A lethal syndrome in mice following administration of carbon tetrachloride and cycloheximide, and its prevention by heparin treatment

Abstract

When a hepatotoxic dose of CCl 4 is followed in 6 h (but not in 18 h) by 30 μg per g body weight of cycloheximide, a lethal, shock-like state develops. This is prevented by heparin treatment. This lethal syndrome is compared with other, similar, induced lethal states in which cycloheximide plays an essential role, and in which heparin is life-saving. It is postulated that, after CCl 4, a phase of procoagulant activity occurs in the dying centrilobular zone hepatocytes, but that unimpaired protein synthesis permits responsive release of endogenous heparin and thereby prevents thrombosis in centrilobular sinusoids. Cycloheximide is thought to inhibit this heparin release and to allow a transient episode of occlusive centrilobular microthrombosis with consequent irreversible ischaemic damage to the mid-gut.