Effect of Galectin-3 Inhibition on Hepatocyte Nuclear Factors 4α and 1α Expression in Liver after Acetaminophen Long-term Induced Toxicity

Abdel-Monem, Mahmoud A.; Salem, Ahmed M.; Mahdy, Karam A.; El-Saeed, Gamila S.M.; Farrag, Abdel-Razik H.; Hassan, Nahla S.

doi:10.21608/ejchem.2021.92576.4382

Effect of Galectin-3 Inhibition on Hepatocyte Nuclear Factors 4α and 1α Expression in Liver after Acetaminophen Long-term Induced Toxicity

Document Type : Original Article

Authors

¹ Department of Medical Biochemistry, National Research Centre, Cairo, Egypt.

² Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.

³ Department of Pathology, National Research Centre, Cairo, Egypt.

10.21608/ejchem.2021.92576.4382

Abstract

Acetaminophen (APAP) induced liver injury can occur through acute or repeated administration of high doses. Hepatocyte nuclear factors HNF4α and HNF1α are key transcription factors involved in regulating the expression of drug metabolism enzymes and are affected by proinflammatory cytokines. Meanwhile galectin-3 (Gal-3) is a β-galactoside-binding lectin implicated in the regulation of macrophage activation and secretion of inflammatory mediators. This study aimed to evaluate the impact of galectin-3 inhibition on HNF4α and HNF1α gene expression after long-term administration of APAP, and to investigate the resulted effect on APAP induced hepatotoxicity. The study was performed on thirty two Wistar rats divided equally into four groups; control group, modified citrus pectin (MCP) (Gal-3 inhibitor) receiving group, APAP receiving group, and APAP plus MCP receiving group. APAP induced inhibition of liver HNF4α and HNF1α gene expression, and elevation of liver Gal-3 and tumor necrosis factor- α levels (TNF-α), depletion of reduced glutathione and its maintaining enzymes, besides elevation in levels of serum liver function parameters and appearance of necrotic areas in the liver. Gal-3 inhibition preserved HNF4α and HNF1α gene expression, TNF-α, and each of reduced glutathione and its maintaining enzymes near normal levels. It also significantly reduced APAP induced hepatotoxicity.

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