In vitro assessment of the neurotoxic and neuroprotective effects of N-acetyl-l-cysteine (NAC) on the rat sciatic nerve fibers

N-acetyl-l-cysteine (NAC), at a concentration of 1–60 mM, has been previously used extensively for protection in a variety of cell cultures against the deleterious effects of various compounds. The results of this in vitro study show that NAC has certain unusual effects on the evoked compound action potential (CAP) of the rat sciatic nerve fibers. Firstly, at concentrations of 5.0, 3.5 and 2.5 mM, concentrations used by others as a protectant for cell cultures, NAC inhibits the action potentials of the sciatic nerve fibers completely in a concentration-dependent manner within a few minutes or hours (2.5 mM). Secondly, the acute inhibitory action of NAC on the CAP of the nerve fibers was not spontaneously reversible, but as soon as NAC was replaced with saline there was a partial (∼75%) recovery in the function of the nerve fibers. Thirdly, the no observed effect concentration for NAC was estimated to be 1 mM. The paradox is that NAC at 1 mM not only had no effect on the nerve fibers, but it became an excellent neuroprotective compound, giving almost 100% neuroprotection against cadmium-induced neurotoxicity. The results show a possible effect of NAC on voltage-gated sodium and potassium channels. The observed neuroprotective-neurotoxic properties of NAC require careful reconsideration of its use in either in vitro studies or in vivo pharmaceutical applications.