Journal of Xenobiotics最新文献

Male reproductive health is increasingly threatened by endocrine-disrupting chemicals (EDCs), which interfere with hormonal homeostasis and reproductive physiology. Rising rates of male infertility have been linked to greater exposure to pollutants such as heavy metals, phthalates, pesticides, and bisphenol A. These compounds act through multiple mechanisms, including oxidative stress, apoptosis, receptor-mediated disruption of estrogenic and androgenic signaling, alterations in the hypothalamic-pituitary-gonadal (HPG) axis, and heritable epigenetic changes. Such disruptions impair key outcomes like sperm concentration, motility, morphology, DNA integrity, and steroidogenesis. Evidence from animal studies and human epidemiology consistently demonstrates these harmful effects, with biomarkers of EDC exposure correlating with reduced semen quality, hormonal imbalances, and infertility. Beyond individual health, infertility linked to EDCs carries significant social and economic costs. This review evaluates regulatory frameworks, highlights methodological challenges in risk assessment, and synthesizes mechanistic and clinical evidence. Particular attention is given to unresolved issues such as non-monotonic dose responses, mixture effects, low-dose exposures, and transgenerational impacts. Future priorities include refining biomonitoring, addressing mixture risks, and strengthening international regulation. By integrating mechanistic, clinical, and policy insights, this review underscores the urgent need for strategies to mitigate EDC-related threats to male reproductive health.

Non-nutritive artificial sweeteners (NASs) are xenobiotics widely used in the food industry as sugar substitutes, since they provide few to no calories compared to sucrose. While NASs are considered safe at the acceptable daily intake (ADI) established by regulatory agencies, there is increasing controversy regarding their potential ability to promote metabolic derangements, especially to disrupt the gut microbiome balance. In this study, we analyzed a large cohort of the most commonly consumed beverages in Spain, categorizing them by the type of soda to determine the composition and content of the most frequently used NASs in the food industry. All commercial NAS formulations analyzed contained mixtures of different NASs. The NAS contents were always within regulated limits, although some samples yielded values close to these thresholds. Most soda samples analyzed contained NASs, even though the majority were not labeled as "zero sugars", "no sugar added", or "reduced calories", which may mislead consumers. A preliminary statistical evaluation of the obtained results (cluster analysis) suggests that beverages can be grouped into three distinct clusters based on the total amount of NAS present in the samples. Differences in the total NAS content were significant among the three groups, with one cluster showing two- and four-fold higher levels than the others.

Ultrafine particles (UFPs) containing polycyclic aromatic hydrocarbons (PAHs) benzo[a]pyrene (BaP), are linked to pollution-induced health concerns, with skin being highly susceptible to contamination. Understanding the metabolic fate of these environmental pollutants in the skin is crucial. Moreover, traditional in vitro models often lack metabolic competency, while animal testing raises ethical concerns. This study introduces a novel approach combining stable isotope labeling (SIL) and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to investigate BaP metabolism. The physiologically relevant 3D reconstructed human epidermis (RHE) model was used. RHE models were exposed to BaP and deuterium-labeled BaP (BaP-d12). These analyses, followed by data analysis incorporating stable isotope filtering, revealed the presence of five distinct BaP phase I metabolites, including mono-hydroxylated, dihydroxylated, and quinone derivatives. This study demonstrates the power of coupling stable isotope labeling with LC-HRMS for the comprehensive characterization of BaP metabolic pathways in human skin. The identification of specific metabolites enhances our understanding of BaP detoxification mechanisms and their potential adverse effects. This analytical approach holds promise for investigating the metabolic fate of various other environmental pollutants.

Endocrine disruptors contaminate indoor and outdoor air, water, and food. Besides modifications of the androgen/estrogen balance, endocrine disruptors can alter thyroid function, metabolic balance, immune defenses, and brain development during fetal life, childhood, and adolescence. Among the consequences of fetal exposure to endocrine disruptors, neurobehavioral disorders, particularly psychiatric disorders (for example, schizophrenia and bipolar disorder), attention deficit disorders, and mood disorders, occupy a special place. Therefore, endocrine disruptors are also neuroendocrine disruptors. This review article first summarizes the direct and transgenerational effects of endocrine disruptors. Then, data from a French national cohort of patients whose mothers were treated with synthetic hormones (estrogens and/or progestogens) during their pregnancy(ies) are used to describe the psychiatric disorders developed by children exposed in utero and the multigenerational and potentially transgenerational impacts.

Background: Prostate cancer (PC) progression is strongly driven by dysregulated signaling pathways, with NF-κB playing a central role. Sesquiterpene lactones have been reported to modulate this pathway. This study evaluated and compared the cytotoxic effects of two structurally distinct sesquiterpene lactones: Tatridin A, a germacranolide, and desacetyl-β-cyclopyrethrosin, a eudesmanolide derivative. Their mechanisms of action were also examined, focusing on oxidative stress induction and NF-κB modulation. Methods: Chemical structures were confirmed by NMR and X-ray crystallography. Cytotoxicity was assessed in DU-145 and 22Rv1 PC cells using real-time cell analysis. Reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were measured with fluorometric assays. NF-κB activity was determined in THP-1 reporter cells and by Western blot of IκBα phosphorylation. Results: Tatridin A markedly reduced viability, showing lower IC₅₀ values (81.4 ± 2.7 µM in DU-145 and 50.7 ± 1.9 µM in 22Rv1 cells) than desacetyl-β-cyclopyrethrosin (166.9 ± 3.2 µM and 290.3 ± 8.3 µM, respectively). It also inhibited proliferation at markedly lower concentrations, with clonogenic IC₅₀ values of 7.7 µM in DU-145 and 5.24 µM in 22Rv1cells. Both compounds increased ROS, but tatridin A induced earlier and stronger responses and ΔΨm loss. Furthermore, tatridin A more effectively inhibited NF-κB signaling than classical inhibitors. Conclusions: Tatridin A exerts cytotoxic effects through oxidative stress, mitochondrial impairment, and NF-κB inhibition, supporting the therapeutic potential of germacranolides for the treatment of advanced PC.

