Frontiers in toxicology最新文献

{"title":"Oral metal immunotoxicity in rodents: a recoverability-aware systematic review and within-study quantitative reanalysis of splenic SRBC-TDAR.","authors":"Iliana C Martínez-Ortiz, Igor Garcia-Atutxa, Carlos Machain-Williams, Miguel Ángel Reyes-López, Francisca Villanueva-Flores","doi":"10.3389/ftox.2026.1855035","DOIUrl":"10.3389/ftox.2026.1855035","url":null,"abstract":"<p><strong>Introduction: </strong>Public toxicology databases are increasingly used for evidence synthesis, but their value depends not only on the availability of studies but also on whether endpoint-level data can be recovered for reuse. Using the Chemical Effects in Biological Systems (CEBS) database as the primary source, we reviewed oral heavy-metal immunotoxicity in rodents.</p><p><strong>Methods: </strong>We assessed whether splenic sheep red blood cell (SRBC) T-dependent antibody response data, measured as antibody-forming/plaque-forming cells (TDAR AFC/PFC), were sufficiently recoverable for structured synthesis and quantitative reanalysis. Recoverability was defined as the availability of endpoint information needed for reuse, including group size, mean, and variance when quantitative reanalysis was attempted.</p><p><strong>Results: </strong>Fifteen records were screened, and 12 records were retained across vanadium, chromium, tungsten, cadmium, and lead; one of these 12 records contained separate lead and cadmium exposure arms. Three retained records were CEBS package-level studies, yielding 30 module-level entries spanning primary AFC, serum anti-SRBC IgM, natural killer (NK) cell function, splenic phenotype, hematology, body weight, and organ weights. Only one retained study, which examined sodium metavanadate in female B6C3F1/N mice exposed via drinking water for 28 days, provided a fully recoverable primary dataset with extractable group sizes, means, and variances, enabling quantitative reanalysis of five AFC contrasts from 31.3 to 500 ppm. AFC/10⁶ spleen cells shifted from +5.2% at 31.3 ppm to -29.6% at 500 ppm (lnRR -0.351, 95% CI -0.634 to -0.067), and benchmark-like thresholds for 10%, 20%, and 25% AFC decline were estimated at approximately 84, 184, and 283 ppm, respectively. The same package revealed marked assay- and normalization-dependent divergence, with plaque-based AFC declining, ELISpot-based IgM AFC increasing, and serum IgM and NK responses showing limited concordance.</p><p><strong>Discussion: </strong>Overall, CEBS module-level data supported a stronger endpoint-centered synthesis than narrative review alone. However, incomplete endpoint recoverability, rather than study scarcity, remained the main barrier to broader quantitative integration across oral metal studies.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1855035"},"PeriodicalIF":5.1,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674887","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":"Intestinal toxicity of functionalized polystyrene nanoplastics in NOD2 models of Crohn's disease susceptibility.","authors":"Manon Dussol, Sandrine Ménard, Margaux Papin, Maeva Boulée, Vérane Bard, Melvin Airaud, Daphna Fenel, Christine Moriscot, Frédérick Barreau, Marie Carriere","doi":"10.3389/ftox.2026.1839932","DOIUrl":"10.3389/ftox.2026.1839932","url":null,"abstract":"<p><p>The daily use of plastic products leads to exposure of populations via ingestion, which may affect intestinal health. While a wealth of studies has documented the impact of micro- and nanoplastics (MNPLs) on models representing healthy human intestine, less is known about their impact on sensitive populations, particularly those at risk of developing inflammatory bowel diseases. This study explored the intestinal response to carboxylated and aminated polystyrene particles (50-500 nm PS-COOH and 50 nm PS-NH₂) <i>in vivo</i> and <i>in vitro</i> in models of genetic susceptibility to Crohn's disease. These models included nucleotide-binding oligomerization domain-2 wild-type and knock-out mice (Nod2 ^<i>WT</i> and Nod2 ^<i>KO</i> , respectively) and co-cultures of Caco-2 and HT29-MTX cells, with Caco2 cells stably expressing either wild-type NOD2 or the NOD2 ^{<i>1007fs</i>} variant, which is strongly associated with Crohn's disease. <i>In vitro,</i> the co-cultures were used either in a non-differentiated state (<i>i.e.