Protective effects of BML-111, a lipoxin A(4) receptor agonist, on carbon tetrachloride-induced liver injury in mice.
BACKGROUND
Lipoxins (LX) are trihydroxytetraene-containing eicosanoids that display unique anti-inflammatory and pro-resolving actions during various inflammatory conditions, but the pathophysiological significance of LX in liver disorders remains unknown.


METHODS
In the present study, we used a murine model of carbon tetrachloride (CCl(4))-induced acute liver injury to investigate the effects of LX on the progression of acute liver injury.


RESULTS
The results indicated that the lipoxin A(4) receptor (ALX) was upregulated after giving CCl(4). BML-111, a commercially available ALX agonist, effectively protected the liver from CCl(4)-induced injury as evidenced by decreased serum aminotransferase (ALT, AST) levels and improved histological damage. The dampened liver injury was accompanied byreduced malondialdehyde (MDA) content in liver homogenates and decreased concentration of tumor necrosis factor-alpha (TNF-alpha) in the serum. Most interestingly, BML-111 markedly upregulated hepatic heme oxygenase-1 (HO-1) expression in CCl(4)-treated mice, which might provide antioxidative activities in the liver.


CONCLUSIONS
These data indicate that ALX agonist BML-111 plays a critical protective role in CCl(4)-induced acute liver injury through limiting the inflammatory response and promoting antioxidative protein expression.
Zhang
Li
L
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wan
Jingyuan
J
Li
Hongzhong
H
Wu
Ping
P
Jin
Shengwei
S
Zhou
Xiaoyan
X
Yuan
Ping
P
Xiong
Wei
W
Li
Yongsheng
Y
Ye
Duyun
D