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.
Deguchi
Kentaro
K
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmacy, Okayama University, Okayama, Japan.
Hayashi
Takeshi
T
Nagotani
Shoko
S
Sehara
Yoshihide
Y
Zhang
Hanzhe
H
Tsuchiya
Atsushi
A
Ohta
Yasuyuki
Y
Tomiyama
Koji
K
Morimoto
Nobutoshi
N
Miyazaki
Masahiro
M
Huh
Nam-Ho
NH
Nakao
Atsunori
A
Kamiya
Tatsushi
T
Abe
Koji
K
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