Role of iron in ricin-induced lipid peroxidation and superoxide production.
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.
Muldoon
D F
DF
Dept. of Pharmacology, Creighton University Health Sciences Center, Omaha, NE 68178, USA.
Hassoun
E A
EA
Stohs
S J
SJ
D000818:Animals; D005260:Female; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000187:drug effects; D012276:Ricin / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D012276:Ricin; D007501:Iron