Hepatoprotective role of nitric oxide in an experimental model of chronic iron overload

Chronic iron overload (CIO) enhances nitric oxide ((NO)-N-center dot) production in the liver, which may represent a hepatoprotective mechanism against CIO toxicity. In order to test this hypothesis, the influence of CIO (diet enriched with 3% (wt/wt) carbonyl-iron for 8 weeks) in the absence or presence of the (NO)-N-center dot synthase (NOS) inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) on NOS activity, extracellular signal-regulated kinase (ERK1/2) and NF-kappa B activation was studied, in relation to ferritin expression and liver morphology. CIO increased liver NOS activity, ERK1/2 phosphorylation, NF-kappa B DNA binding, and ferritin expression, with normal liver histology. These changes were suppressed by combined CIO and L-NAME treatment, with the resulting inflammatory response of the liver. It is concluded that (NO)-N-center dot response induced by CIO represents a molecular mechanism affording protection against iron toxicity, which is related to both the activation of the ERK/NF-kappa B pathway involving inducible NOS expression and ferritin upregulation, changes that may be interrelated. (c) 2006 Elsevier Inc. All rights reserved.