[Nordihydroguaiaretic acid partially inhibits inflammatory responses after focal cerebral ischemia in rats].
The aim of the present study is to investigate the role of nordihydroguaiaretic acid (NDGA) on inflammatory cells accumulation after focal cerebral ischemia and the underlying mechanism. Focal cerebral ischemia was induced by 30 min of middle cerebral artery occlusion (MCAO) followed by 72 h of reperfusion. NDGA (5 and 10 mg/kg) was administered intraperitoneally 30 min, 2, 24, 48 h after reperfusion, respectively. The brain injuries were observed by neurological and histological examination. Endogenous IgG exudation, neutrophils and macrophages/microglia accumulation, and intercellular adhesion molecule-1 (ICAM-1) protein expression were determined by immunohistochemistry 72 h after reperfusion. ICAM-1 mRNA was determined by RT-PCR 72 h after reperfusion. The catalysates of 5-lipoxygenase (5-LOX), leukotriene B4 (LTB4) and cysteinyl leukotrienes (CysLTs), were evaluated by ELISA 3 h after reperfusion. The results showed that NDGA ameliorated neurological dysfunction, decreased infarct volume, and inhibited endogenous IgG exudation, neutrophils infiltration, ICAM-1 mRNA and protein expression 72 h after reperfusion. Moreover, NDGA reduced the levels of LTB4 and CysLTs 3 h after reperfusion. However, NDGA did not reduce the accumulation of macrophages/microglia 72 h after reperfusion. These results suggest that NDGA decreases neutrophil infiltration in the subacute phase of focal cerebral ischemia via inhibiting 5-LOX activation.
Chu
Li-Sheng
LS
Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China. chulisheng@21cn.com
Fang
San-Hua
SH
Zhou
Yu
Y
Yin
Yuan-Jun
YJ
Ke
Qing
Q
Chen
Wei-Yan
WY
Wei
Er-Qing
EQ
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control
D007074:Immunoglobulin G; D016859:Lipoxygenase Inhibitors; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4; D009637:Masoprocol; D001094:Arachidonate 5-Lipoxygenase