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

Research output: Contribution to journalArticle

52 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number1 58-1
DOIs
StatePublished - Jul 2005
Externally publishedYes

Fingerprint

Heme Oxygenase (Decyclizing)
Estradiol
Heme Oxygenase-1
Up-Regulation
Hemorrhage
Wounds and Injuries
Resuscitation
Liver
Estrogens
Portal Pressure
Proestrus
Hemorrhagic Shock
Enzyme Inhibitors
Blood Volume
Reperfusion Injury
Alanine Transaminase
Heme
Serum Albumin
Cardiac Output
Laparotomy

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

Mechanism of salutary effects of estradiol on organ function after trauma-hemorrhage : Upregulation of heme oxygenase. / Szalay, László; Shimizu, Tomoharu; Schwacha, Martin G; Choudhry, Mashkoor A.; Rue, Loring W.; Bland, Kirby I.; Chaudry, Irshad H.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 289, No. 1 58-1, 07.2005.

Research output: Contribution to journalArticle

Szalay, László ; Shimizu, Tomoharu ; Schwacha, Martin G ; Choudhry, Mashkoor A. ; Rue, Loring W. ; Bland, Kirby I. ; Chaudry, Irshad H. / Mechanism of salutary effects of estradiol on organ function after trauma-hemorrhage : Upregulation of heme oxygenase. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 289, No. 1 58-1.
@article{1116dc99fc2847d0aa8bbe5770372506,
title = "Mechanism of salutary effects of estradiol on organ function after trauma-hemorrhage: Upregulation of heme oxygenase",
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.",
keywords = "Chromium mesoporphyrin, Heart, Heme oxygenase-1, Hemorrhagic shock, Liver",
author = "L{\'a}szl{\'o} Szalay and Tomoharu Shimizu and Schwacha, {Martin G} and Choudhry, {Mashkoor A.} and Rue, {Loring W.} and Bland, {Kirby I.} and Chaudry, {Irshad H.}",
year = "2005",
month = "7",
doi = "10.1152/ajpheart.01247.2004",
language = "English (US)",
volume = "289",
journal = "American Journal of Physiology - Renal Physiology",
issn = "0363-6127",
publisher = "American Physiological Society",
number = "1 58-1",

}

TY - JOUR

T1 - Mechanism of salutary effects of estradiol on organ function after trauma-hemorrhage

T2 - Upregulation of heme oxygenase

AU - Szalay, László

AU - Shimizu, Tomoharu

AU - Schwacha, Martin G

AU - Choudhry, Mashkoor A.

AU - Rue, Loring W.

AU - Bland, Kirby I.

AU - Chaudry, Irshad H.

PY - 2005/7

Y1 - 2005/7

N2 - 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.

AB - 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.

KW - Chromium mesoporphyrin

KW - Heart

KW - Heme oxygenase-1

KW - Hemorrhagic shock

KW - Liver

UR - http://www.scopus.com/inward/record.url?scp=21644480112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21644480112&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.01247.2004

DO - 10.1152/ajpheart.01247.2004

M3 - Article

C2 - 15734876

AN - SCOPUS:21644480112

VL - 289

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

IS - 1 58-1

ER -