Ferulic acid interventions ameliorate NDEA-CCl4-induced hepatocellular carcinoma via Nrf2 and p53 upregulation and Akt/PKB-NF-κB-TNF-α pathway downregulation in male Wistar rats

Abstract

Hepatocellular carcinoma is a prevalent form of liver cancer that is life threatening. Many chemically synthesized anti-cancer drugs have various degrees of side effects. Hence, this study investigated the effect of FEAC interventions on NDEA-CCl4-induced HCAR in male Wistar rats. HCAR was induced by intraperitoneal administration of 200 mg/kg of NDEA and 0.5 mL/kg CCl4 (as a promoter of HCAR). Following the induction of HCAR, rats were treated differently with two different doses (25 and 50 mg/kg) of FEAC. HCAR induction was confirmed by the significant elevation of serum levels of ALT, AST, and α-FP. Also elevated significantly were liver levels of Akt/PKB, NF-κB, TNF-α, MDA, GSH, and activities of GST, SOD, and CAT, while levels of liver p53 and Nrf2 were significantly lowered compared with normal rats. Treatment interventions with both 25 and 50 mg/kg of FEAC against the DEN-CCl4-induced HCAR gave comparable effects, marked by a significant reduction in the levels of serum ALT, AST and α-FP, as well as liver levels of MDA, GSH, Akt/PKB, NF-κB, TNF-α, GST, SOD, and CAT, while levels of liver p53 and Nrf2 were significantly elevated compared with normal rats. Put together and judging by the outcomes of this study, FEAC being a potent antioxidant may also be potent against chemical-induced HCAR via upregulation of p53 and Nrf2, as well as downregulation of the Akt/PKB-NF-κB pathway in rats.