</i>, 24 h post-seeding) or after differentiation into a tight, mucus-secreting epithelium. Results showed that <i>in vivo</i>, single oral administration of PS-COOH particles impaired the paracellular permeability of the ileum of Nod2 ^<i>WT</i> mice. Both PS-COOH and PS-NH₂ reduced the number of goblet cells in Nod2 ^<i>WT</i> and Nod2 ^<i>KO</i> mice as well as Muc4 secretion in Nod2 ^<i>WT</i> mice, and PS-COOH reduced Muc4 secretion in Nod2 ^<i>KO</i> mice. Single oral administration of PS-COOH or PS-NH₂ altered mRNA expression of genes involved in the production of antimicrobial peptide, inflammation, mucin secretion and endoplasmic reticulum stress pathways, in both Nod2 ^<i>WT</i> and Nod2 ^<i>KO</i> mice. <i>In vitro,</i> PS-COOH showed no impact in Caco2-NOD2 ^{<i>1007fs</i>} /HT29-MTX and in Caco2-NOD2 ^<i>WT</i> /HT29-MTX, whereas PS-NH₂ induced a similar toxic response in both cell systems. The intensity of this response depended on the cells' differentiation status and on the mode of exposure, <i>i.e.,</i> acute versus repeated. Overall, this study explored, for the first time, the response of models of genetic susceptibility to Crohn's disease to exposure to PS-COOH and PS-NH₂ nanoplastics (NPLs). The obtained data provide new insight into how populations at risk of developing CD respond to PS-COOH and PS-NH₂ NPLs, i.e., new knowledge related to the impact of NPLs on this vulnerable population.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1839932"},"PeriodicalIF":5.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671486","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":"Chronic exposure to mining-contaminated borehole water impairs the entire male reproductive axis: partial mitigation by alpha-lipoic acid in Wistar rats.","authors":"Festus Toochukwu Okposhi, Collins Nduka Esomchi, Kenneth Tochukwu Onwe, Leslie Ogechi Onumajuru, Ernest Maduabuchi Omeje, Favour Chioma Onwumere, Precious Chidiogo Ugwu, Goodness Emmanuella Onukogu, Jennifer Obianuju Olisaeke, Chinwendu Princess Victor, Chiemerie Promise Omeh, Bianca Adanna Onele","doi":"10.3389/ftox.2026.1899884","DOIUrl":"10.3389/ftox.2026.1899884","url":null,"abstract":"<p><strong>Introduction: </strong>Mining activities, industrial discharges, and poor waste management in many developing countries, including Nigeria, have led to widespread contamination of groundwater with mixtures of heavy metals such as lead, cadmium, arsenic, and mercury. In mining-impacted regions of Ebonyi State, borehole water, the primary drinking source for rural communities regularly exceeds WHO permissible limits, resulting in chronic low-dose exposure that threatens male reproductive health through disruption of the entire hypothalamus-pituitary-gonadal (HPG) axis. This study investigated the reproductive toxicity of naturally contaminated borehole water and evaluated the protective and therapeutic potential of alpha-lipoic acid (ALA) in adult male Wistar rats.</p><p><strong>Methodology: </strong>Thirty adult male Wistar rats were divided into five groups (n = 5): normal control, heavy metal-contaminated water only (28 days), ALA only (25 mg/kg), post-treatment (contaminated water 28 days followed by ALA 14 days), and pre-treatment (ALA 14 days followed by contaminated water 28 days). Water from a mining area in Ebonyi State, Nigeria, contained Pb (2.4 mg/L), Cd (1.7 mg/L), As (1.2 mg/L), and Hg (0.8 mg/L), exceeding WHO limits. After sacrifice, serum hormones (GnRH, FSH, LH, testosterone), antioxidant status, inflammatory markers, sperm parameters, steroidogenic enzymes, and histopathology of the hypothalamus, pituitary, and testes were assessed.</p><p><strong>Results: </strong>Contaminated water significantly reduced body weight, organ weights, sperm quality, GnRH, FSH, testosterone, antioxidant enzymes, and steroidogenic protein expression while increasing inflammation and histopathological damage across the HPG axis. Post-treatment with ALA significantly improved most parameters compared to the heavy metal-only group, whereas pre-treatment offered limited protection. However, neither regimen fully restored values to control levels.</p><p><strong>Conclusion: </strong>Chronic exposure to naturally heavy metal-contaminated drinking water induces profound multi-level HPG axis dysfunction. Alpha-lipoic acid at 25 mg/kg provides significant but incomplete protection, with post-exposure administration being more effective. These findings highlight the need for higher doses or combination therapies and underscore the urgent public health risk in affected regions.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1899884"},"PeriodicalIF":5.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655180","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":"Editorial: European partnership on the assessment of risks from chemicals (PARC): continued focus on new approach methodologies (NAMs) and data gap filling.","authors":"Anna Beronius, Erwin Roggen, Terje Svingen","doi":"10.3389/ftox.2026.1903700","DOIUrl":"10.3389/ftox.2026.1903700","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1903700"},"PeriodicalIF":5.