Frontiers in toxicology最新文献

Aluminum is toxic to both humans and animals. Exposure to AlCl₃ can lead to kidney function damage, yet the specific underlying mechanism remains elusive. This study aimed to investigate whether ferroptosis is involved in the renal toxicity induced by AlCl₃ exposure in mice and to elucidate its potential molecular mechanism. Forty-eight C57BL mice were randomly assigned to six groups, with eight mice in each group: a control group, low -, medium -, and high - dose aluminum exposure groups, a ferroptosis inhibitor group, and a ferroptosis inhibitor + high - dose aluminum exposure group. Mice in the aluminum exposure groups received intraperitoneal injections of different doses of AlCl₃ solution for 4 weeks (5 times per week), while the ferroptosis inhibitor group was intraperitoneally injected with Fer - 1 for 4 weeks (2 times per week). After the experimental period, multiple indicators were examined. The results demonstrated that AlCl₃ exposure impaired the renal function and structure of mice. It also led to an increase in lipid peroxidation products, Fe²⁺, and Al content in renal tissue. Moreover, the expression levels of genes and proteins such as GPX4 and Nrf2 were decreased, whereas the expression levels of the ACSL4 gene and protein were increased.However, after pretreatment with Fer - 1, the aforementioned indicators were ameliorated. Specifically, the expression of ACSL4 decreased, and the expression of GPX4 and other related factors increased.In conclusion, this study suggests that AlCl₃ exposure may trigger ferroptosis in renal tissue cells by inhibiting the NRF2 pathway, thereby causing kidney function damage in mice. These findings provide a novel perspective on the mechanism of AlCl₃ - induced renal toxicity.

Introduction: Bisphenol A (BPA), a pervasive endocrine-disrupting chemical, impairs male reproductive health via oxidative stress, hormonal dysregulation, and hypothalamic-pituitary-gonadal (HPG) axis disruption. Flavonoids, widely present in plant-derived foods and medicinal herbs, possess antioxidant and steroidogenic modulatory properties that may counteract BPA toxicity, yet preclinical findings remain inconsistent. This study aims to systematically evaluate and quantitatively synthesize preclinical evidence on the protective effects of flavonoids against BPA-induced male reproductive toxicity.

Methods: Using PRISMA 2020 guidelines, Web of Science, Scopus, and PubMed were searched up to September 2024. Eligible studies involved BPA exposure in male rodents with flavonoid co-treatment and reported reproductive endpoints. Hormonal and oxidative stress biomarkers were pooled using a random-effects model, expressed as standardized mean differences (SMDs), with heterogeneity assessed by I² statistics. Twenty studies were included.

Results: BPA significantly reduced testosterone (SMD = -4.91), estradiol (SMD = -2.72), follicle-stimulating hormone (FSH) (SMD = -7.71), and luteinizing hormone (SMD = -5.54), while increasing malondialdehyde and reducing antioxidant enzymes (SOD, CAT, GPx, and GSH).

Discussion: Flavonoid co-treatment significantly improved hormonal profiles and oxidative balance, with the greatest recovery in FSH. High heterogeneity (I² > 84%) reflected variability in doses, treatment duration, compound purity, and species. Flavonoids exhibit marked ameliorative potential against BPA-induced reproductive toxicity in preclinical models, largely through hormonal regulation and oxidative stress mitigation. Standardized protocols and dose-response studies are essential to enhance reproducibility and translational relevance.

Cadmium (Cd) and glyphosate (Gly) are widespread aquatic contaminants known to impair reproductive function in freshwater fish. This study evaluated the effects of Cd, Gly, and their combined exposure on sperm quality and fertilization success in Prochilodus magdalenae, a commercially and ecologically important Neotropical species. Adult males were exposed to environmentally relevant concentrations of Cd, Gly, and a Cd + Gly mixture. Sperm motility parameters, membrane and mitochondrial integrity, DNA fragmentation, fertilization rate, and hatching success were assessed. Cd exposure significantly reduced sperm motility at 25 mg/L (45.0%), while Gly induced motility impairment at concentrations above 10 mg/L. Co-exposure to Cd and Gly further exacerbated the decline in motility (p < 0.05). Cd also caused significant mitochondrial and membrane damage at 25 mg/L, whereas Gly produced moderate alterations (p < 0.05). Fertilization rates declined across all treatments, with complete inhibition (0.0%) observed at the highest combined concentrations (Cd 25 mg/L + Gly 40 mg/L). No significant differences were found in sperm DNA fragmentation. This study shows that combined exposure to cadmium and glyphosate has a stronger negative impact on fish sperm quality than individual exposure. The effects depend on concentration, involving oxidative stress and alterations in motility and membrane integrity. These results contribute to understanding how mixed contaminants affect fish reproduction and emphasize the need for long-term studies under realistic environmental conditions.

