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

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-GaIN, 400 mg/kg, i.p.) and lipopolysaccharide (LPS, 10 mu g/kg, i.p.). The effects of quercetin (50 mg/kg, i.p) on D-GaIN toxicity was evaluated by standard biochemical, RT-PCR and Western blot methods. Administration of D-GaIN/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-GaIN/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-GaIN/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-GaIN/LPS hepatotoxicity. (c) 2013 Elsevier B.V. All rights reserved.