Carbon monoxide-bound red blood cell resuscitation ameliorates hepatic injury induced by massive hemorrhage and red blood cell resuscitation via hepatic cytochrome P450 protection in hemorrhagic shock rats

Shigeru Ogaki, Kazuaki Taguchi, Hiroshi Watanabe, Yu Ishima, Masaki Otagiri, Toru Maruyama

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Red blood cell (RBC) transfusions are the gold standard in cases of massive hemorrhage, but induce hepatic ischemia-reperfusion injury, a serious complication associated with hemorrhage and RBC resuscitation. Thus, the development of a novel resuscitable fluid that is not associated with hepatic ischemia-reperfusion injury would be desirable. It was reported that exogenous carbon monoxide (CO) treatment ameliorated hepatic ischemia-reperfusion injury accompanying liver transplantation. This suggests that transfusions with CO-bound RBC (CO-RBC) might protect against hepatic ischemia-reperfusion injury following massive hemorrhage and resuscitation compared with RBC resuscitation. To investigate this, we created a hemorrhagic shock model rat, followed by resuscitation with RBC and CO-RBC. Hepatic ischemia-reperfusion injury and the destruction of hepatic cytochrome P450 (CYP) were significantly ameliorated in the CO-RBC resuscitation group compared with the RBC resuscitation group. The free heme derived from the destruction of hepatic CYP was correlated with hepatic oxidation and injury, suggesting that CO-RBC was a major factor in the amelioration of hepatic ischemia-reperfusion injury induced by hemorrhage and resuscitation via hepatic CYP protection. These results indicate that CO-RBC has potential for use as a resuscitative fluid in blood transfusion and does not suffer from the limitations associated with the RBC transfusions that are currently in use.

Original languageEnglish
Pages (from-to)2199-2206
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume103
Issue number7
DOIs
Publication statusPublished - 2014 Jul
Externally publishedYes

Keywords

  • cytochrome P450
  • drug effects
  • drug transport
  • hepatic metabolism
  • pharmacokinetics

ASJC Scopus subject areas

  • Pharmaceutical Science

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