Ammonia, octanoate and a mercaptan depress regeneration of normal rat liver after partial hepatectomy.

Abstract

Four injections of subcoma doses of ammonium acetate, octanoic acid or dimethyl disulfide during the first 24 hr after two-lobe hepatectomy in normal rats markedly depressed DNA synthesis as reflected by liver thymidine kinase activity or the incorporation of tritiated thymidine into hepatic DNA. Recovery from the depressant effects of the three toxins took 16 to 28 hr. Similar doses of the same toxins injected hourly for 3 or 5 hr after the two-lobe hepatectomy had similar depressant effects on the early peak of ornithine decarboxylase activity measured at 4 or 6 hr. Recovery occurred within 3 hr perhaps because of the very short half-life of ornithine decarboxylase and its rapid regeneration time. These observations may have implications for the lack of regeneration observed in many patients with fulminant hepatic failure who have accumulated sufficient ammonia, methanethiol and fatty acids over periods of days or weeks to become encephalopathic.