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Protection by intraperitoneal administration of bone marrow-derived stem cells of lipopolysaccharide-induced brain and liver damage in mice

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Abstract

Stem cells induce functional improvement in experimental and clinical studies, but its mechanism is still not known. This paper studies the effect of a single systemic injection of bone marrow-derived stem cell (BM-SC) suspension on brain oxidative stress and on pathological changes induced in the brain and liver of mice by lipopolysaccharide (LPS) endotoxin. Moreover, the possible cholinergic modulation of stem cell effects was also studied. Mice were treated with intraperitoneal (i.p.) injection of stem cell suspension or saline with or without subcutaneous atropine (1 mg/kg) at time of LPS (200 μg/kg, i.p.) administration and euthanized 4 h later. Results showed that the administration of LPS increased oxidative stress in the brain. Malondialdehyde (MDA) and nitric oxide increased along with decreased reduced glutathione (GSH) and paraoxonase 1 (PON1) activity. Neuronal degeneration, pyknotic nuclei with vacuolation in the cortex, striatum, and hippocampus were observed. In the liver, degeneration of hepatocytes and inflammatory cell infiltration were found. Intense caspase-3 expression also occurred in brain and liver tissue of LPS-treated mice. Stem cell treatment by itself showed no significant effects on brain levels of MDA, nitric oxide, or GSH, but decreased PON1 activity. In LPS-treated mice, BM-SCs had no effect on brain MDA or nitric oxide, but increased GSH compared with the LPS control group. Meanwhile, brain PON1 activity decreased after BM-SCs injection. Stem cells, however, reduced neuronal damage in the cortex, striatum, and hippocampus and also decreased inflammatory cell infiltration and hepatocyte degeneration in the liver. These effects showed a decrease after treatment with atropine. Immunohistochemical expression of caspase-3 and cyclooxygenase-2 in liver and brain tissue of LPS-treated mice was markedly inhibited by BM-SCs. The study indicates that the attenuation of tissue damage by BM-SCs was not due to a decreased oxidative stress. Rather, anti-apoptotic and anti-inflammatory mechanisms are likely to underlie the beneficial effects of BM-SCs injection. Our results also suggest the involvement of cholinergic mechanism in the effects of BM-SCs.

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  1. Department of Toxicology and Narcotics, National Research Centre, Tahrir St., Dokki, Cairo, Egypt

    Omar M. E. Abdel-Salam & Marawa El-Sayed El-Shamarka

  2. Department of Medical Biochemistry, National Research Centre, Tahrir St., Dokki, Cairo, Egypt

    Eman R. Youness

  3. Department of Pathology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt

    Enayat A. Omara

  4. Department of Pharmacology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt

    Amany A. Sleem

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  1. Omar M. E. Abdel-Salam
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Abdel-Salam, O.M.E., Youness, E.R., Omara, E.A. et al. Protection by intraperitoneal administration of bone marrow-derived stem cells of lipopolysaccharide-induced brain and liver damage in mice. Comp Clin Pathol 25, 107–118 (2016). https://doi.org/10.1007/s00580-015-2149-1

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