Zonisamide Attenuates MPP(+)-Induced Oxidative Toxicity Through Modulation of Ca²⁺ Signaling and Caspase-3 Activity in Neuronal PC12 Cells

Abstract

Parkinson’s disease is an incurable progressive neurological condition caused by a degeneration of dopamine-producing cells characterized by motor and non-motor symptoms. The major mechanisms of the antiepileptic actions of ZNS are inhibition of voltage-gated Na⁺ channel, T-type voltage-sensitive Ca²⁺ channel, Ca²⁺-induced Ca²⁺ releasing system, and neuronal depolarization-induced glutamate release; and enhancement of release of inhibitory neurotransmitters; however, the detailed mechanism of antiparkinsonian effects of ZNS remains to be clarified. We aimed to investigate to the effect of ZNS on the oxidative stress, cell viability, Ca²⁺ signaling, and caspase activity that induced by the MPP⁺ model of Parkinson’s in neuronal PC12 cells. Neuronal PC12 cells were divided into four groups namely, control, ZNS, MPP⁺, and ZNS+MPP⁺ groups. The dose and duration of ZNS and MPP⁺ were determined according to cell viability (MTT) analysis which used to assess the cell viability. The cells in ZNS, MPP⁺, and ZNS+MPP⁺ groups were incubated for 5 h with 100 μM ZNS, 10 h with 100 μM MPP⁺, and 10 h with ZNS and MPP⁺, respectively. Lipid peroxidation and cytosolic free Ca²⁺ concentrations were higher in the MPP⁺ group than in control although their levels were lower in ZNS and the ZNS+MPP⁺ groups than in control. Reduced glutathione and glutathione peroxidase values were lower in the MPP⁺ group although they were higher in the ZNS and the ZNS+MPP⁺ groups than in control. Caspase-3 activity was lower in the ZNS group than in the MPP⁺ group. In conclusion, ZNS induced modulator effects on the oxidative stress, intracellular Ca²⁺, and the caspase-3 values in an experimental model of Parkinson disease.