ATTENUATION BY 7-NITROINDAZOLE OF FLUORIDE-INDUCED TOXICITY IN SH-SY5Y CELLS EXPOSED TO HIGH FLUORIDE: EFFECTS ON NITRIC OXIDE, NITRIC OXIDE SYNTHETASE ACTIVITY, nNOS, AND APOPTOSIS.

The purpose of the present research was to study the influence of a high level of fluoride on the expression of nitric oxide (NO) and the activity of nitric oxide synthase (nNOS) in a human neuroblastoma cell line (SH-SY5Y cells) and the attenuating effect of 7-nitroindazole (7-NI) on any fluoride-induyced toxicity. The cultured SH-SY5Y cells were exposed to different concentrations of fluoride [0.02-4.0 ppm of fluoride ion (F-) prepared with NaF] and also treated with 7-NI (0.001 ppm) plus fluoride (2 ppm of F-). The detection of the content of NO and the activity of nNOS, in the cultured cells and the medium, was by the photometric method; the detection of apoptosis of the cells was by flow cytometry; and the detection of the expression of nNOS at the protein level was by Western blotting. The results showed that after exposure to high fluoride the content of NO and the activity of NOS in both the SH-SY5Y cells and their culture medium, the protein expression of nNOS, and the apoptotic rate in the cells were all significantly increased in a dose-dependent manner. Interestingly, the increases in the content of NO, the activity of NOS, the protein level of nNOS, and apoptosis in the cells, resulting from the exposure of high fluoride, were all significantly attenuated by using 7-NI. The data indicate that 7-NI may be able to play an important role in ameliorating the toxic effects of fluoride on the NO system and apoptosis. [ABSTRACT FROM AUTHOR]