Protective action of 9-hydroxypinoresinol against oxidative damage in brain of mice challenged with kainic acid.
The neuroprotective effect of 9-hydroxypinoresinol was examined in mice challenged with kainic acid (KA), a potent central nervous system excitotoxin. For this purpose, mice were administered intraperitoneally with 9-hydroxypinoresinol before KA injection. A remarkable neuroprotective effect was observed with a single dose of 9-hydroxypinoresinol (30 mg kg(-1)) 24 h before KA challenge. Furthermore, 9-hydroxypinoresinol (20 mg kg(-1)) administered for 3 days before KA challenge reduced the mortality (60%) induced by KA to zero, and alleviated behavioural signs of KA neurotoxicity. Additionally, pretreatment with 9-hydroxypinoresinol (20 mg kg(-1)) prevented the decrease in the levels of total glutathione (GSH) and thiobarbituric acid reactive substances (P < 0.05). GSH peroxidase activity in brain tissue was restored to control levels, although GSH reductase activity and GSH S-transferase activity were not affected. Such a protective action was also observed even with a lower dose (10 mg kg(-1)) of 9-hydroxypinoresinol administered for 3 days, albeit to a lesser extent. From the results, it is proposed that 9-hydroxypinoresinol exerts a potent neuroprotective effect mainly by preventing oxidative stress in brain tissue of mice challenged with KA.
Cui
Hui Song
HS
College of Pharmacy, Chungnam National University, Gung-dong 220, Yuseong-gu, Daejeon 305-764, Korea.
Sok
Dai-Eun
DE
Min
Byung Sun
BS
Kim
Mee Ree
MR
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009498:Neurotoxins / Q000633:toxicity*; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
C520275:9-hydroxypinoresinol; D000975:Antioxidants; D017705:Lignans; D009498:Neurotoxins; D017392:Thiobarbituric Acid Reactive Substances; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D007608:Kainic Acid