KEAP1/NRF2 Mediated Activation of Oxidative Stress in Aflatoxin B1 Induced Early and Advanced Stage of Hepatocellular Carcinoma
Year: 2025
Type: article
Abstract: Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer in humans and is frequently caused by excessive alcohol intake and the eating of foods contaminated with aflatoxin. The most dangerous kind of aflatoxin, AFB1, is directly associated with a higher occurrence of HCC. The present work investigated the possible impacts of prolonged exposure to AFB1 on KEAP1-NRF2 molecules and oxidative stress profiles. Rats induced with HCC were euthanized on the 15th and 45th days of AFB1 treatment, categorised as early and advanced HCC control groups, respectively. The findings of this investigation indicate that levels of antioxidant enzymes such as catalase, glutathione peroxidase, glutathione-S-transferase, and total GSH decrease dramatically during various stages of HCC. Furthermore, this results in an increase in the concentrations of hydrogen peroxide, lipid peroxidation, and advanced oxidation protein products. Results showed that AFB1 significantly decreased the protein expression of KEAP1, while increased the protein expression of NRF2 at day 15 (early stage) when compared with protein expression at day 45 (advanced stage). To our knowledge, this study is the first to suggest that targeting KEAP1/NRF2 mediated regulation of oxidative stress in different stages of alcohol-AFB1-induced HCC helps to understand the underlying mechanism and provides new insights into developing therapeutic targets early.
DOI: 10.1002/jbt.70624
Authors: Nidhi Gupta, Vinodinee Dubey, Raj Kumar Koiri
Institution: Dr. Hari Singh Gour University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G154666667, G4426106715
OpenAlex ID: W4416723256