The Role of Mesenchymal Stem Cells with Ascorbic Acid and N-Acetylcysteine on TNF-α, IL 1β, and NF-κβ Expressions in Acute Pancreatitis in Albino Rats

Abstract

Severe acute pancreatitis (SAP) is a necrotic pancreatic inflammation associated with high mortality rate (up to 70%). Bone marrow (BM) mesenchymal stem cells (MSCs) have been investigated in pancreatic cellular regeneration, but still their effects are controversial. Therefore, the present study is aimed at examining the enrichment of the stem cells with ascorbic acid (AA) and N-acetylcysteine (NAC) and explore their combined action on the expression of the inflammatory cytokines: interleukin 1β (IL 1β), tumor necrosis factor-α (TNF-α), and nuclear factor-κβ (NF-κβ). A total of twenty adult male Sprague-Dawley albino rats were divided into four groups: the control group, cerulein group (to induce acute pancreatitis), BM-MSCs group, and combined BM-MSCs with AA and NAC group. Homing and proliferation of stem cells were revealed by the appearance of PKH26-labelled BM-MSCs in the islets of Langerhans. AA and NAC combination with BM-MSCs (group IV) was demonstrated to affect the expression of the inflammatory cytokines: IL 1β, TNF-α, and NF-κβ. In addition, improvement of the biochemical and histological parameters is represented in increasing body weight, normal blood glucose, and insulin levels and regeneration of the islet cells. Immunohistochemical studies showed an increase in proliferating cell nuclear antigen (PCNA) and decrease in caspase-3 reactions, detected markedly in group IV, after the marked distortion of the classic pancreatic lobular architecture was induced by cerulein. It could be concluded that treatment with BM-MSCs combined with antioxidants could provide a promising therapy for acute pancreatitis and improve the degeneration, apoptosis, necrosis, and inflammatory processes of the islets of Langerhans. TNF-α, IL 1β, and NF-κβ are essential biomarkers for the evaluation of MSC regenerative effectiveness.

Total flavonoids of Chrysanthemum indicum L inhibit acute pancreatitis through suppressing apoptosis and inflammation

“…TNF-α can also activate NF-κB, and further cause a magnified inflammatory reaction [ 22 ]. Therefore, regulation of TNF-α could not only alleviate the symptoms of AP, reduce the release of inflammatory mediators, but also inhibit NF-κB activation [ 23 ]. In this study, we found that TFC markedly inhibited the production of TNF-α in both in vivo (Fig.…”

Comparison between the Regenerative and Therapeutic Impacts of Bone Marrow Mesenchymal Stem Cells and Adipose Mesenchymal Stem Cells Pre-Treated with Melatonin on Liver Fibrosis

“…The cells were then trypsinized with 0.25% trypsin (Sigma, St. Louis, MO, USA, T1426) in 1 mL EDTA (Sigma, St. Louis, MO, USA, E6758) for five minutes at 37 °C and centrifuged at 2400 rpm for 20 min. The first passage was performed with the suspension and incubation of the cell pellets in 25 cm 2 culture flasks [ 31 , 44 ]. The adipose tissue was taken from the abdomen of Sprague Dawley albino rats after their sacrifice.…”

“…249900 (Rn_Tnfrsf1a_1_SG QuantiTect Primer Assay, ID QT00388346; Rn_Il1b_1_SG QuantiTect Primer Assay, ID QT00181657; and Rn_Nfkb2_1_SG, ID QT00396823), with the housekeeping gene ACTB Primer sequence. All the samples were analyzed using the 5-plex Rotor-Gene PCR Analyzer (Qiagen, Hilden, Germany) with the 2ΔΔCt method [ 44 , 49 ].…”

Evaluating the Immunopathogenesis of Diabetes After Acute Pancreatitis in the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study

“…The implication is that inflammatory cell damage from AP is not limited to the exocrine compartment but also the endocrine compartment, and specifically the islet cells, which can exacerbate AP severity. 11 In mice with preexisting DM mimicked via either permanent (Ins2Akita) or conditional (EL-CreER/−/IRfl/fl or PACIRKO) loss of insulin signaling, the severity of AP in 2 models of AP induction (palmitoleic acid/ethanol and cerulein) was far worse than in control mice, 12 providing a link between immune changes in the context of DM and inflammation induced by AP. Beyond these studies, there is little evidence of immune-mediated cytotoxicity linking AP and DM, although other AP-associated molecular signals may contribute to DM development.…”

“…In a rat model of cerulein-induced AP, islet cell integrity was maintained by the addition of bone marrow–derived mesenchymal stem cells in the presence of ascorbic acid and N -acetylcysteine, which effectively blocked IL-1ß, TNF-α, and nuclear factor κB. The implication is that inflammatory cell damage from AP is not limited to the exocrine compartment but also the endocrine compartment, and specifically the islet cells, which can exacerbate AP severity 11 . In mice with preexisting DM mimicked via either permanent (Ins2Akita) or conditional (EL-CreER/−/IRfl/fl or PACIRKO) loss of insulin signaling, the severity of AP in 2 models of AP induction (palmitoleic acid/ethanol and cerulein) was far worse than in control mice, 12 providing a link between immune changes in the context of DM and inflammation induced by AP.…”