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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Kimberly E Hawkins; Kelly M DeMars; Jonathan Singh; Changjun Yang; Henry S Cho; Jan C Frankowski; Sylvain Doré; Eduardo Candelario-Jalil Journal: J Neurochem Date: 2013-12-01 Impact factor: 5.372