MiP2005: Session 7

Mitochondrial Physiology Network 10.9: 91 (2005) - download pdf


Relation between free iron and mitochondrial superoxide radicals during endotoxic shock.

Christina Piskernik1, S Haindl1, C Kober1, H Nohl2, S Bahrami1, H Redl1, AV Kozlov1

1Ludwig Boltzmann Inst. Experimental Clinical Traumatology and Research Center of AUVA, Vienna; 2Research Inst. Pharmacology Toxicology, University of Veterinary Medicine, Vienna, Austria. - christina.piskernik@lbitrauma.org

    Oxidative stress plays an important role in the development of multiple organ failure in sepsis and endotoxic shock. Free iron is a metabolically active metal ion that increases the effects of free radical production by enhanced hydroxyl radical generation through the Fenton reaction with hydrogen peroxide. Mitochondrial superoxide radicals (SR) are considered as the main source of hydrogen peroxide. In this study we compared the levels of free iron and mitochondrial SR in endotoxic shock induced by intraperitoneal (i.p.) or intravenous (i.v.) LPS administration. Adult male Sprague-Dawley rats were injected with lipopolysaccharide (LPS) at a dose of 8 mg/kg (i.v. or i.p.) or 20 mg/kg LPS (i.p.). 16 hours after LPS application the levels of transferrin iron in blood, free iron in tissue, and mitochondrial SR were detected by means of electron paramagnetic resonance (EPR) spectroscopy. Transferrin iron levels in blood showed a significant decrease in all groups of LPS treated rats compared to control animals, suggesting the translocation of iron in tissues, mainly into tissue ferritin. However, part of this iron can appear as free iron. The injection of 8 mg LPS/kg (i.p.) did not result in an increase either in mitochondrial SR or in free iron levels. The injection of 20 mg LPS/kg (i.p.) resulted in a significant increase in both mitochondrial SR and free iron levels, accompanied by an increased mortality rate. The challenge with 8 mg LPS/kg (i.v.), also accompanied by an increased mortality rate, resulted in a significant increase in mitochondrial SR and in a trend to increase free iron levels. Since liver is the first target tissue for i.p. injection and lung for i.v., respectively, we determined free iron levels in lung after 8 mg/kg LPS i.v. administration, but did not find any change. Our data show that increased levels of free iron and mitochondrial SR in tissue may depend on the dose and the route of LPS administration and that under certain conditions free iron may amplify the oxidative potential of mitochondrial SR.

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Mitochondrial Physiology