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655166","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":"Oxygen-enhanced assembloid-based vascularized intestinal-on-a-chip for radioprotective drug evaluation.","authors":"Yuting Guo, Meiling Fu, Yuan Pang","doi":"10.3389/ftox.2026.1863392","DOIUrl":"10.3389/ftox.2026.1863392","url":null,"abstract":"<p><strong>Background: </strong>The intestine plays essential roles in digestion, immunity, and metabolism, but is highly sensitive to ionizing radiation during cancer treatment or environmental exposure. Although three-dimensional intestinal models more accurately replicate tissue architecture than conventional monolayers, they are frequently limited by insufficient oxygen delivery, leading to hypoxia-associated functional impairment. Incorporating physiologically relevant oxygenation strategies remains a key challenge in advanced <i>in vitro</i> systems. This study aimed to establish a physiologically relevant <i>in vitro</i> intestinal model by improving oxygen mass transfer within three-dimensional tissue constructs, thereby enhancing structural organization and functional maturation, and subsequently applying the system to investigate radiation-related mechanisms and evaluate potential protective agents.</p><p><strong>Methods: </strong>Based on a microengineered 3D cell-assembly platform, intestinal epithelial cells, endothelial cells, and fibroblasts were spatially organized to form a structured intestinal tissue model. The composition of the cells was optimised to improve tissue uniformity and the function of the epithelial barrier. To alleviate hypoxia in the three-dimensional construct, an oxygen-permeable microwell system was employed to enhance oxygen diffusion and promote epithelial differentiation, as evidenced by the upregulation of <i>Isx</i>, <i>Cyp3a5</i>, and <i>Tff3</i>. A vascularized chip that recapitulated the <i>in vivo</i> intestinal-stromal-vascular interface was created by incorporating microvascular networks self-assembled from endothelial cells within a hydrogel matrix.</p><p><strong>Results: </strong>Following radiation exposure, the model exhibited characteristic symptoms of intestinal injury, such as decreased cell viability, impaired E-cadherin signaling, and compromised epithelial barrier integrity. Treatment with dimethyloxalylglycine (DMOG) mitigated these effects, confirming it's utility for assessing radioprotective drugs.</p><p><strong>Conclusion: </strong>This vascularized intestinal-on-a-chip model closely mimics the structure and function of the human intestinal microenvironment. It serves as a robust <i>in vitro</i> platform for studying radiation-induced intestinal injury and for screening candidate protective agents, offering valuable applications in radiation protection and regenerative medicine research.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1863392"},"PeriodicalIF":5.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632895","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":"Case Report: A hypothesis-generating case of gadolinium retention and persistent symptoms after MRI despite normal renal function in a patient with hypermobile Ehlers-Danlos syndrome.","authors":"Cassandra Cox, Abigail Unruh, Brent Wagner, G Patricia Escobar, Catriona Walsh, Olivia X Jastrzemski, Ian Henderson, Joshua DeAguero","doi":"10.3389/ftox.2026.1846464","DOIUrl":"10.3389/ftox.2026.1846464","url":null,"abstract":"<p><p>Gadolinium-based contrast agents are commonly used to enhance magnetic resonance imaging. In 2006, Thomas Grobner identified a link between these agents and nephrogenic systemic fibrosis in patients with renal impairment. Gadolinium exposure has also been associated with acute kidney injury, skin plaques, and encephalopathy. Even in patients with normal kidney function, gadolinium may be retained in tissues for prolonged periods after contrast administration. Some patients develop persistent and varied symptoms following exposure. Although Richard Semelka and colleagues proposed the term gadolinium deposition disease, uncertainty regarding causality and pathophysiology has led to the growing adoption of the more neutral description: symptoms associated with gadolinium exposure. We describe a patient with normal renal function and Ehlos-Danlos Syndrome who developed persistent symptoms following a single gadopiclenol-enhanced magnetic resonance imaging study. Serial testing demonstrated prolonged urinary gadolinium excretion despite normal kidney function and an undetectable blood gadolinium concentration. Gadolinium remained detectable in the urine long after the expected period of elimination. The patient's clinical manifestations persisted for an extended period following exposure. We hypothesize that slow redistribution of gadolinium from retained tissue stores contributed to the prolonged urinary excretion observed in this patient. We also discuss theoretical host-susceptibility factors that may have increased her risk of gadolinium retention following gadolinium-enhanced magnetic resonance imaging. However, this case adds to the ongoing discussion regarding the clinical significance and potential mechanisms of persistent gadolinium retention in patients with normal renal function.