Journal of Xenobiotics最新文献

{"title":"Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico Studies.","authors":"Heba M Abdou, Ghada M Abd Elmageed, Hussein K Hussein, Imane Yamari, Samir Chtita, Lamia M El-Samad, Mohamed A Hassan","doi":"10.3390/jox15010016","DOIUrl":"10.3390/jox15010016","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is an intricate disease correlated with many metabolic deregulations, including disordered glucose metabolism, oxidative stress, inflammation, and cellular apoptosis due to hepatic gluconeogenesis aberrations. However, there is no radical therapy to inhibit hepatic gluconeogenesis disturbances yet. We thus sought to probe the effectiveness and uncover the potential mechanism of quercetin (QCT) and silk sericin (SS) in mitigating hyperglycemia-induced hepatic gluconeogenesis disorder, which remains obscure. Administration of QCT and SS to diabetic male albino rats markedly restored the levels of glucose, insulin, advanced glycation end-products (AGEs), liver function enzymes, alpha-fetoprotein (AFP), globulin, and glycogen, in addition to hepatic carbohydrate metabolizing enzymes and gluconeogenesis in comparison with diabetic rats. Furthermore, treatment with QCT and SS modulated hepatic malondialdehyde (MD), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), nitric oxide, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β), in addition to serum interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), implying their effectiveness in safeguarding cells against oxidative impairment and inflammation. Remarkably, QCT and SS treatments led to the upregulation of expression of phosphatidylinositol 3-kinases (PI3K), phospho-Akt (p-Akt), and forkhead box-O1 (FOXO1) genes in hepatic tissues compared to diabetic rats, orchestrating these singling pathways for curtailing hyperglycemia and pernicious consequences in hepatic tissues. Importantly, immunohistochemical investigations exhibited downregulation of caspase-3 expression in rats treated with QCT and SS compared to diabetic animals. Beyond that, the histopathological results of hepatic tissues demonstrated notable correlations with biochemical findings. Interestingly, the in silico results supported the in vivo findings, showing notable binding affinities of QCT and SS to PI3K, GPx, and TNF-α proteins. These results imply that QCT and SS could mitigate oxidative stress and inflammation and regulate hepatic gluconeogenesis in diabetic rats. However, QCT revealed greater molecular interactions with the studied proteins than SS. Overall, our results emphasize that QCT and SS have significant therapeutic effects on attenuating hyperglycemia-induced hepatic gluconeogenesis, with QCT showing superior effectiveness.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025120","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":"Impact of Ex Vivo Bisphenol A Exposure on Gut Microbiota Dysbiosis and Its Association with Childhood Obesity.","authors":"Gracia Luque, Pilar Ortiz, Alfonso Torres-Sánchez, Alicia Ruiz-Rodríguez, Ana López-Moreno, Margarita Aguilera","doi":"10.3390/jox15010014","DOIUrl":"10.3390/jox15010014","url":null,"abstract":"<p><p>Dietary exposure to the plasticiser bisphenol A (BPA), an obesogenic and endocrine disruptor from plastic and epoxy resin industries, remains prevalent despite regulatory restriction and food safety efforts. BPA can be accumulated in humans and animals, potentially exerting differential health effects based on individual metabolic capacity. This pilot study examines the impact of direct ex vivo BPA exposure on the gut microbiota of obese and normal-weight children, using 16S rRNA amplicon sequencing and anaerobic culturing combined methods. Results showed that direct xenobiotic exposure induced modifications in microbial taxa relative abundance, community structure, and diversity. Specifically, BPA reduced the abundance of bacteria belonging to the phylum <i>Bacteroidota</i>, while taxa from the phylum <i>Actinomycetota</i> were promoted. Consistently, <i>Bacteroides</i> species were classified as sensitive to BPA, whereas bacteria belonging to the class <i>Clostridia</i> were identified as resistant to BPA in our culturomics analysis. Some of the altered bacterial abundance patterns were common for both the BPA-exposed groups and the obese non-exposed group in our pilot study. These findings were also corroborated in a larger cohort of children. Future research will be essential to evaluate these microbial taxa as potential biomarkers for biomonitoring the effect of BPA and its role as an obesogenic substance in children.