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.
Oyagi
A
A
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
Oida
Y
Y
Hara
H
H
Izuta
H
H
Shimazawa
M
M
Matsunaga
N
N
Adachi
T
T
Hara
H
H
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000814:Aniline Compounds / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009447:Neuroblastoma / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000517:prevention & control*; D010879:Piperazines / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism
D018663:Adrenergic Agents; D000814:Aniline Compounds; D000975:Antioxidants; D010879:Piperazines; D017382:Reactive Oxygen Species; C413884:SUN N8075; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D006861:Hydrogen Peroxide