Prevention of nitric oxide-mediated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease in mice by tea phenolic epigallocatechin 3-gallate.
In animal models of Parkinson's disease (PD), the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is mediated by oxidative stress, especially by nitric oxide (NO). Inhibition of NO synthase (NOS) activity in the brain produces a neuroprotective effect against PD induced by MPTP Green tea containing high levels of (-)-epigallocatechin 3-gallate (EGCG) was administered to test whether EGCG attenuates MPTP-induced PD in mice through the inhibition of NOS expression. Both tea and the oral administration of EGCG prevented the loss of tyrosine hydroxylase (TH)-positive cells in the substantia nigra (SN) and of TH activity in the striatum. These treatments also preserved striatal levels of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid (HVA). Both tea and EGCG decreased expressions of nNOS in the substantia nigra. Also tea plus MPTP and EGCG plus MPTP treatments decreased expressions of neuronal NO synthase (nNOS) at the similar levels of EGCG treatment group. Therefore, the preventive effects of tea and EGCG may be explained by the inhibition of nNOS in the substantia nigra.
Choi
Ji-Young
JY
Department of Pharmacology, Medicinal Toxicology Research Center, Inha University, Inchon, South Korea.
Park
Chang-Shin
CS
Kim
Dae-Joong
DJ
Cho
Myung-Haeng
MH
Jin
Byung-Kwan
BK
Pie
Jae-Eun
JE
Chung
Woon-Gye
WG
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015259:Dopamine Agents / Q000633:toxicity*; D006719:Homovanillic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000517:prevention & control*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology; D013662:Tea / Q000737:chemistry*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D012333:RNA, Messenger; D013662:Tea; D015102:3,4-Dihydroxyphenylacetic Acid; D009569:Nitric Oxide; D002392:Catechin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C045651:epigallocatechin gallate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D014446:Tyrosine 3-Monooxygenase; D006719:Homovanillic Acid