Anti-inflammatory effects of the selective phosphodiesterase 3 inhibitor, cilostazol, and antioxidants, enzymatically-modified isoquercitrin and α-lipoic acid, reduce dextran sulphate sodium-induced colorectal mucosal injury in mice
| Autor: | Shim-mo Hayashi, Hajime Abe, Makoto Shibutani, Toshinori Yoshida, Tohru Kihara, Michi Nakamura, Yumi Kangawa, Yoshiki Seto, Taishi Miyashita |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chemokine Necrosis medicine.medical_treatment Phosphodiesterase 3 Anti-Inflammatory Agents Tetrazoles Pharmacology Phosphodiesterase 3 Inhibitors Toxicology Inflammatory bowel disease Antioxidants Pathology and Forensic Medicine Mice 03 medical and health sciences Animals Medicine Platelet activation Colitis Oligonucleotide Array Sequence Analysis Mice Inbred BALB C Thioctic Acid biology business.industry Dextran Sulfate Cell Biology General Medicine medicine.disease digestive system diseases Cilostazol Disease Models Animal 030104 developmental biology Cytokine Immunology biology.protein Female Quercetin Tumor necrosis factor alpha medicine.symptom business |
| Zdroj: | Experimental and Toxicologic Pathology. 69:179-186 |
| ISSN: | 0940-2993 |
| DOI: | 10.1016/j.etp.2016.12.004 |
| Popis: | Developing effective treatments and preventing inflammatory bowel disease (IBD) are urgent challenges in improving patients' health. It has been suggested that platelet activation and reactive oxidative species generation are involved in the pathogenesis of IBD. We examined the inhibitory effects of a selective phosphodiesterase-3 inhibitor, cilostazol (CZ), and two antioxidants, enzymatically modified isoquercitrin (EMIQ) and α-lipoic acid (ALA), against dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were treated with 0.3% CZ, 1.5% EMIQ, and 0.2% ALA in their feed. Colitis was induced by administering 5% DSS in drinking water for 8days. The inhibitory effects of these substances were evaluated by measuring relevant clinical symptoms (faecal blood, diarrhoea, and body weight loss), colon length, plasma cytokine and chemokine levels, whole genome gene expression, and histopathology. Diarrhoea was suppressed by each treatment, while CZ prevented shortening of the colon length. All treatment groups exhibited decreased plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α compared with the DSS group. Microarray analysis showed that cell adhesion, cytoskeleton regulation, cell proliferation, and apoptosis, which might be related to inflammatory cell infiltration and mucosal healing, were affected in all the groups. DSS-induced mucosal injuries such as mucosal loss, submucosal oedema, and inflammatory cell infiltration in the distal colon were prevented by CZ or antioxidant treatment. These results suggest that anti-inflammatory effects of these agents reduced DSS-induced mucosal injuries in mice and, therefore, may provide therapeutic benefits in IBD. |
| Databáze: | OpenAIRE |
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