Molecular Endocrinology and Toxicology Laboratory (METLab), Department of Zoology, Banaras Hindu University, Varanasi, India.
Molecular Endocrinology and Toxicology Laboratory (METLab), Department of Zoology, Banaras Hindu University, Varanasi, India.
Neurotoxicol Teratol. 2023 Nov-Dec;100:107304. doi: 10.1016/j.ntt.2023.107304. Epub 2023 Oct 5.
Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that has been widely detected in the environment and is known to accumulate in organisms, including humans. The study investigated dose-dependent mortality, hatching rates, malformations, lipid accumulation, lipid metabolism alterations, and impacts on cholinergic neurotransmission. Increasing PFOS concentration led to higher mortality, hindered hatching, and caused concentration-dependent malformations, indicating severe abnormalities in developing zebrafish. The results also demonstrated that PFOS exposure led to a significant increase in total lipids, triglycerides, total cholesterol, and LDL in a concentration-dependent manner, while HDL cholesterol levels were significantly decreased. Additionally, PFOS exposure led to a significant decrease in glucose levels. The study identified TGs, TCHO, and glucose as the most sensitive biomarkers in assessing lipid metabolism alterations. The study also revealed altered expression of genes involved in lipid metabolism, including upregulation of fasn, acaca, and hmgcr and downregulation of ldlr, pparα, and abca1, as well as decreased lipoprotein lipase (LPL) and increased fatty acid synthase (FAS) activity,suggesting an impact on fatty acid synthesis, cholesterol uptake, and lipid transport. Additionally, PFOS exposure led to impaired cholinergic neurotransmission, evidenced by a concentration-dependent inhibition of acetylcholinesterase activity, altered gene expressions related to neural development and function, and reduced Na/K-ATPase activity. STRING network analysis highlighted two distinct gene clusters related to lipid metabolism and cholinergic neurotransmission, with potential interactions through the pparα-creb1 pathway. Overall, this study provide important insights into the potential health risks associated with PFOS exposure, including dyslipidemia, cardiovascular disease, impaired glucose metabolism, and neurotoxicity. Further research is needed to fully elucidate the underlying mechanisms and potential long-term effects of PFOS exposure.
全氟辛烷磺酸 (PFOS) 是一种持久性有机污染物，已广泛存在于环境中，并已知在生物体中积累，包括人类。本研究调查了剂量依赖性死亡率、孵化率、畸形、脂质积累、脂质代谢改变以及对胆碱能神经传递的影响。随着 PFOS 浓度的增加，死亡率升高，孵化受阻，并导致浓度依赖性畸形，表明发育中的斑马鱼存在严重的异常。研究结果还表明，PFOS 暴露会导致总脂质、甘油三酯、总胆固醇和 LDL 显著增加，呈浓度依赖性，而高密度脂蛋白胆固醇水平显著降低。此外，PFOS 暴露会导致血糖水平显著降低。该研究确定 TGs、TCHO 和葡萄糖是评估脂质代谢改变的最敏感生物标志物。研究还揭示了参与脂质代谢的基因表达的改变，包括 fasn、acaca 和 hmgcr 的上调以及 ldlr、pparα 和 abca1 的下调，以及脂蛋白脂肪酶 (LPL) 的减少和脂肪酸合成酶 (FAS) 活性的增加，表明对脂肪酸合成、胆固醇摄取和脂质转运有影响。此外，PFOS 暴露会导致胆碱能神经传递受损，这表现为乙酰胆碱酯酶活性的浓度依赖性抑制、与神经发育和功能相关的基因表达改变以及 Na/K-ATPase 活性降低。STRING 网络分析突出了与脂质代谢和胆碱能神经传递相关的两个不同基因簇，通过 pparα-creb1 途径存在潜在的相互作用。总的来说，本研究提供了关于 PFOS 暴露相关潜在健康风险的重要见解，包括血脂异常、心血管疾病、葡萄糖代谢受损和神经毒性。需要进一步研究以充分阐明 PFOS 暴露的潜在机制和潜在长期影响。
