Avenanthramide-C ameliorate doxorubicin-induced hepatotoxicity via modulating Akt/GSK-3β and Wnt-4/β-Catenin pathways in male rats.

BACKGROUND: Doxorubicin (DOX) drugs used in cancer treatment can cause various adverse effects, including hepatotoxicity. Natural-derived constituents have shown promising effects in alleviating chemotherapy-induced toxicities. This study addressed the effect of Avenanthramides-C (AVN-C) treatment in rats with DOX-indued hepatotoxicity. METHODS: AutoDock Vina was used for the molecular docking investigations. In silico toxicity prediction for AVN-C and DOX was performed using the Pro Tox-III server. Four groups of ten male Sprague-Dawley rats were created: Group 1 (Gp1) served as a negative control, Gp2 received an intraperitoneal (i.p.) injection of AVN-C (10 mg/kg), Gp3 received an i.p. dose of DOX (4 mg/kg) weekly for a month, and Gp4 received the same dose of DOX as G3 and AVN-C as G2. Histopathological, molecular, and biochemical analyses were conducted 1 month later. RESULTS: The study showed that treatment with AVN-C significantly ameliorated DOX-induced hepatotoxicity in rats by restoring biochemical alterations, boosting antioxidant activity, reducing inflammation, and modulating the Akt/GSK-3β and Wnt-4/β-Catenin signaling pathways in male rats. CONCLUSION: This study is the first to demonstrate the therapeutic effects of AVN-C therapy on DOX-induced liver damage in male rats. Therefore, AVN-C could have a pronounced palliative effect on the hepatotoxicity caused by DOX treatment. These findings suggest that AVN-C could potentially alleviate the hepatotoxicity associated with DOX-based chemotherapy.