Zonisamide (ZNS), an
antiepileptic drug having beneficial effects also against
Parkinson's disease symptoms, has proven to display an
antioxidant effects in different experimental models. In the present study, the effects of ZNS on
rotenone-induced cell injury were investigated in human
neuroblastoma SH-SY5Y cells differentiated towards a neuronal phenotype. Cell cultures were exposed for 24 h to 500 nM
rotenone with or without pre-treatment with 10-100 μM ZNS. Then, the following parameters were analyzed: (a) cell viability; (b) intracellular
reactive oxygen species production; (c) mitochondrial transmembrane potential; (d) cell
necrosis and apoptosis; (e)
caspase-3 activity. ZNS dose-dependently suppressed
rotenone-induced cell damage through a decrease in intracellular ROS production, and restoring mitochondrial membrane potential. Similarly to ZNS effects, the treatment with N-acetyl-
cysteine (100 μM) displayed significant protective effects against
rotenone-induced ROS production and Δψm at 4 and 12 h respectively, reaching the maximal extent at 24 h. Additionally, ZNS displayed antiapoptotic effects, as demonstrated by flow cytometric analysis of
annexin V/
propidium iodide double staining, and significant attenuated
rotenone-increased
caspase 3 activity. On the whole, these findings suggest that ZNS preserves mitochondrial functions and counteracts apoptotic signalling mechanisms mainly by an
antioxidant action. Thus, ZNS might have beneficial effect against neuronal cell degeneration in different experimental models involving
mitochondrial dysfunction.