title: 3,4-Dihydroxyphenylacetic acid, a microbiota-derived metabolite of quercetin, attenuates acetaminophen (APAP)-induced liver injury through activation of Nrf-2.
abstract: 1. Acetaminophen (APAP) overdose leads to severe hepatotoxicity. 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 APAP-induced liver injury. 2. Mice were treated intragastrically with DOPAC (10, 20 or 50 mg/kg) for 3 days before APAP (300 mg/kg) injection. 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. 3. Our data provide evidence that DOPAC protected the liver against APAP-induced injury, which is involved in Nrf-2 activation, implying that DOPAC can be considered as a potential natural hepatoprotective agent.
authors.affiliation: a College of Veterinary Medicine, Xinjiang Agricultural University , Urumqi , PR China and.|b College of Veterinary Medicine, Northwest A&F University , Yangling , PR China.
authors.forename: Huiting
authors.initials: H
authors.lastname: Xue
authors.affiliation: b College of Veterinary Medicine, Northwest A&F University , Yangling , PR China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Xie
authors.affiliation: b College of Veterinary Medicine, Northwest A&F University , Yangling , PR China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: b College of Veterinary Medicine, Northwest A&F University , Yangling , PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: b College of Veterinary Medicine, Northwest A&F University , Yangling , PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: a College of Veterinary Medicine, Xinjiang Agricultural University , Urumqi , PR China and.
authors.forename: Hongqiong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: a College of Veterinary Medicine, Xinjiang Agricultural University , Urumqi , PR China and.|b College of Veterinary Medicine, Northwest A&F University , Yangling , PR China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology*; D000082:Acetaminophen; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D051379:Mice; D064307:Microbiota; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D011794:Quercetin / Q000378:metabolism*
chemical_list: D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D000082:Acetaminophen; D011794:Quercetin
keywords: 3,4-Dihydroxyphenylacetic acid; Nrf-2; acetaminophen; hepatic detoxification; quercetin