Aug 2026· Journal of Applied Toxicology· 0 citations· 60 references
Medicine
TL;DR
Findings highlight the critical role of ferroptosis dysregulation in TPHP-induced acute and chronic toxicities in HcerEpic cells, suggesting that TPHP may be a potential risk factor for CC and underscoring the need for further attention to the health risks associated with OPE exposure.
Abstract
The increasing global use of organophosphate esters (OPEs) has raised concerns about their environmental and health impacts, with evidence suggesting adverse effects on reproductive system health. As a widely used OPE, triphenyl phosphate (TPHP) has drawn attention for its endocrine-disrupting properties; however, its effects on cervical epithelial cells and association with cervical diseases remain unclear. In this study, analysis of 12 urinary OPE metabolites (mOPEs) in 116 cervical cancer (CC) cases and 116 controls revealed that multiple exposure biomarkers, particularly those related to TPHP exposure, were significantly positively associated with CC risk, suggesting a potential link between OPE exposure and disease development. In toxicological experiments, acute exposure to TPHP (50 μM, 24 h) induced significant cytotoxicity in human cervical epithelial cells (HcerEpic), characterized by reduced cell viability, cell cycle disruption, apoptosis, and oxidative stress. Conversely, chronic low-dose exposure (100 nM, 30 weeks) conferred a survival advantage to HcerEpic cells and enhanced their epithelial-mesenchymal transition (EMT) capacity, with enhanced tumor formation ability observed in a nude mouse xenograft model. Transcriptomic analysis revealed that ferroptosis was a significantly enriched pathway in both exposure models. Furthermore, experimental validation confirmed that acute TPHP exposure induced ferroptosis in HcerEpic cells, whereas chronically exposed cells exhibited ferroptosis resistance. Collectively, our findings highlight the critical role of ferroptosis dysregulation in TPHP-induced acute and chronic toxicities in HcerEpic cells, suggesting that TPHP may be a potential risk factor for CC and underscoring the need for further attention to the health risks associated with OPE exposure.
Bisphenol F (BPF) has been widely used as a major substitute for bisphenol A (BPA) in numerous consumer and industrial products. Its environmental presence is increasingly documented, with frequent detections in surface water, sediment, and sewage sludge across various countries, often at notably high detection rates and concentrations. BPF exhibits a range of adverse effects, including developmental toxicity, neurotoxicity, oxidative stress, and endocrine‑disrupting activity. It also disrupts the reproductive and endocrine systems by altering the metabolism or synthesis of endogenous hormones or through more complex epigenetic mechanisms. Given that BPF induces multiple toxicities, including effects on developing germ cells, such epigenetic alterations in the germline genome may transmit harmful consequences to subsequent generations. In this review, we summarize the reported concentrations and detection of BPF in the aquatic environments, followed by a review of the literature on its multifaceted toxicity of BPF exposure. We aim to provide a comprehensive assessment of its potential ecological and organismal health risks. Nevertheless, significant knowledge gaps remain. Future studies should prioritize environmentally relevant chronic exposure, mixture toxicity, identification of BPF‑specific biomarkers, and multigenerational ecological impacts.
Qing-Ping Chen, Xiang Li, Du-Juan Pi et al.· Aquatic Toxicology· 0 citations
Microplastics (<5 mm) are widespread environmental contaminants, with increasing human exposure through ingestion, inhalation, and dermal contact. Their presence in terrestrial, aquatic, and atmospheric systems, along with detection in human tissues such as blood, lungs, placenta, and the gastrointestinal tract, highlights their bioavailability and potential health risks. Owing to their small size, high surface-area-to-volume ratio, and surface reactivity, microplastics can interact with biological molecules and cells, raising concerns about their role in disease development. This review presents a mechanistic perspective on microplastic-induced carcinogenesis. Microplastics can enter the body via multiple routes and disrupt cellular homeostasis by inducing oxidative stress, chronic inflammation, mitochondrial dysfunction, and genotoxicity. These effects contribute to genomic instability and dysregulation of key signaling pathways, including NF-κB, MAPK, and PI3K/Akt, which are associated with tumor initiation and progression. Additionally, microplastics act as "Trojan horse" carriers, facilitating the transport of co-contaminants such as heavy metals, persistent organic pollutants, and microbial agents, thereby enhancing their bioavailability and toxicity. The combined effects of microplastics and associated toxicants amplify oxidative stress, inflammatory responses, and epigenetic alterations, promoting a pro-tumorigenic environment. Despite growing evidence, significant knowledge gaps remain regarding long-term exposure, the behavior of nanoplastics in biological systems, and their direct link to cancer. This review emphasizes the need for integrated and interdisciplinary research to better understand microplastic-associated carcinogenesis and to support effective risk assessment and regulatory strategies.
The expanding use of aluminum oxide nanoparticles (Al₂O₃-NPs) across industrial applications necessitates evaluating their biological interactions and potential environmental risks. This study provides a comprehensive assessment of the cytotoxic, genotoxic, and molecular effects of Al₂O₃-NPs on Musca domestica larvae, a suitable model for nanoparticle-induced toxicity. Biochemical analyses showed significant elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities following exposure, indicating cellular damage. Flow cytometric analysis revealed marked alterations in cell cycle progression, including decreased G₀–G₁ phase populations and increased S, G₂–M, and pre-G₁ (apoptotic) fractions, reflecting DNA damage and cell cycle arrest. Complementary viability assays demonstrated substantial reductions in cell viability and increased early and late apoptosis, while necrosis remained minimal. Molecular docking indicated strong and selective binding of Al₂O₃-NPs to cytochrome P450, characterized by a stable hydrogen bond at SER410, suggesting preferential interactions with detoxification pathways. Correspondingly, several cytochrome P450 genes, particularly CYP6A36 and CYP6G4, were significantly upregulated, reflecting an adaptive detoxification response to nanoparticle-induced stress. Collectively, the findings demonstrate that Al₂O₃-NPs disrupt cellular homeostasis in insects through oxidative, apoptotic, and detoxification-mediated mechanisms, providing important insights into the mechanistic toxicology and environmental implications of aluminum-based nanomaterials.
