Hepatic inflammatory responses to alphaalpha-cross-linked hemoglobin infusion in rats
| Autor: | Ruth E. Billings, Joan M. Przybocki, John M. Collier, Thomas A. McCalden |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Nitric Oxide Synthase Type II Hepatitis Animal medicine.disease_cause Pathology and Forensic Medicine Rats Sprague-Dawley chemistry.chemical_compound Hemoglobins Internal medicine medicine Animals Infusions Intravenous Heme Liver injury biology Aspirin Chemistry Nitric oxide synthase 2 General Medicine medicine.disease Rats Nitric oxide synthase Red blood cell Oxidative Stress Endocrinology medicine.anatomical_structure Biochemistry Liver Enzyme Induction Toxicity Heme Oxygenase (Decyclizing) biology.protein Hemoglobin Inflammation Mediators Nitric Oxide Synthase Oxidative stress Heme Oxygenase-1 |
| Zdroj: | The Journal of laboratory and clinical medicine. 131(5) |
| ISSN: | 0022-2143 |
| Popis: | Cross-linked hemoglobin (alphaalpha-Hb) may be a useful red blood cell substitute if it can be administered safely. However, cell-free hemoglobin has inherent properties that may cause oxidant-mediated toxicity. We investigated whether alphaalpha-Hb induces oxidative or inflammatory responses that lead to liver damage. alphaalpha-Hb (0.5 or 1.0 gm/kg) was infused into rats, and indices of liver injury, inflammation, and oxidative stress were examined. Although focal hepatic necrosis was noted at 24 hours, plasma alanine aminotransferase activity was not increased and lesions were resolved by 48 hours. Modest neutrophil accumulation in hepatic vessels, but not sinusoids, occurred at 24 hours. Heme oxygenase-1 (HO-1) protein and activity were induced in a dose- and time-dependent manner, with maximal induction at 24 hours. Plasma tumor necrosis factor-alpha levels were not significantly increased. Additional cytokine- and oxidant-mediated events such as nuclear transcription factor-kappaB activation and nitric oxide synthase induction were not observed. These results suggest that alphaalpha-Hb-derived products such as heme and ferric iron (Fe3+), potent inducers of HO-1, are responsible for increasing HO-1. HO-1 induction may be a protective response by the liver to metabolize excess heme and Fe3+, thereby providing antioxidative products to counter the potentially damaging oxidants produced by Fe3+-catalyzed reactions. |
| Databáze: | OpenAIRE |
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