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.
Gower
J D
JD
Section of Surgical Research, Clinical Research Centre, Harrow, Middlesex, UK.
Baldock
R J
RJ
O'Sullivan
A M
AM
Doré
C J
CJ
Coid
C R
CR
Green
C J
CJ
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