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Additional benefit of combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cell against sepsis-induced kidney injury.
- Source :
-
Journal of pineal research [J Pineal Res] 2014 Aug; Vol. 57 (1), pp. 16-32. Date of Electronic Publication: 2014 May 15. - Publication Year :
- 2014
-
Abstract
- This study tested whether combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSCs) offered additional benefit in ameliorating sepsis-induced acute kidney injury. Adult male Sprague-Dawley rats (n = 65) were randomized equally into five groups: Sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating TNF-α level at post-CLP 6 hr was highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups (all P < 0.001). Immune reactivity as reflected in the number of splenic helper-, cytoxic-, and regulatory-T cells at post-CLP 72 hr exhibited the same pattern as that of circulating TNF-α among all groups (P < 0.001). The histological scoring of kidney injury and the number of F4/80+ and CD14+ cells in kidney were highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, and higher in CLP-A-ADMSC than in CLP-melatonin-A-ADMSC groups (all P < 0.001). Changes in protein expressions of inflammatory (RANTES, TNF-1α, NF-κB, MMP-9, MIP-1, IL-1β), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-β) markers, reactive-oxygen-species (NOX-1, NOX-2), and oxidative stress displayed a pattern identical to that of kidney injury score among the five groups (all P < 0.001). Expressions of antioxidants (GR+, GPx+, HO-1, NQO-1+) were lowest in SC group and highest in CLP-melatonin-A-ADMSC group, lower in CLP than in CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin- than in CLP-A-ADMSC-tretaed animals (all P < 0.001). In conclusion, combined treatment with melatonin and A-ADMSC was superior to A-ADMSC alone in protecting the kidneys from sepsis-induced injury.<br /> (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Acute Kidney Injury etiology
Acute Kidney Injury metabolism
Animals
Blotting, Western
Immunohistochemistry
Male
Mesenchymal Stem Cells physiology
Oxidative Stress
Rats
Sepsis metabolism
Tumor Necrosis Factor-alpha
Acute Kidney Injury drug therapy
Acute Kidney Injury therapy
Adipose Tissue cytology
Mesenchymal Stem Cell Transplantation methods
Mesenchymal Stem Cells cytology
Sepsis complications
Subjects
Details
- Language :
- English
- ISSN :
- 1600-079X
- Volume :
- 57
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of pineal research
- Publication Type :
- Academic Journal
- Accession number :
- 24761983
- Full Text :
- https://doi.org/10.1111/jpi.12140