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Histochemistry and Cell Biology

, Volume 151, Issue 3, pp 249–262 | Cite as

Bone marrow-derived mesenchymal stem cells ameliorate liver injury in a rat model of sepsis by activating Nrf2 signaling

  • Sally A. Selim
  • Samia A. Abd El-Baset
  • Asmaa A. A. KattaiaEmail author
  • Eman M. Askar
  • Eman Abd Elkader
Original Paper

Abstract

Sepsis is a fatal condition that leads to serious systemic inflammation and multiple organ dysfunction syndromes. This study was designed to investigate the possible therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) on sepsis-induced liver injury. We also aimed to examine the role of Nrf2 activation in modulating the response to sepsis following BMSCs treatment. Twenty-four adult male albino rats were assigned to: control, lipopolysaccharide (LPS) and LPS-stem cell groups. Liver samples were processed for light and electron microscope examinations. Immunohistochemical localization of BAX, proliferating cell nuclear antigen and nuclear factor-erythroid 2-related factor 2 (Nrf2) was carried out. Liver homogenates were prepared for assessment of reduced glutathione, glutathione peroxidase, tumor necrosis factor-alpha and interleukin-6 and also real-time PCR analysis of Nrf2 expression. BMSCs treatment improved the histopathological changes of the liver, enhanced tissue regeneration and decreased apoptosis following sepsis. We reported highly significant enhancement in Nrf2 expressions at mRNA and protein levels in the LPS-stem cell group compared with the LPS group. The up regulation of Nrf2 was probably implicated in decreasing inflammatory cytokine levels and counteracting oxidative stress induced by sepsis. Thus, BMSCs therapies could be a viable approach to treat sepsis-induced liver damage by activating Nrf2 signaling.

Keywords

Stem cells Sepsis Nrf2 Liver histopathology TNF-α IL-6 

Abbreviations

ABC

Avidin–biotin complex

ALT

Serum alanine aminotransferase

AST

Aspartate aminotransferase

BMSCs

Bone marrow-derived mesenchymal stem cells

DAB

3,3′-Diaminobenzidine

DMEM

Dulbecco’s modified Eagle’s medium

ELISA

Enzyme-linked immunosorbent assay

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

GPX

Glutathione peroxidase

GSH

Reduced glutathione

H&E

Hematoxylin and eosin

HO-1

Heme oxygenase-1

IL-6

Interleukin-6

LPS

Lipopolysaccharide

MiRNAs

MicroRNAs

MSCs

Mesenchymal stem cells

NO

Nitric oxide

Nrf2

Nuclear factor-erythroid 2-related factor 2

p

Probability values

PBS

Phosphate-buffered saline

PCNA

Proliferating cell nuclear antigen

RCMB

Regional Centre of Mycology and Biotechnology

Real-time PCR

Real-time polymerase chain reaction

ROS

Reactive oxygen species

TLR4

Toll-like receptor

TNF-α

Tumor necrosis factor-alpha

UCT

Ultra-cut

Notes

Compliance with ethical standards

Ethical standards

This study was performed in compliance with institutional guidelines for the care and use of experimental animals and approved by the Medical Research Ethics Committee of Zagazig University (Egypt).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Histology and Cell Biology, Faculty of MedicineZagazig UniversityZagazigEgypt
  2. 2.Department of Biochemistry, Faculty of MedicineZagazig UniversityZagazigEgypt

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