Abstract
This study tested the hypothesis that melatonin (Mel) and adipose-derived mesenchymal stem cell-derived exosomes effectively suppress dextran sulfate sodium (DSS)-induced acute inflammatory colitis (AIC) in rats. To determine whether Mel-exosome treatment could ameliorate the severity of AIC, we treated Sprague Dawley rats with DSS-induced AIC with Mel, exosomes, or combined Mel-exosome therapy and evaluated the effects on AIC. First, to induce an inflammatory response in vitro, we treated HT-29 cells with lipopolysaccharide (LPS) and evaluated the response to Mel and/or exosome treatment. We found that expression of NOX-1, NOX-2, MMP-9, NF-κB, iNOS, ICAM-1, and COX-2 was significantly higher in HT-29 cells treated with LPS than in control cells, and was significantly reduced by either exosome or Mel treatment (P<0.001 for all). In vivo, flow cytometric analysis showed that, compared to untreated rats with AIC, the number of circulating inflammatory cells was lowest in rats treated with combined Mel-exosome treatment than in rats treated with either Mel or exosomes alone (P<0.0001). Compared with controls, as well as Mel or exosome treatment alone, combined Mel-exosome treatment ameliorated the effects of DSS-induced AIC as evidenced by changes in the expression of markers for inflammation, oxidative stress, apoptosis, and fibrosis (P<0.0001 for all). Additionally, histopathological findings showed that colon injury score, expression of inflammatory and DNA-damage markers, and bloody stool were all improved following combined Mel-exosome treatment (P<0.0001 for all). In conclusion, combined Mel-exosome treatment significantly protected the rat colon against DSS-induced AIC injury.
Original language | English |
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Article number | AJTR0092470 |
Pages (from-to) | 2706-2724 |
Number of pages | 19 |
Journal | American Journal of Translational Research |
Volume | 11 |
Issue number | 5 |
State | Published - 2019 |
Bibliographical note
Publisher Copyright:© 2019, E-Century Publishing Corporation. All rights reserved.
Keywords
- Acute colitis
- Dextran sulfate sodium
- Exosom
- Inflammation
- Melatonin
- Oxidative stress