Hepatoprotective role of nitric oxide in an experimental model of chronic iron overload.
Chronic iron overload (CIO) enhances nitric oxide (*NO) 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 synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on NOS activity, extracellular signal-regulated kinase (ERK1/2) and NF-kappaB activation was studied, in relation to ferritin expression and liver morphology. CIO increased liver NOS activity, ERK1/2 phosphorylation, NF-kappaB 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 response induced by CIO represents a molecular mechanism affording protection against iron toxicity, which is related to both the activation of the ERK/NF-kappaB pathway involving inducible NOS expression and ferritin upregulation, changes that may be interrelated.
Cornejo
Pamela
P
Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Casilla 70000, Santiago-7, Chile.
Fernández
Virginia
V
Vial
María T
MT
Videla
Luis A
LA
D000818:Animals; D001483:Base Sequence; D002908:Chronic Disease; D017931:DNA Primers; D004195:Disease Models, Animal; D007501:Iron / Q000008:administration & dosage*; D019190:Iron Overload / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D017931:DNA Primers; D009569:Nitric Oxide; D007501:Iron