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

Oluwatobi T Somade; Babajide O Ajayi; Olubisi E Adeyi; Temitope A Dada; Mukodaz A Ayofe; David C Inalu; Opeyemi I Ajiboye; Olaoluwawunmi M Shonoiki; Aminat O Adelabu; Rasaq T Onikola; Ismaila D Isiaka; Opeyemi Omotoso; Adewale S James; Tunde O Olaniyan; Ayodeji M Adegoke; Adio J Akamo; Babatunji E Oyinloye; Ezekiel Adewole

doi:10.1016/j.toxrep.2024.01.006

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

Toxicol Rep. 2024 Jan 14:12:119-127. doi: 10.1016/j.toxrep.2024.01.006. eCollection 2024 Jun.

Authors

Oluwatobi T Somade¹, Babajide O Ajayi², Olubisi E Adeyi¹, Temitope A Dada¹, Mukodaz A Ayofe¹, David C Inalu¹, Opeyemi I Ajiboye¹, Olaoluwawunmi M Shonoiki¹, Aminat O Adelabu¹, Rasaq T Onikola³, Ismaila D Isiaka⁴, Opeyemi Omotoso¹, Adewale S James⁵, Tunde O Olaniyan⁶, Ayodeji M Adegoke⁷, Adio J Akamo¹, Babatunji E Oyinloye⁸, Ezekiel Adewole⁹

Affiliations

¹ Department of Biochemistry, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria.
² Department of Chemical Sciences, Faculty of Natural Sciences, Ajayi Crowther University, Oyo, Nigeria.
³ Key Laboratory of Green Process and Engineering, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
⁴ Center for Bacteria and Viruses Resources and Bioinformation, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
⁵ School of Biomedical Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
⁶ Instituto Politécnico Nacional, Centro de Biotecnologĭa Genómica, Reynosa 88710, Mexico.
⁷ Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan 200005, Nigeria.
⁸ Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, PMB, 5454, Ado-Ekiti 360001, Nigeria.
⁹ Industrial Chemistry Unit, Department of Chemical Sciences, College of Sciences, Afe Babalola University, Ado-Ekiti, Nigeria.

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.

Keywords: Akt; DEN; Ferulic acid; Hepatocellular carcinoma; NF-κB; Nrf2; P53; α-FP.