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

Abstract

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.

Hepatoprotective Effect of Polyphenol‐Enriched Fraction from Folium Microcos on Oxidative Stress and Apoptosis in Acetaminophen‐Induced Liver Injury in Mice

“…In this study, administration of APAP to mice dramatically reduced liver antioxidant capacity, as characterized by remarkable increase in MDA content and decrease in hepatic levels of SOD, CAT, GSH-Px, and GSH, which are often regarded as indicators of oxidative stress response [6, 7, 10]. However, FMF pretreatment distinctly reversed the changes in parameters of hepatic oxidative damage (Figure 5).…”

Byproduct Generated During the Elaboration Process of Isotonic Beverage as a Natural Source of Bioactive Compounds

“…In this way, hesperidin was a compound in abundance in FVR and it is possible to apply this residue as a source to obtain these pharmacological compounds. Scopoletin supplementation reversed alcoholic hepatosteatosis (Lee & Lee, ) andpaeonol contributed to reduce hepatic inflammation (Ding et al., ). Future studies on the synergistic effects of phenolics compounds as protectors against drug‐induced acute liver failure can use FVR.…”

Silkworm pupa oil attenuates acetaminophen‐induced acute liver injury by inhibiting oxidative stress‐mediated NF‐κB signaling

“…Except for the reduction of GSH, APAP also decreases the activities of antioxidative enzymes to further enhance oxidative stress (O'Brien et al, 2000). Inhibition of hepatic oxidative stress and inflammation attenuates hepatotoxicity induced by APAP (Ding et al, 2016;Huang et al, 2017). Inhibition of hepatic oxidative stress and inflammation attenuates hepatotoxicity induced by APAP (Ding et al, 2016;Huang et al, 2017).…”