Metformin Attenuates Brain Injury by Inhibiting Inflammation and Regulating Tight Junction Proteins in Septic Rats

(Pages: 29-37)
Fatima Ismail Hassan, Ph.D, 1,#Tina Didari, Ph.D, 1,#Maryam Baeeri, Ph.D, 1Mahdi Gholami, M.Sc, 2Hamed Haghi-Aminjan, Ph.D., 3Madiha Khalid, M.SC., 1Mona Navaei-Nigjeh, Ph.D., 1Mahban Rahimifard, M.Sc., 1Sara Solgi, M.Sc., 1Mohammad Abdollahi, Ph.D., 1,2,*Mojtaba Mojtahedzadeh, Pharm.D., 1,2,*
Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
*Corresponding Address: Pharmaceutical Sciences Research Center (PSRC) The Institute of Pharmaceutical Sciences (TIPS) Tehran University of Medical Sciences Tehran Iran Emails:mohammad@tums.ac.ir,mojtahed@tums.ac.ir

These authors contributed equally to this work.

Any use, distribution, reproduction or abstract of this publication in any medium, with the exception of commercial purposes, is permitted provided the original work is properly cited This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ismail Hassan Fatima, Didari Tina, Baeeri Maryam, Gholami Mahdi, Haghi-Aminjan Hamed, Khalid Madiha, Navaei-Nigjeh Mona, Rahimifard Mahban, Solgi Sara, Abdollahi Mohammad, Mojtahedzadeh Mojtaba. Metformin Attenuates Brain Injury by Inhibiting Inflammation and Regulating Tight Junction Proteins in Septic Rats. Cell J. 2020; 22(): 29-37.

Abstract

Objective

Metformin has a potent inhibitory activity against inflammation and oxidative stress, which inevitably occur in sepsis-associated encephalopathy (SAE). The precise mechanisms underlying neuroprotective effects of metformin in SAE, are still unclear. In the present work, the protective effect of metformin on SAE using cecal ligation and puncture (CLP) model of sepsis, was assessed.

Materials and Methods

In this experimental study, CLP procedure was performed in Wistar rats and 50 mg/kg metformin was administered immediately. Specific markers of sepsis severity, inflammation, blood brain barrier (BBB) dysfunction, and brain injury, were investigated. Specific assay kits and real-time polymerase chain reaction (RT-PCR) were used. Histopathological assessment was also carried out.

Results

Treatment with metformin decreased murine sepsis score (MSS), lactate, platelet lymphocyte ratio (PLR), and high mobility group box (HMGB1) levels. The expression levels of claudin 3 (Cldn3) and claudin 5 (Cldn5) were increased following treatment with metformin. Metformin decreased the expression of S100b, neuron specific enolase (Nse), and glial fibrillary acidic protein (Gfap).

Conclusion

Our study suggests that metformin may inhibit inflammation and increase tight junction protein expressions which may improve BBB function and attenuate CLP-induced brain injury. Hence, the potential beneficial effects of metformin in sepsis, should be considered in future.