Anti-inflammatory and Antioxidant Effects of Ketotifen Against Gentamicin-Induced Hepatotoxicity Through NF-κB Pathway Suppression
| Author | Mahdieh Sadat Badiee | en |
| Author | Masoud Mahdavinia | en |
| Author | Ali Hasan Rahmani | en |
| Author | Ehsan Saburi | en |
| Author | Fereshtesadat Fakhredini | en |
| Author | Nooshin Ghadiri | en |
| Orcid | Mahdieh Sadat Badiee [0000-0001-7405-5950] | en |
| Orcid | Masoud Mahdavinia [0000-0001-9448-1500] | en |
| Orcid | Ali Hasan Rahmani [0009-0009-5320-991X] | en |
| Orcid | Fereshtesadat Fakhredini [0000-0002-7766-3369] | en |
| Issued Date | 2025-08-31 | en |
| Abstract | Background: Gentamicin (GEN) is one of the most effective aminoglycoside antibiotics, and its repeated use leads to impaired liver function. The antioxidant, anti-inflammatory, and anti-apoptotic properties of ketotifen (KTF) as a first-generation antihistamine have been proven in various studies. Objectives: The present study aimed to evaluate the hepatoprotective effects of KTF against GEN-induced toxicity in mice, focusing on inflammation, oxidative stress, and NF-κB modulation. Methods: Thirty-seven male NMRI mice were randomly divided into 5 groups (n = 6 - 10), including: Control (normal saline 80 mL/kg, i.p, n = 6), GEN (80 mg/kg, i.p, n = 10), KTF (3 mg/kg, i.p, n = 7), and groups treated with GEN 80 mg/kg + KTF 2 mg/kg (n = 7) and GEN 80 mg/kg + KTF 3 mg/kg (n = 7). On day 8 of the study, mice were anesthetized, and their liver tissue was removed. Oxidative stress and inflammation factors, NF-κB protein expression were evaluated, and histological examinations were conducted. Results: Ketotifen resulted in significant reductions in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), thiobarbituric acid-reactive substances (TBARS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β), and NF-κB expression, and significant increases in total thiol and the activities of antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) compared to the GEN group (P < 0.001). Histopathology results confirmed this finding. Conclusions: The results of this study showed that KTF can significantly improve GEN-induced liver injury in mice. The hepatoprotective mechanism of KTF is through inhibiting inflammation, reducing oxidative stress, and modulating the NF-κB signaling pathway. This research can provide a new approach to the treatment of liver injury and help identify new drugs. | en |
| DOI | https://doi.org/10.5812/jjnpp-162430 | en |
| Keyword | Ketotifen, Gentamicin | en |
| Keyword | Hepatotoxicity | en |
| Keyword | Inflammation | en |
| Keyword | NF-Κb Signaling Pathway | en |
| Publisher | Brieflands | en |
| Title | Anti-inflammatory and Antioxidant Effects of Ketotifen Against Gentamicin-Induced Hepatotoxicity Through NF-κB Pathway Suppression | en |
| Type | Research Article | en |