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025152","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 Issue of \"Smart Drugs\" on the Example of Modafinil: Toxicological Analysis of Evidences and Biological Samples.","authors":"Karolina Nowak, Agnieszka Chłopaś-Konowałek, Paweł Szpot, Marcin Zawadzki","doi":"10.3390/jox15010015","DOIUrl":"10.3390/jox15010015","url":null,"abstract":"<p><p>Cognitive enhancement through stimulants such as modafinil is becoming increasingly popular, with many individuals using prescription stimulants for non-medical purposes to improve alertness, attention, and mood. The misuse of such substances has raised concerns, particularly in forensic toxicology. The UHPLC-QqQ-MS/MS method was developed to quantify modafinil in evidentiary samples and biological materials. Additionally, the authors noted the presence of sodium adducts during the analysis of samples with high concentrations of modafinil. The method was validated for accuracy, precision, and linearity, with a concentration range of 0.1-10.0 µg/mL for the evidences and 1.0-100.0 ng/mL for blood. The method successfully detected modafinil as the sole substance in all evidences, with concentrations ranging from 90.7 to 120.8 mg, corresponding to 45.5% to 80.5% of the labeled dose. The method was applied to real post-mortem human cases, where, among others, the concentration of modafinil in blood was 110 ng/mL, whereas, in another case, the concentration of modafinil in the putrefaction fluid exceeded 1000 ng/mL. The developed UHPLC-QqQ-MS/MS method is effective for the quantification of modafinil in evidentiary samples and biological materials, offering a reliable tool for forensic toxicology applications. This method can be used to evaluate modafinil use in both legal and illicit contexts, including cases of overdose or misuse.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025157","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":"Endocrine Disrupting Toxicity of Bisphenol A and Its Analogs: Implications in the Neuro-Immune Milieu.","authors":"Erica Buoso, Mirco Masi, Roberta Valeria Limosani, Chiara Oliviero, Sabrina Saeed, Martina Iulini, Francesca Carlotta Passoni, Marco Racchi, Emanuela Corsini","doi":"10.3390/jox15010013","DOIUrl":"10.3390/jox15010013","url":null,"abstract":"<p><p>Endocrine-disrupting chemicals (EDCs) are natural or synthetic substances that are able to interfere with hormonal systems and alter their physiological signaling. EDCs have been recognized as a public health issue due to their widespread use, environmental persistence and the potential levels of long-term exposure with implications in multiple pathological conditions. Their reported adverse effects pose critical concerns about their use, warranting their strict regulation. This is the case of bisphenol A (BPA), a well-known EDC whose tolerable daily intake (TDI) was re-evaluated in 2023 by the European Food Safety Authority (EFSA), and the immune system has been identified as the most sensitive to BPA exposure. Increasing scientific evidence indicates that EDCs can interfere with several hormone receptors, pathways and interacting proteins, resulting in a complex, cell context-dependent response that may differ among tissues. In this regard, the neuronal and immune systems are important targets of hormonal signaling and are now emerging as critical players in endocrine disruption. Here, we use BPA and its analogs as proof-of-concept EDCs to address their detrimental effects on the immune and nervous systems and to highlight complex interrelationships within the immune-neuroendocrine network (INEN). Finally, we propose that Receptor for Activated C Kinase 1 (RACK1), an important target for EDCs and a valuable screening tool, could serve as a central hub in our toxicology model to explain bisphenol-mediated adverse effects on the INEN.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025151","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":"Chlorpyrifos Acts as a Positive Modulator and an Agonist of <i>N</i>-Methyl-d-Aspartate (NMDA) Receptors: A Novel Mechanism of Chlorpyrifos-Induced Neurotoxicity.","authors":"Mahmoud Awad Sherif, Wayne G Carter, Ian R Mellor","doi":"10.3390/jox15010012","DOIUrl":"10.3390/jox15010012","url":null,"abstract":"<p><p>Chlorpyrifos (CPF) is a broad-spectrum organophosphate insecticide. Long-term exposure to low levels of CPF is associated with neurodevelopmental and neurodegenerative disorders. The mechanisms leading to these effects are still not fully understood. Normal NMDA receptor (NMDAR) function is essential for neuronal development and higher brain functionality, while its inappropriate stimulation results in neurological deficits. Thus, the current study aimed to investigate the role of NMDARs in CPF-induced neurotoxicity. We show that NMDARs mediate CPF-induced excitotoxicity in differentiated human fetal cortical neuronal ReNcell CX stem cells. In addition, by using two-electrode voltage clamp electrophysiology of <i>Xenopus</i> oocytes expressing NMDARs, we show CPF potentiation of both GluN1-1a/GluN2A (EC₅₀ ≈ 40 nM) and GluN1-1a/GluN2B (EC₅₀ ≈ 55 nM) receptors, as well as reductions (approximately halved) in the NMDA EC₅₀s and direct activation by 10 μM CPF of both receptor types. In silico molecular docking validated CPF's association with NMDARs through relatively high affinity binding (-8.82 kcal/mol) to a modulator site at the GluN1-GluN2A interface of the ligand-binding domains.