Search Results (1,095)

Hypothermia-related deaths present significant diagnostic challenges due to non-specific and often inconsistent autopsy findings. This study investigated the histological and immunohistochemical alterations associated with primary and secondary hypothermia in an experimental Rattus norvegicus model, focusing on the effects of benzodiazepine and alcohol ingestion. Twenty-one male rats were divided into three groups: control (K), benzodiazepine-treated (B), and alcohol-treated (A). After two weeks of substance administration, hypothermia was induced and multiple organ samples were analyzed. Histologically, renal tissue showed hydropic and vacuolar degeneration, congestion, and acute tubular injury across all groups, with no significant differences in E-cadherin expression. Lung samples revealed congestion, emphysema, and hemorrhage, with more pronounced vascular congestion in the alcohol and benzodiazepine groups. Cardiac tissue exhibited vacuolar degeneration and protein denaturation, particularly in substance-exposed animals. The spleen showed preserved architecture but increased erythrocyte infiltration and significantly elevated myeloperoxidase (MPO)-positive granulocytes in the intoxicated groups. Liver samples demonstrated congestion, focal necrosis, and subcapsular hemorrhage, especially in the alcohol group. Immunohistochemical analysis revealed statistically significant differences in MPO expression in both lung and spleen tissues, with the highest levels observed in the benzodiazepine group. Similarly, CK7 and CK20 expression in the gastroesophageal junction was significantly elevated in both alcohol- and benzodiazepine-treated animals compared to the controls. In contrast, E-cadherin expression in the kidney did not differ significantly among the groups. These findings suggest that specific histological and immunohistochemical patterns, particularly involving pulmonary, cardiac, hepatic, and splenic tissues, may help differentiate primary hypothermia from substance-related secondary hypothermia. The study underscores the value of integrating toxicological, histological, and molecular analyses to enhance the forensic assessment of hypothermia-related fatalities. Future research should aim to validate these markers in human autopsy series and explore additional molecular indicators to refine diagnostic accuracy in forensic pathology. Full article

Perfluoroalkyl substances (PFASs) possess immunosuppressive properties. However, their association with rheumatoid arthritis (RA) risk remains inconclusive across epidemiological studies. This study integrates population-based and mechanistic evidence to clarify the relationship between PFAS exposure and RA. We analyzed 8743 U.S. adults from the NHANES (2005–2018), assessing individual and mixed exposures to PFOA, PFOS, PFNA, and PFHxS using multivariable logistic regression, Bayesian kernel machine regression, quantile g-computation, and weighted quantile sum models. Network toxicology and molecular docking were utilized to identify core targets mediating immune disruption. The results showed that elevated PFOA (OR = 1.63, 95% CI: 1.41–1.89), PFOS (OR = 1.41, 1.25–1.58), and PFNA (OR = 1.40, 1.20–1.63) levels significantly increased RA risk. Mixture analyses indicated a positive joint effect (WQS OR = 1.06, 1.02–1.10; qgcomp OR = 1.26, 1.16–1.38), with PFOA as the primary contributor. Stratified analyses revealed stronger effects in females (PFOA Q4 OR = 3.75, 2.36–5.97) and older adults (≥60 years). Core targets included EGFR, SRC, TP53, and CTNNB1. PFAS mixtures increase RA risk, dominated by PFOA and modulated by sex/age. These findings help reconcile prior contradictions by identifying key molecular targets and vulnerable subpopulations, supporting regulatory attention to PFAS mixture exposure. Full article

The use of opioids for cancer-related pain is essential but poses significant challenges due to the risk of misuse and the development of opioid use disorder (OUD). This review takes a multidisciplinary perspective based on the current scientific literature to analyze the pharmacological mechanisms, classification, and therapeutic roles of opioids in oncology. Key risk factors for opioid misuse—including psychiatric comorbidities, prior substance use, and insufficient clinical monitoring—are discussed in conjunction with validated tools for pain assessment and international guidelines. The review emphasizes the importance of integrating toxicological, pharmacological, physiological, and public health perspectives to promote rational opioid use. Pharmacogenetic variability is explored as a determinant of treatment response and addiction risk, underscoring the value of personalized medicine. Evidence-based strategies such as early screening, psychosocial interventions, and the use of buprenorphine-naloxone are presented as effective measures for managing OUD in cancer patients. Ultimately, this work advocates for safe, patient-centered opioid prescribing practices that ensure effective pain relief without compromising safety or quality of life. Full article

