Attenuation of rotenone toxicity in SY5Y cells by by taurine and N-acetyl cysteine alone or in combination

There is accumulating evidence that supports the involvement of reactive oxygen species (ROS), mitochondrial dysfunction and inflammation in the pathogenesis of neurodegen- erative diseases. Thus, it is plausible that a multi-targeted therapeutic approach may be a more effective strategy to retard or even potentially halt the progression of the disease. Taurine is an organic acid that has a role in the regulation of oxidative stress and promoting mitochondrial normal functions, and N-Acetyl cysteine (NAC) is a well-known anti-oxidant and glutathione precursor. The main purpose of this study was to examine the cytoprotective effects of taurine alone or in combination with NAC against rotenone- induced toxicity in the SH-SY5Y neuroblastoma cell line. Taurine treatment produced a concentration-dependent reduction in rotenone-induced cell death. From this, we tested sub-effective concentrations of taurine in combination with low, sub-effective concentra- tions of NAC against rotenone toxicity, and found the combined treatment afforded greater cytoprotection than either treatment alone. The combined taurine/NAC treatment also attenuated rotenone-induced reductions in aconitase activity suggesting the cytoprotec- tion afforded by the combined treatment may be associated with anti-oxidative mechan- isms. Together, our data suggest that a multi-targeted approach may yield new avenues of research exploring the utility of combining therapeutic agents with different mechanisms of actions at concentrations lower than previously tested and shown to be cytoprotective.