Medical Research and Evaluation Facility and Studies Supporting the MedicalChemical Defense Program. Time and Dose Response Characterization of the Prevention of HD-Induced NAD+ Depletion and HD-Induced Cytotoxicity by Niacinamide and Niacin

摘要

Studies were conducted under this task to Assess the time and concentrationdependent nature of niacinamide (NM) protection against HD-induced NAD+ depletion and cytotoxicity. The HD concentrations used assess the time dependent nature of cytotoxicity and NAD+ depletion, and the impact of NM and niacin (NI) treatment were 13,62, 101, and 171 mu-M HD. Three concentrations of NM and NI were (0.01,0.1 and 1 mM) selected by USAMRICD for evaluation at 2, 4,8, 12, 16,20,24,48, and 72 hours after exposure to HD. Cytotoxicity and total culture NAD+ content were assessed. NAD+ concentrations following the addition of 1 mM NM frequently were significantly greater than those observed for the HD-exposed controls especially at 171mu-M HD. Multiple addition of NM had little protective effect relative to that by provided by pretreatment alone. At the 171mu-M HD concentration, the single addition of NM provided marginal but statistically significant (p<=0.05) protection. Comparisons of the different NM addition modes yielded mixed results, but usually the number of viable cells was greater with multiple additions of NM. NI did not provide protection against HD-induced NAD+ depletion or cytotoxicity.