PMID- 35052720
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240405
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 10
IP  - 1
DP  - 2021 Dec 25
TI  - 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-kappaB)/Interleukin-18 (IL-18).
LID - 10.3390/biomedicines10010040 [doi]
LID - 40
AB  - 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% v/v 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 (p < 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-kappaB) and Caspase-3 with histopathological 
      changes. Moreover, DAPA significantly (p < 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-kappaB, 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-kappaB/IL-18 pathways, thus preserving colon function. 
      Antioxidant, anti-inflammatory, and anti-apoptotic properties of DAPA are 
      implicated in its observed therapeutic benefits.
FAU - ElMahdy, Mohamed Kh
AU  - ElMahdy MK
AD  - Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New 
      Damietta 34518, Egypt.
FAU - Antar, Samar A
AU  - Antar SA
AD  - Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New 
      Damietta 34518, Egypt.
FAU - Elmahallawy, Ehab Kotb
AU  - Elmahallawy EK
AUID- ORCID: 0000-0003-4484-3678
AD  - Department of Zoonoses, Faculty of Veterinary Medicine, Sohag University, Sohag 
      82524, Egypt.
FAU - Abdo, Walied
AU  - Abdo W
AD  - Department of Veterinary Pathology, Faculty of Veterinary Medicine, Kafrelsheikh 
      University, Kafrelsheikh 33516, Egypt.
FAU - Hijazy, Hayfa Hussin Ali
AU  - Hijazy HHA
AD  - Department of Family Education, Faculty of Education, Umm Al-Qura University, 
      Makka Al-Mukarama 21955, Saudi Arabia.
FAU - Albrakati, Ashraf
AU  - Albrakati A
AUID- ORCID: 0000-0002-4116-7865
AD  - Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 
      11099, Taif 21944, Saudi Arabia.
FAU - Khodir, Ahmed E
AU  - Khodir AE
AD  - Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New 
      Damietta 34518, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20211225
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC8773032
OTO - NOTNLM
OT  - Dapagliflozin
OT  - anti-apoptotic
OT  - anti-inflammatory-inflammasome-MCP1-IL-18
OT  - ulcerative colitis
COIS- The authors declare no conflict of interest that can potentially influence the 
      results of this study.
EDAT- 2022/01/22 06:00
MHDA- 2022/01/22 06:01
PMCR- 2021/12/25
CRDT- 2022/01/21 01:03
PHST- 2021/12/01 00:00 [received]
PHST- 2021/12/15 00:00 [revised]
PHST- 2021/12/19 00:00 [accepted]
PHST- 2022/01/21 01:03 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/01/22 06:01 [medline]
PHST- 2021/12/25 00:00 [pmc-release]
AID - biomedicines10010040 [pii]
AID - biomedicines-10-00040 [pii]
AID - 10.3390/biomedicines10010040 [doi]
PST - epublish
SO  - Biomedicines. 2021 Dec 25;10(1):40. doi: 10.3390/biomedicines10010040.