Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
Food Chem Toxicol. 2012 Mar;50(3-4):583-9. doi: 10.1016/j.fct.2011.12.015. Epub 2011 Dec 17.
Fluoride intoxication and dexamethasone treatment produce deleterious effects in bone and brain. The aim of this study was to evaluate the effect of fluoride (F) and dexamethasone (Dex) co-exposure on oxidative stress and apoptosis in osteoblast-like MC3T3-E1 and hippocampal HT22 cell lines. Co-exposure to F and Dex resulted in a concentration-dependent decrease in cell viability, induction of apoptosis and increased generation of reactive oxygen species (ROS) and nitric oxide (NO) following 72 h of incubation. Fluoride-induced apoptosis in MC3T3-E1 and HT22 cells was attenuated by catalase and L-NNMA, indicating a role for H2O2 and NO as mediators of cytotoxicity. Dexamethasone-induced apoptosis was associated with H2O2 generation in both cell lines and it was attenuated during co-incubation with catalase. These data indicate that co-exposure to F and Dex amplifies their respective cytotoxicity in H2O2- and NO-dependent manner. As flavonoid fisetin prevented F- and Dex-induced cytotoxicity the potential role of this product in pharmacology and diet may be considered.
氟中毒和地塞米松治疗会对骨骼和大脑造成有害影响。本研究旨在评估氟（F）和地塞米松（Dex）共同暴露对成骨样 MC3T3-E1 和海马 HT22 细胞系氧化应激和细胞凋亡的影响。共同暴露于 F 和 Dex 会导致细胞活力呈浓度依赖性下降，在孵育 72 小时后，诱导细胞凋亡并增加活性氧（ROS）和一氧化氮（NO）的产生。在 MC3T3-E1 和 HT22 细胞中，氟化物诱导的细胞凋亡可被过氧化氢酶和 L-NNMA 减弱，表明 H2O2 和 NO 作为细胞毒性的介质发挥作用。地塞米松诱导的细胞凋亡与两种细胞系中 H2O2 的产生有关，并且在与过氧化氢酶共同孵育时被减弱。这些数据表明，F 和 Dex 的共同暴露以 H2O2 和 NO 依赖性方式放大了它们各自的细胞毒性。由于类黄酮非瑟酮可预防 F 和 Dex 诱导的细胞毒性，因此可以考虑该产品在药理学和饮食中的潜在作用。
