Journal of Xenobiotics最新文献

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.

Healthcare waste (HCW) represents a growing yet frequently underestimated threat to public health, due to its complex toxicological profile. Exposure to HCW has been associated with a broad spectrum of adverse effects, including infections of bacterial, viral, or fungal origin, as well as systemic consequences such as endocrine disruption, metabolic disturbances, and mutagenic, carcinogenic, or teratogenic outcomes. These risks are particularly elevated among healthcare professionals and waste management personnel, who are directly exposed to hazardous materials. This narrative review aims to consolidate current knowledge on the toxic potential of HCW, emphasizing the variability of risks according to waste category and point of origin. A critical reevaluation of the toxicity-health risk-waste management triad is needed to strengthen preventive and protective strategies in both clinical and waste-handling settings, and the review is therefore structured around targeted questions along this axis. Priority should be given to waste prevention, minimization, and segregation at source, as downstream treatment processes may introduce additional hazards. Each category of hazardous HCW exhibits specific mechanisms of toxicity, underlining the importance of targeted and informed management approaches. Future directions should include enhanced training for waste handlers, the development of unified regulatory frameworks, and improved international data collection and reporting systems. Strengthening these components is essential for reducing occupational and environmental health risks and ensuring safer conditions across healthcare systems.

Microplastics (MPs) are increasingly recognized as widespread environmental contaminants, with confirmed presence in human tissues and biological fluids through ingestion, inhalation, and direct systemic exposure. Their potential impacts on human health have become an important subject of scientific investigation. The detection and quantification of MPs, particularly nanoplastics, in complex biological matrices remain challenging because of their low concentrations, diverse physicochemical properties, and interference from organic and inorganic matter. This review presents a critical assessment of current methods for the separation and detection of MPs from human-relevant samples. It examines pre-treatment, separation, and analytical approaches including physical filtration, density-based separation, chemical and enzymatic digestion, vibrational spectroscopy, thermal analysis, and electron microscopy, highlighting their principles, advantages, and limitations. Key challenges such as low sample throughput, absence of standardized procedures, and the difficulty of nanoplastic detection are identified as major barriers to accurate exposure assessment and risk evaluation. Recent advances, including functionalized adsorbents, improved anti-fouling membranes, integrated microfluidic systems, and artificial intelligence-assisted spectral analysis, are discussed for their potential to provide sensitive, scalable, and standardized analytical workflows. By integrating current challenges with recent innovations, this review aims to guide multidisciplinary research toward the development of reliable and reproducible detection strategies that can support MPs exposure assessment and inform evidence-based health policies.

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is essential for physiological processes such as development and wound healing, but its dysregulation contributes to a range of pathological conditions including cancer, diabetic retinopathy, and chronic inflammation. In recent years, marine-derived compounds have emerged as promising multitarget agents with anti-angiogenic potential. Posidonia oceanica, a Mediterranean seagrass traditionally used in folk medicine, is increasingly recognized for its pharmacological properties, including antioxidant, anti-inflammatory, and anti-invasive activities. This study investigated the effects of a hydroethanolic extract from P. oceanica leaves (POE) on human Endothelial Colony-Forming Cells (ECFCs), a subpopulation of endothelial progenitor cells with high proliferative and vessel-forming capacity, and a relevant model for studying pathological angiogenesis. ECFCs were treated with POE (4-8 µg/mL), and cell viability, morphology, migration, invasion, tube formation, oxidative stress, and activation markers were evaluated. POE did not alter ECFC morphology or viability, as confirmed by Trypan Blue and MTT assays. However, functional assays revealed that POE significantly impaired ECFC migration, invasion, and in vitro angiogenesis in a dose-dependent manner. Under VEGF (Vascular endothelial growth factor) stimulation, POE reduced intracellular ROS accumulation and downregulated key redox-regulating genes (hTRX1, hTRX2, PRDX2, AKR1C1, AKR1B10). Western blot analysis showed that POE inhibited VEGF-induced phosphorylation of KDR, mTOR and p-ERK, while p-AKT remained elevated, indicating selective disruption of VEGF downstream signaling. Furthermore, POE reduced the expression of pro-inflammatory and pro-coagulant markers (VCAM-1, ICAM-1, TF) and partially reversed TNF-α-induced endothelial activation. These findings suggest that POE exerts anti-angiogenic effects through a multitargeted mechanism, supporting its potential as a natural therapeutic agent for diseases characterized by aberrant angiogenesis.

Firefighters are inherently exposed to soot and polycyclic aromatic hydrocarbons (PAHs) at work. In this repeated measures study, we assessed if three different interventions reduced PAH exposure. For each sub-study, the firefighters participated in two sampling periods and thereby served as their own controls. The first period served as baseline, while the second period was the intervention period where the participants received education on health effects of soot, information on own PAH exposure, and participated in one of three interventions: (1) sauna after fire calls, (2) use of fire suits with improved barrier, and (3) showering after every fire call. We recruited 26 firefighters from three different fire stations. Dermal wipes were assessed for 16 PAHs and spot urine for eight hydroxylated metabolites. Pre-shift PAH burden was significantly reduced compared to our previous biomonitoring study. Post-shift levels of two PAH metabolites (1-hydroxypyrene and 1-hydroxyfluorene) were increased for firefighters after a work shift without fire calls compared to pre-shift. The sauna intervention significantly reduced the levels of all the measured urinary PAH metabolites while the dermal PAH exposure remained unaffected. The fire suit intervention yielded more inconsistent results. While standard shower reduced dermal PAH levels, no additional effects were observed for the shower intervention.