Metformin Alleviates Lipopolysaccharide-induced Acute Lung Injury through Suppressing Toll-like Receptor 4 Signaling
-
Haleh Vaez
,
Moslem Najafi
,
Negisa Seyed Toutounchi
,
Jaleh Barar
,
Abolfazl Barzegari
,
Alireza Garjani
Abstract
Signaling AMP-activated protein kinase (AMPK), an energy sensing enzyme, has been implicated in controlling inflammation. In this study we investigated whether activation of AMPK by metformin could protect the lung from lipopolysaccharide (LPS)-induced acute injury by inhibitingng TLR4 pathway. Male Wistar rats were randomly divided into 3 groups (n=6): control group received normal saline (0.5 mL), LPS group received LPS (0.5 mg/kg), and metformin-treated group received LPS and metformin (100 mg/kg). Nine hours later nuclear factor-κB (NF-κB), phosphorylated, and non-phosphorylated AMPK using western blot, and the rate of TLR4 mRNA expression using real-time PCR were assessed in the lung tissue. To evaluate neutrophil infiltration, the myeloperoxidase (MPO) activity was measured. The severity of the lung damage was assessed by histological examinations. It was found that the ratio of p-AMPKα to AMPKα was significantly upregulated by 22% (p<0.05) in the lungs obtained from the metformin group. In LPS-treated rats, we observed a high expression of TLR4 in the tissue along with increased levels of MyD88, NF-κB, and TNFα. Metformin considerably reduced all these parameters. Histological examinations revealed that metformin remarkably attenuated congestion and inflammatory cellular infiltration into the alveolar walls and also decreased MPO activity by 37% (p<0.05). We conclude that metformin could protect the lung tissue against LPS-evoked TLR4 activation and the protective effect can be related to the activation of AMPK.
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| Issue | Vol 15, No 6 (2016) | |
| Section | Original Article(s) | |
| Keywords | ||
| AMP-activated protein kinase Lipopolysaccharide Lung Metformin Sepsis Toll-like receptors | ||
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