The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice
Uncontrolled chronic inflammation and necrosis is characteristic of inflammatory bowel disease (IBD). This study aimed to investigate the effect of necrosis inhibitor (NI, NecroX-7) on a dextran sulfate sodium (DSS) induced chronic colitis model of mice. DSS was administered on days 1–5, and the NI...
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MDPI AG
2023-01-01
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| Online Access: | https://www.mdpi.com/1999-4923/15/1/222 |
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| author | Dongwoo Kim Ja Seol Koo Soon Ha Kim Yeong Seo Park Jung Wan Choe Seung Young Kim Jong Jin Hyun Sung Woo Jung Young Kul Jung Hyung Joon Yim |
| author_facet | Dongwoo Kim Ja Seol Koo Soon Ha Kim Yeong Seo Park Jung Wan Choe Seung Young Kim Jong Jin Hyun Sung Woo Jung Young Kul Jung Hyung Joon Yim |
| author_sort | Dongwoo Kim |
| collection | DOAJ |
| description | Uncontrolled chronic inflammation and necrosis is characteristic of inflammatory bowel disease (IBD). This study aimed to investigate the effect of necrosis inhibitor (NI, NecroX-7) on a dextran sulfate sodium (DSS) induced chronic colitis model of mice. DSS was administered on days 1–5, and the NI was administered intraperitoneally (3 mg/kg, 30 mg/kg) on days 1, 3, and 5 as well as every other day during the first five days of a three-week cycle. Three cycles of administration were performed. Colitis was evaluated based on the disease activity index (DAI) score, colon length, and histological score. Reverse transcription polymerase chain reaction testing, the Western blot assay, and immunohistochemical staining were performed to determine inflammatory cytokine levels. The NI reduced body weight change and the DAI score. Colon length and the histological score were longer and lower in the NI-treated groups, respectively. The NI decreased the expression of pro-inflammatory cytokines, particularly in tumor necrosis factor alpha (TNF-α) and phosphorylated nuclear factor kappa B (p-NF-κB). Immunohistochemical staining revealed decreased inducible nitric oxide synthase (iNOS) and high mobility group box 1 (HMGB1) levels. Overall, the NI improved DSS induced chronic colitis by attenuating the mRNA expression of pro-inflammatory cytokines such as TNF-α. Therefore, NI use is a potential, novel treatment approach for IBD. |
| first_indexed | 2024-03-09T11:27:33Z |
| format | Article |
| id | doaj.art-6e0088289ce140f689b0ee9868c3aa28 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:27:33Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6e0088289ce140f689b0ee9868c3aa282023-11-30T23:59:23ZengMDPI AGPharmaceutics1999-49232023-01-0115122210.3390/pharmaceutics15010222The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in MiceDongwoo Kim0Ja Seol Koo1Soon Ha Kim2Yeong Seo Park3Jung Wan Choe4Seung Young Kim5Jong Jin Hyun6Sung Woo Jung7Young Kul Jung8Hyung Joon Yim9Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul 02841, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul 02841, Republic of KoreaMitoImmune Therapeutics Inc., Seoul 06123, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul 02841, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul 02841, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul 02841, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul 02841, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul 02841, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul 02841, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul 02841, Republic of KoreaUncontrolled chronic inflammation and necrosis is characteristic of inflammatory bowel disease (IBD). This study aimed to investigate the effect of necrosis inhibitor (NI, NecroX-7) on a dextran sulfate sodium (DSS) induced chronic colitis model of mice. DSS was administered on days 1–5, and the NI was administered intraperitoneally (3 mg/kg, 30 mg/kg) on days 1, 3, and 5 as well as every other day during the first five days of a three-week cycle. Three cycles of administration were performed. Colitis was evaluated based on the disease activity index (DAI) score, colon length, and histological score. Reverse transcription polymerase chain reaction testing, the Western blot assay, and immunohistochemical staining were performed to determine inflammatory cytokine levels. The NI reduced body weight change and the DAI score. Colon length and the histological score were longer and lower in the NI-treated groups, respectively. The NI decreased the expression of pro-inflammatory cytokines, particularly in tumor necrosis factor alpha (TNF-α) and phosphorylated nuclear factor kappa B (p-NF-κB). Immunohistochemical staining revealed decreased inducible nitric oxide synthase (iNOS) and high mobility group box 1 (HMGB1) levels. Overall, the NI improved DSS induced chronic colitis by attenuating the mRNA expression of pro-inflammatory cytokines such as TNF-α. Therefore, NI use is a potential, novel treatment approach for IBD.https://www.mdpi.com/1999-4923/15/1/222necrosis inhibitorchronic colitisinflammatory bowel disease |
| spellingShingle | Dongwoo Kim Ja Seol Koo Soon Ha Kim Yeong Seo Park Jung Wan Choe Seung Young Kim Jong Jin Hyun Sung Woo Jung Young Kul Jung Hyung Joon Yim The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice Pharmaceutics necrosis inhibitor chronic colitis inflammatory bowel disease |
| title | The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice |
| title_full | The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice |
| title_fullStr | The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice |
| title_full_unstemmed | The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice |
| title_short | The Effect of Necrosis Inhibitor on Dextran Sulfate Sodium Induced Chronic Colitis Model in Mice |
| title_sort | effect of necrosis inhibitor on dextran sulfate sodium induced chronic colitis model in mice |
| topic | necrosis inhibitor chronic colitis inflammatory bowel disease |
| url | https://www.mdpi.com/1999-4923/15/1/222 |
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