Protective Effects of SUN N8075, a Novel Agent with Antioxidant Properties, in in Vitro and in Vivo Models of Parkinson's Disease

SUN N8075 is a novel antioxidant with neuroprotective properties. This study was designed to elucidate its neuroprotective effects against 6-hydroxy dopamine (6-OHDA)-induced cell death and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity (known as in vitro and in vivo models of Parkinson's disease, respectively). In the in vitro study, on human neuroblastoma SH-SY5Y cells, SUN N8075 decreased the hydrogen peroxide (H2O2)-induced production of reactive oxygen species and protected against 6-OHDA-induced cell death. In the in vivo study, SUN N8075, when injected intraperitoneally (i.p.) twice with a 5-h interval, inhibited lipid peroxidation (viz. the production of thiobarbituric acid reactive substance) in the mouse forebrain at 1 h after the second injection. Mice were injected i.p. with MPTP (10 mg/kg) four times at 1-h intervals, and brains were analyzed 7 days later. SUN N8075 at 30 mg/kg (i.p., twice) exhibited a protective effect against the MPTP-induced decrease in tyrosine hydroxylase (TH)-positive fibers in the striatum. Moreover, SUN N8075 at 10 and 30 mg/kg (i.p., twice) had a similar protective effect against the MPTP-induced decrease in TH-positive cells in the substantia nigra. Further, SUN N8075 30 mg/kg (i.p. twice) markedly suppressed the MPTP-induced accumulation of 8-hydroxy-deoxyguanosine (8-OHdG) in the striatum. These findings indicate that SUN N8075 exerts protective effects, at least in part via an anti-oxidation mechanism, in these in vitro and in vivo models of Parkinson's disease.