Background: Chronic relapsing colitis involves immune dysregulation and oxidative stress, making monotherapies often insufficient. This study investigates a therapeutic strategy combining doxycycline (Dox), an immunomodulatory antibiotic, with Arthrospira platensis extracts to enhance anti-inflammatory and antioxidant effects, improving remission and controlling relapse. Methods: Ethanolic (ES) and aqueous (AS) extracts of A. platensis were chemically characterized by GC-MS after derivatization. Colitis was induced in mice using two intrarectal DNBS administrations spaced 7 days apart, with oral treatments (Dox, ES, AS, or combinations) given daily between doses. Disease progression was evaluated through clinical monitoring, histological scoring, and biochemical analysis, including MPO and CAT activities, as well as NO, MDA, and GSH levels. Results: GC-MS identified 16 bioactive compounds in each extract. ES contained mainly fatty acids and amino acids, whereas AS was rich in polysaccharides and phytol. Combined doxycycline and A. platensis extracts significantly enhanced recovery in reactivated DNBS colitis compared to monotherapies. Each treatment alone reduced disease severity, but their combination showed synergistic effects, significantly reducing disease activity index (p < 0.001), restoring mucosal integrity, and modulating inflammatory and oxidative markers (p < 0.001). Conclusion: Doxycycline potentiates the anti-colitic effects of A. platensis extracts via complementary mechanisms, offering a promising combination for managing relapsing colitis.

In this study, the use of spent coffee waste as a green precursor of polyphenolic compounds, which are subsequently employed as reducing agents for the synthesis of zero-valent iron nanoparticles (nZVI) aimed at the efficient removal of dyes from aqueous systems, has been investigated. The nanoparticles, generated in situ in the presence of controlled amounts of hydrogen peroxide, were applied in the removal of organic dyes-including methylene blue, methyl orange, and orange G-through a heterogeneous Fenton-like catalytic process. The synthesized nZVI were thoroughly characterized by nitrogen adsorption at 77 K, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and powder X-ray diffraction (XRD). A statistical design of experiments and response surface methodology were employed to evaluate the effect of polyphenol, Fe(III), and H₂O₂ concentrations on dye removal efficiency. Results showed that under optimized conditions, a 100% removal efficiency could be achieved. This work highlights the potential of nZVI synthesized from agro-industrial waste through sustainable routes as an effective solution for water remediation, contributing to circular economy strategies and environmental protection.

End-of-life tyre (ELT) management is still a hot topic due to implications for sustainability and human health. This review aims to summarise the findings concerning the chemicals' bio-accessibility/availability from the granular tyre-derived infill material used in sport surfaces. We included 14 original research articles and 5 reports (grey literature). The results included the analysis concerning volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), phthalates, metal(loid)s and other substances. The release of some dangerous chemicals was demonstrated, even though results must be considered critically. However, the chemicals' bioaccessibility shows a highly nuanced picture and is not, per se, sufficient to determine the risk for the exposed subjects. The lack of bioavailability and epidemiological studies analysing the exposures in real scenarios resulted in one of the main issues concerning a proper evaluation of the potential risks for human health.

Methylphenidate (MPH) and its active enantiomer, dexmethylphenidate, are widely prescribed as first-line therapies for attention deficit hyperactivity disorder (ADHD), yet their increasing non-medical use highlights significant clinical and toxicological challenges. MPH blocks dopamine (DAT) and norepinephrine (NET) transporters, thereby elevating synaptic catecholamine levels. While this underpins therapeutic efficacy, prolonged or abusive exposure has been associated with mitochondrial impairment, disrupted bioenergetics, and excessive reactive oxygen species (ROS) production, which collectively contribute to neuronal stress and long-term neurotoxicity. Growing evidence suggests that the gut-brain axis may critically influence MPH outcomes: diet-induced shifts in microbiome composition appear to regulate oxidative stress, neuroinflammation, and drug metabolism, opening potential avenues for dietary or probiotic interventions. From a forensic perspective, the detection and monitoring of MPH misuse require advanced methodologies, including enantioselective LC-MS/MS and analysis of alternative matrices such as hair or oral fluids, which enable retrospective exposure assessment and improves abuse surveillance. Despite its established therapeutic profile, MPH remains a compound with a narrow balance between clinical benefit and toxicological risk. Future directions should prioritize longitudinal human studies, biomarker identification for abuse monitoring, and the development of mitochondria-targeted therapies to minimize adverse outcomes and enhance safety in long-term treatment.

This study evaluated the acute toxicity of the hydroethanolic extract and the butanolic fraction of Piper marginatum Jacq., following the OECD Guideline 423. Oral and intraperitoneal exposure of CD-1 mice was used in single-dose and repeated-dose schedules. No mortality or significant behavioral alterations were observed. Body weight remained stable during treatment, and histopathological analysis revealed only mild to moderate alterations, mainly in the liver, kidneys, and lungs. These results indicate the absence of acute systemic toxicity under the conditions evaluated. Preliminary phytochemical analysis and metabolomic profile analysis by LC-QTOF/MS revealed a diverse composition of secondary metabolites, including alkaloids, flavonoids, phenylpropanoids, and sphingolipids. Compounds with known biological activity and some with potential toxicity were identified. The findings support the safe use of Piper marginatum extracts in short-term applications and suggest further subchronic toxicity studies and mechanistic evaluation. This research provides fundamental data for preclinical characterization and standardization of extracts of plant origin.