KEY WORDS: Al₂O₃-NPs, Cell cycle, Apoptosis, Molecular docking
Bull. Chem. Soc. Ethiop. 2026, 40(11), 2489-2502
DOI: https://dx.doi.org/10.4314/bcse.v40i11.15
M. Germoush, Maged M. A. Fouda, Shaymaa H. Mahmoud· Bulletin of the Chemical Soc...· 0 citations
Triclosan (TCS) is a broad-spectrum antimicrobial agent that has raised public health concerns due to its continuous environmental release and human exposure. Previous studies suggest that TCS may disrupt endocrine function. Nonetheless, the toxicological effects on the female reproductive system, notably on ovarian granulosa cells, and the underlying pathways remain poorly understood. This study was designed to examine the toxic effects of TCS on human granulosa cells and the related mechanisms. To this end, human granulosa cell lines (KGN and SVOG) were treated in vitro with varying doses of TCS. The results demonstrated that TCS exposure led to marked cytotoxicity and DNA damage in a dose-dependent manner. Transcriptomic profiling showed that TCS markedly affected pathways associated with mitochondrial respiratory chain function and DNA repair mechanisms within granulosa cells. Subsequent mechanistic studies revealed that TCS led to mitochondrial dysfunction, as evidenced by reduced activity of mitochondrial respiratory chain complex I and a marked increase in mitochondrial ROS levels. Application of the mitochondria-targeted antioxidant MitoTEMPOL significantly alleviated the ROS accumulation and DNA damage induced by TCS. Specifically, we found that TCS exposure suppressed the synthesis of glutathione (GSH), a key component of the endogenous antioxidant defense system. The decline in GSH synthesis was further confirmed to be an upstream initiating factor for TCS-induced mitochondrial ROS production and DNA damage in granulosa cells, as evidenced by glutathione monoethyl ester (GSH-MEE) pretreatment. These findings reveal a previously unrecognized molecular mechanism by which TCS impairs ovarian reserve function, thereby providing important theoretical insights for assessing the reproductive toxicity risk of TCS and suggesting that antioxidants targeting GSH and mitochondria may represent a potential intervention strategy.
As a persistent organic pollutant (POP), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) can accumulate through the food chain and enter the human body. Most existing studies have focused on short-term toxicity, with insufficient understanding of its chronic toxicity. In this study, a 6-month chronic exposure model was established in C3H/He mice via intragastric gavage. Hematological analysis and biochemistry tests were conducted, and organ coefficients along with histopathological changes were analyzed. Additionally, liver ultrasound elastography was assessed. The results showed that BDE-47 could significantly reduce renal index, serum levels of albumin (ALB), triglycerides (TG), and urea (UREA), increase uric acid (UA) levels, cause a dose-dependent decrease in liver elasticity, and lead to hepatic steatosis, atrophy of seminal vesicle epithelium, shedding of spermatogenic cells, and infiltration of splenic macrophages. Collectively, this study has confirmed that BDE-47 has significant chronic toxicity to mammals, providing a new basis for subsequent toxicological research and safety risk evaluation.
Wei Deng, Xiao-Jing Liu, Xiaobing Wu et al.· Food and Chemical Toxicology· 0 citations
Perfluorodecanoic acid (PFDA) is a perfluoroalkyl substance characterized by high environmental persistence and bioaccumulation potential, with a propensity to accumulate in the reproductive system. However, its toxicological effects on ovarian function remain poorly understood. This study employed mouse primary ovarian granulosa cells (mGCs) and a human ovarian granulosa cell line (SVOG) as in vitro models, combined with in vivo exposure experiments in female C57 mice. We systematically assessed cell viability, oxidative stress, inflammation, and senescence-associated phenotypes using MTT assays, ROS detection, Sa-β-gal staining, Western blotting, immunofluorescence, H&E staining, and immunohistochemistry. The results demonstrated that PFDA dose‑dependently reduced the viability and proliferation of mouse primary granulosa cells (mGCs) and human SVOG cells, as determined by CCK8 and EdU assays, induced oxidative stress and inflammation, and triggered cellular senescence. Furthermore, PFDA exposure led to ovarian follicular depletion, significantly decreased serum AMH and E2 levels, and increased FSH levels, recapitulating a premature ovarian insufficiency‑like phenotype. Mechanistically, PFDA impaired mitochondrial function, causing ROS accumulation and disrupting mitochondrial dynamics, leading to excessive mitochondrial fission. The release of mitochondrial DNA into the cytoplasm activated the cGAS-STING signaling pathway. The subsequent oxidative stress-inflammatory cascade drove ovarian cellular senescence.This study presents new experimental evidence on PFDA's reproductive toxicity and its impact on ovarian aging, providing a foundation for risk assessment and intervention strategies concerning this environmental pollutant.
Yang Su, Huiyi Xie, Xiuli Lian et al.· Tissue & Cell· 0 citations
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