Assessment of the Protective Effects of Omega-3 Fatty acid and Vitamin E Against Carbamazepine Hepatotoxicity in Rats by Alteration of Liver Enzymes, Antioxidant and Inflammatory Markers

Background: Drug-induced liver injury (DILI) is a significant public health problem. Carbamazepine (CBZ), an antiepileptic medicine used in the treatment of epilepsy, has been associated with the development of DILI, potentially progressing to liver failure. Previous studies suggested that omega-3 fatty acids and vitamin E possess antioxidant and anti-inflammatory characteristics. However, the protective roles of omega-3 fatty acids and vitamin E against CBZ-induced toxicity remain controversial. Methods: Thirty rats were randomly divided into five groups: group I (control), group II, (CBZ only), group III (CBZ+omega-3 fatty acids), group IV (CBZ+vitamin E), and group V (CBZ+omega-3 fatty acids and vitamin E). Liver enzymes, oxidative stress biomarkers (glutathione, malondialdehyde), proinflammatory cytokines, and cytokeratin 18 gene expression levels were assessed using standard techniques. Results: Liver enzymes, proinflammatory cytokines, malondialdehyde and cytokeratin 18 gene expressions reduced significantly (P<0.01) in groups III, IV, and V in comparison to group II, while glutathione was higher than in the induction group II (P<0.01). Conclusion: These findings suggest that omega-3 fatty acids and vitamin E exert protective effects against CBZ-induced hepatotoxicity, likely through antioxidant and anti-inflammatory mechanisms.