BML-11, a lipoxin receptor agonist, protected carbon tetrachloride-induced hepatic fibrosis in rats.

Abstract

Inflammation plays an important role in the occurrence and development of fibrosis. Lipoxins (LXs) and BML-111 (lipoxin A4 agonist) have been approved for potent anti-inflammatory properties. Previously, we and others had showed LXs and BML-111 could protect acute hepatic injury, inhibit the growth and invasion of hepatic tumor. However, there are few reports dealing with their effects on hepatic fibrosis. To explore whether LXs and the analog could interrupt the process of hepatic fibrosis, the effects of BML-111 on tetrachloride-induced hepatic fibrosis were observed and the possible mechanism were discussed. Sprague-Dawley rats were induced liver fibrosis by carbon tetrachloride (CCl4) for 10 weeks with or without BML-111, and the histopathology and collagen content were employed to quantify hepatic necro-inflammation and fibrosis. Moreover, the expression levels of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and platelet-derived growth factor (PDGF) were examined via Western blot or ELISA. Rats treated with BML-111 improved hepatic necro-inflammation and inhibited hepatic fibrosis in association with reduction of α-SMA expression and decreased collagen deposition. Furthermore, BML-111 could downregulate the expressions of TGF-β1 and PDGF significantly. BML-111 played a critical protective role in CCl4-induced hepatic fibrosis through inhibiting the levels of TGF-β1 and PDGF in rats.

• Authors: Xiao-Yan Zhou, Zhong-Jian Yu, Dan Yan, Hong-Mei Wang, Yong-Hong Huang, Juan Sha, Fang-Yun Xu, Zhen-Yu Cai, Wei-Ping Min
• Journal: Inflammation (Inflammation) Vol. 36 Issue 5 Pg. 1101-6 (Oct 2013) ISSN: 1573-2576 [Electronic] United States
• PMID: 23640201 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester
• Actins
• Heptanoic Acids
• Platelet-Derived Growth Factor
• Receptors, Lipoxin
• Transforming Growth Factor beta1
• lipoxin A(4) receptor, rat
• smooth muscle actin, rat
• Collagen
• Carbon Tetrachloride

Topics

• Actins (biosynthesis)
• Animals
• Carbon Tetrachloride
• Collagen (biosynthesis)
• Down-Regulation (drug effects)
• Gene Expression
• Heptanoic Acids (pharmacology)
• Inflammation (drug therapy)
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis (chemically induced, prevention & control)
• Platelet-Derived Growth Factor (biosynthesis, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Lipoxin (agonists)
• Transforming Growth Factor beta1 (biosynthesis, blood, metabolism)