Barium chloride (BaCl₂), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl₂-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl₂ exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl₂ exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl₂ exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl₂-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl₂-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article

Over the past years, increasing attention has been drawn to the adverse effects of agricultural pesticide use on pollinators, with honeybees being especially vulnerable. The aim of this study was to evaluate the levels of residues detectable and/or quantifiable of neonicotinoid pesticides and other pesticides in biological materials (bees, bee brood, etc.) and beehive products (honey, pollen, etc.) applied as seed dressings in rapeseed and sunflower plants in two growing seasons (2020–2021) in fields located in three agro-climatic regions in Romania. The study involved the comparative sampling of hive products (honey, pollen, adult bees, and brood) from experimental and control apiaries, followed by pesticide residue analysis in an accredited laboratory (Primoris) using validated chromatographic techniques (LC-MS/MS and GC-MS). Toxicological analyses of 96 samples, including bees, bee brood, honey, and pollen, confirmed the presence of residues in 46 samples, including 10 bee samples, 10 bee brood samples, 18 honey samples, and 8 pollen bread samples. The mean pesticide residue concentrations detected in hive products were 0.032 mg/kg in honey, 0.061 mg/kg in pollen, 0.167 mg/kg in bees, and 0.371 mg/kg in bee brood. The results highlight the exposure of honeybee colonies to multiple sources of pesticide residue contamination, under conditions where legal recommendations for the controlled application of agricultural treatments are not followed. The study provides relevant evidence for strengthening the risk assessment framework and underscores the need for adopting stricter monitoring and regulatory measures to ensure the protection of honeybee colony health. Full article

Volatile organic compounds (VOCs) are highly volatile chemicals in natural and anthropogenic environments, significantly affecting indoor air quality. Major sources of indoor VOCs include emissions from building materials, furnishings, and consumer products. Natural wood products release VOCs, including terpenes and aldehydes, which exert diverse health effects ranging from mild respiratory irritation to severe outcomes, such as formaldehyde-induced carcinogenicity. The temporal dynamics of VOC emissions were investigated, and the toxicological and physiological effects of the VOCs emitted by two types of natural wood, Korean Red Pine (Pinus densiflora) and Japanese Cypress (Chamaecyparis obtusa), were evaluated. Using female C57BL/6 mice as an animal model, the exposure setups included phytoncides, formaldehyde, and intact wood samples over short- and long-term durations. The exposure effects were assessed using oxidative stress markers, antioxidant enzyme activity, hepatic and renal biomarkers, and inflammatory cytokine profiles. Long-term exposure to Korean Red Pine and Japanese Cypress wood VOCs did not induce significant pathological changes. Japanese Cypress exhibited more distinct benefits, including enhanced oxidative stress mitigation, reduced systemic toxicity, and lower pro-inflammatory cytokine levels compared to the negative control group, attributable to its more favorable VOC emission profile. These findings highlight the potential health and environmental benefits of natural wood VOCs and offer valuable insights for optimizing timber use, improving indoor air quality, and informing public health policies. Full article

Exposure to xenobiotics causes pathophysiological changes in fish, including oxidative stress and neurotoxicity. Here, we describe the biochemical mechanisms underlying oxidative stress (i.e., redox imbalance) and the biochemical markers commonly used to assess its level. Neurotoxicity biomarkers used in fish include behavioral, histological, molecular, neurotransmitter-related, and enzymatic parameters, among which acetylcholinesterase (AChE) activity is the most commonly measured. We therefore also review the changes in AChE activity in fish exposed to common xenobiotics. In most cases, AChE activity decreased in a concentration- and time-dependent manner, although some studies reported no change or even an increase. We emphasize the relevance of all the parameters discussed in the context of fish toxicology studies. Full article

