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. 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.
Section of Surgical Research, Clinical Research Centre, Harrow, Middlesex, UK.
J D
JD
Gower
R J
RJ
Baldock
A M
AM
O'Sullivan
C J
CJ
Doré
C R
CR
Coid
C J
CJ
Green
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001393:Azoles / Q000627:therapeutic use*; D003676:Deferoxamine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000037:antagonists & inhibitors; D004926:Escherichia coli; D005260:Female; D005313:Fetal Death / Q000517:prevention & control*; D005327:Fetal Resorption / Q000139:chemically induced / Q000517:prevention & control*; D054833:Isoindoles; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D016566:Organoselenium Compounds; D011247:Pregnancy; D012643:Selenium / Q000627:therapeutic use*; D013154:Spleen / Q000033:anatomy & histology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001393:Azoles; D004731:Endotoxins; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D012643:Selenium; D003676:Deferoxamine