Treatment of Lipoxin A(4) and its analogue on low-dose endotoxin induced preeclampsia in rat and possible mechanisms

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 34; no. 4; pp. 677 - 685
• Main Authors: Lin, Feng, Zeng, Pan, Xu, Zhangye, Ye, Duyun, Yu, Xiaofang, Wang, Ni, Tang, Jie, Zhou, Ye, Huang, Yinping
• Format: Journal Article
• Language: English
• Published: United States 01.12.2012
• Subjects: Albuminuria - chemically induced; Albuminuria - drug therapy; Albuminuria - physiopathology; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Apoptosis - drug effects; Blood Pressure - drug effects; Cell Line; Cell Proliferation - drug effects; Cytokines - genetics; Female; Heptanoic Acids - pharmacology; Heptanoic Acids - therapeutic use; Humans; Lipopolysaccharides; Lipoxins - pharmacology; Lipoxins - therapeutic use; Pre-Eclampsia - chemically induced; Pre-Eclampsia - drug therapy; Pre-Eclampsia - physiopathology; Pregnancy; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism
• ISSN: 1873-1708
• DOI: 10.1016/j.reprotox.2012.09.009

Preeclampsia (PE) is known to represent an exaggerated maternal inflammatory response to pregnancy. Lipoxin A(4) (LXA(4)), considered as an endogenous stop signal in inflammation, has been extensively studied pre clinically for its inflammatory pro-resolving effects. Thus, in the current study, we tested the effect of BML-111 (synthetic analogue of LXA(4)) on experimental PE rats induced by low-dose endotoxin (LPS) and of LXA(4) on human extravillous trophoblast cell line (TEV-1). In vivo experiment results showed that systolic blood pressure, 24 h-urinary albumin excretion, serum TNF-α and IL-8 levels and morphologic damage of placenta and kidney caused by LPS were all effectively alleviated by BML-111. LXA(4) also inhibited LPS-triggered apoptosis, activation of NF-κB, TNF-α and IL-8 mRNA and protein expression in TEV-1 cells. At the same time, BML-111 protected the cells from LPS-reduced proliferation. The current study demonstrated for the first time that LXA(4) could alleviate the symptoms of PE in endotoxin exposed rats.