Coincidental increase of leukotriene B4 between cerebral cortex and lung tissue of sensitized rats.
OBJECTIVE
To explore the changes of leukotrienes (LT) in cerebral cortex and lung tissues in ovalbumin-induced rat asthma model and effects of different anti-asthma drugs on the changes.


METHODS
Aerosol antigen-induced changes of inflammation in bronchoalveolar lavage fluids (BALF), pulmonary and brain histologic section in sensitized rats were investigated. Changes of LTB4 and LTC4 in lung and cerebral cortex homogenates were analyzed by reverse-phase high performance liquid chromatography (RP-HPLC).


RESULTS
The number of inflammatory cells in BALF and the score of lung and brain histological examination from antigen- challenged rats were significantly higher than that from control group (P<0.05). Dexamethason (DXM, 0.5 mg/kg, ip) and ketotifen fumarate (KF, 5 mg/kg, ig) markedly reduced total leukocyte number in BALF, and inhibited eosinophil accumulation, reduced the infiltration of eosinophils, and improved mucous edema and epithelial lesion of bronchi and bronchioles. In addition, RP-HPLC results shown LTB4 in lung and cerebral cortex homogenates were increased in antigen-challenged rats [(4.1+/-2.4) ng/g and (1.5+/-0.9) ng/g, respectively] compared with control group [(1.55+/-0.21) ng/g and (0.7+/-0.3) ng/g, respectively, P<0.05], both DXM (0.5 mg/kg, ip) and KF (5 mg/kg, ig) reduced LTB4 amount in lung[(1.4+/-0.6) ng/g and (1.8+/-0.7) ng/g] and cerebral cortex homogenates [(0.5+/-0.4) ng/g and (0.7+/-0.4) ng/g] in asthma rats. LTC4 content in lung homogenates in asthma rats was increased compared with control group [(1.9+/-0.9) ng/g and (0.5+/-0.3) ng/g, respectively] (P<0.05), but it has no change in cerebral cortex homogenates. DXM (0.5 mg/kg, ip) and KF (5 mg/kg, ig) reduced LTC4 amount in lung homogenates in asthma rats [(0.8+/-0.6) ng/g and (1.0+/-0.3) ng/g, respectively] (P<0.05).


CONCLUSIONS
The results indicate there is coincidental increase of LTB4 between central nervous system and lung tissues in asthma rats. DXM and KF can inhibit the change.
Deng
Yang-Mei
YM
Zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of China, Medical School of Zhejiang University, Hangzhou 310031, China. dym999@zju.edu.cn
Xie
Qiang-Min
QM
Chen
Ji-Qiang
JQ
Bian
Ru-Lian
RL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007665:Ketotifen / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism*; D017997:Leukotriene C4 / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D010047:Ovalbumin; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D006634:Histamine H1 Antagonists; D007975:Leukotriene B4; D017997:Leukotriene C4; D003907:Dexamethasone; D010047:Ovalbumin; D007665:Ketotifen