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Role of iron in ricin-induced lipid peroxidation and superoxide production
D F Muldoon1, E A Hassoun, S J Stohs
1Dept. of Pharmacology, Creighton University Health Sciences Center, Omaha, NE 68178, USA.
Abstract:
Ricin has been shown to induce oxidative stress in the livers of mice in vivo. These studies examined ricin-induced hepatic microsomal lipid peroxidation in mice, and the modulation thereof by iron and desferrioxamine. In addition, the studies investigated the production of superoxide anion by microsomes, mitochondria, and macrophages. Ricin (25 micrograms/kg, in vivo) increased microsomal lipid peroxidation by approximately 1.8-fold relative to control animals. This effect was abrogated by adding desferrioxamine to the microsomes. Fe2+ increased lipid peroxidation approximately 15-fold and 5-fold when added to microsomes from control and ricin-treated animals, respectively. Adding ricin to microsomes from control animals, however, decreased lipid peroxidation in a concentration-dependent manner. Desferrioxamine decreased lipid peroxidation by 47% and 64% in the absence and presence of ricin (5 micrograms/ml), respectively. Ricin, added to mitochondria from untreated animals decreased lipid peroxidation by 26% and 17% in the presence and absence of Fe2+, respectively. The administration of ricin (5 and 25 micrograms/kg) to mice increased microsomal, mitochondrial and macrophage superoxide anion production, in a dose-dependent fashion. The results suggest that iron mediated production of superoxide anion may be involved in the process of oxidative stress induced by ricin.
Insights
Ricin exposure increases liver oxidative stress and lipid peroxidation in mice. Iron appears to mediate this effect, potentially through superoxide anion production, suggesting a key mechanism in ricin toxicity.
Area of Science:
- Toxicology
- Biochemistry
- Cell Biology
Background:
- Ricin is a potent toxin known to induce cellular damage.
- Oxidative stress is implicated in the pathogenesis of ricin toxicity.
- Hepatic lipid peroxidation is a marker of oxidative damage.
Purpose of the Study:
- To investigate ricin-induced hepatic microsomal lipid peroxidation in mice.
- To examine the role of iron and desferrioxamine in modulating this peroxidation.
- To assess ricin's effect on superoxide anion production in various cellular components.
Main Methods:
- In vivo administration of ricin to mice.
- In vitro analysis of hepatic microsomal lipid peroxidation.
- Measurement of superoxide anion production by microsomes, mitochondria, and macrophages.
- Assessment of iron (Fe2+) and desferrioxamine effects on lipid peroxidation.
Main Results:
- Ricin administration significantly increased hepatic microsomal lipid peroxidation in vivo.
- Iron (Fe2+) exacerbated lipid peroxidation, while desferrioxamine mitigated it.
- Ricin exposure increased superoxide anion production in microsomes, mitochondria, and macrophages in a dose-dependent manner.
- In vitro, ricin's effect on lipid peroxidation was concentration-dependent and modulated by iron and desferrioxamine.
Conclusions:
- Iron-mediated pathways and superoxide anion production are likely involved in ricin-induced hepatic oxidative stress.
- Desferrioxamine may offer a protective effect against ricin-induced lipid peroxidation.
- Understanding these mechanisms is crucial for developing potential countermeasures against ricin toxicity.