Abstract
Iron ions multiply damaging potential of reactive oxygen species by catalysing Fenton reaction. The aim of this study was to clarify whether bacterial endotoxin (lipopolysaccharide) influence iron metabolism in a manner which increases the intracellular levels of potentially dangerous "free" iron in liver. "Free" iron levels in liver (EPR-spectroscopy) were increased at 4h after endotoxin challenge. Expression of transferrin receptor (reverse transcription polymerase chain reaction) was decreased, suggesting that the observed increase in "free" iron levels is not a consequence of increased iron uptake. The expression of haem oxygenase-1 (HO-1) was increased, while that of ferritin was decreased. HO-1 degrades haem thereby liberating iron, and can thus increase intracellular iron levels. Cytochrome p450, a potential substrate for HO-1, is known to degrade in endotoxic shock. We have found a positive correlation between HO-1 expression and "free" iron levels and a negative correlation between HO-1 expression and respiratory function of mitochondria. In-vitro we have shown that within all products of HO-1 only free iron reduced the performance of mitochondria. Our data suggest that endotoxin induces upregulation of HO-1, leading to degradation of P450 and subsequent increase in intracellular free iron levels. The latter possibly contributes to liver damage.
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