Reduction of cerebral infarction in rats by biliverdin associated with amelioration of oxidative stress.
Biliverdin (BV), one of the byproducts of heme catalysis through heme oxygenase (HO) system, is a scavenger of reactive oxygen species (ROS). We hypothesized that BV treatment could protect rat brain cells from oxidative injuries via its anti-oxidant efficacies. Cerebral infarction was induced by transient middle cerebral artery occlusion (tMCAO) for 90 min, followed by reperfusion. BV or vehicle was administered intraperitoneally immediately after reperfusion. The size of the cerebral infarction 2 days after tMCAO was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) stain. Superoxide generation 4 h after tMCAO was determined by detection of oxidized hydroethidine. In addition, the oxidative impairment of neurons were immunohistochemically assessed by stain for lipid peroxidation with 4-hydroxy-2-nonenal (4-HNE) and damaged DNA with 8-hydroxy-2'-deoxyguanosine (8-OHdG). BV treatment significantly reduced infarct volume of the cerebral cortices associated with less superoxide production and decreased oxidative injuries of brain cells. The present study demonstrated that treatment with BV ameliorated the oxidative injuries on neurons and decreased brain infarct size in rat tMCAO model.
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmacy, Okayama University, Okayama, Japan.
Kentaro
K
Deguchi
Takeshi
T
Hayashi
Shoko
S
Nagotani
Yoshihide
Y
Sehara
Hanzhe
H
Zhang
Atsushi
A
Tsuchiya
Yasuyuki
Y
Ohta
Koji
K
Tomiyama
Nobutoshi
N
Morimoto
Masahiro
M
Miyazaki
Nam-Ho
NH
Huh
Atsunori
A
Nakao
Tatsushi
T
Kamiya
Koji
K
Abe
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001664:Biliverdine / Q000378:metabolism / Q000494:pharmacology*; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010617:Phenanthridines; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D013778:Tetrazolium Salts; D016896:Treatment Outcome
D000447:Aldehydes; D000975:Antioxidants; D018696:Neuroprotective Agents; D010617:Phenanthridines; D013778:Tetrazolium Salts; D013481:Superoxides; C058428:hydroethidine; C027576:4-hydroxy-2-nonenal; D001664:Biliverdine