Mechanism of salutary effects of estradiol on organ function after trauma-hemorrhage: Upregulation of heme oxygenase

László Szalay, Tomoharu Shimizu, Martin G. Schwacha, Mashkoor A. Choudhry, Loring W. Rue, Kirby I. Bland, Irshad H. Chaudry

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52 Scopus citations

Abstract

A growing body of evidence indicates that heme degradation products may counteract the deleterious consequences of hypoxia and/or ischemia-reperfusion injury. Because heme oxygenase (HO)-1 induction after adverse circulatory conditions is known to be protective, and because females in the proestrus cycle (with high estrogen) have better hepatic function and less hepatic damage than males after trauma-hemorrhage, we hypothesized that estrogen administration in males after trauma-hemorrhage will upregulate HO activity and protect the organs against dysfunction and injury. To test this hypothesis, male Sprague-Dawley rats underwent 5-cm laparotomy and hemorrhagic shock (35-40 mmHg for 93 ± 2 min), followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17β-Estradiol and/or the specific HO enzyme inhibitor chromium mesoporphyrin (CrMP) were administered at the end of resuscitation, and the animals were killed 24 h thereafter. Trauma-hemorrhage reduced cardiac output, myocardial contractility, and serum albumin levels. Portal pressure and serum alanine aminotransferase levels were markedly increased under those conditions. These parameters were significantly improved in the 17β-estradiol-treated rats. Estradiol treatment also induced increased HO-1 mRNA expression, HO-1 protein levels, and HO enzymatic activity in cardiac and hepatic tissue compared with vehicle-treated trauma-hemorrhage rats. Administration of the HO inhibitor CrMP prevented the estradiol-induced attenuation of shock-induced organ dysfunction and damage. Thus the salutary effects of estradiol administration on organ function after trauma-hemorrhage are mediated in part via upregulation of HO-1 expression and activity.

Original languageEnglish (US)
Pages (from-to)H92-H98
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number1 58-1
DOIs
StatePublished - Jul 1 2005
Externally publishedYes

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Keywords

  • Chromium mesoporphyrin
  • Heart
  • Heme oxygenase-1
  • Hemorrhagic shock
  • Liver

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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