Parenteral monoacetoacetin and liver regeneration interaction after partial hepatectomy in the rat

Abstract

Parenteral nutrients can be used to manipulate cell proliferation after partial hepatectomy. The relationship among macronutrients--glucose, monoacetoacetin, amino acids--and liver regeneration after partial hepatectomy was investigated. Male rats were anesthetized, received a 70% hepatectomy, and received a low-dose infusion of (1) glucose or (2) monoacetoacetin and a high-dose infusion of (3) glucose, (4) glycerol-glucose, or (5) monoacetoacetin-glucose beginning 6 hours after surgery. The five nonprotein nutrient combinations were infused with and without amino acids. Rats were killed 48 hours after partial hepatectomy, and the label and mitotic indices were determined. Each of the five treatments had a higher label index with amino acids present than with amino acids absent. Low-dose glucose and monoacetoacetin as well as high-dose glucose and glucose-glycerol had higher mitotic indices with amino acids than without amino acids. High-dose monoacetoacetin-glucose was associated with a greater mitotic index than was any other nonprotein substrate treatment, and this response was independent of amino acids being present or absent. In summary, (1) amino acids were needed for maximal cell proliferation rate; (2) the absence of amino acids and not the presence of glucose resulted in reduction of the label and mitotic indices for regenerating liver; (3) high-dose monoacetoacetin increased mitosis with or without amino acids; and (4) monoacetoacetin activity was dose dependent. The results indicate that the best nutrient for treatment of patients with liver injury is acetoacetate. The second best nutrient would be the combination of high-dose glucose and amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)