Studies On The Protective Effects Of Polyphenols Attenuates Acetaminophen-induced Liver Injury And Its Mechanism

Polyphenols are rich in plant foods.Polyphenols have an influence on food in bitter,taste,color,flavor,smell and oxidation stability.Natural polyphenols have been extensively studied and found to have many important biological activities.Reactive oxygen species(ROS)play an important role in cardiovascular disease,cancer,aging,neurodegenerative diseases and diabetes.More attention has been paid to natural polyphenols,which is not only the largest class of phytochemicals,phenolic compounds have attracted increasing attention as potential agents for preventing and treating many oxidative stress-related diseases.3,4-dihydroxyphenylacetic acid(DOPAC)is a scarcely studied microbiota-derived metabolite of quercetin.The aim of this study was to determine the protective effect of DOPAC against acetaminophen(APAP)induced liver injury.Mice were treated intragastrically with DOPAC(10,20 or 50 mg/kg)for 3 days before APAP(300 mg/kg)injection.Results showed that APAP alone caused increase in serum aminotransferase levels and changes in hepatic histopathology.APAP also promoted oxidative stress by increasing lipid peroxidation and decreasing anti-oxidant enzyme activities.These events led to hepatocellular necrosis and reduced liver function.DOPAC increased nuclear factor erythroid 2-related factor 2(Nrf-2)translocation to the nucleus and enhanced the expression of phase II enzymes and anti-oxidant enzymes,and thereby reduced APAP hepatotoxicity and enhanced anti-oxidant ability.Our data provide evidence that DOPAC protected the liver against APAP-induced injury,which is involved in Nrf-2 activation.4-hydroxyphenylacetic acid(4-HPA)is a major microbiota-derived metabolite of polyphenols.This study seeked to investigate the ability of 4-HPA responses to treat APAP toxicity,as well as the mechanisms involved.Mice induced with APAP hepatotoxicity were treated intragastrically with 4-HPA(6,12,or 25 mg/kg).The mice treated with 4-HPA experienced better outcomes than those who received only one dose of APAP(300 mg/kg).APAP caused a remarkable increase in oxidative stress markers,peroxynitrite formation,and fewer activated phase II enzymes.Moreover,4-HPA increased Nrf-2 translocation to the nucleus and enhanced the activity of phase II enzymes and anti-oxidant enzymes,and thereby could ameliorate APAP-induced liver injury.DOPAC and 4-HPA are the main metabolites in the gastrointestinal tract,and also as the bioactive components in the diet,which can significantly alleviate the liver injury induced by APAP.Affecting the expression of Nrf-2,promote the transformation of APAP into non-toxic form and play a protective role.At the same time,it can inhibit the activity of CYP2E1,alleviate the oxidative stress of liver,and alleviate the liver toxicity induced by APAP,suggesting that DOPAC and 4-HPA can be used as a new type of potential natural liver protective drugs.The present study has revealed that as an active area of bioactive dietary constituents,4-HPA could protect the liver against APAP-induced injury,implying that 4-HPA may be utilized as a new potential natural hepatoprotective drug.