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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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General Research Article

The Protective Role of Etoricoxib Against Diethylnitrosamine/2-acetylaminofluorene- Induced Hepatocarcinogenesis in Wistar Rats: The Impact of NF-κB/COX-2/PGE2 Signaling

Author(s): Gaber Ali, Hany Omar*, Fatema Hersi, Amira Abo-Youssef, Osama Ahmed and Wafaa Mohamed

Volume 15, Issue 1, 2022

Published on: 11 August, 2021

Article ID: e080721194609 Pages: 11

DOI: 10.2174/1874467214666210708103752

Price: $65

Abstract

Background: Liver cancer ranks as the 7th and 5th leading cause of cancer morbidity worldwide in men and women, respectively. Hepatocellular Carcinoma (HCC) is the most common type of liver cancer and is associated with an increasing global burden of Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH).

Objective: The present study aimed to investigate the possible chemopreventive effect of etoricoxib on diethylnitrosamine (DENA) and 2-acetylaminofluorene (2AAF)-induced HCC in male Wistar rats.

Methods: HCC was induced by DENA (150 mg/kg/week; i.p) for 2 weeks, then 2AAF (20 mg/kg; p.o) every other day for three successive weeks. Etoricoxib (0.6 mg/kg, p.o.) was given to DENA/ 2AAF-administered rats for 20 weeks.

Results: Etoricoxib significantly suppressed alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19.9) as liver tumor biomarkers. It also decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels while increased serum albumin levels. Besides, it alleviated DENA/2AAF-induced histopathological abrasions and inflammatory cell infiltration. Furthermore, etoricoxib showed a potent antioxidant effect, supported by a significant lipid peroxide reduction and elevation in superoxide dismutase activity and GSH content. In addition, Etoricoxib significantly down-regulated the protein expression of interleukin 1 beta (IL-1β), tumor necrosis factor α (TNFα), nuclear Factor-kappa B (NF-κB), phosphorylated nuclear Factor-kappa B (p-NF-κB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2).

Conclusion: In conclusion, the current results proved that etoricoxib possesses an anticarcinogenic effect via its antioxidant, anti-inflammatory, and modulation of NF-κB/COX-2/PGE2 signaling.

Keywords: Apoptosis, DENA, etoricoxib, hepatocellular carcinoma, inflammation, nonalcoholic fatty liver disease.

Graphical Abstract

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