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


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.


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



Avidin–biotin complex


Serum alanine aminotransferase


Aspartate aminotransferase


Bone marrow-derived mesenchymal stem cells




Dulbecco’s modified Eagle’s medium


Enzyme-linked immunosorbent assay


Glyceraldehyde-3-phosphate dehydrogenase


Glutathione peroxidase


Reduced glutathione


Hematoxylin and eosin


Heme oxygenase-1








Mesenchymal stem cells


Nitric oxide


Nuclear factor-erythroid 2-related factor 2


Probability values


Phosphate-buffered saline


Proliferating cell nuclear antigen


Regional Centre of Mycology and Biotechnology

Real-time PCR

Real-time polymerase chain reaction


Reactive oxygen species


Toll-like receptor


Tumor necrosis factor-alpha




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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