Background/Objectives: The incorporation of bioactive molecules into mesoporous carriers is a promising strategy to improve stability, solubility, and therapeutic efficacy. In this study, we report for the first time the encapsulation of the synthetic chalcone 4-Cl into KIT-6 mesoporous silica and evaluate its cytotoxicity, toxicological profile, and pharmacological activities (antinociceptive, anti-inflammatory, and anxiolytic) using an in vivo zebrafish (Danio rerio) model. Methods: Zebrafish were orally dosed with 4-Cl, 4-Cl/KIT-6, or KIT-6 (4, 20, 40 mg/kg) and mortality was recorded for 96 h. For analgesia, zebrafish pretreated with 4-Cl, 4-Cl/KIT-6, KIT-6, or morphine received a tail stimulus (0.1% formalin). Locomotor activity (quadrant crossings) was monitored for 30 min to assess analgesia (neurogenic: 0–5 min; inflammatory: 15–30 min). For inflammation, abdominal edema and weight gain were assessed 4 h after intraperitoneal carrageenan (1.5%). Zebrafish (n = 6/group) received 4-Cl, 4-Cl/KIT-6, or KIT-6 (4, 20, 40 mg/kg, p.o.). Controls received ibuprofen (100 mg/kg, p.o.) or 3% DMSO. Weight was measured hourly for 4 h post-carrageenan (difference between baseline and hourly weights). Results: Physicochemical characterizations confirmed successful encapsulation without compromising the ordered structure of KIT-6, as evidenced by a significant reduction in surface area and pore volume, indicating efficient drug incorporation. In vivo assays demonstrated that the 4-Cl/KIT-6 formulation maintained the pharmacological activities of the free chalcone, reduced toxicity, and, notably, revealed a significant anxiolytic effect for the first time. Conclusions: These findings highlight KIT-6 as a promising platform for chalcone delivery systems and provide a solid basis for future preclinical investigations. Full article

Background: Cardiovascular diseases, particularly hypertension, and gastrointestinal disorders represent major public health concerns in Mexico. Although a range of pharmacological treatments exists, their use is associated with adverse effects, highlighting the need for safer therapeutic alternatives. Species of the Ipomoea genus are widely employed in Mexican traditional medicine (MTM) for their purgative, anti-inflammatory, analgesic, and sedative properties. Particularly, Ipomoea purpurea is traditionally used as a diuretic and purgative; its leaves and stems are applied topically for their anti-inflammatory and soothing effects. This study aimed to determine their phytochemical composition and to evaluate the associated vasodilatory activity, modulatory effects on intestinal smooth-muscle motility, and toxicological effects of the methanolic (ME-Ip) and dichloromethane (DE-Ip) extracts obtained from the aerial parts of I. purpurea. Methods: The phytochemical composition of the ME-Ip and DE-Ip extracts of I. purpurea was assessed using UPLC-QTOF-MS and GC-MS, respectively. For both extracts, the vasodilatory activity and effects on intestinal smooth muscle were investigated using ex vivo models incorporating isolated rat aorta and ileum, respectively, whereas acute toxicity was evaluated in vivo. Results: Phytochemical analysis revealed, for the first time, the presence of two glycosylated flavonoids within the Ipomoea genus; likewise, constituents with potential anti-inflammatory activity were detected. The identified compounds in I. purpurea extracts may contribute to the vasodilatory, biphasic, and purgative effects observed in this species. The EC₅₀ values for the vasodilatory effects of the methanolic (ME-Ip) and dichloromethane (DE-Ip) extracts were 0.80 and 0.72 mg/mL, respectively. In the initial phase of the experiments on isolated ileal tissues, both extracts induced a spasmodic (contractile) effect on basal motility, with ME-Ip exhibiting higher potency (EC₅₀ = 27.11 μg/mL) compared to DE-Ip (EC₅₀ = 1765 μg/mL). In contrast, during the final phase of the experiments, both extracts demonstrated a spasmolytic effect, with EC₅₀ values of 0.43 mg/mL for ME-Ip and 0.34 mg/mL for DE-Ip. In addition, both extracts exhibited low levels of acute toxicity. Conclusions: The phytochemical profile and the vasodilatory and biphasic effects of the I. purpurea extracts explain, in part, the use of I. purpurea in MTM. The absence of acute toxic effects constitutes a preliminary step in the toxicological safety assessment of I. purpurea extracts and demonstrates their potential for the development of phytopharmaceutic agents as adjuvants for the treatment of cardiovascular and gastrointestinal disorders. Full article