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1846464"},"PeriodicalIF":5.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655211","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":"Editorial: From North to South: a global perspective on the impact of endocrine disruptors on reproductive development and function.","authors":"Cassy M Spiller, Andrea B Webster, Terje Svingen, Anderson J Martino-Andrade","doi":"10.3389/ftox.2026.1915721","DOIUrl":"10.3389/ftox.2026.1915721","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1915721"},"PeriodicalIF":5.1,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13405523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610671","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":"Material-dependent oxygen transport governs ischemia-reperfusion injury and drug response in a kidney microphysiological system.","authors":"Naokata Kutsuzawa, Hiroko Nakamura, Kenta Shinha, Hiroshi Kimura","doi":"10.3389/ftox.2026.1854389","DOIUrl":"10.3389/ftox.2026.1854389","url":null,"abstract":"<p><p>Oxygen availability is a critical yet often overlooked factor in cell culture, and discrepancies between nominal oxygen settings and the actual cellular microenvironment can compromise model validity. This limitation is particularly relevant in modeling ischemia-reperfusion (I/R) injury, where dynamic changes in oxygen supply critically influence cellular responses. In particular, the role of oxygen transport in microphysiological systems and conventional culture platforms remains insufficiently understood, limiting the reproducibility of disease models and the interpretation of drug responses. In this study, we systematically evaluated oxygen supply and cellular responses in three culture platforms: cell culture inserts, polydimethylsiloxane (polydimethylsiloxane)-based microfluidic chips, and polyethylene terephthalate (polyethylene terephthalate)-based microfluidic chips with identical geometries but different oxygen permeabilities. Oxygen distribution and oxygen consumption rate (OCR) were estimated using finite element method (FEM) simulations, and the resulting predictions were interpreted in the context of experimental observations obtained with RPTEC/TERT1 cells under I/R conditions. Cellular responses were assessed by morphology, viability, and gene expression analysis, and pharmacological responses were evaluated using the renoprotective compound CDDO. finite element method analysis revealed that oxygen availability at the cell surface varied markedly among platforms despite identical nominal oxygen conditions. PDMS chips maintained high oxygen levels due to high gas permeability, preventing the establishment of oxygen-limited conditions, whereas PET chips and inserts exhibited significant oxygen depletion. These differences were consistent with experimental observations: PDMS chips failed to induce I/R-associated cellular injury, whereas PET chips and inserts enabled hypoxia-induced responses. Furthermore, drug responses varied across platforms, with CDDO exhibiting distinct efficacy profiles depending on the severity of oxygen limitation. These findings indicate that oxygen transport, rather than nominal oxygen settings, is a major determinant of cellular phenotype and drug response <i>in vitro</i>. This study provides a framework for designing physiologically relevant cell culture systems based on oxygen transport principles and highlights the importance of integrating material properties, device design, and culture conditions to achieve accurate and reproducible biological outcomes.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1854389"},"PeriodicalIF":5.1,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581275","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 regrettable substitutions: a proposal for a tiered testing approach for BPA alternatives under the PARC initiative.","authors":"Kiara Aiello-Holden, Kristina Bartmann, Franca Maria Buratti, Nicolas J Cabaton, Lucia Coppola, Emanuela Corsini, Antonio De la Vieja, Hubert Dirven, Maria Dusinska, Naouale El Yamani, Nina Franko, Johanna M Gostner, Nathalie Grova, Louise Gütter, Patricia Iglesias-Hernández, Martina Iulini, Anja Kodila, Yvonne Kohl, Gabriele Lori, Henriqueta Louro, Francesca Marcon, Sakina Mhaouty-Kodja, Archibold Mposhi, Lydie Naulé, Simonetta Palleschi, Barbara Rossi, Elise Rundén-Pran, Francesca Salani, Nicoletta Santori, Maria João Silva, Marija Sollner