TPEN attenuates hepatic apoptotic ischemia/reperfusion injury and remote early cardiac dysfunction

E. Hochhauser, Z. Ben-Ari, O. Pappo, Y. Chepurko, B. A. Vidne

Research output: Contribution to journalArticlepeer-review

Abstract

The release of cardioactive substances during hepatic ischemia/reperfusion injury generates toxic free radicals that inflict hepatic and remote cardiac damage. The aim of the study was to determine whether TPEN, a potent iron chelator, ameliorates the apoptotic hepatic and cardiac function injuries. Three groups of isolated rat livers were studied: (1) continuously perfused with Krebs-Henseleit solution; (2) subjected to 120 min of ischemia and 15 min of reperfusion; (3) as in group 2, with TPEN administered prior to ischemia. Isolated hearts were perfused for 65 min with the effluent of the reperfused livers. Results showed that TPEN administration reduced the release of norepinephrine, epinephrine, dopamine, prostaglandin E2 and angiotensin II, decreased intrahepatic caspase-3 activity, and decreased the mean hepatocyte apoptotic index (TUNEL assay) (p = 0.001). Perfusion with post-ischemic hepatic effluent caused a transient 15-min increase in left ventricular contraction and coronary flow (p < 0.05), followed by a decrease in cardiac function at one hour. TPEN reduced the transient elevation in left ventricular contraction p < 0.05), but did not prevent the subsequent decrease in cardiac function. In conclusion, TPEN attenuates post-ischemic apoptotic hepatic injury by modulating caspase-3-like activity and reduces the cardioactive substances released from the liver.

Original languageEnglish
Pages (from-to)53-62
Number of pages10
JournalApoptosis : an international journal on programmed cell death
Volume10
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Caspase 3
  • Hepatic injury
  • TPEN

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