Regenerative enzyme activity of the liver after partial hepatectomy or toxic injury depressed by continuous NH4+ infusion.

Persistent slight or modest increments in blood ammonia level resulting from continuous intravenous infusion of NH4+ depressed hepatic thymidine kinase (TK) activity (DNA synthesis) by 30% after two-lobe (70%) hepatectomy, by 32% after subtotal (90%) hepatectomy, by 80% after massive injury with 1400 mg/kg acetaminophen, and by 92% after massive injury with 1000 mg/kg galactosamine. Ornithine decarboxylase activity (reflecting initiation of regeneration) was similarly depressed by 65% after 70% hepatectomy, by 58% after acetaminophen, and by 87% after galactosamine. It was not depressed after 90% hepatectomy. Intermittent marked but transient increments in blood ammonia level resulted in similar but slightly smaller enzyme reductions after the injuries with the toxins, and a reduction of 92% in TK activity after 70% hepatectomy. Thus, after toxic injury, both regenerative enzymes were substantially depressed by excess ammonia, whether present transiently in large amounts or persistently in small amounts. After partial hepatectomy, TK activity was similarly depressed by the large transient amounts of ammonia but was less affected by the persistent smaller amounts.