Protection by ebselen against endotoxin shock in rats or mice sensitized by galactosamine.

Oral pretreatment with greater than 1 mg/kg ebselen protected Wistar rats from shock induced by 20 mg/kg endotoxin when heart stroke volume after 60 min. was taken as a measure. Similarly, the drug protected male NMRI mice sensitized by 700 mg/kg galactosamine and treated with 33 micrograms/kg endotoxin against fulminant hepatitis assessed by transaminases release after nine hours. The validity of the model was checked by administration of drugs interfering with arachidonate metabolism. Chemical depletion of hepatic glutathione resulted in an apparent protection from galactosamine/endotoxin shock in mice. It is concluded that peptido-leukotrienes are likely to be responsible for the manifestation of this pathophysiological condition.