17-Beta-estradiol protects the liver against warm ischemia/reperfusion injury and is associated with increased serum nitric oxide and decreased tumor necrosis factor-alpha
Autor: | Devin E. Eckhoff, J. Anthony Thompson, Luc Frenette, Juan L. Contreras, Guadalupe Bilbao |
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Rok vydání: | 2002 |
Předmět: |
Male
medicine.medical_specialty Endothelium Neutrophils medicine.medical_treatment Ischemia Liver transplantation Nitric Oxide Nitric oxide Mice chemistry.chemical_compound Internal medicine Cell Adhesion Animals Medicine Dose-Response Relationship Drug Estradiol medicine.diagnostic_test Tumor Necrosis Factor-alpha business.industry Temperature medicine.disease Mice Inbred C57BL Disease Models Animal Dose–response relationship Endocrinology medicine.anatomical_structure Liver chemistry Cytoprotection Reperfusion Injury Liver biopsy Surgery Endothelium Vascular Liver function business Reperfusion injury |
Zdroj: | Surgery. 132:302-309 |
ISSN: | 0039-6060 |
Popis: | Ischemia/reperfusion injury (I/R injury) to the liver can occur in low-flow states associated with trauma and shock and surgical procedures such as liver transplantation. Recent studies have shown that the administration of the female sex hormone 17-beta-estradiol after trauma-hemorrhage in animals restores depressed cardiac, hepatocellular, and immune functions. In this study we evaluated the effects of 17-beta-estradiol on I/R injury to the liver.The medial lobe of the liver in normal male C57BL/6 mice was clamped at its base for 90 minutes. 17-Beta-estradiol was given 1 hour before I/R injury at 40 and 4000 microg/kg intraperitoneally. Biochemical analysis was performed, and liver biopsy specimens were obtained at 24 hours.A dose-dependent reduction in aspartate aminotransferase level was observed in animals (n = 8) given estradiol (243 +/- 23 IU/L) compared with saline-treated animals (902 +/- 42 IU/L, P.001). The majority (90%) of the cytoprotective effect of estradiol was reverted by ICI 182,780 (a potent estrogen receptor antagonist). A significant increase in serum nitric oxide (NO) level was observed in animals given estradiol compared with controls; the effect was reversed by ICI 182,780 and N-nitro-L-arginine-methyl ester (an inhibitor of NO synthesis). A reduction in serum tumor necrosis factor-alpha was observed after injury in animals given estradiol compared with controls (30.2 +/- 11.1 vs 75.8 +/- 17.2 pg/mL, P.001). Estradiol treatment significantly reduced liver necrosis, disintegration of hepatic cords, and neutrophil infiltration in an estrogen receptor-dependent manner.Estradiol administration significantly reduced injury after I/R to the liver, an effect that is mainly receptor-mediated and is associated with increased serum NO, decreased TNF-alpha, and decreased number of neutrophils in liver biopsy specimens. Estrogen therapy may be important in clinical conditions associated with I/R injury to the liver. |
Databáze: | OpenAIRE |
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