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Protective effect of metformin on a rat model of lipopolysaccharide‐induced preeclampsia
Author(s) -
Hu Jilin,
Zhang Jinman,
Zhu Baosheng
Publication year - 2019
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12501
Subject(s) - oxidative stress , nitric oxide , malondialdehyde , lipopolysaccharide , metformin , superoxide dismutase , preeclampsia , nitric oxide synthase , pharmacology , endocrinology , medicine , chemistry , biology , pregnancy , genetics , diabetes mellitus
Recent in vitro and clinical studies have found that metformin (MET) may play a preventive or therapeutic role in preeclampsia (PE) and may be a candidate drug for the prevention and/or treatment of PE. In this study, we used lipopolysaccharide (LPS) to induce a PE‐like rat model and investigated the intervention effect of MET from the perspectives of clinical manifestations, placental morphology, serum marker for placental injury, systemic inflammatory response and oxidative/nitrative stress, and placental nuclear factor‐κB (NF‐κB) signaling. The results showed that MET improved LPS‐induced hypertension, proteinuria, fetal growth restriction (FGR) and stillbirth, alleviated placental injury and decreased maternal serum marker alpha‐fetoprotein (MS‐AFP) level; MET suppressed LPS‐induced TNF‐α and IL‐6 productions, reduced oxidative/nitrative stress as evidenced by increased superoxide dismutase (SOD) activity, decreased inducible nitric oxide synthase (iNOS) activity, and decreased levels of malondialdehyde (MDA) and nitric oxide (NO); MET inhibited LPS‐induced NF‐κB activation in placentas. Based on these findings, it can be concluded that MET is beneficial to the PE‐like rat model by protecting placentas from injury, suppressing systemic inflammatory response and oxidative/nitrative stress, and inhibiting placental NF‐κB signaling pathway. MET is a promising drug for prevention and/or treatment of PE.