Neuroprotective effect of phytic acid in Parkinson's disease

Abstract

Disrupted iron metabolism and excess iron accumulation has been reported in the brains of Parkinson’s disease (PD) patients. Because excessive iron can induce oxidative stress subsequently causing degradation of nigral dopaminergic neurons in PD, we determined the protective effect of a naturally occurring iron chelator, phytic acid (IP6), on 1-methyl-4phenylpyridinium (MPP) induced cell death in immortalized rat mesencephalic/dopaminergic cells (N27 cells). Cell death was induced with MPP in normal and iron-excess conditions and cytotoxicity was measured by thiazolyl blue tetrazolium bromide (MTT assay) and trypan blue staining. Apoptotic cell death was also measured with caspase-3 activity, DNA fragmentation, and Hoechst nuclear staining. IP6 (30 μmol/L) increased cell viability by 19% (p<0.05) and decreased cell death by 22% (p<0.05), compared to MPP treatment. A 3-fold increase in caspase-3 activity (P<0.001) and a 2-fold increase in DNA fragmentation (P<0.05) with MPP treatment was decreased by 55% (P<0.01) and 52% (P<0.05), respectively with IP6. IP6 (30 and 100 μmol/L) increased cell survival by 18% (p<0.05) and 42% (p<0.001), respectively in iron-excess conditions. Based on caspase-3 activity, a 40% and 52% (P<0.001) protection with 30 μmol/L and 100 μmol/L 34 IP6, respectively was observed in iron excess. Similarly, a 45% reduction (P<0.001) in DNA fragmentation was found. In addition, Hoechst nuclear staining results confirmed the protective effect of IP6 against apoptosis. Collectively, our results demonstrate a significant neuroprotective effect of phytate in a cell culture model of PD.