Minocycline inhibits 5-lipoxygenase activation and brain inflammation after focal cerebral ischemia in rats.
OBJECTIVE
To determine whether the anti-inflammatory effect of minocycline on postischemic brain injury is mediated by the inhibition of 5-lipoxygenase (5-LOX) expression and enzymatic activation in rats.


METHODS
Focal cerebral ischemia was induced for 30 min with middle cerebral artery occlusion, followed by reperfusion. The ischemic injuries, endogenous IgG exudation, the accumulation of neutrophils and macrophage/microglia, and 5-LOX mRNA expression were determined 72 h after reperfusion. 5-LOX metabolites (leukotriene B4 and cysteinyl leukotrienes) were measured 3 h after reperfusion.


RESULTS
Minocycline (22.5 and 45 mg/kg, ip, for 3 d) attenuated ischemic injuries, IgG exudation, and the accumulation of neutrophils and macrophage/microglia 72 h after reperfusion. It also inhibited 5-LOX expression 72 h after reperfusion and the production of leukotrienes 3 h after reperfusion.


CONCLUSIONS
Minocycline inhibited postischemic brain inflammation, which might be partly mediated by the inhibition of 5-LOX expression and enzymatic activation.
Chu
Li-Sheng
LS
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Fang
San-Hua
SH
Zhou
Yu
Y
Yu
Guo-Liang
GL
Wang
Meng-Ling
ML
Zhang
Wei-Ping
WP
Wei
Er-Qing
EQ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D004660:Encephalitis / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery; D016859:Lipoxygenase Inhibitors; D008297:Male; D008911:Minocycline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase; D008911:Minocycline