Affiliation:
1. Department of Medical Biochemistry, National Research Centre, Cairo, Egypt. Postal Code: 12622.
2. Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
3. Department of Pathology, National Research Centre, Cairo, Egypt.
Abstract
Introduction: Hepatocyte nuclear factors HNF4α and HNF1α, key transcription factors that regulate drug metabolism enzymes expression, were linked to inflammation. Galectin-3 (Gal-3) is a multi-role animal lectin which is involved in inflammation. This study aims to evaluate the impact of galectin-3 inhibition, by using modified citrus pectin (MCP), on HNF4α and HNF1α gene expression levels after acetaminophen (APAP) induced acute liver injury in Wistar rats. Materials and Methods: Sixty-four male Wistar rats were divided into four groups as follows; control, MCP, APAP and MCP plus APAP administered groups. The groups received APAP were divided into three subgroups each; in which rats were sacrificed after 24, 48 and 72 hours (h) from APAP administration. Expression levels of HNF4α and HNF1α, beside levels of Gal-3, tumor necrosis factor- α (TNF-α), Cytochrome P450 2E1 (CYP2E1), reduced glutathione (GSH), glutathione reductase (GR) and peroxidase (GPx) activities, liver function parameters were evaluated, along with histopathological study of the liver. Results: APAP high dose induced inhibition of liver HNF4α and HNF1α gene expression, CYP2E1 and GSH levels, GR and GPx activities, and increased hepatic Gal-3, TNF-α and serum liver function parameters levels, besides inducing hepatic necrosis. The toxic effects were stronger after 24 h then declined gradually after 48 h and 72 h. Inhibiting Gal-3 functionality after APAP high dose administration reduced TNF-α level and retrieved liver levels of HNF4α and HNF1α expression, CYP2E1, GSH, GR and GPx closer to normal control levels. Conclusion: Inhibiting Gal-3 functionality affects HNF4α and HNF1α gene expression levels and reduced inflammation after APAP high dose administration.
Subject
Pharmacology (medical),Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
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