 |
|
Administration of Progesterone After Trauma and Hemorrhagic Shock Prevents Hepatocellular Injury
Joachim F. Kuebler, MD;
Yukihiro Yokoyama, MD;
Doraid Jarrar, MD;
Balazs Toth, MD;
Loring W. Rue III, MD;
Kirby I. Bland, MD;
Ping Wang, MD;
Irshad H. Chaudry, PhD
Arch Surg. 2003;138:727-734.
Hypothesis Administration of a single dose of progesterone following trauma and hemorrhage in progesterone-deficient rats would ameliorate the inflammatory response and hepatocellular damage.
Setting A university laboratory.
Interventions Ovariectomized female Sprague-Dawley rats (250-350 g; Charles River Laboratories, Wilmington, Mass) underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma), were bled to a mean arterial blood pressure of 35 mm Hg for about 90 minutes, and then were resuscitated using Ringer lactate solution. Progesterone (25 mg/kg of body weight) or vehicle was administered subcutaneously at the end of resuscitation. In additional animals, Kupffer cells were isolated following trauma, hemorrhage, and resuscitation and treated in vitro with progesterone, lipopolysaccharide, or both.
Main Outcome Measures Six hours following resuscitation, plasma tumor necrosis factor  (TNF-) and interleukin 6 (IL-6) levels and liver myeloperoxidase activity were determined. Hepatocellular function (maximum velocity of indocyanine green clearance [Vmax] and the efficiency of the active transport or Michaelis-Menten constant [Km]) and plasma levels of transaminases were measured 20 hours after resuscitation. Kupffer cell IL-6 and TNF- production were assessed.
Results Plasma levels of TNF-, IL-6, aspartate aminotransferase, and alanine aminotransferase, as well as hepatic myeloperoxidase activity were increased, whereas indocyanine green clearance was depressed in vehicle-treated rats following trauma-hemorrhage. Animals treated with progesterone showed significantly reduced levels of the TNF-, IL-6, and transaminases as well as reduced myeloperoxidase activity in the liver. Progesterone-treated animals showed increased Vmax and Kmax values for indocyanine green. In vitro treatment of Kupffer cells with progesterone decreased TNF- production but did not affect the production of IL-6.
Conclusion Progesterone administration following trauma-hemorrhage ameliorates the proinflammatory response and, subsequently, the hepatocellular injury via direct action on immunocompetent cells.
From the Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham.
RELATED ARTICLE
This Month in Archives of Surgery
Arch Surg. 2003;138(7):699.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Estrus cycle: influence on cardiac function following trauma-hemorrhage
Yang et al.
Am. J. Physiol. Heart Circ. Physiol. 2006;291:H2807-H2815.
ABSTRACT
| FULL TEXT
Maintenance of lung myeloperoxidase activity in proestrus females after trauma-hemorrhage: upregulation of heme oxygenase-1
Yu et al.
Am. J. Physiol. Lung Cell. Mol. Physiol. 2006;291:L400-L406.
ABSTRACT
| FULL TEXT
Role of Thromboxane in Producing Hepatic Injury During Hepatic Stress
Yokoyama et al.
Arch Surg 2005;140:801-807.
ABSTRACT
| FULL TEXT
The Case for Progesterone
STEIN
Ann. N. Y. Acad. Sci. 2005;1052:152-169.
ABSTRACT
| FULL TEXT
Insights into the role of interleukin-6 in the induction of hepatic injury after trauma-hemorrhagic shock
Toth et al.
J. Appl. Physiol. 2004;97:2184-2189.
ABSTRACT
| FULL TEXT
The Effect of Inhibition of a Major Cell Signaling Pathway Following Trauma Hemorrhage on Hepatic Injury and Interleukin 6 Levels
Jarrar et al.
Arch Surg 2004;139:896-901.
ABSTRACT
| FULL TEXT
Salutary effects of androstenediol on cardiac function and splanchnic perfusion after trauma-hemorrhage
Shimizu et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004;287:R386-R390.
ABSTRACT
| FULL TEXT
|
