Chronic alcohol administration affects purine nucleotide catabolism in vivo

AimsTo investigate the relationship between chronic alcohol administration and purine nucleotide metabolism in vivo.Main methodsRat models of alcohol dependence and withdrawal were used. The concentrations of uric acid (UAC), urea nitrogen (UREA), creatinine (CREA), and beta-2-microglobulin (β2-M) and creatinine clearance rate (CCR) in plasma were measured. The PLC method was used to detect the absolute content of purine nucleotides in different tissues. Enzymatic activities of adenosine deaminase (ADA), xanthine oxidase (XO), ribose 5-phosphate pyrophosphokinase (RPPPK), glutamine phosphoribosylpyrophosphate amidotransferase (GPRPPAT), hypoxanthine-guanine phosphate ribose transferase (HGPRT), and adenine phosphoribosyltransferase (APRT) in the tissues were analyzed. Real-time PCR was used to determine the relative level of ADA and XO.Key findingsThe renal function of rats with alcohol dependence was normal. Further, the content of purine nucleotides (GMP, AMP, GTP, and ATP) in tissues of the rats was decreased, which indicated that the increased uric acid should be derived from the decomposition of nucleotides in vivo. The activity of XO and ADA increased, and their mRNA expression was enhanced in the alcohol dependence group, but there was no significant difference in the activity of RPPPK and GPRPPAT in the liver, small intestine, and muscle; furthermore, no significant difference in the activity of HGPRT and APRT was observed in the brain.SignificanceThese results indicate that chronic alcohol administration might enhance the catabolism of purine nucleotides in tissues by inducing gene expression of ADA and XO, leading to elevation of plasma uric acid levels.