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025150","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":"Assessing Variability in Children's Exposure to Contaminants in Food: A Longitudinal Non-Targeted Analysis Study in Miami, Florida.","authors":"Luciana Teresa Dias Cappelini, Olutobi Daniel Ogunbiyi, Vinícius Guimarães Ferreira, Mymuna Monem, Carolina Cuchimaque Lugo, Monica Beatriz Perez, Piero Gardinali, Florence George, Daniel M Bagner, Natalia Quinete","doi":"10.3390/jox15010011","DOIUrl":"10.3390/jox15010011","url":null,"abstract":"<p><p>Food is essential for human survival; however, food can be an important route of exposure to contaminants. This study investigated the presence and distribution of anthropogenic contaminants in food consumed by families with small children in South Florida, United States, evaluating seasonal and socio-economic variabilities in chemical composition. QuEChERS protocols, followed by non-targeted analysis (NTA) using an LC-Orbitrap HRMS system, were used for the comprehensive screening of organic contaminants. The compounds were annotated and identified with the Compound Discoverer (CD) software, and contaminant distributions were analyzed using boxplots and Principal Component Analysis (PCA). The results showed significant seasonal and socio-economic differences in contaminant distributions (<i>p</i> < 0.05). In the wet season, a predominance of polymers and surfactants, such as dodecanedioic acid and N-dodecylacrylamide, were found in food, which might be due to increased transport of industrial pollutants during increased precipitation, while plasticizers (e.g., bis(2-ethylhexyl) phthalate) and drugs (e.g., warfarin) were more prevalent during the dry season, which could be related to less dilution effects in this period. A higher abundance of 1-nitrosopiperidine, present in cured meats, was noted in food from upper socio-economic classes, while the lower class showed higher abundance of benzocaine, a common topical anesthetic.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025131","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":"Nanoplastic-Induced Developmental Toxicity in Ascidians: Comparative Analysis of Chorionated and Dechorionated <i>Phallusia mammillata</i> Embryos.","authors":"Maria Concetta Eliso, Ilaria Corsi, Antonietta Spagnuolo, Rémi Dumollard","doi":"10.3390/jox15010010","DOIUrl":"10.3390/jox15010010","url":null,"abstract":"<p><p>Nanoplastics pose a growing threat to marine ecosystems, particularly affecting the early developmental stages of marine organisms. This study investigates the effects of amino-modified polystyrene nanoparticles (PS-NH₂, 50 nm) on the embryonic development of <i>Phallusia mammillata</i>, a model ascidian species. Both chorionated and dechorionated embryos were exposed to increasing concentrations of PS-NH₂ so morphological alterations could be assessed with a high-content analysis of the phenotypes and genotoxicity. PS-NH₂ induced the same morphological alterations in both chorionated and dechorionated embryos, with dechorionated embryos being more sensitive (EC₅₀ = 3.0 μg mL^-1) than chorionated ones (EC₅₀ = 6.26 μg mL^-1). Interestingly, results from the morphological analysis showed two concentration-dependent mechanisms of action: (i) at concentrations near the EC₅₀, neurodevelopmental abnormalities resembling the ones induced by exposure to known endocrine disruptors (EDs) were observed, and (ii) at higher concentrations (15 μg mL^-1 and 7.5 μg mL^-1 for chorionated and dechorionated embryos, respectively), a nonspecific toxicity was evident, likely due to general oxidative stress. The phenotypes resulting from the PS-NH₂ treatment were not related to DNA damage, as revealed by a genotoxicity assay performed on neurula embryos. Our data suggest that PS-NH₂-induced toxicity is primarily mediated through oxidative stress, probably triggered by interactions between the positive charges of the PS NPs and the negative charges on the cell membranes. The lack of a protective chorion further exacerbated these effects, highlighting its role in mitigating/protecting against NP-induced damage.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025154","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":"Cardiotoxicity of Chemotherapy: A Multi-OMIC Perspective.","authors":"Yan Ma, Mandy O J Grootaert, Raj N Sewduth","doi":"10.3390/jox15010009","DOIUrl":"10.3390/jox15010009","url":null,"abstract":"<p><p>Chemotherapy-induced cardiotoxicity is a critical issue in cardio-oncology, as cancer treatments often lead to severe cardiovascular complications. Approximately 10% of cancer patients succumb to cardiovascular problems, with lung cancer patients frequently experiencing arrhythmias, cardiac failure, tamponade, and cardiac metastasis. The cardiotoxic effects of anti-cancer treatments manifest at both cellular and tissue levels, causing deformation of cardiomyocytes, leading to contractility issues and fibrosis. Repeated irradiation and chemotherapy increase the risk of valvular, pericardial, or myocardial diseases. Multi-OMICs analyses reveal that targeting specific pathways as well as specific protein modifications, such as ubiquitination and phosphorylation, could offer potential therapeutic alternatives to current treatments, including Angiotensin converting enzymes (ACE) inhibitors and beta-blockers that mitigate symptoms but do not prevent cardiomyocyte death, highlighting the need for more effective therapies to manage cardiovascular defects in cancer survivors. This review explores the xenobiotic nature of chemotherapy agents and their impact on cardiovascular health, aiming to identify novel biomarkers and therapeutic targets to mitigate cardiotoxicity.