Heme metabolism, oxidative and nitrosative markers in a mouse model of Hemochromatosis: Effect of Isoflurane, ethanol and 5-aminolevulinic acid

Abstract

Hereditary hemochromatosis (HH) is characterized by iron homeostasis alterations. Association between HH and Porphyria Cutanea Tarda has been reported. The aim was to characterize oxidative and nitrosative stress status and its relationship with heme metabolism in a hemochromatosis mouse model (Hfe-/-), and to evaluate the effects of Isoflurane, ethanol and 5-aminolevulinic acid (ALA). Male and female Hfe−/− and wild-type C57BL/6J mice received Isoflurane (2 ml/kg); ethanol (30%) or ALA (40 mg/kg). In male Hfe-/-, reduced glutathione (GSH) was diminished respect to C57BL/6J mice. Female Hfe-/- showed higher levels of GSH and total antioxidant capacity than male Hfe-/-. Catalase activity was lower in male and female Hfe-/- than in controls. 5-Aminolevulinic acid synthetase activity was higher in male and female Hfe-/- than in controls. In male Hfe-/-, Porphobilinogen deaminase (PBG-D) activity was augmented and Heme oxygenase (HO) activity was diminished probably to avoid iron increase. Isoflurane and ethanol reduced PBG-D and increased HO activities. HO induction would indicate oxidative stress instauration being more striking due to ethanol that also induced Superoxide dismutase activity. Isoflurane reduced Nitric Oxide Synthase expression. ALA altered antioxidant system. In Hfe-/- mice different metabolisms were altered being more affected by the drugs studied. Findings here described would contribute to increase the knowledge about the association between HH and the Porphyrias and about the effects of volatile anaesthetics on different metabolisms in genetic models of Porphyrias and associated diseases.