroblastoma cells was associated with metabolic mitochondrial dysfunction. However, the neurobehavioural changes observed in orally exposed rats occurred at significantly lower brain concentrations than would be predicted to lead to neural cell death. Nevertheless, direct comparisons between acute in vitro exposures and chronic in vivo outcomes should be interpreted cautiously.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13301412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319879","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}