title: HMG CoA reductase inhibitors reduce ischemic brain injury of Wistar rats through decreasing oxidative stress on neurons.
abstract: Statins possess neuroprotective effect against ischemic damage, but how they protect neurons is not exactly made clear. We speculated that anti-oxidative property of statins is implicated, and investigated statins' influences on the oxidative neuronal damage in the brain after ischemia. After 14 days of atorvastatin, pitavastatin, simvastatin, or vehicle administration, 90 min of middle cerebral artery occlusion was imposed on Wistar rats. The production of 4-hydroxynonenal (HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), both of which are oxidative stress markers, as well as infarction formation were investigated at 1 day after the reperfusion. In the vehicle group, massive infarction was confirmed and HNE and 8-OHdG are robustly produced. In the statins-treated group, the infarction was smaller and the HNE and 8-OHdG production was less prominent than the vehicle group. Among the statins investigated, simvastatin was most effective for reducing oxidative stress and infarction volume, which may be brought by its highly lipophilic property. Reduction of oxidative stress by statins may be one main reason in ameliorating ischemic brain damage in rats.
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. thayashi@cc.okayama-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Hamakawa
authors.forename: Shoko
authors.initials: S
authors.lastname: Nagotani
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Kentaro
authors.initials: K
authors.lastname: Deguchi
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Sehara
authors.forename: Hanzhe
authors.initials: H
authors.lastname: Zhang
authors.forename: Isao
authors.initials: I
authors.lastname: Nagano
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D000447:Aldehydes; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D002784:Cholesterol; C027576:4-hydroxy-2-nonenal