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BML-11, A Lipoxin Receptor Agonist, Protected Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats

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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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 81100299), Science and Technology Plan of Department of Health of Jiangxi Province (no. 20122020), and Natural Science Foundation of Jiangxi province (no. 20114BAB215010).

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Authors and Affiliations

  1. Department of Pathophysiology, Medical College of Nanchang University, 461 BaYi Road, Jiangxi Province, Nanchang, 330006, China

    Xiao-Yan Zhou, Hong-Mei Wang, Yong-Hong Huang, Fang-Yun Xu, Zhen-Yu Cai & Wei-Ping Min

  2. Department of Pharmacology, Medical College of Nanchang University, 461 BaYi Road, Jiangxi Province, Nanchang, 330006, China

    Zhong-Jian Yu & Dan Yan

  3. Jiangxi Academy of Medical Sciences, Nanchang, 330006, China

    Wei-Ping Min

  4. First Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Juan Sha

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  1. Xiao-Yan Zhou
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Correspondence to Wei-Ping Min.

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Xiao-Yan Zhou and Zhong-Jian Yu contributed equally to this paper.

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Zhou, XY., Yu, ZJ., Yan, D. et al. BML-11, A Lipoxin Receptor Agonist, Protected Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats. Inflammation 36, 1101–1106 (2013). https://doi.org/10.1007/s10753-013-9643-x

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  • DOI: https://doi.org/10.1007/s10753-013-9643-x

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