Cheng Hao, Li Yulian, Liu Fasheng, Zhu Shanshan, Chen Li, Lu Huiqiang, Shi Xiaowen, Huang Ling
Jiangxi Province Key Laboratory of Organ Development and Epigenetics, Clinical Medical Research Center, Affiliated Hospital of Jinggangshan University, Basic, Medicine College of Jinggangshan University, Ji'an, 343009, China.
Department of Interventional and Vascular Surgery, Affiliated Hospital of Jinggangshan University, Clinical Medical College of Jinggangshan University, Ji'an, 343009, Jiangxi, China.
Sci Rep. 2025 Aug 7;15(1):28858. doi: 10.1038/s41598-025-14524-9.
Butylated hydroxytoluene (BHT) is widely employed as an antioxidant in various industries. However, concerns persist regarding its safety and environmental impact, as its toxicological mechanisms remain poorly understood. Zebrafish embryos were exposed to BHT at 3, 5, and 7 mg/L to assess developmental toxicity. BHT exposure dose-dependently induced spinal cord malformations concomitant with reduced larval motility. Mechanistically, BHT suppressed Hedgehog signaling, evidenced by dysregulation of Shha, Gli1, and Smo. Notably, pharmacological activation of the Hh pathway by SAG rescued both structural defects and gene expression anomalies, confirming Hh inhibition as the primary toxicity mechanism. These results indicate that BHT inhibits Hh signaling, disrupting floor plate function and leading to spinal curvature.
丁基羟基甲苯（BHT）在各个行业中被广泛用作抗氧化剂。然而，由于其毒理学机制仍知之甚少，人们对其安全性和环境影响的担忧依然存在。将斑马鱼胚胎暴露于浓度为3、5和7毫克/升的BHT中，以评估其发育毒性。暴露于BHT会剂量依赖性地诱导脊髓畸形，并伴有幼虫运动能力下降。从机制上讲，BHT抑制了刺猬信号通路，这可通过Shha、Gli1和Smo的失调得到证明。值得注意的是，SAG对Hh通路的药理学激活挽救了结构缺陷和基因表达异常，证实了Hh抑制是主要的毒性机制。这些结果表明，BHT抑制Hh信号通路，破坏底板功能并导致脊柱弯曲。
