Rupatadine protects the intestinal mucosa from injury by 5-flurouracil via modulation of inflammation, apoptosis and intestinal permeability
| Autor: | Mervat Z. Mohamed, Hanaa H. Mohammed |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Aspartic Acid Proteases Health Toxicology and Mutagenesis Rupatadine Interleukin-1beta Apoptosis Pharmacology Toxicology Nitric Oxide Permeability Histamine receptor chemistry.chemical_compound Intestinal mucosa Malondialdehyde medicine Animals Cysteine Intestinal Mucosa Rats Wistar Peroxidase Inflammation Chemical Health and Safety Intestinal permeability Platelet-activating factor biology business.industry Caspase 3 Interleukin-6 Tumor Necrosis Factor-alpha Public Health Environmental and Occupational Health NF-kappa B General Medicine medicine.disease Intestinal epithelium Glutathione Rats Interleukin-10 chemistry Myeloperoxidase Carboxymethylcellulose Sodium biology.protein Irritants Fluorouracil business Histamine medicine.drug |
| Zdroj: | Drug and chemical toxicology. 45(6) |
| ISSN: | 1525-6014 |
| Popis: | Fluorouracil (5-FU) is a widely used chemotherapeutic agent in various malignant tumors. However, intestinal toxicity is considered the irritant unavoidable adverse effect during the course therapy. The aim of the current study was to screen the effect of a new selective histamine receptor 1 blocker and platelet-activating factor (PAF) blocker on 5-FU induced intestinal toxicity. Five groups (6 rats each) of adult male rats (Wistar) were arranged as follows: (1) control group that was treated with carboxymethylcellulose, (2) a group that received rupatadine (higher dose) only, (3) a group that received 5-FU and (4) and (5) groups that received 5-FU plus lower or higher dose rupatadine, respectively. At end of the experiment, we determined intestinal malondialdehyde (MDA), glutathione reduced (GSH), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin 1β, 6, 10 (IL-1β, IL-6, IL-10), PAF, histamine, myeloperoxidase, cysteine-aspartic acid protease-3 (caspase-3), and nuclear factor kappa B (NF-κB) as well as the histological analysis. 5-FU injection caused marked elevation of MDA, NO, TNF-α, IL-1β, IL-6, PAF, histamine, myeloperoxidase, caspase-3, and NF-κB expressions. The intoxicated animals showed deficient GSH and IL-10 along with significant loss of villi, disorganized crypts, and inflammatory cell infiltration. Rupatadine pretreatment reduced the previously mentioned parameters, preserved a nearly normal intestinal mucosa picture with replenished GSH and elevated IL-10. In conclusion, rupatadine is a dual histamine receptor 1, and a PAF blocker could reduce 5-FU-induced oxidative damage, inflammation, apoptosis, and ulceration of the intestinal epithelium. Rupatadine may be a valuable modality to decrease 5-FU induced intestinal mucositis. |
| Databáze: | OpenAIRE |
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