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Hepatic ischemia/reperfusion is a common problem encountered under many clinical conditions, and it occurs in a variety of surgical procedures. Possible consequences include liver failure and/or multi-organ system failure, both of which have high rates of morbidity and mortality.1,2 Efforts to minimize the extent of injury incurred during the ischemic period or to maximize reparative process following ischemia have importance for survival.3 In vivo 31P-nuclear magnetic resonance (NMR) spectroscopy has been used to follow the response of hepatic high-energy phosphates during hepatic ischemia/reperfusion.4 It measures the continuous changes of hepatic adenosine triphosphate (ATP) levels and their metabolites, and is an effective tool to evaluate the serial data in the individual following drug treatment.

Recent investigations of enterai nutritients or artificial feedings with nucleotides and nucleosides suggested that they potentiate the bio-defense activity in immunologically compromised patients in the intensive care units.1 Decreased T lymphocyte functions with dietary nuclear acid deficiency and reversal by ribonucleic acid (RNA) supplement are reported.2–4 In surgical stress, macrophages and/or polymorphonuclear leukocytes (PMNs) are considered as key factors in the pathogenesis of systemic inflammatory response leading to septic shock by producing humoral mediators under endotoxin stimulation. We reported that dietary nucleic acid deficiency inhibited lipopolysaccharide (LPS) uptake and humoral mediators secretion by peritoneal macrophages in rats.5 However, it is not known whether dietary nucleic acid influences on PMN functions. Blocking of Mac-1 (CDllb/CD18) and/or lymphocyte function-associated antigen-1 (LFA-1, CD 11 a/CD 18) which are the adhesion proteins involved in the integrin superfamily, reduce the number of PMNs accumulating in the tissue and attenuate the oxidant stress of infiltrated PMNs.6,11 Phagocytes, such as PMNs and macrophages, undergo an oxidative burst in response to phagocytic or membrane stimuli, with generation and release of a variety of reactive oxygen metabolites.

Purine metabolism is a key metabolic process after partial hepatectomy in the synthesis of DNA and RNA, and in the energy metabolism for hepatic regeneration1. However it is not evaluated in clinical situations due to the difficulty in measuring changes of purine levels in the liver itself. In order to get a basic understanding of purine metabolism in clinical hepatectomy cases, blood samples are used for analysis in this study. Also, the liver is the main nondietary source of purines in mammalian cells2 and changes in blood level may affect purine metabolism in various tissues.

Purine and pyrimidine are essential for cellular proliferation1, 2, 3. But, purine and pyrimidine are synthesized from glutamine in de novo synthesis pathway and cultured cancer cells do not require them in the medium. This is the reason that utilization of nucleosides by human cancer cells and their changes with 5 fluorouracil (5FU), the fluorinated analogue of uracil which is used in chemotherapy for various tumors2, 3, has not been reported. In this study, as a source of purine and pyrimidine, a solution containing a mixture of nucleosides and a nucleotide (OG-VI), developed recently as a nutritional supplement4, was used in the medium. It consists of purines, guanosine 5’-mono-phosphate (5’-GMP) and inosine, and pyrimidines, cytidine, uridine, and thymidine (TdR). It is known to increases hepatic regeneration and improve protein metabolism after partial hepatectomy in rats5, 6, and increase DNA synthesis in primary cultured hepatocytes7.

The importance of dietary nucleic acid in modulation of immune function without disease has been reported in nutritional disorder except under surgical stress. Dietary nucleic acid deficiency decreases T lymphocytes function1 and dietary ribonucleic acid (RNA) enhances immune response2. However, it is not known whether dietary nucleic acid influences on macrophage function. Recently, monocytes/macrophages are considered as key factors in the pathogenesis of systemic inflammatory response leading to septic shock by producing humoral mediators under endotoxin stimulation3, 4. Therefore, the aim of this study is to evaluate the influence of dietary nucleic acid deficiency on endotoxin shock and macrophage functions stimulated with lipopolysaccharide (LPS), which is the major component of endotoxin. Then, the effect of intraperitoneal administration of a nucleotide and nucleosides mixture solution (OG-VI)5 was evaluated.