Nano- (NPs) and microplastics (MPs) are ubiquitous and raising concerns about their toxicity. A popular model for studying acute toxicity is Danio rerio. This study investigated the acute toxicity in FET test of polystyrene nanoparticles (500 nm, nanoPS) at different concentrations (0.01, 0.1, and 0.2 mg/mL), with different surface groups (non-modified, amine, carboxyl) and discuss the toxicological contribution of commercially added compounds. Different behavioural tests were used to investigate the neurotoxicity of nanoPS and sodium azide: coiling assay test, light–dark preference test, and colour preference test. Sodium azide and other preservatives are often present in commercially available NP and MP solutions frequently used in microplastic toxicity tests, but their effects on the results remain largely unknown. In the FET test, nanoPS did not increase mortality or affect the heart rate or body length. A higher hatching rate was observed at 48 hpf. Although nanoPS showed no acute toxicity, behavioural tests revealed subtle neurotoxic effects (changes in colour preference), suggesting a potential impact on neurological function. Additionally, sodium azide exhibited toxicity, indicating that additives may confound toxicity assessments. This highlights the need for careful consideration of preservatives in nanoparticle research to avoid misleading conclusions. Full article

Food safety concerns related to pesticide residues in fruits and vegetables have increased globally, particularly in regions where monitoring programs are scarce or inconsistent. This study provides the first multi-year evaluation of pesticide contamination and associated dietary risks in Cape Verde, an African island nation increasingly reliant on imported produce. A total of 570 samples of fruits and vegetables—both locally produced and imported—were collected from major markets across the country between 2017 and 2020 and analyzed using validated multiresidue methods based on gas chromatography coupled to Ion Trap mass spectrometry (GC-IT-MS/MS), and both gas and liquid chromatography coupled to triple quadrupole tandem mass spectrometry (GC-QqQ-MS/MS and LC-QqQ-MS/MS). Residues were detected in 63.9% of fruits and 13.2% of vegetables, with imported fruits showing the highest contamination levels and diversity of compounds. Although only one sample exceeded the maximum residue limits (MRLs) set by the European Union, 80 different active substances were quantified—many of them not authorized under the current EU pesticide residue legislation. Dietary exposure was estimated using median residue levels and real consumption data from the national nutrition survey (ENCAVE 2019), enabling a refined risk assessment based on actual consumption patterns. The cumulative hazard index for the adult population was 0.416, below the toxicological threshold of concern. However, when adjusted for children aged 6–11 years—taking into account body weight and relative consumption—the cumulative index approached 1.0, suggesting a potential health risk for this vulnerable group. A limited number of compounds, including omethoate, oxamyl, imazalil, and dithiocarbamates, accounted for most of the risk. Many are banned or heavily restricted in the EU, highlighting regulatory asymmetries in global food trade. These findings underscore the urgent need for strengthened residue monitoring in Cape Verde, particularly for imported products, and support the adoption of risk-based food safety policies that consider population-specific vulnerabilities and mixture effects. The methodological framework used here can serve as a model for other low-resource countries seeking to integrate analytical data with dietary exposure in a One Health context. Full article

Human milk has been used for over 70 years to monitor pollutants such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). Despite the growing body of data, our understanding of the pollutant exposome, particularly co-exposure patterns and their interactions, remains limited. Artificial intelligence (AI) offers considerable potential to enhance biomonitoring efforts through advanced data modelling, yet its application to pollutant dynamics in complex biological matrices such as human milk remains underutilized. This study applied an AI-based framework, integrating machine learning, metaheuristic hyperparameter optimization, explainable AI, and postprocessing, to analyze PCB-170 levels in breast milk samples from 186 mothers in Zadar, Croatia. Among 24 analyzed POPs, the most influential predictors of PCB-170 concentrations were hexa- and hepta-chlorinated PCBs (PCB-180, -153, and -138), alongside p,p’-DDE. Maternal age and other POPs exhibited negligible global influence. SHAP-based interaction analysis revealed pronounced co-behavior among highly chlorinated congeners, especially PCB-138–PCB-153, PCB-138–PCB-180, and PCB-180–PCB-153. These findings highlight the importance of examining pollutant interactions rather than individual contributions alone. They also advocate for the revision of current monitoring strategies to prioritize multi-pollutant assessment and focus on toxicologically relevant PCB groups, improving risk evaluation in real-world exposure scenarios. Full article

