Laboratory for Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, 5019 Monastir, Tunisia.
Université Paris-Saclay, Inserm, UMR-S 1180, 92296 Châtenay-Malabry, France.
Environ Toxicol Pharmacol. 2022 Aug;94:103919. doi: 10.1016/j.etap.2022.103919. Epub 2022 Jun 23.
Tebuconazole (TEB) is a common triazole fungicide that has been widely applied in the treatment of fungal diseases. It is reported that TEB could exert harmful effects on mammals' health. However, the molecular mechanism involved in TEB toxicity remain undefined. Our study aimed to investigate the mechanisms of TEB-induced toxicity in intestinal cells. We found that TEB stimulates apoptosis through the mitochondrial pathway. Additionally, TEB triggers endoplasmic reticulum (ER) stress as demonstrated by the activation of the three arms of unfolded protein response (UPR). The incubation with the chemical chaperone 4-phenylbutyrate (4-PBA) alleviated ER stress and reduced TEB-induced apoptosis, suggesting that ER stress plays an important role in mediating TEB-induced toxicity. Furthermore, inhibition of ROS by N-acetylcysteine (NAC) inhibited TEB-induced ER stress and apoptosis. Taken together, these findings suggest that TEB exerts its toxic effects in HCT116 cells by inducing apoptosis through ROS-mediated ER stress and mitochondrial apoptotic pathway.
戊唑醇（TEB）是一种常见的三唑类杀菌剂，已广泛应用于真菌病的治疗。有报道称，TEB 可能对哺乳动物的健康产生有害影响。然而，TEB 毒性涉及的分子机制仍未阐明。我们的研究旨在探讨 TEB 诱导的肠细胞毒性的机制。我们发现 TEB 通过线粒体途径刺激细胞凋亡。此外，TEB 触发未折叠蛋白反应（UPR）的三个分支，表明内质网（ER）应激。用化学伴侣 4-苯基丁酸（4-PBA）孵育可减轻 ER 应激并减少 TEB 诱导的细胞凋亡，表明 ER 应激在介导 TEB 诱导的毒性中起重要作用。此外，通过 N-乙酰半胱氨酸（NAC）抑制 ROS 抑制了 TEB 诱导的 ER 应激和细胞凋亡。综上所述，这些发现表明，TEB 通过 ROS 介导的 ER 应激和线粒体凋亡途径诱导细胞凋亡，从而对 HCT116 细胞发挥其毒性作用。
