School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou 550025, China.
Guizhou Provincial Center for Disease Control and Prevention, Guiyang, Guizhou 550004, China; School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou 550025, China.
Ecotoxicol Environ Saf. 2022 Aug;241:113750. doi: 10.1016/j.ecoenv.2022.113750. Epub 2022 Jun 10.
Dibutyl phthalate (DBP) and Benzo(a)pyrene (BaP) are ubiquitous contaminants in environment and foodstuffs, which increase the chance of their combined exposure to humans in daily life. However, the combined effects of DBP and BaP on liver and the underlying mechanisms are still unclear. In this study, we explored the combined effects of DBP and BaP on liver and the potential mechanisms in a rat model. We found that DBP and BaP co-exposure activated the MyD88/NF-κB pathway through increasing TLR4 acetylation (TLR4ac) level, leading to the imbalance of pro-inflammatory factors (CXCL-13, IL-6 and TNF-α) and anti-inflammatory factors (IL-10), ultimately resulting in liver tissue damage and functional changes. Sporoderm-broken spores of Ganoderma lucidum (SSGL) had strong alleviating effects on liver injury induced by DBP and BaP co-exposure. Our study found that SSGL suppressed TLR4ac-regulated MyD88/NF-κB signaling to reduce the release of pro-inflammatory factors, and promote the secretion of IL-10, thus alleviating liver injury caused by DBP and BaP co-exposure. In conclusion, SSGL contributed to liver protection against DBP and BaP-induced liver injury in rats via suppressing the TLR4ac-regulated MyD88/NF-κB signaling.
邻苯二甲酸二丁酯（DBP）和苯并[a]芘（BaP）是环境和食品中普遍存在的污染物，这增加了它们在日常生活中同时暴露于人体的机会。然而，DBP 和 BaP 对肝脏的联合作用及其潜在机制仍不清楚。在这项研究中，我们在大鼠模型中探索了 DBP 和 BaP 联合暴露对肝脏的联合作用及其潜在机制。我们发现，DBP 和 BaP 共同暴露通过增加 TLR4 乙酰化（TLR4ac）水平激活了 MyD88/NF-κB 途径，导致促炎因子（CXCL-13、IL-6 和 TNF-α）和抗炎因子（IL-10）失衡，最终导致肝组织损伤和功能改变。灵芝破壁孢子（SSGL）对 DBP 和 BaP 共同暴露引起的肝损伤具有很强的缓解作用。我们的研究发现，SSGL 通过抑制 TLR4ac 调节的 MyD88/NF-κB 信号通路来减少促炎因子的释放，并促进 IL-10 的分泌，从而缓解 DBP 和 BaP 共同暴露引起的肝损伤。总之，SSGL 通过抑制 TLR4ac 调节的 MyD88/NF-κB 信号通路，有助于保护大鼠免受 DBP 和 BaP 诱导的肝损伤。
