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
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23537890
DOI
10.1016/j.fitote.2013.03.016
PII: S0367-326X(13)00073-7
Knihovny.cz E-resources
- MeSH
- Antioxidants pharmacology therapeutic use MeSH
- Nitrites metabolism MeSH
- Phytotherapy MeSH
- Galactosamine toxicity MeSH
- Heme Oxygenase-1 metabolism MeSH
- Liver drug effects enzymology metabolism MeSH
- Rabbits MeSH
- Rats MeSH
- Chemical and Drug Induced Liver Injury drug therapy genetics metabolism MeSH
- Lipopolysaccharides MeSH
- RNA, Messenger metabolism MeSH
- Mice MeSH
- Rats, Wistar MeSH
- Quercetin pharmacology therapeutic use MeSH
- Plant Extracts pharmacology therapeutic use MeSH
- Liver Failure drug therapy genetics metabolism MeSH
- Nitric Oxide Synthase metabolism MeSH
- Transaminases blood MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Rats MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antioxidants MeSH
- Nitrites MeSH
- Galactosamine MeSH
- Heme Oxygenase-1 MeSH
- Lipopolysaccharides MeSH
- RNA, Messenger MeSH
- Quercetin MeSH
- Plant Extracts MeSH
- Nitric Oxide Synthase MeSH
- Transaminases MeSH
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.
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