Mohammad Aadil Bhat, Supriya Roy, Suneela Dhaneshwar, Swatantra Kumar, Shailendra K Saxena
{"title":"地氯雷他定具有抗炎和抗氧化作用，可改善 TNBS 引起的大鼠实验性结肠炎。","authors":"Mohammad Aadil Bhat, Supriya Roy, Suneela Dhaneshwar, Swatantra Kumar, Shailendra K Saxena","doi":"10.1080/08923973.2024.2360043","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Intestinal mucosal immune cells, notably mast cells, are pivotal in ulcerative colitis (UC) pathophysiology. Its activation elevates tissue concentrations of histamine. Inhibiting colonic histamine release could be an effective therapeutic strategy for treating UC. Experimental model like 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats mimic human IBD, aiding treatment investigations. Drug repurposing is a promising strategy to explore new indications for established drugs. Desloratadine (DES) is second-generation antihistamine utilized for managing allergies by blocking histamine action in the body. It also has reported anti-inflammatory and antioxidant actions.</p><p><strong>Objective: </strong>DES was investigated for its repurposing potential in UC by preclinical screening in TNBS-induced colitis in Wistar rats.</p><p><strong>Methods: </strong>Therapeutic efficacy of DES was evaluated both individually and in combination with standard drug 5-aminosalicylicacid (5-ASA). Rats were orally administered DES (10 mg/kg), 5-ASA (25 mg/kg), and DES + 5-ASA (5 mg + 12.15 mg) following the induction of colitis. Parameters including disease activity score rate (DASR), colon/body weight ratio (CBWR), colon length, diameter, pH, histological injury, and scoring were evaluated. Inflammatory biomarkers such as IL-1β, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed.</p><p><strong>Results: </strong>Significant protective effects of DES, especially in combination with 5-ASA, against TNBS-induced inflammation were observed as evidenced by reduced DASR, CBWR, and improved colon morphology. Drugs significantly lowered plasma and colon histamine and, cytokines levels. GSH restoration, and decreased MDA content were also observed.</p><p><strong>Conclusion: </strong>DES and DES + 5-ASA demonstrated potential in alleviating colonic inflammation associated with TNBS-induced colitis in rats. The effect can be attributed to its antihistamine, anticytokine, and antioxidative properties.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"436-449"},"PeriodicalIF":2.9000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Desloratadine <i>via</i> its anti-inflammatory and antioxidative properties ameliorates TNBS-induced experimental colitis in rats.\",\"authors\":\"Mohammad Aadil Bhat, Supriya Roy, Suneela Dhaneshwar, Swatantra Kumar, Shailendra K Saxena\",\"doi\":\"10.1080/08923973.2024.2360043\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Intestinal mucosal immune cells, notably mast cells, are pivotal in ulcerative colitis (UC) pathophysiology. Its activation elevates tissue concentrations of histamine. Inhibiting colonic histamine release could be an effective therapeutic strategy for treating UC. Experimental model like 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats mimic human IBD, aiding treatment investigations. Drug repurposing is a promising strategy to explore new indications for established drugs. Desloratadine (DES) is second-generation antihistamine utilized for managing allergies by blocking histamine action in the body. It also has reported anti-inflammatory and antioxidant actions.</p><p><strong>Objective: </strong>DES was investigated for its repurposing potential in UC by preclinical screening in TNBS-induced colitis in Wistar rats.</p><p><strong>Methods: </strong>Therapeutic efficacy of DES was evaluated both individually and in combination with standard drug 5-aminosalicylicacid (5-ASA). Rats were orally administered DES (10 mg/kg), 5-ASA (25 mg/kg), and DES + 5-ASA (5 mg + 12.15 mg) following the induction of colitis. Parameters including disease activity score rate (DASR), colon/body weight ratio (CBWR), colon length, diameter, pH, histological injury, and scoring were evaluated. Inflammatory biomarkers such as IL-1β, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed.</p><p><strong>Results: </strong>Significant protective effects of DES, especially in combination with 5-ASA, against TNBS-induced inflammation were observed as evidenced by reduced DASR, CBWR, and improved colon morphology. Drugs significantly lowered plasma and colon histamine and, cytokines levels. GSH restoration, and decreased MDA content were also observed.</p><p><strong>Conclusion: </strong>DES and DES + 5-ASA demonstrated potential in alleviating colonic inflammation associated with TNBS-induced colitis in rats. 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Desloratadine via its anti-inflammatory and antioxidative properties ameliorates TNBS-induced experimental colitis in rats.
Background: Intestinal mucosal immune cells, notably mast cells, are pivotal in ulcerative colitis (UC) pathophysiology. Its activation elevates tissue concentrations of histamine. Inhibiting colonic histamine release could be an effective therapeutic strategy for treating UC. Experimental model like 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats mimic human IBD, aiding treatment investigations. Drug repurposing is a promising strategy to explore new indications for established drugs. Desloratadine (DES) is second-generation antihistamine utilized for managing allergies by blocking histamine action in the body. It also has reported anti-inflammatory and antioxidant actions.
Objective: DES was investigated for its repurposing potential in UC by preclinical screening in TNBS-induced colitis in Wistar rats.
Methods: Therapeutic efficacy of DES was evaluated both individually and in combination with standard drug 5-aminosalicylicacid (5-ASA). Rats were orally administered DES (10 mg/kg), 5-ASA (25 mg/kg), and DES + 5-ASA (5 mg + 12.15 mg) following the induction of colitis. Parameters including disease activity score rate (DASR), colon/body weight ratio (CBWR), colon length, diameter, pH, histological injury, and scoring were evaluated. Inflammatory biomarkers such as IL-1β, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed.
Results: Significant protective effects of DES, especially in combination with 5-ASA, against TNBS-induced inflammation were observed as evidenced by reduced DASR, CBWR, and improved colon morphology. Drugs significantly lowered plasma and colon histamine and, cytokines levels. GSH restoration, and decreased MDA content were also observed.
Conclusion: DES and DES + 5-ASA demonstrated potential in alleviating colonic inflammation associated with TNBS-induced colitis in rats. The effect can be attributed to its antihistamine, anticytokine, and antioxidative properties.
期刊介绍：
The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal.
The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome.
With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more.
Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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