In this study, we report that inhaled nanosized elongated mineral particles (EMPs) reach the human central nervous system (CNS) via two neuronal pathways, cranial nerve I (olfactorius) and cranial nerve V (trigeminus), from deposits on the nasal mucosa. High-resolution analytical imaging of autopsied brain tissues from eleven members of a Religious Orders Study (ROS) cohort (Rush Alzheimer's Disease Center) indicated that EMPs translocate from their nasal deposits to the brain either by the olfactory pathway (presence in the olfactory bulb (OB), olfactory tract, and amygdala) or by the trigeminal pathway (presence in the cerebellum). Sub-nanometer imaging and immunohistochemical (IHC) labeling were used to detect corpora amylacea (CA), abundant numbers of endogenous ferritin nanoparticles, and myelin damage as indicators of inflammation or oxidative stress. The majority of EMPs in the OB were identified as inorganic crystalline and amorphous SiO₂ fibers. Amphibole-like fibers (Mg/Si/Fe) were present (length from 25 up to 200 nm), along with lengthened nanoplastics and metallic or carbonaceous fibers. Extensive and consistent demyelination, phosphorylation, wall thickening, and CA bodies (size ranging from 10 nm to ∼10 μm) are present in all studied brain tissues. EMPs are frequently observed inside and outside of CA bodies that occur in close proximity to neurons with myelin damage. The majority of EMPs show shedding of nanosized fiber fragments and ions from their long fiber surfaces and the formation of carbon-rich coronas (physiochemical alterations: bioprocessing). Similar to spherical nanoparticles, EMPs show a tendency to bioprocess, which involves interacting with microglia, astrocytes, and CA. In conclusion, we note that although the presence of ambient EMPs in the OB, amygdala, and cerebellum of human brains is consistent with neuronal translocation from nasal deposits of inhaled EMPs to the human CNS, it remains important to further investigate the potential contribution of nano-EMPs entering from the blood compartment by crossing the blood-brain barrier (BBB) and other potential routes to the CNS.

Introduction: Ultrasonic water (UW) is a novel category of functional drinking water. This study aimed to investigate its laxative efficacy and underlying mechanisms using a constipation model in SD rats, while also conducting a comprehensive safety evaluation.

Methods: A rat constipation model was established to assess the purgative effect of UW. Safety was systematically evaluated through acute oral toxicity tests, subacute oral toxicity tests, a bone marrow cell micronucleus test, and an Ames test. Serum levels of gastrointestinal hormones-including motilin, substance P, vasoactive intestinal peptide, acetylcholinesterase, and somatostatin-were measured to explore potential mechanisms.

Results and discussion: UW significantly improved constipation symptoms of the test SD rats, with a significant increase in body weight (16.03 ± 5.32%) compared to the model group (8.67 ± 4.02%, P < 0.05). Compared to the model group, serum levels of excitatory gastrointestinal hormones were significantly elevated 4.20% (motilin), 10.87% (substance P), 36.69% (vasoactive intestinal peptide) and 12.89% (acetylcholinesterase) (P < 0.05), while somatostatin, was markedly reduced 22.40% (P < 0.05), respectively. Acute oral LD50 values of UW were higher than 20000 mg/kg, indicating practical non-toxicity. In the subacute toxicity test, compared to those in the control group, performances, blood routine indexes and serum biochemical indexes of the rats in the UW group showed no statistical difference (P > 0.05), and all the organs and tissues of the rats in both groups maintained normal morphology. Micronucleus effect of UW was not found when the dosage of UW was up to 20000 mg/kg. UW also showed no mutagenic activity on standard test strains. In summary, UW exhibited favorable purgative effect and safety.

Microplastic (MP) and nanoplastic (NP) pollution represents a pervasive environmental issue, raising significant concerns regarding potential neurotoxicity and impacts on brain health. This review synthesizes recent research findings to provide a comprehensive overview of the effects of MPs/NPs on the brain. Evidence demonstrates that MPs/NPs can cross critical biological barriers, including the blood-brain barrier and the placenta, gaining access to the central nervous system (CNS) and the developing fetal brain, influenced by particle size, charge, and the biomolecular corona. Once present, MPs/NPs trigger multiple detrimental pathways, including oxidative stress, persistent neuroinflammation involving microglia and astrocytes, mitochondrial dysfunction leading to energy deficits, disruption of crucial neurotransmitter systems, and direct neuronal damage. Critically, NPs have been shown to promote the aggregation of proteins implicated in neurodegeneration, such as alpha-synuclein. These mechanistic disturbances translate into observable adverse outcomes in experimental models, ranging from cognitive impairments in learning and memory to behavioral abnormalities and pathologies resembling human neurodegenerative and neurodevelopmental disorders. Toxicity is modulated by particle characteristics, co-exposures, and host factors like age and sex, with indirect effects via the gut-brain axis also playing a significant role. While current evidence, primarily from animal models often using high doses, strongly indicates a neurotoxic potential, significant research gaps remain concerning human risk assessment under chronic, low-level environmental exposure conditions and the effects of environmentally aged, mixed-plastic particles. Future research should prioritize human studies, environmentally realistic exposure scenarios, and differentiating direct versus indirect neurotoxic mechanisms to accurately evaluate the threat MPs/NPs pose to human brain health.

