A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18)
Colon illnesses, particularly ulcerative colitis, are considered a major cause of death in both men and women around the world. The present study investigated the underlying molecular mechanisms for the potential anti-inflammatory effect of Dapagliflozin (DAPA) against ulcerative colitis (UC) induce...
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MDPI AG
2021-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/1/40 |
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| author | Mohamed Kh. ElMahdy Samar A. Antar Ehab Kotb Elmahallawy Walied Abdo Hayfa Hussin Ali Hijazy Ashraf Albrakati Ahmed E. Khodir |
| author_facet | Mohamed Kh. ElMahdy Samar A. Antar Ehab Kotb Elmahallawy Walied Abdo Hayfa Hussin Ali Hijazy Ashraf Albrakati Ahmed E. Khodir |
| author_sort | Mohamed Kh. ElMahdy |
| collection | DOAJ |
| description | Colon illnesses, particularly ulcerative colitis, are considered a major cause of death in both men and women around the world. The present study investigated the underlying molecular mechanisms for the potential anti-inflammatory effect of Dapagliflozin (DAPA) against ulcerative colitis (UC) induced by intracolonic instillation of 3% <i>v</i>/<i>v</i> acetic acid (AA). DAPA was administered to rats (1 mg/kg, orally) for two weeks during the treatment regimen. Interestingly, compared to the normal group, a marked increase in the index of colon/body weight, colon weight/colon length ratio, serum lactate dehydrogenase (LDH), and C-reactive protein (CRP), besides decrease in the serum total antioxidant capacity (TAC), were reported in the AA control group (<i>p</i> ˂ 0.05). Elevation in colon monocyte chemoattractant protein (MCP1), Interleukin 18 (IL-18), and inflammasome contents were also reported in the AA control group in comparison with the normal group. In addition, colon-specimen immunohistochemical staining revealed increased expression of nuclear factor-kappa B (NF-κB) and Caspase-3 with histopathological changes. Moreover, DAPA significantly (<i>p</i> ˂ 0.05) reduced the colon/body weight index, colon weight/colon length ratio, clinical evaluation, and macroscopic scoring of UC, and preserved the histopathological architecture of tissues. The inflammatory biomarkers, including colon MCP1, IL-18, inflammasome, Caspase-3, and NF-κB, were suppressed following DAPA treatment and oxidants/antioxidants hemostasis was also restored. Collectively, the present data demonstrate that DAPA represents an attractive approach to ameliorating ulcerative colitis through inhibiting MCP1/NF-κB/IL-18 pathways, thus preserving colon function. Antioxidant, anti-inflammatory, and anti-apoptotic properties of DAPA are implicated in its observed therapeutic benefits. |
| first_indexed | 2024-03-10T01:52:51Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T01:52:51Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-541c07574baa41468f8c1cc2d3058b502023-11-23T13:02:47ZengMDPI AGBiomedicines2227-90592021-12-011014010.3390/biomedicines10010040A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18)Mohamed Kh. ElMahdy0Samar A. Antar1Ehab Kotb Elmahallawy2Walied Abdo3Hayfa Hussin Ali Hijazy4Ashraf Albrakati5Ahmed E. Khodir6Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, EgyptDepartment of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, EgyptDepartment of Zoonoses, Faculty of Veterinary Medicine, Sohag University, Sohag 82524, EgyptDepartment of Veterinary Pathology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, EgyptDepartment of Family Education, Faculty of Education, Umm Al-Qura University, Makka Al-Mukarama 21955, Saudi ArabiaDepartment of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, EgyptColon illnesses, particularly ulcerative colitis, are considered a major cause of death in both men and women around the world. The present study investigated the underlying molecular mechanisms for the potential anti-inflammatory effect of Dapagliflozin (DAPA) against ulcerative colitis (UC) induced by intracolonic instillation of 3% <i>v</i>/<i>v</i> acetic acid (AA). DAPA was administered to rats (1 mg/kg, orally) for two weeks during the treatment regimen. Interestingly, compared to the normal group, a marked increase in the index of colon/body weight, colon weight/colon length ratio, serum lactate dehydrogenase (LDH), and C-reactive protein (CRP), besides decrease in the serum total antioxidant capacity (TAC), were reported in the AA control group (<i>p</i> ˂ 0.05). Elevation in colon monocyte chemoattractant protein (MCP1), Interleukin 18 (IL-18), and inflammasome contents were also reported in the AA control group in comparison with the normal group. In addition, colon-specimen immunohistochemical staining revealed increased expression of nuclear factor-kappa B (NF-κB) and Caspase-3 with histopathological changes. Moreover, DAPA significantly (<i>p</i> ˂ 0.05) reduced the colon/body weight index, colon weight/colon length ratio, clinical evaluation, and macroscopic scoring of UC, and preserved the histopathological architecture of tissues. The inflammatory biomarkers, including colon MCP1, IL-18, inflammasome, Caspase-3, and NF-κB, were suppressed following DAPA treatment and oxidants/antioxidants hemostasis was also restored. Collectively, the present data demonstrate that DAPA represents an attractive approach to ameliorating ulcerative colitis through inhibiting MCP1/NF-κB/IL-18 pathways, thus preserving colon function. Antioxidant, anti-inflammatory, and anti-apoptotic properties of DAPA are implicated in its observed therapeutic benefits.https://www.mdpi.com/2227-9059/10/1/40Dapagliflozinulcerative colitisanti-apoptoticanti-inflammatory-inflammasome-MCP1-IL-18 |
| spellingShingle | Mohamed Kh. ElMahdy Samar A. Antar Ehab Kotb Elmahallawy Walied Abdo Hayfa Hussin Ali Hijazy Ashraf Albrakati Ahmed E. Khodir A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18) Biomedicines Dapagliflozin ulcerative colitis anti-apoptotic anti-inflammatory-inflammasome-MCP1-IL-18 |
| title | A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18) |
| title_full | A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18) |
| title_fullStr | A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18) |
| title_full_unstemmed | A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18) |
| title_short | A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18) |
| title_sort | novel role of dapagliflozin in mitigation of acetic acid induced ulcerative colitis by modulation of monocyte chemoattractant protein 1 mcp 1 nuclear factor kappa b nf κb interleukin 18 il 18 |
| topic | Dapagliflozin ulcerative colitis anti-apoptotic anti-inflammatory-inflammasome-MCP1-IL-18 |
| url | https://www.mdpi.com/2227-9059/10/1/40 |
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