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Published on: July 27, 2022
Biotin/sulfasalazine combination therapy alleviates acetic acid-induced ulcerative colitis in rats via modulation of
Sahar A Helmy1, Mahmoud M Samaha2, Al Shaima G Abd El Salam3
1Department of Biochemistry, Faculty of Pharmacy, Mansoura University, P. O. Box 35516, Mansoura, Egypt. saharabdelgawad@mans.edu.eg.
Abstract:
Ulcerative colitis (UC) is a chronic idiopathic mucosal inflammation of colon. The lack of effective remedies urges us to search for new remedies to effectively cure UC. The current study aims to explore the potential therapeutic effect of sulfasalazine (SLZ)/Biotin combination in ameliorating acetic acid (AA)-evoked UC in rats. SLZ (100 mg/kg), Biotin (6 mg/kg) and SLZ plus Biotin were administered orally for 8 days followed by injection of AA (2 mL, 3% v/v) intra-rectally to induce UC on the 8th day. SLZ/Biotin combination therapy attenuated AA-induced UC as proved by mitigation of pathological colonic abnormalities and decrease in disease activity index, colon mass index, colon weight/length ratio, LDH and CRP serum levels. This was associated with a considerable restoration of redox state in colon; MDA, NO and GSH contents. Furthermore, SLZ/Biotin combination therapy reduced colonic inflammation as confirmed by the remarkable decrement of S1P, S1PR1, IL-23, STAT3, and P-STAT3 colonic levels along with downregulation of colonic COX-2 and NF-κB protein expressions. Biotin as add-on therapy to SLZ markedly alleviates AA-induced UC via modulating S1P/S1PR1/NF-kB/ IL-23/STAT3 inflammatory signaling pathway with subsequent inhibition of COX-2.
Insights
Sulfasalazine (SLZ) combined with Biotin effectively treats ulcerative colitis (UC) in rats. This combination therapy reduced inflammation and restored colon health, offering a promising new treatment for UC.
Area of Science:
- Gastroenterology
- Pharmacology
- Inflammation Research
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited effective treatments.
- Novel therapeutic strategies are needed to manage UC effectively.
Purpose of the Study:
- To investigate the therapeutic potential of combining sulfasalazine (SLZ) and Biotin for acetic acid (AA)-induced UC in a rat model.
- To elucidate the underlying mechanisms of action for the SLZ/Biotin combination therapy.
Main Methods:
- Ulcerative colitis was induced in rats using intra-rectal acetic acid injection.
- Rats were treated with SLZ, Biotin, or a combination of both for 8 days.
- Disease activity, colonic pathology, serum markers (LDH, CRP), redox status (MDA, NO, GSH), and inflammatory markers (S1P, S1PR1, IL-23, STAT3, P-STAT3, COX-2, NF-κB) were assessed.
Main Results:
- SLZ/Biotin combination therapy significantly attenuated UC symptoms, reducing colonic damage and disease activity index.
- The treatment restored redox balance in the colon by modulating MDA, NO, and GSH levels.
- Combination therapy markedly decreased colonic levels of S1P, S1PR1, IL-23, STAT3, P-STAT3, COX-2, and NF-κB, indicating reduced inflammation.
Conclusions:
- Biotin as an add-on to SLZ demonstrates significant therapeutic efficacy in an experimental model of UC.
- The combination therapy alleviates UC by modulating the S1P/S1PR1/NF-kB/IL-23/STAT3 inflammatory pathway and inhibiting COX-2.
- This combination represents a promising therapeutic approach for managing ulcerative colitis.
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