17-Beta-estradiol protects the liver against warm ischemia/reperfusion injury and is associated with increased serum nitric oxide and decreased tumor necrosis factor …

DE Eckhoff, G Bilbao, L Frenette, JA Thompson… - Surgery, 2002 - Elsevier
DE Eckhoff, G Bilbao, L Frenette, JA Thompson, JL Contreras
Surgery, 2002Elsevier
Background. 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-β-estradiol
after trauma-hemorrhage in animals restores depressed cardiac, hepatocellular, and
immune functions. In this study we evaluated the effects of 17-β-estradiol on I/R injury to the
liver. Methods. The medial lobe of the liver in normal male C57BL/6 mice was clamped at its …
Background
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-β-estradiol after trauma-hemorrhage in animals restores depressed cardiac, hepatocellular, and immune functions. In this study we evaluated the effects of 17-β-estradiol on I/R injury to the liver.
Methods
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 μg/kg intraperitoneally. Biochemical analysis was performed, and liver biopsy specimens were obtained at 24 hours.
Results
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-α 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.
Conclusions
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-α, 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. (Surgery 2002;132:302-9.)
Elsevier