title: Comparative effects of Quercetin and SRT1720 against D-galactosamine/lipopolysaccharide-induced hepatotoxicity in rats: biochemical and molecular biological investigations.
abstract: OBJECTIVE
  Quercetin, a plant flavonoid with potent antioxidant action, has been shown to be ameliorative against different types of liver insults, including D-Galactosamine/Lipopolysaccharide (D-GalN/LPS). The notion that its cytoprotective effects are SIRT1 mediated is still controversial. In this work, we examined whether the synthetic allosteric SIRT1 activator, SRT1720, may similarly attenuate D-GalN/LPS-induced hepatotoxicity.
  
  
  METHODS
  Male Wistar rats were randomly assigned into 6 groups: (1) Control, (2) Quercetin, (3) SRT1720, (4) D-GalN/LPS, (5) Quercetin + D-GalN/LPS and (6) SRT1720 + D-GalN/LPS. After twenty-four hours, the effects of these treatments were evaluated by biochemical studies, real-time PCR and Western blot.
  
  
  RESULTS
  D-GalN/LPS treatment downregulated SIRT1 expression and markedly increased the aminotransferase, bilirubin and conjugated diene levels. Conversely, quercetin and SRT1720 pretreatments upregulated SIRT1 expression and decreased the levels of the aforementioned markers. Quercetin had more profound effect on SIRT1 expression than SRT1720. Moreover, quercetin was more efficacious than SRT1720 in combatting the cytotoxic effects of D-GalN/LPS, as evidenced by lower markers of liver injury.
  
  
  CONCLUSIONS
  These results strongly suggest the involvement of SIRT1 in the cytoprotective effects of quercetin and SRT1720 against D-GalN/LPS-induced hepatotoxicity.
authors.affiliation: Institute of Pharmacology, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. mighty.kemelo@lf1.cuni.cz.
authors.forename: M K
authors.initials: MK
authors.lastname: Kemelo
authors.forename: A
authors.initials: A
authors.lastname: Horinek
authors.forename: N K
authors.initials: NK
authors.lastname: Canová
authors.forename: H
authors.initials: H
authors.lastname: Farghali
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001663:Bilirubin / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D015536:Down-Regulation / Q000187:drug effects; D005688:Galactosamine / Q000009:adverse effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D011794:Quercetin / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006576:Heterocyclic Compounds, 4 or More Rings; D008070:Lipopolysaccharides; C525422:SRT1720; D005688:Galactosamine; D011794:Quercetin; D000410:Alanine Transaminase; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D001663:Bilirubin