Uridine-5'-triphosphate protects against hepatic- ischemic/reperfusion injury in mice

Ziv Ben-Ari, Orit Pappo, Smadar Yitzhaki, Yelena Cheporko, Asher Shainberg, Tova Zinman, Amiram Ravid, Romi Zemel, Larisa Bachmatov, Efrat Kurtzwald, Eytan Mor, Edith Hochhauser

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


BACKGROUND AND AIM.: Mitochondrial calcium overload triggers apoptosis and also regulates ATP production. ATP and uridine-5'-triphosphate (UTP) depletion from hepatic tissue after ischemia causes cell death. ATP and UTP binds to cell membranes of the hepatocytes through P2Y receptors. Our aim was to investigate the role of UTP on the hepatic injury induced by ischemia. METHODS.: Isolated mouse livers were randomly divided into five groups: (1) control group; (2) ischemic group (90 min); (3) as group 2, but with the administration of UTP; (4) as group 2, but with the administration of suramin, a P2Y antagonist; and (5) as group 3, but with the simultaneous administration of suramin and UTP. RESULTS.: There was a postischemic significant reduction in the release of liver enzymes in the animals pretreated with UTP, the intrahepatic caspase-3 activity was significantly decreased, and the intrahepatic ATP content increased compared with group 2 (ischemic untreated). UTP prevented intracellular Ca overload after hypoxia in hepatocyte cultures. In the UTP-treated groups, significantly fewer apoptotic hepatocyte cells were noted by weaker activation of caspase-3 and by the transferase-mediated dUTP nick end labeling assay. The administration of suramin prevented the beneficial effect of endogenous ATP. UTP treatment attenuated the degradation of IκBα (nuclear factor-kappaB inhibitor) by 80% during reperfusion with no effect on c-Jun N terminal kinase phosphorylation. CONCLUSION.: The administration of UTP before induction of ischemia-reperfusion can attenuate hepatic injury. UTP administration decreased cytosolic Ca overload in hypoxic conditions. UTP-mediated protective effects may be regulated through nuclear factor- kappaB inactivation. These findings have important implications for the potential use of UTP in ischemic hepatic injury.

Original languageEnglish
Pages (from-to)1155-1162
Number of pages8
Issue number8
StatePublished - 27 Apr 2009


  • Apoptosis
  • Ca
  • Ischemia-reperfusion
  • UTP


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