Cycloheximide or nordihydroguaiaretic acid protects mice against the lethal and hepatocytolytic effects of a combined challenge with D-galactosamine and bacterial endotoxin.
Both cycloheximide and nordihydroguaiaretic acid protect mice against the fatalities and associated panlobular hepatocyte necrosis that follow a challenge with D-galactosamine and bacterial endotoxin. It is proposed that cycloheximide acts as an inhibitor of the endotoxin-induced activation of phospholipase A2, thereby inhibiting the synthesis of leukotrienes which is now known to be a prerequisite for tumour necrosis factor-alpha (TNF) biosynthesis, the latter cytokine being regarded as the terminal mediator of the fatal D-galactosamine and endotoxin-induced syndrome. Nordihydroguaiaretic acid protection is explained by its inhibition of lipoxygenase enzymes, and thus ultimately of TNF production in response to endotoxin.
Parry
E W
EW
Department of Human Anatomy and Cell Biology, The University, Liverpool, U.K.
D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D003513:Cycloheximide / Q000494:pharmacology*; D005688:Galactosamine / Q000037:antagonists & inhibitors*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA
D001427:Bacterial Toxins; D005688:Galactosamine; D009637:Masoprocol; D003513:Cycloheximide