Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, China.
Arch Toxicol. 2018 Nov;92(11):3277-3289. doi: 10.1007/s00204-018-2305-x. Epub 2018 Sep 17.
Previous studies have reported that excessive fluoride exposure induced liver damage. However, the underlying mechanism of fluoride-induced hepatic toxicity is still unclear. Hence, this study was aimed to evaluate the fluoride-induced apoptosis, autophagy, and IL-17 signaling pathway-related genes to explore the possible mechanisms of NaF-induced liver injury in mice. For this, 48 male mice were allotted randomly to four groups, treated with deionized water, 25, 50, 100 mg/L NaF for 150 days continuously. Our results suggested that treatment with NaF decreased the PAS staining-positive area, with a concomitant increase in liver score, and serum ALT and AST levels which indicated that NaF induced the liver injury. In addition, the qRT-PCR, immunohistochemistry, and western blotting results indicated that NaF exposure activated IL-17 signaling, apoptosis, and autophagy pathways. In summary, these results suggested that NaF induced apoptosis and autophagy in liver by activating the IL-17 signaling pathway, eventually leading to impaired liver function.
先前的研究报告指出，过量的氟暴露会导致肝脏损伤。然而，氟诱导肝毒性的潜在机制尚不清楚。因此，本研究旨在评估氟化物诱导的细胞凋亡、自噬和 IL-17 信号通路相关基因，以探讨 NaF 诱导小鼠肝损伤的可能机制。为此，将 48 只雄性小鼠随机分为四组，连续 150 天用去离子水、25、50、100mg/L 的 NaF 处理。我们的结果表明，NaF 处理降低了 PAS 染色阳性区域，同时肝评分、血清 ALT 和 AST 水平升高，这表明 NaF 引起了肝损伤。此外，qRT-PCR、免疫组织化学和 Western blot 结果表明，NaF 暴露通过激活 IL-17 信号通路诱导细胞凋亡和自噬。总之，这些结果表明，NaF 通过激活 IL-17 信号通路诱导肝脏细胞凋亡和自噬，最终导致肝功能受损。
