Endotoxin and the liver. III. Modification of acute carbon tetrachloride injury by polymyxin b--an antiendotoxin.

Previous work suggests that endotoxin of enteric origin may contribute to both acute and chronic liver injury by other agents. In particular, evidence exists that endotoxin tolerance modifies biochemical and histological evidence of carbon tetrachloride hepatotoxicity. The present study was undertaken to ascertain whether another method of modifying endotoxicity would protect against carbon tetrachloride (CCl4) damage as well. The antibiotic polymyxin B (PB) has unique antiendotoxin properties not shared by gentamicin sulfate, an antibiotic with a similar antibacterial spectrum. In groups of rats pretreated with either PB, gentamicin, or diluent, the LD100 of an oral dose of CCl4 was reduced by PB to an LD50, but the gentamicin pretreatment was without effect. When a sublethal dose of CCl4 was administered, both the SGOT and SGPT values were significantly lower in the PB group of rats. This biochemical protection was mirrored in the striking lack of histological liver necrosis in these animals, protection not shared by the gentamicin group or controls. The incidence of endotoxemia 24 hr after CCl4 as detected by lead acetate enhancement was also reduced by PB pretreatment. These findings further support the contention that endotoxins from the gut may be major contributors to the extent of liver injury induced by an unrelated toxin.