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Biochemical and Molecular Actions of Nutritients

Dietary Nucleotides Enhance the Liver Redox State and Protein Synthesis in Cirrhotic Rats¹

María José Pérez^*, Fermín Sánchez-Medina, Maribel Torres, Angel Gil and Antonio Suárez²

Department of Biochemistry and Molecular Biology, University of Granada, Granada, Spain; ^* Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain; and Department of Experimental Biology, University of Jaen, Spain

²To whom correspondence should be addressed. E-mail: asuarez{at}ugr.es.

Cirrhosis is characterized by altered lipid and protein metabolism and an excessive accumulation of extracellular matrix components. The aim of this work was to determine the effect of dietary nucleotide intake on the intracellular pools of nucleic acids and nucleotides, hepatic redox state, and protein synthesis during cirrhosis. Rats were given 300 mg/L thioacetamide (TAA) in drinking water and were fed diets without (TAA–Nt) or with nucleotides (Nt) (TAA+Nt, 3 g each of AMP, inosine 5'-monophosphate, CMP, GMP, and UMP per kg diet) for 4 mo. The degree of liver histological injury was less in group TAA+Nt than in TAA–Nt. The intake of nucleotides significantly increased the hepatic concentration of total nucleotides, adenine nucleotides, and ATP+ADP+AMP. Interestingly, the concentration of CDP-choline, a nucleotide necessary for phospholipid synthesis, was significantly higher in TAA+Nt than in TAA–Nt. The hepatic pyruvate:lactate (P = 0.075) and acetoacetate:ß-hydrodybutyrate (P < 0.05) ratios, indicators of cytosolic and mitochondrial redox states, were lower in TAA–Nt than in TAA+Nt. The total protein concentration was higher in the livers of TAA+Nt than in TAA–Nt. Although there were no differences in the expression of the albumin gene, the hepatic albumin concentration was significantly higher in TAA+Nt than in TAA–Nt. These data indicate that the reduction of liver injury in nucleotide-supplemented rats may be due to the increased intracellular availability of key metabolic nucleotides, the restoration of mitochondrial function, and the augmentation of protein synthesis.

KEY WORDS: • dietary nucleotides • thioacetamide • cirrhosis • redox state • protein synthesis