Kupffer cell inactivation by carbon monoxide bound to red blood cells preserves hepatic cytochrome P450 via anti-oxidant and anti-inflammatory effects exerted through the HMGB1/TLR-4 pathway during resuscitation from hemorrhagic shock
| Autor: | Hiroshi Watanabe, Yu Ishima, Kazuaki Taguchi, Hitoshi Maeda, Toru Maruyama, Masaki Otagiri, Shigeru Ogaki |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Resuscitation Erythrocytes Kupffer Cells Midazolam medicine.medical_treatment Ischemia Gadolinium Shock Hemorrhagic Pharmacology HMGB1 Biochemistry Antioxidants Rats Sprague-Dawley Cytochrome P-450 Enzyme System medicine Animals Chromans HMGB1 Protein chemistry.chemical_classification Carbon Monoxide Reactive oxygen species biology Kupffer cell Cytochrome P450 Macrophage Activation medicine.disease Toll-Like Receptor 4 Red blood cell medicine.anatomical_structure Cytokine Liver chemistry Immunology biology.protein Cytokines Erythrocyte Transfusion |
| Zdroj: | Biochemical Pharmacology. 97:310-319 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/j.bcp.2015.07.035 |
| Popis: | Red blood cell (RBC) transfusions for controlling hemorrhaging induce systemic ischemia reperfusion, resulting in a decrease in hepatic cytochrome P450 (CYP) levels. Carbon monoxide (CO), when bound to red blood cells (CO-RBC) has the potential to protect the hepatic CYP protein to produce a resuscitative effect in a hemorrhagic shock rat model. The aim of this study was to investigate the mechanism by which CO-RBC resuscitation from a massive hemorrhage protects against a decrease in hepatic CYP. In the early phase (∼1h) after a hemorrhage and RBC resuscitation, hepatic CYP protein levels were significantly decreased with increasing hepatic free heme levels, but were maintained by a pre-treatment of gadolinium chloride (GdCl3), a Kupffer cell inhibitor, and Trolox, an anti-oxidant agent, as well as CO-RBC resuscitation. Under these conditions, the production of reactive oxygen species (ROS) derived from activated Kupffer cells was increased, but this increase was suppressed by CO-RBC resuscitation. At a late phase (6∼24h), CYP mRNA levels decreased after hemorrhage and RBC resuscitation, but not in the case of CO-RBC resuscitation. The increases in plasma IL-6 and TNF-α levels were decreased by CO-RBC resuscitation via the suppression of the toll-like receptor-4 (TLR-4) and the expression of the high mobility group box-1 (HMGB-1). Hepatic CYP protection after a hemorrhage and CO-RBC resuscitation can be attributed to the inactivation of Kupffer cells, resulting in the suppression of ROS production in the early phase and the suppression of inflammatory cytokine production via the TLR-4/HMGB-1signal pathway in the late phase. |
| Databáze: | OpenAIRE |
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