N-Acetylcysteine enhances the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation in rats with severe acute pancreatitis

Pancreatology. 2019 Mar;19(2):258-265. doi: 10.1016/j.pan.2019.01.004. Epub 2019 Jan 11.

Abstract

Background: Severe acute pancreatitis (SAP) is a high mortality disease, for which there is a lack of effective therapies. Previous research has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs), which have immunomodulatory and antioxidant properties, have potential for the treatment of SAP. It remains unclear, however, whether the free radical scavenger N-acetylcysteine (NAC) can enhance the therapeutic efficacy of BMSC transplantation in SAP. In this study, we investigated the effect of combining treatment with NAC and BMSCs in a rat model of SAP.

Methods: SAP was induced by injection of sodium taurocholate into the pancreatic duct and, after successful induction of SAP, the rats were treated with BMSCs and NAC, either singly or in combination.

Results: After 3 days, serum levels of amylase, proinflammatory factors, malondialdehyde, and reactive oxygen species were significantly decreased in animals treated with BMSCs or NAC, compared with vehicle-treated animals. In contrast, total glutathione, superoxide dismutase and catalase were markedly increased after treatment with BMSCs or NAC. However, oxidative stress markers and inflammatory factors were significantly improved in the SAP + BMSCs + NAC group compared with those in the SAP + NAC group and the SAP + BMSCs group.

Conclusions: Combined NAC and BMSC therapy was found to alleviate oxidative stress damage to the pancreas and to inhibit the inflammatory response to a significantly greater extent than single therapy with either BMSCs or NAC. Because NAC enhances the therapeutic efficacy of BMSC transplantation in a rat model of SAP, combined therapy may provide a promising new approach for the treatment of SAP.

Keywords: Anti-inflammatory; Antioxidant; BMSCs; NAC; SAP.

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Acute Disease
  • Animals
  • Bone Marrow Cells*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Oxidative Stress
  • Pancreatitis / chemically induced*
  • Pancreatitis / drug therapy*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Taurocholic Acid / toxicity

Substances

  • Taurocholic Acid
  • Acetylcysteine