Rebamipide Mitigates Paracetamol-Induced Hepatotoxicity by Modulating TLR4/NF-κB and STAT3 Signaling Pathways in Rats | ||
| Journal of Advanced Pharmacy Research | ||
| Volume 9, Issue 4, October 2025, Pages 229-243 PDF (1.36 M) | ||
| Document Type: Research Article | ||
| DOI: 10.21608/aprh.2025.398843.1323 | ||
| Authors | ||
| rana El-habaak* 1; Mohamed M. Elbadr2; Elsayed Kamal Elsayed Elsayed3; Nashwad Hamad4; Engy El Morsy5 | ||
| 1Pharmacist, the Therapeutic Medicine Administration, Health Directorate, Assiut, Ministry of Health and Population, Egypt | ||
| 2Associate Professor, Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt | ||
| 3Lecturer of Pharmacology and toxicology, faculty of Pharmacy, Helwan University | ||
| 4Lecturer, Department of Pathology, Faculty of Veterinary Medicine, Assiut University, Egypt | ||
| 5Pharmacology & Toxicology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt | ||
| Abstract | ||
| Background: Rebamipide (Reba) is an amino acid analog approved for gastric mucosal protection. It exhibits anti-inflammatory and antioxidant properties by inhibiting neutrophil adhesion, diminishing the secretion of inflammatory cytokines, and limiting the production of reactive oxygen species (ROS). Objective: The present study aimed to evaluate the hepatoprotective effects of Reba in the context of paracetamol (PCM)-induced acute liver failure in rats. Methods: Animals were categorized into five distinct groups: control (vehicle), PCM (2 g/kg, p.o. on day 14), NAC (200 mg/kg for 13 days plus PCM on day 14), and Reba-treated groups (100 mg/kg and 200 mg/kg for 13 days plus PCM on day 14). Results: Reba treatment at both doses resulted in an enhancement of liver function. This is indicated by reduced serum transaminase levels, liver weight (LW), and the liver weight-to-body weight ratio (LW/BW). Oxidative stress was mitigated, evidenced by decreased malondialdehyde (MDA) and elevated glutathione (GSH) and catalase (Cat) levels. Reba also exerted a strong anti-inflammatory effect, significantly lowering TNF-α, IL-6, and NF-κB levels. Additionally, Reba decreased hepatic apoptosis, marked by downregulation of pro-apoptotic Bax and Caspase3 along with the upregulation of anti-apoptotic Bcl2. The compound also suppressed the TLR4-MyD88-NF-κB signaling pathway and significantly attenuated activation of the STAT3/p-STAT3 axis. Conclusion: Reba effectively protects against PCM-induced hepatic injury due to its anti-inflammatory, antioxidant, and anti-apoptotic actions. These findings indicate its promise as a therapeutic option for preventing acute hepatic damage. | ||
| Keywords | ||
| Rebamipide; Paracetamol; Hepatoprotection; Oxidative stress; Inflammation | ||
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