Dolenc, Emanuela Testai, Mónica Torres-Ruiz, Jonathan Turner, Catherine Viguié, Daniel Zalko, Sabrina Tait","doi":"10.3389/ftox.2026.1815869","DOIUrl":"10.3389/ftox.2026.1815869","url":null,"abstract":"<p><p>Bisphenol A (BPA) alternatives are increasingly used in the manufacture of industrial and consumer products, following regulatory restrictions on BPA. However, insufficient safety data on these substitutes raise concern as regards potential regrettable substitutions. Under the EU Partnership for the Assessment of Risks from Chemicals (PARC), Work Package 5 (WP5) addresses this challenge by applying a human-relevant tiered hazard assessment strategy grounded on OECD test guidelines as first tier and expanding the battery to include NAMs (New Approach Methodologies). Eight BPA alternatives were prioritized for studies addressing key toxicological endpoints, namely, endocrine disruption (ED), developmental neurotoxicity (DNT), immunotoxicity, genotoxicity and carcinogenicity and metabolic fate examination (detoxification vs. potential bioactivation), to enable early identification of biological activity and support cross-endpoint prioritization. This manuscript describes the structure and implementation of the testing framework. This integrated testing strategy proposes a structured approach to identify substances of potential concern, guide targeted higher-tier studies, and support regulatory prioritization. PARC WP5 framework is testing whether coordinated NAM-based methods may contribute to next-generation risk assessment and help prevent regrettable substitutions among BPA alternatives for rapid regulatory adoption. Detailed experimental results will be reported separately upon completion of the project.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1815869"},"PeriodicalIF":5.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564022","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 role of mycotoxins in lipid metabolism and homeostasis: a systematic review.","authors":"Bernadett Csókay, Eszter Ruff, Zsuzsanna Szőke, Levente Sára, Balázs Komoróczy, Apolka Szentirmay, Márkó Unicsovics, Katalin Sára-Popovics, Dóra Holéci, Balázs Hamar","doi":"10.3389/ftox.2026.1870680","DOIUrl":"10.3389/ftox.2026.1870680","url":null,"abstract":"<p><strong>Background: </strong>Mycotoxins are widespread food contaminants that pose a significant global health concern. While their hepatotoxic, nephrotoxic, and carcinogenic effects are well established and characterized, their effects on adipose tissue biology and systemic lipid regulation remain incompletely understood. Given adipose tissue's central role in lipid homeostasis, endocrine regulation, and as a storage reservoir for adipophilic compounds, understanding these effects is critical.</p><p><strong>Methods: </strong>This systematic review was conducted in accordance with the PRISMA 2020 guidelines, and prospectively registered to PROSPERO (CRD42022287044). A comprehensive literature search was conducted in CENTRAL, Embase, and MEDLINE (PubMed) through 16 January 2026. Experimental <i>in vivo</i> and <i>in vitro</i> studies examining the effects of mycotoxins on adipose tissue, lipid metabolism, or mycotoxin distribution in fat tissue were included. Risk of bias in animal studies was assessed using the SYRCLE Risk of Bias Tool. A descriptive qualitative synthesis was performed.</p><p><strong>Results: </strong>Twenty-one experimental studies met the inclusion criteria. Across animal models, mycotoxin exposure consistently disrupted lipid homeostasis, leading to elevated serum triglyceride, cholesterol, LDL, and VLDL levels, alongside reduced HDL concentrations. These effects were mediated through toxin-specific mechanisms, including inhibition of <i>ppar</i>α signaling by aflatoxins and ochratoxin, suppression of <i>pparγ</i> by deoxynivalenol, and activation of <i>pparγ</i> by zearalenone. Mycotoxins also impaired adipokine secretion, with reduced leptin and adiponectin levels, and were associated with insulin resistance and altered glucose metabolism. Importantly, although mycotoxins are primarily metabolized in the liver, multiple studies demonstrated substantial accumulation and prolonged retention in adipose tissue, suggesting a secondary toxicokinetic reservoir.</p><p><strong>Conclusion: </strong>Mycotoxins exert significant, toxin-specific effects on lipid metabolism and adipose tissue function and may contribute to cardiometabolic dysfunction. Adipose tissue appears to play a key role in mycotoxin bioaccumulation, with potential implications for chronic exposure and delayed systemic toxicity.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1870680"},"PeriodicalIF":5.1,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610695","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}