Gallic Acid and Dodecyl Gallate Prevents Carbon Tetrachloride-Induced Acute and Chronic Hepatotoxicity by Enhancing Hepatic Antioxidant Status and Increasing p53 Expression

• Published in: Biological & pharmaceutical bulletin Vol. 40; no. 4; pp. 425 - 434
• Main Authors: Perazzoli, Marlene Raimunda Andreola, Perondi, Camila Katerin, Baratto, Cesar Milton, Winter, Evelyn, Creczynski-Pasa, Tânia Beatriz, Locatelli, Claudriana
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 2017; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Acids; Acute Disease; Animals; antioxidant status; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Carbon tetrachloride; Carbon Tetrachloride - toxicity; Cell death; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - prevention & control; Chronic Disease; Dose-Response Relationship, Drug; End Stage Liver Disease - chemically induced; End Stage Liver Disease - metabolism; End Stage Liver Disease - prevention & control; Enzymes; Fibrosis; Gallic acid; Gallic Acid - analogs & derivatives; Gallic Acid - pharmacology; Gallic Acid - therapeutic use; Gene Expression; Genes, p53 - drug effects; Genes, p53 - physiology; Glutathione; Hepatocytes; Hepatotoxicity; Lipid peroxidation; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver diseases; Male; Oxidative Stress - drug effects; Oxidative Stress - physiology; p53 gene; p53 Protein; Random Allocation; Rats; Rats, Wistar; Rodents; Trihydroxybenzoic acid
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b16-00782

Gallic acid (3,4,5-trihydroxybenzoic acid, GA), a natural phenolic acid has been reported as a strong antioxidant. Therefore the present study was designed to evaluate the effects of GA and dodecyl gallate (DGA) against acute and chronic carbon tetrachloride (CCl4)-induced hepatotoxicity. For acute model, rats were orally treated with GA and DGA for 7 d prior to CCl4 by intraperitoneally (i.p.) injection. For the chronic model, rats were orally treated with GA or DGA and CCl4 i.p. twice a week for four weeks. In both acute and chronic models, the CCl4-treated groups showed significantly increase in serum hepatic enzyme activities and histopathologic alterations, as well as a disruption in antioxidative status. In contrast, the treatment with GA and DGA restored serum hepatic enzymes activities, improved histopathologic alterations, increased glutathione (GSH) and decreased lipid peroxidation levels. The activities of liver antioxidant enzymes were increased by GA and DGA only in acute model. The expression of p53 gene increased about 3.5 times after GA and DGA treatments, which could result in cell death of damaged hepatocytes preventing of a lifelong liver failure. Thus, these results suggest that GA and DGA has the potential to prevent liver damages as the case of fibrosis condition.