Protection against endotoxin-induced foetal resorption in mice by desferrioxamine and ebselen

Endotoxin was administered to mice on their 13th day of pregnancy at doses which caused the resorption of approximately 50% of the implanted foetuses. The iron chelator desferrioxamine was found to significantly inhibit the percentage of resorptions induced by endotoxin in a dose-dependent manner. T...

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Bibliographic Details
Published in:International journal of experimental pathology 1990-08, Vol.71 (4), p.433-440
Main Authors: Gower, J D, Baldock, R J, O'Sullivan, A M, Doré, C J, Coid, C R, Green, C J
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Antioxidants - therapeutic use
Azoles - therapeutic use
Deferoxamine - therapeutic use
Dose-Response Relationship, Drug
Endotoxins - antagonists & inhibitors
Escherichia coli
Female
Fetal Death - prevention & control
Fetal Resorption - chemically induced
Fetal Resorption - prevention & control
Mice
Organ Size - drug effects
Organoselenium Compounds
Pregnancy
Selenium - therapeutic use
Spleen - anatomy & histology
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Summary:Endotoxin was administered to mice on their 13th day of pregnancy at doses which caused the resorption of approximately 50% of the implanted foetuses. The iron chelator desferrioxamine was found to significantly inhibit the percentage of resorptions induced by endotoxin in a dose-dependent manner. The highest dose of desferrioxamine (5 mg) given intravenously 30 min prior to, immediately after, and 4 and 24 h after endotoxin inoculation, reduced the percentage of resorptions from 56.9 to 17.9%. Administration of the novel selenium-containing compound ebselen, which is both an antioxidant and an inhibitor of leukotriene synthesis, was also found to significantly protect against endotoxin-induced foetal resorptions, reducing the percentage of resorbed foetuses from 52.9 to 26.0% when given at a dose of 50 mg/kg (s.c.) at the time of endotoxin inoculation and 24 and 48 h following. Both these compounds also significantly reduced the increase in spleen weights observed when the mice were given endotoxin. These results provide evidence that the iron-catalysed production of hydroxyl radicals from other oxygen-derived species and the formation of leukotrienes play an important role in the mechanism by which endotoxin causes foetal resorptions in the mouse.
ISSN:0959-9673
1365-2613