Affiliation:
1. Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College Saveetha Institute of Medical and Technical Sciences Chennai India
2. Laboratory for Artificial Intelligence and Molecular Modelling, Center for Global Health Research Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences Chennai India
Abstract
AbstractAcetaminophen (APAP) in high doses causes acute liver injury and acute liver failure. Ethyl gallate (EG) is a natural polyphenol, possessing antioxidant, anti‐inflammatory, and anti‐microbial properties. Therefore, in this study, we evaluated the protective role of EG against APAP‐induced acute liver injury in mice. Acute liver injury was induced by a single dose of APAP (400 mg/kg., i.p.). In separate groups, EG (10 mg/kg), EG (20 mg/kg), and N‐acetylcysteine (NAC; 1200 mg/kg., i.p.) were administered concurrently with APAP. The mice were sacrificed after 24 h of treatment. Liver marker enzymes of hepatotoxicity, antioxidant markers, inflammatory markers, and histopathological studies were done. APAP administration caused a significant elevation of marker enzymes of hepatotoxicity and lipid peroxidation. APAP administration also decreased enzymic and nonenzymic antioxidants. Acute APAP intoxication induced nuclear factor κ B, tumor necrosis factor‐α, interleukin‐1, p65, and p52 and downregulated IκB gene expressions. Our histopathological studies have confirmed the presence of centrilobular necrosis, 24 h after APAP intoxication. All the above abnormalities were significantly inhibited in groups of mice that were concurrently administered with APAP + EG and APAP + NAC. Our in silico analysis further confirms that hydroxyl groups of EG interact with the above inflammatory proteins at the 3,4,5‐trihydroxybenzoic acid region. These effects of EG against APAP‐induced acute liver injury could be attributed to its antioxidative, free radical scavenging, and anti‐inflammatory potentials. Therefore, this study suggests that EG can be an efficient therapeutic approach to protect the liver from APAP intoxication.
Subject
Molecular Medicine,Biochemistry,Drug Discovery,Pharmacology,Organic Chemistry