ABSTRACT
This study was designed to investigate the potential effects and underlying mechanism of adipose tissue-derived mesenchymal stem cells (MSCs) on allergic inflammation compared to Montelukast as an antileukotriene drug in a rat model of allergic rhinitis (AR). The effect of MSCs was evaluated in albino rats that were randomly divided into four (control, AR, AR + Montelukast, and AR + MSCs) groups. Rats of AR group were sensitized by ovalbumin (OVA) and then challenged with daily nasal drops of OVA diluted in sterile physiological saline (50 µL/nostril, 100 mg/mL, 10% OVA) from day 15 to day 21 of treatment with/without Montelukast (1 h before each challenge) or MSCs I/P injection (1 × 106 MCSs; weekly for three constitutive weeks). Both Montelukast and MSCs treatment started from day 15 of the experiment. At the end of the 5th week, blood samples were collected from all rats for immunological assays, histological, and molecular biology examinations. Both oral Montelukast and intraperitoneal injection of MSCs significantly reduced allergic symptoms and OVA-specific immunoglobulin E (IgE), IgG1, IgG2a and histamine as well as increasing prostaglandin E2 (PGE2). Further analysis revealed that induction of nasal innate cytokines, such as interleukin (IL)-4 and TNF-α; and chemokines, such as CCL11 and vascular cell adhesion molecule-1 (VCAM-1), were suppressed; and transforming growth factor-ß (TGF-ß) was up-regulated in Montelukast and MSCs-treated groups with superior effect to MSCs, which explained their underlying mechanism. In addition, the adipose tissue-derived MSCs-treated group had more restoring effects on nasal mucosa structure demonstrated by electron microscopical examination.
Subject(s)
Adipose Tissue/cytology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Rhinitis, Allergic/immunology , Rhinitis, Allergic/therapy , Animals , Cells, Cultured , Chemokine CCL11/genetics , Chemokine CCL11/metabolism , Disease Models, Animal , Interleukin-4/genetics , Interleukin-4/metabolism , Male , Nasal Mucosa/pathology , Nasal Mucosa/ultrastructure , Rats , Rhinitis, Allergic/blood , Rhinitis, Allergic/genetics , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolismABSTRACT
INTRODUCTION: Shigella flexneri is a Gram-negative bacteria that has the ability to invade the epithelium of the colon and cause colon ulcers. METHODOLOGY: The ability of isolated Shigella flexneri from bloody diarrhea to cause colon ulcers was investigated by histopathological examination via oral administration of the bacteria to adult male albino Sprague-Dawley rats. The antibacterial activity of thyme oil, ciprofloxacin, and their combination were evaluated in vitro and in vivo. RESULTS: Oral administration of 12×108 CFU/mL of S. flexneri was able to cause colon ulcers. Thyme oil had the highest antibacterial activity among other investigated oils (minimum inhibitory concentration [MIC] 150µL/L). Ciprofloxacin had the highest antimicrobial activity against S. flexneri (MIC 0.4mg/L). The synergism between thyme oil and ciprofloxacin showed the maximum growth inhibition of S. flexneri. The synergistic activity of thyme oil and ciprofloxacin succeeded in healing the epithelial surface of the colon and decreased the inflammation of the lamina propria; it also decreased the bacterial load in the infected colon, while the commercial drug failed to heal the colon ulcer. Thyme oil, ciprofloxacin, and their combination showed different degrees of effects on the bacterial cell structure by transmission and scanning electron microscopes. CONCLUSIONS: The combination of thyme oil and ciprofloxacin gave synergistic activity, which proved to be more effective in inhibiting the growth of ulcer-forming S. flexneri, healing the colon ulcer, and decreasing infiltration of the lamina propria with inflammatory cells.
