title: The involvement of heme oxygenase 1 but not nitric oxide synthase 2 in a hepatoprotective action of quercetin in lipopolysaccharide-induced hepatotoxicity of D-galactosamine sensitized rats.
abstract: The objective of this study was to evaluate potential hepatoprotective capabilities of quercetin in relation to its modulation of the HO-1 and NOS-2 activities in an experimental model of fulminant liver failure. Liver insult was induced by in vivo administration of D-galactosamine (d-GalN, 400 mg/kg, i.p.) and lipopolysaccharide (LPS, 10 μg/kg, i.p.). The effects of quercetin (50 mg/kg, i.p) on D-GalN toxicity was evaluated by standard biochemical, RT-PCR and Western blot methods. Administration of d-GalN/LPS combination resulted in significantly higher plasma levels of aminotransferases, as well as increased mRNA and protein expressions of both HO-1 and NOS-2 enzymes. Quercetin exhibited cytoprotective effects on the liver, as evidenced by decreased aminotransferase plasma levels. Additionally, quercetin treatment in D-GalN/LPS treated rats significantly increased HO-1 mRNA and its protein expressions. On the contrary, quercetin did not exhibit any significant effects on the levels of nitrites, and NOS-2 mRNA and protein expressions in D-GalN/LPS treated rats. Quercetin when given alone did not have any significant changes on liver enzymes nor HO-1 and NOS-2 mRNA and protein expressions. It can be concluded that the quercetin's induction of HO-1 and its byproducts, without concomitant NOS-2 activity reduction, is among mechanisms contributing to the hepatoprotective effect in D-GalN/LPS hepatotoxicity.
authors.affiliation: Institute of Pharmacology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. nalekic@gmail.com
authors.forename: Nataša
authors.initials: N
authors.lastname: Lekić
authors.forename: Nikolina Kutinová
authors.initials: NK
authors.lastname: Canová
authors.forename: Aleš
authors.initials: A
authors.lastname: Hořínek
authors.forename: Hassan
authors.initials: H
authors.lastname: Farghali
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005688:Galactosamine / Q000633:toxicity; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017093:Liver Failure / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011794:Quercetin / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D000637:Transaminases / Q000097:blood
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D009573:Nitrites; D010936:Plant Extracts; D012333:RNA, Messenger; D005688:Galactosamine; D011794:Quercetin; D019001:Nitric Oxide Synthase; D051547:Heme Oxygenase-1; D000637:Transaminases