Rebamipide Mitigates Paracetamol-Induced Hepatotoxicity by Modulating TLR4/NF-κB and STAT3 Signaling Pathways in Rats | ||
| Journal of Advanced Pharmacy Research | ||
| Articles in Press, Accepted Manuscript, Available Online from 01 October 2025 | ||
| 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 | ||
| 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). The present study aimed to evaluate the hepatoprotective effects of Reba in the context of paracetamol (PCM)-induced acute liver failure in rats. 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). 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. In 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 | ||
|
Statistics Article View: 93 |
||
