Nolan J P, Leibowitz A I
Gastroenterology. 1978 Sep;75(3):445-9.
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.
先前的研究表明，肠道来源的内毒素可能与其他因素共同导致急慢性肝损伤。特别是，有证据表明内毒素耐受性会改变四氯化碳肝毒性的生化和组织学表现。本研究旨在确定另一种改变内毒素毒性的方法是否也能预防四氯化碳（CCl4）损伤。抗生素多粘菌素B（PB）具有独特的抗内毒素特性，而具有相似抗菌谱的抗生素硫酸庆大霉素则没有这种特性。在用PB、庆大霉素或稀释剂预处理的大鼠组中，口服CCl4的LD100被PB降低至LD50，但庆大霉素预处理无效。当给予亚致死剂量的CCl4时，PB组大鼠的SGOT和SGPT值均显著较低。这种生化保护在这些动物明显缺乏组织学肝坏死中得到体现，而庆大霉素组或对照组则没有这种保护。PB预处理还降低了用醋酸铅增强法检测的CCl4后24小时内毒素血症的发生率。这些发现进一步支持了以下观点，即来自肠道的内毒素可能是由无关毒素引起的肝损伤程度的主要促成因素。
