anti-inflammatory and antioxidant effects of ketotifen against gentamicin-induced hepatotoxicity through nf-κb pathway suppression

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.