Background: Micro-pollutants, such as particulate matter, heavy metals, endocrine-disrupting compounds, and persistent organic pollutants, raise significant concerns regarding reproductive health in both humans and animals.

Methods: This systematic review and meta-analysis, conducted according to PRISMA guidelines, assessed available evidence on micro-pollutant exposure and reproductive outcomes. Out of 2,134 records identified, 52 studies (31 human, 21 animal) met inclusion criteria.

Results: Exposure to micro-pollutants was consistently associated with adverse reproductive outcomes. Human studies reported increased risks of irregular menstruation, preterm delivery (OR = 1.42), intrauterine growth restriction (OR = 1.36), and reductions in sperm concentration (SMD = -0.48) and testosterone levels. A meta-analysis of 23 studies confirmed these associations, while animal studies provided mechanistic support, including histological damage and epigenetic modifications. Despite substantial heterogeneity, the overall quality of included studies was moderate-to-high.

Conclusion: Evidence indicates that micro-pollutants are strongly associated with impaired reproductive health. While causality cannot be definitively established due to observational study designs, the consistency of findings across populations, pollutants, and species highlights an urgent need for further research and regulatory measures to mitigate reproductive risks.

Introduction: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants with potential immunotoxic effects. Most toxicological studies have focused on long-chain PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). However, short-chain and ultra-short-chain alternatives, including trifluoroacetic acid (TFA), are increasingly used despite limited toxicological data.

Methods: This study evaluated and compared the immunotoxic effects of PFAS with varying chain lengths-long-, short-, ultra-short-chain compounds, and fluoropolymer representatives (polytetrafluoroethylene, PTFE)-using human-relevant new approach methodologies (NAMs). Two complementary in vitro models were employed. Peripheral blood mononuclear cells (PBMCs) from healthy donors to assess antibody (IgG and IgM) production. THP-1-derived dendritic cells (DCs) to evaluate maturation marker expression (CD83, CD86, HLA-DR). Environmentally and occupationally relevant PFAS concentrations were tested.

Results: PFOS, PFOA, and perfluorononanoic acid (PFNA) suppressed antibody production and impaired DC maturation in a concentration-dependent manner, consistent with previous in vivo and epidemiological data. Short-chain PFAS (PFHxS, PFBS, PFHxA, PFBA) showed modest to intermediate immunomodulatory activity, with subtle immunosuppressive trends in female donors. Notably, TFA reduced antibody production at levels comparable to PFOS, indicating that chain length alone is not a reliable predictor of immunotoxic potential. PTFE exhibited no suppressive effects; instead, increased antibody release was observed in female donors, suggesting possible sex-dependent immunostimulation.

Discussion: Findings support a nuanced, compound-specific approach to PFAS risk assessment rather than a simple long- vs. short-chain distinction. In vitro NAMs provided mechanistic, human-relevant insights and reinforce their integration into regulatory frameworks.

Introduction: This study investigated the effects of cadmium (Cd) and β-cypermethrin (β-CP), both singly and in combination, on oxidative stress responses and tissue morphology in zebrafish.

Methods: Through acute exposure experiments, we evaluated the acute toxicity and behavioral responses of zebrafish to these two compounds.

Results: The LC50 values of contaminants for zebrafish at 24 h, 48 h, 72 h, and 96 h were 25.36, 22.94, 20.36, and 17.83 mg/L for Cd, and 6.41, 4.96, 4.23, and 3.75 μg/L for β-CP, respectively. The results showed that β- CP exhibited higher acute toxicity compared to Cd, with pronounced toxic reactions including body curling, convulsions, accelerated operculum flapping, and significantly reduced swimming ability. In contrast, cadmium (Cd) elicited milder acute toxicity symptoms yet significantly disrupted key oxidative stress parameters, including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). During the chronic co-exposure phase, the combined treatment of Cd and β-cypermethrin (β-CP) resulted in more severe toxicity than individual exposures, as supported by marked bioaccumulation of both contaminants and extensive histopathological impairments-such as neuronal degeneration in the brain, hepatocyte necrosis in the liver, and villus atrophy in the intestine. Quantitative assessments further indicated that the co-exposure provoked the strongest oxidative stress response, with the highest increases observed during the acute phase-reaching up to 75% for SOD, 51% for CAT, and 52% for MDA relative to the control group (P < 0.05).

Discussion: This study revealed the severe toxic effects of combined exposure to Cd and β-CP on zebrafish, underscoring the need for increased attention to the potential ecological risks of heavy metal and pesticide pollution in aquatic environments.