Metformin Alleviates Lipopolysaccharide-induced Acute Lung Injury through Suppressing Toll-like Receptor 4 Signaling.

Journal: Iranian journal of allergy, asthma, and immunology
PMID: 28129682

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.

Authors

  • Haleh Vaez
    Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran AND Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Moslem Najafi
    Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Negisa Seyed Toutounchi
    Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Jaleh Barar
    Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Abolfazl Barzegari
    Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Alireza Garjani
    Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

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