Kidney and Liver Injuries After Major Burns in Rats Are Prevented by Resolvin D2
| Autor: | Rahmi Oklu, Tomohiro Kurihara, Daniel Irimia, Gaofeng Zhao, Amir Ibrahim, Anil V. Nair, Dennis Brown, Alan J. Fischman, Yoshitaka Inoue, Aleksandr Vasilyev, Ronald G. Tompkins, Yong Ming Yu |
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| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine medicine.medical_specialty Docosahexaenoic Acids Kidney Function Tests Critical Care and Intensive Care Medicine Article Sepsis Random Allocation 03 medical and health sciences 0302 clinical medicine Liver Function Tests Internal medicine medicine Animals Hepatic Insufficiency Prospective Studies Renal Insufficiency Rats Wistar Blood urea nitrogen Acute tubular necrosis Inflammation Liver injury Kidney medicine.diagnostic_test business.industry Body Weight Hemodynamics Acute kidney injury 030208 emergency & critical care medicine medicine.disease Rats Disease Models Animal Low Density Lipoprotein Receptor-Related Protein-2 030104 developmental biology Endocrinology medicine.anatomical_structure Blood chemistry Immunology Inflammation Mediators Burns Liver function tests business Blood Chemical Analysis |
| Zdroj: | Critical Care Medicine. 44:e241-e252 |
| ISSN: | 0090-3493 |
| DOI: | 10.1097/ccm.0000000000001397 |
| Popis: | Objectives Innate immune dysfunction after major burn injuries increases the susceptibility to organ failure. Lipid mediators of inflammation resolution, e.g., resolvin D2, have been shown recently to restore neutrophil functionality and reduce mortality rate in a rat model of major burn injury. However, the physiological mechanisms responsible for the benefic activity of resolvin D2 are not well understood. Design Prospective randomized animal investigation. Setting Academic research setting. Subjects Wistar male rats. Interventions Animals were subjected to a full-thickness burn of 30% total body surface area. Two hours after burn, 25 ng/kg resolvin D2 was administered IV and repeated every day, for 8 days. At day 10 post burn, 2 mg/kg of lipopolysaccharide was administered IV, and the presence of renal and hepatic injuries was evaluated at day 11 post burn by histology, immunohistochemistry, and relevant blood chemistry. Measurements and main results In untreated animals, we found significant tissue damage in the kidneys and liver, consistent with acute tubular necrosis and multifocal necrosis, and changes in blood chemistry, reflecting the deterioration of renal and hepatic functions. We detected less tissue damage and significantly lower values of blood urea nitrogen (26.4 ± 2.1 vs 36.0 ± 9.3 mg/dL; p ≤ 0.001), alanine aminotransferase (266.5 ± 295.2 vs 861.8 ± 813.7 U/L; p ≤ 0.01), and total bilirubin (0.13 ± 0.05 vs 0.30 ± 0.14 mg/dL; p ≤ 0.01) in resolvin D2-treated rats than in untreated animals. The mean blood pressure of all animals was above 65 mm Hg, indicating adequate tissue perfusion throughout the experiments. We measured significantly larger amounts of chromatin in the circulation of untreated than of resolvin D2-treated rats (575.1 ± 331.0 vs 264.1 ± 122.4 ng/mL; p ≤ 0.05) and identified neutrophil extracellular traps in kidney and liver tissues from untreated rats, consistent with the tissue damage. Conclusions Pathologic changes in kidney and liver tissues in a rat model of major burn and endotoxin insults are ameliorated by resolvin D2. |
| Databáze: | OpenAIRE |
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