JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2026
·Vol. 40
·期 6
·e70946
·
IF 3.6
Lizhi Dai,Jingxuan Wang,Jia Liu,Zheyuan Cao,Yuhao Zhang,Youchong Li,Tong Yu,Jianhua Xiao
2-Ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant frequently detected in environmental matrices and poses potential health risks. However, its cardiotoxic effects on mammalian cardiomyocytes and the underlying molecular mechanisms remain largely unclear. Niacin (NIA), an essential water-soluble vitamin, exhibits potent antioxidant, anti-inflammatory, and mitochondrial-protective activities. In this study, we investigated EHDPHP-induced toxicity in H9C2 cardiomyocytes and the protective effects of NIA. Cells were exposed to 100 μM EHDPHP alone or in combination with 400, 600, and 800 μM NIA. EHDPHP exposure significantly reduced cell viability, disrupted the balance between pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-18) and the anti-inflammatory cytokine IL-10, and induced oxidative stress, as evidenced by elevated ROS, MitoSOX, and MDA levels alongside decreased activities of antioxidant enzymes (SOD, GSH, GSH-Px, and CAT). Additionally, EHDPHP disturbed mitochondrial dynamics by promoting fission and inhibiting fusion, impaired mitochondrial biogenesis via downregulation of AMPK and PGC-1α, triggered excessive mitophagy through PINK1, PRKN, and LC3 upregulation, and activated pyroptosis via GSDMD, NLRP3, and Caspase-1. Bioinformatics analyses confirmed the interconnected regulatory network among mitochondrial dynamics, mitophagy, pyroptosis, and inflammatory signaling in EHDPHP-induced cardiomyocyte injury. Notably, NIA intervention dose-dependently mitigated these detrimental effects, restoring cell viability, alleviating inflammation and oxidative stress, rebalancing mitochondrial fusion and fission, rescuing biogenesis, normalizing mitophagy, and inhibiting pyroptosis. These findings reveal a pathological cascade through which EHDPHP induces cardiomyocyte injury and demonstrate that NIA confers cardioprotection by targeting multiple pathological pathways. This study provides novel mechanistic insights into EHDPHP-induced cardiotoxicity and highlights NIA as a promising nutritional intervention for reducing cardiovascular risks associated with environmental pollutants.
✓ 已验证
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2022
·
IF 5.168
Yi Yang,Xiangjie Wang,Haolin Zhang,Jiali Li,Jingyi Chen,Miao Yu,Guangxing Li,Ruili Zhang,Ming Ge
Organophosphorus flame retardants (OPFRs) are increasingly being used in many industries since brominated flame retardants (BFRs) have been phase-out. However, OPFRs are associated with environmental pollution and animal health risks, especially in the farming industry. Nevertheless, no study has evaluated the toxicity of OPFRs, as a new flame retardant, on avian species. In order to investigate the specific toxic effects of 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure on chickens and the molecular biological mechanisms that cause damage to the organism, the chicken liver has been studied as a potential target organ for toxic effects. In this study, 7-day-old male chickens were treated with different concentrations of EHDPHP to further investigate the toxicity and mechanisms of OPRs on birds. The samples were taken at 14 d, 28 d, and 42 d for analysis. EHDPHP exposure affected the growth and development of chickens. Furthermore, the microstructural and ultrastructural observations clearly reflected the damage caused by EHDPHP exposure to the livers. The levels of the liver tissue asparate aminotransferase (AST) and alanine aminotransferase (ALT) decreased with increasing gavage dose. In contrast, the levels of oxidative stress in chicken liver and the mRNA expression of related factors increased with increasing gavage dose. In addition, EHDPHP exposure increased liver tissue iron content and affected mRNA expression and protein levels of ferroptosis-related factors in livers. Besides, ferroptosis causes inflammation, thus promoting the synthesis and release of inflammatory factors. This research indicates that EHDPHP can damage chicken livers through oxidative stress and ferroptosis.
研究领域:
毒理学
·
环境科学
·
分子生物学
·
动物健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2025
·Vol. 39
·期 9
·e70449
·
IF 2.8
Dai Lizhi,Yu Tong,Wang Jingxuan,Li Youchong,Cao Zheyuan,Xiao Jianhua
2-ethylhexyl diphenyl phosphate (EHDPHP), a ubiquitous organic phosphorus flame retardant, is extensively employed in food packaging, flame retardancy applications, and other industrial processes as a crucial chemical. However, recent discoveries have underscored its diverse toxic effects, posing a severe potential threat to biological health. Skeletal muscle, vital for locomotion, relies heavily on proper differentiation during development and maintenance for strength and functionality. This study investigated the impact of EHDPHP on skeletal muscle differentiation by culturing C2C12 cells with varying concentrations of EHDPHP during induction of differentiation, as well as constructing a mouse muscle injury repair model through oral administration of 30 μg/kg EHDPHP for 7 weeks. Exposure to EHDPHP was found to impede skeletal muscle differentiation in mice. Utilizing techniques such as western blot analysis, RNA-seq, and qRT-PCR, our preliminary analysis revealed that low concentrations of EHDPHP inhibited the expression of ACTC1, subsequently suppressing MyoG and MYH2 expression levels, thereby hindering C2C12 myoblast differentiation. Furthermore, EHDPHP exposure disrupted the repair process of muscle injury in mice and compromised the integrity of the repaired tissue. In conclusion, these findings elucidate the detrimental effects of EHDPHP exposure on muscle differentiation, uncovering its muscle toxicity.
研究领域:
毒理学
·
分子生物学
·
细胞生物学
·
药理学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）