The effect of a nucleotide-nucleosidesolution on hepatic regeneration in rats after partial hepatectomy and in primary monolayer culture of hepatocytes

Purine and pyrimidine metabolism is a key process after hepatic surgery. To evaluate the effect of purine and pyrimidinesupplementation on hepatic regeneration, the following clinical in vitro and in vivo experiments were performed. Changes in blood nucleotides, nucleosides and nucleobase were analyzed by high performance liquid chromatography in patients and rats after partial hepatectomy. The effect of supplementation of nucleotide-nucleoside solution (OG-VI) or their components on nucleic acids syntheses in primary monolayer cultured hepatocytes and preoperative intraperitoneal injection of OG-VI on hepatic regeneration in the partially hepatectomized rats were evaluated. Blood purine and pyrimidine levels in patients change after hepatectomy and their changes indicate increased salvage synthesis of purine and pyrimidine in the regenerating liver. Addition of appropriate amounts of inosine, GMP, uridine, or thymidine, the substrates for salvage purine and pyrimidine syntheses, to primary cultures of hepatocytes enhanced both DNA and RNA syntheses by the salvage and de novo pathways. The OG-VI mixture also enhanced the syntheses of DNA and RNA. Preoperative administration of OG-VI to partially-hepatectomized rats enhances hepatic DNA synthesis in a way similar to the in vitro study.