THE EFFECT OF SODIUM FLUORIDE ON ALUMINUM-INDUCED OXIDATIVE STRESS AND APOPTOSIS OF PC12 IN VITRO

The aim of the present investigation was to determine the effects of sodium fluoride (NaF) on aluminum-induced toxicity in PC12 cells, a rat pheochromocytoma cell line, including cell death and changes in apoptosis, mitochondrial membrane potential (MMP), and oxidative stress. Aluminum (Al) and the fluoride ion (F) are known as plausible pathological factors in the pathogenesis of neu rodegenerative disease. Conflicting results have been reported on the interaction of fluoride and aluminum on cell toxicity. PC12 cells were treated with various concentrations of aluminum maltolate (Almal) in the presence and absence of NaF (50-2400 nM) in vitro. A MTT (3-[4,5dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to determine cell viability. 7AAD/annexin-V and 2',7'-dichlorofluorescin diacetate (DCFDA) flow cytometric methods were used to quantify the effects of NaF on Al-induced apoptosis and reactive oxygen species (ROS) generation, respectively. The mitochondrial membrane potential (MMP) was monitored using the retention of rhodamine 123. Catalase activity was determined by measuring the rate of H2O2 decomposition. Almal exposure increased cell death dose dependently and significantly (IC5o=1090 nM). ROS generation and apoptosis were increased while MMP and catalase activity were reduced following treatment with Almal. NaF ameliorated the Almal-induced cell toxicity in low concentrations while augmenting the Almal effects at high concentrations. The present data suggest F has antagonistic impacts on Al-induced cell toxicity in low concentrations while acting synergistically with Al to induce cell toxicity at high concentrations.