Over the past few decades, scientific interest in mycotoxins—fungal metabolites that pose serious concern to food safety, crop health, and both human and animal health—has increased. While major mycotoxins such as aflatoxins, ochratoxins, deoxynivalenol, fumonisins, zearalenone, citrinin, patulin, and ergot alkaloids are well studied, emerging mycotoxins remain underexplored and insufficiently investigated. Among these, moniliformin (MON) is frequently detected in maize-based food and feed; however, the absence of regulatory limits and standardized detection methods limits effective monitoring and comprehensive risk assessment. The European Food Safety Authority highlights insufficient occurrence and toxicological data as challenges to regulatory development. This study compares three analytical methods—CE-DAD, HPLC-DAD, and HPLC-MS/MS—for moniliformin detection and quantification in maize, evaluating linear range, correlation coefficients, detection and quantification limits, accuracy, and precision. Results show that CE-DAD and HPLC-MS/MS provide reliable and comparable sensitivity and selectivity, while HPLC-DAD is less sensitive. Application to real samples enabled deterministic dietary exposure estimation based on consumption, supporting preliminary risk characterization. This research provides a critical comparison that supports the advancement of improved monitoring and risk assessment frameworks, representing a key step toward innovating the detection of under-monitored mycotoxins and laying the groundwork for future regulatory and preventive measures targeting MON. Full article

Infant clothing represents a critical yet overlooked exposure pathway for heavy metals, with significant implications for child health and sustainable consumption. This study investigates cadmium (Cd) and chromium (Cr) contamination in 33 textile samples, integrating in vitro bioaccessibility assays, cytotoxicity analysis, and risk assessment models to evaluate dermal exposure risks. Results reveal that 80% of samples exceeded OEKO-TEX Class I limits for As (mean 1.01 mg/kg), Cd (max 0.25 mg/kg), and Cr (max 4.32 mg/kg), with infant clothing showing unacceptable hazard indices (HI = 1.13) due to Cd (HQ = 1.12). Artificial sweat extraction demonstrated high bioaccessibility for Cr (37.8%) and Ni (28.5%), while keratinocyte exposure triggered oxidative stress (131% ROS increase) and dose-dependent cytotoxicity (22–59% viability reduction). Dark-colored synthetic fabrics exhibited elevated metal loads, linking industrial dye practices to health hazards. These findings underscore systemic gaps in textile safety regulations, particularly for low- and middle-income countries reliant on cost-effective apparel. We propose three policy levers: (1) tightening infant textile standards for Cd/Cr, (2) incentivizing non-toxic dye technologies, and (3) harmonizing global labeling requirements. By bridging toxicological evidence with circular economy principles, this work advances strategies to mitigate heavy metal exposure while supporting Sustainable Development Goals (SDGs) 3 (health), 12 (responsible consumption), and 12.4 (chemical safety). Full article

Pteridium aquilinum (bracken fern) poses a global threat to biodiversity and to the health of both animals and humans due to its toxic metabolites and aggressive ecological expansion. In northern Spain, particularly in regions of intensive livestock farming, these risks may be exacerbated, calling for urgent assessment and monitoring strategies. In this study, we implemented a multidisciplinary approach to evaluate the toxicological and ecological relevance of P. aquilinum through four key actions: (a) quantification of pterosins A and B in young fronds (croziers) using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS); (b) analysis of in vivo genotoxicity of aqueous extracts using Drosophila melanogaster as a model organism; (c) a large-scale survey of local livestock farmers to assess awareness and perceived impact of bracken; and (d) the development and field application of a drone-based mapping tool to assess the spatial distribution of the species at the regional level. Our results confirm the consistent presence of pterosins A and B in croziers, with concentrations ranging from 0.17 to 2.20 mg/g dry weight for PtrB and 13.39 to 257 µg/g for PtrA. Both metabolite concentrations and genotoxicity levels were found to correlate with latitude and, importantly, with each other. All tested samples exhibited genotoxic activity, with notable differences among them. The farmer survey (n = 212) revealed that only 50% of respondents were aware of the toxic risks posed by bracken, indicating a need for targeted outreach. The drone-assisted mapping approach proved to be a promising tool for identifying bracken-dominated areas and provides a scalable foundation for future ecological monitoring and land management strategies. Altogether, our findings emphasize that P. aquilinum is not merely a local concern but a globally relevant toxic species whose monitoring and control demand coordinated scientific and policy-based efforts. Full article