The impact of oxidative stress on the neurotoxic effect of acetaminophen

Paracetamol (acetaminophen, APAP) is a commonly-used antipyretic and analgesic. However, there have been reports indicating possible link between its use in pregnancy and impaired neuropsychic development in children. A number of prospective studies of the possible negative effect of acetaminophen on the development of a child after his mother took this drug during pregnancy, as well as the results of studies on glioma cells and neurons in murine cortex, may indicate presence of the neurotoxic effect of acetaminophen. It is currently unclear if paracetamol itself being pharmacologically active neurotropic substance, or its metabolites, one of which – NAPQI (N-acetyl-p-benzoquinone imine) known by its toxic effects in mitochindria, play the most significant role in proposed neurotoxicity. Therefore it seems important to study each metabolite separately. The ability of acetaminophen(paracetamol) in concentrations of 1 mg/ml and 2 mg/ml to reduce cell viability was shown on cells of the PC12 neuronal line using MTT-method, which is based on the ability of mitochondria of viable cells to restore formazan 3-(4,5-dimethylthiazole)-2,5-diphenyl-2-tetrazolium bromide (MTT). Concentrations of 0.125 mg/ml, 0.25 mg/ml and 0.5 mg/ml had no similar impact on cell culture viability. In addition, the impact of hydrogen peroxide (as an inducer of oxidative stress) on the neurotoxic effect of acetaminophen was studied. We demonstrated that in the presence of 0.3 mM or 0.5 mM hydrogen peroxide and acetaminophen in concentrations of 1 mg/ml and 2 mg/ml reliably reduced the percentage of surviving cells. We showed that the decrease of the viability of the cells of the PC12 neuronal line is obvious only after exposure to high concentrations of acetaminophen, especially in the presence of hydrogen peroxide, which means that neurotoxic effect is not likely to occur in vivo.