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025133","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":"Reducing the Formation of Toxic Byproducts During the Photochemical Release of Epinephrine.","authors":"Mikhail A Panfilov, Ezhena S Starodubtseva, Tatyana Yu Karogodina, Alexey Yu Vorob'ev, Alexander E Moskalensky","doi":"10.3390/jox15010008","DOIUrl":"10.3390/jox15010008","url":null,"abstract":"<p><p>Engineered light-sensitive molecules offer a sophisticated toolkit for the manipulation of biological systems with both spatial and temporal precision. Notably, artificial \"caged\" compounds can activate specific receptors solely in response to light exposure. However, the uncaging process can lead to the formation of potentially harmful byproducts. For example, the photochemical release of adrenaline (epinephrine) is accompanied by the formation of adrenochrome, which has neuro- and cardiotoxic effects. To investigate this effect in detail, we synthesized and compared two \"caged\" epinephrine analogs. The first was a classical compound featuring an <i>ortho</i>-nitrobenzyl protecting group attached to the amino group of epinephrine. The second analog retained the <i>ortho</i>-nitrobenzyl group but included an additional carbamate linker. The photolysis of both compounds was conducted under identical conditions, and the resulting products were analyzed using UV-Vis spectroscopy, chromatography, and NMR techniques. Surprisingly, while the classical compound led to the formation of adrenochrome, the carbamate-type caged epinephrine did not produce this byproduct, resulting in the clean release of the active substance. Subsequently, we assessed the novel compound in an in vitro platelet activation assay. The results demonstrated that the uncaging of epinephrine significantly enhances platelet activation, making it a valuable tool for advanced signaling studies.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025156","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":"Joint Effects of Lifestyle Habits and Heavy Metals Exposure on Chronic Stress Among U.S. Adults: Insights from NHANES 2017-2018.","authors":"Esther Ogundipe, Emmanuel Obeng-Gyasi","doi":"10.3390/jox15010007","DOIUrl":"10.3390/jox15010007","url":null,"abstract":"<p><strong>Background: </strong>Chronic stress, characterized by sustained activation of physiological stress response systems, is a key risk factor for numerous health conditions. Allostatic load (AL), a biomarker of cumulative physiological stress, offers a quantitative measure of this burden. Lifestyle habits such as alcohol consumption and smoking, alongside environmental exposures to toxic metals like lead, cadmium, and mercury, were individually implicated in increasing AL. However, the combined impact of these lifestyle habits and environmental factors remains underexplored, particularly in populations facing co-occurring exposures. This study aims to investigate the joint effects of lifestyle habits and environmental factors on AL, using data from the NHANES 2017-2018 cycle. By employing linear regression and Bayesian Kernel Machine Regression (BKMR), we identify key predictors and explore interaction effects, providing new insights into how cumulative exposures contribute to chronic stress. Results from BKMR analysis underscore the importance of addressing combined exposures, particularly the synergistic effects of cadmium and alcohol consumption, in managing physiological stress.</p><p><strong>Methods: </strong>Descriptive statistics were calculated to summarize the dataset, and multivariate linear regression was performed to assess associations between exposures and AL. BKMR was employed to estimate exposure-response functions and posterior inclusion probabilities (PIPs), focusing on identifying key predictors of AL.</p><p><strong>Results: </strong>Descriptive analysis indicated that the mean levels of lead, cadmium, and mercury were 1.23 µg/dL, 0.49 µg/dL, and 1.37 µg/L, respectively. The mean allostatic load was 3.57. Linear regression indicated that alcohol consumption was significantly associated with increased AL (β = 0.0933; 95% CI [0.0369, 0.1497]; <i>p</i> = 0.001). Other exposures, including lead (β = -0.1056; 95% CI [-0.2518 to 0.0408]; <i>p</i> = 0.157), cadmium (β = -0.0001, 95% CI [-0.2037 to 0.2036], <i>p</i> = 0.999), mercury (β = -0.0149; 95% CI [-0.1175 to 0.0877]; <i>p</i> = 0.773), and smoking (β = 0.0129; 95% CI [-0.0086 to 0.0345]; <i>p</i> = 0.508), were not significant. BKMR analysis confirmed alcohol's strong importance for AL, with a PIP of 0.9996, and highlighted a non-linear effect of cadmium (PIP = 0.7526). The interaction between alcohol and cadmium showed a stronger effect on AL at higher exposure levels. In contrast, lead, mercury, and smoking demonstrated minimal effects on AL.</p><p><strong>Conclusions: </strong>Alcohol consumption and cadmium exposure were identified as key contributors to increased allostatic load, while other exposures showed no significant associations. These findings emphasize the importance of addressing lifestyle habits and environmental factors in managing physiological stress.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025153","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}