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
Autor: | Kazuaki Taguchi, Hiroshi Watanabe, Masaki Otagiri, Toru Maruyama, Yu Ishima, Shigeru Ogaki |
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Rok vydání: | 2014 |
Předmět: |
Male
Resuscitation Erythrocytes Blood transfusion medicine.medical_treatment Pharmaceutical Science Heme Shock Hemorrhagic Liver transplantation Rats Sprague-Dawley Cytochrome P-450 Enzyme System Liver Function Tests Pharmacokinetics medicine Animals Carbon Monoxide biology Chemistry Cytochrome P450 hemic and immune systems Disease Models Animal Oxidative Stress Red blood cell medicine.anatomical_structure Liver Reperfusion Injury Anesthesia biology.protein Erythrocyte Transfusion Reactive Oxygen Species Complication Dapsone Drug metabolism circulatory and respiratory physiology |
Zdroj: | Journal of Pharmaceutical Sciences. 103:2199-2206 |
ISSN: | 0022-3549 |
DOI: | 10.1002/jps.24029 |
Popis: | 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. |
Databáze: | OpenAIRE |
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