Attenuating Oxidative Stress by Paeonol Protected against Acetaminophen-Induced Hepatotoxicity in Mice

• Published in: PloS one Vol. 11; no. 5; p. e0154375
• Main Authors: Ding, Yi, Li, Qing, Xu, Yuan, Chen, Yuning, Deng, Yue, Zhi, Feng, Qian, Ke
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04-05-2016; Public Library of Science (PLoS)
• Subjects: Acetaminophen; Acetaminophen - administration & dosage; Acetaminophen - toxicity; Acetophenones - administration & dosage; Acetophenones - pharmacology; Alanine; Alanine transaminase; Alzheimer's disease; Alzheimers disease; Analgesics; Analgesics, Non-Narcotic - administration & dosage; Analgesics, Non-Narcotic - toxicity; Animals; Apoptosis; Aspartate transaminase; Biology and Life Sciences; Brain research; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - prevention & control; Cytokines; Diabetes; Disease Models, Animal; Extracellular signal-regulated kinase; Geriatrics; Glutathione - metabolism; Glutathione Peroxidase - metabolism; Hepatocytes; Hepatology; Hepatotoxicity; Hospitals; Hydrogen peroxide; Inflammation; Inhibition; Interleukin 6; JNK protein; Kinases; Laboratory animals; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver diseases; Male; Malondialdehyde - metabolism; MAP Kinase Signaling System - drug effects; Medical research; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mitochondria; Monocyte chemoattractant protein 1; mRNA; Neurotoxicity; NF-kappa B - metabolism; Overdose; Oxidative stress; Oxidative Stress - drug effects; Oxidizing agents; Permeability; Phosphorylation; Pretreatment; Proteins; Reactive oxygen species; Rodents; Superoxide Dismutase - metabolism; Transaminase; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0154375

Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute liver failure. The purpose of this study was to investigate whether paeonol protected against APAP-induced hepatotoxicity. Mice treated with paeonol (25, 50, 100 mg/kg) received 400 mg/kg acetaminophen intraperitoneally (i.p.) and hepatotoxicity was assessed. Pre-treatment with paeonol for 6 and 24 h ameliorated APAP-induced hepatic necrosis and significantly reduced the serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels in a dose-dependent manner. Post-treatment with 100 mg/kg paeonol ameliorated APAP-induced hepatic necrosis and reduced AST and ALT levels in the serum after APAP administration for 24 h. Western blot revealed that paeonol inhibited APAP-induced phosphorylated JNK protein expression but not p38 and Erk1/2. Moreover, paeonol showed anti-oxidant activities with reducing hepatic MDA contents and increasing hepatic SOD, GSH-PX and GSH levels. Paeonol dose-dependently prevented against H2O2 or APAP-induced LDH releasing and ROS production in primary mouse hepatocytes. In addition, the mRNA levels of pro-inflammatory genes such as TNF-α, MCP-1, IL-1β and IL-6 in the liver were dose-dependently reduced by paeonol pre-treatment. Pre-treatment with paeonol significantly inhibited IKKα/β, IκBα and p65 phosphorylation which contributed to ameliorating APAP-induced hepatic inflammation. Collectively, the present study demonstrates paeonol has a protective ability against APAP-induced hepatotoxicity and might be an effective candidate compound against drug-induced acute liver failure.