Sex Differences in Hepatic Heme Oxygenase Expression and Activity Following Trauma and Hemorrhagic Shock

Balazs Toth, Yukihiro Yokoyama, Joachim F. Kuebler, Martin G Schwacha, Loring W. Rue, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Hypothesis: Sex differentially influences heme oxygenase (HO) expression following trauma and hemorrhagic shock. Design: Prospective controlled animal study. Setting: A university laboratory. Interventions: Female Sprague-Dawley rats in the proestrus stage of their estrus cycle and male rats underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma) and were bled to a mean arterial blood pressure of 35 mm Hg for approximately 90 minutes, after which they were resuscitated with Ringer lactate solution (4 × the shed blood volume). In another group of animals, tin protoporphyrin IX was used to block HO activity. Main Outcome Measures: Liver samples were collected for analysis of HO expression and activity, plasma samples were collected, and alanine transaminase levels were determined 5 hours after resuscitation. Portal pressure and bile production were measured in vivo 5 hours after resuscitation. Results: Trauma and hemorrhage induced a 2-fold increase in hepatic HO1 expression (the inducible form of HO) in proestrus females compared with males. Hepatic expression of HO2 (a constitutive isoform of HO) was unaffected by sex or trauma and hemorrhage. Blockade of HO in vivo with tin protoporphyrin IX abolished the sex differences caused by diverse HO1 expression. Treatment with tin protoporphyrin IX also elevated the portal pressure, decreased bile production, and increased alanine transaminase to similar levels in proestrus females and males following trauma and hemorrhage. Conclusions: Sex influences the hepatic expression of HO1 following trauma and hemorrhage. The enhanced induction of HO1 expression and activity in females after trauma and hemorrhage may attenuate hepatocellular dysfunction and injury by maintaining microcirculation via the increased production of carbon monoxide.

Original languageEnglish (US)
Pages (from-to)1375-1382
Number of pages8
JournalArchives of Surgery
Volume138
Issue number12
DOIs
StatePublished - Dec 2003
Externally publishedYes

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Heme Oxygenase (Decyclizing)
Hemorrhagic Shock
Sex Characteristics
Liver
Wounds and Injuries
Proestrus
Hemorrhage
Portal Pressure
Alanine Transaminase
Resuscitation
Bile
Arterial Pressure
Estrus
Carbon Monoxide
Microcirculation
Blood Volume
Laparotomy
Sprague Dawley Rats
Protein Isoforms
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Surgery

Cite this

Sex Differences in Hepatic Heme Oxygenase Expression and Activity Following Trauma and Hemorrhagic Shock. / Toth, Balazs; Yokoyama, Yukihiro; Kuebler, Joachim F.; Schwacha, Martin G; Rue, Loring W.; Bland, Kirby I.; Chaudry, Irshad H.

In: Archives of Surgery, Vol. 138, No. 12, 12.2003, p. 1375-1382.

Research output: Contribution to journalArticle

Toth, Balazs ; Yokoyama, Yukihiro ; Kuebler, Joachim F. ; Schwacha, Martin G ; Rue, Loring W. ; Bland, Kirby I. ; Chaudry, Irshad H. / Sex Differences in Hepatic Heme Oxygenase Expression and Activity Following Trauma and Hemorrhagic Shock. In: Archives of Surgery. 2003 ; Vol. 138, No. 12. pp. 1375-1382.
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AU - Kuebler, Joachim F.

AU - Schwacha, Martin G

AU - Rue, Loring W.

AU - Bland, Kirby I.

AU - Chaudry, Irshad H.

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N2 - Hypothesis: Sex differentially influences heme oxygenase (HO) expression following trauma and hemorrhagic shock. Design: Prospective controlled animal study. Setting: A university laboratory. Interventions: Female Sprague-Dawley rats in the proestrus stage of their estrus cycle and male rats underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma) and were bled to a mean arterial blood pressure of 35 mm Hg for approximately 90 minutes, after which they were resuscitated with Ringer lactate solution (4 × the shed blood volume). In another group of animals, tin protoporphyrin IX was used to block HO activity. Main Outcome Measures: Liver samples were collected for analysis of HO expression and activity, plasma samples were collected, and alanine transaminase levels were determined 5 hours after resuscitation. Portal pressure and bile production were measured in vivo 5 hours after resuscitation. Results: Trauma and hemorrhage induced a 2-fold increase in hepatic HO1 expression (the inducible form of HO) in proestrus females compared with males. Hepatic expression of HO2 (a constitutive isoform of HO) was unaffected by sex or trauma and hemorrhage. Blockade of HO in vivo with tin protoporphyrin IX abolished the sex differences caused by diverse HO1 expression. Treatment with tin protoporphyrin IX also elevated the portal pressure, decreased bile production, and increased alanine transaminase to similar levels in proestrus females and males following trauma and hemorrhage. Conclusions: Sex influences the hepatic expression of HO1 following trauma and hemorrhage. The enhanced induction of HO1 expression and activity in females after trauma and hemorrhage may attenuate hepatocellular dysfunction and injury by maintaining microcirculation via the increased production of carbon monoxide.

AB - Hypothesis: Sex differentially influences heme oxygenase (HO) expression following trauma and hemorrhagic shock. Design: Prospective controlled animal study. Setting: A university laboratory. Interventions: Female Sprague-Dawley rats in the proestrus stage of their estrus cycle and male rats underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma) and were bled to a mean arterial blood pressure of 35 mm Hg for approximately 90 minutes, after which they were resuscitated with Ringer lactate solution (4 × the shed blood volume). In another group of animals, tin protoporphyrin IX was used to block HO activity. Main Outcome Measures: Liver samples were collected for analysis of HO expression and activity, plasma samples were collected, and alanine transaminase levels were determined 5 hours after resuscitation. Portal pressure and bile production were measured in vivo 5 hours after resuscitation. Results: Trauma and hemorrhage induced a 2-fold increase in hepatic HO1 expression (the inducible form of HO) in proestrus females compared with males. Hepatic expression of HO2 (a constitutive isoform of HO) was unaffected by sex or trauma and hemorrhage. Blockade of HO in vivo with tin protoporphyrin IX abolished the sex differences caused by diverse HO1 expression. Treatment with tin protoporphyrin IX also elevated the portal pressure, decreased bile production, and increased alanine transaminase to similar levels in proestrus females and males following trauma and hemorrhage. Conclusions: Sex influences the hepatic expression of HO1 following trauma and hemorrhage. The enhanced induction of HO1 expression and activity in females after trauma and hemorrhage may attenuate hepatocellular dysfunction and injury by maintaining microcirculation via the increased production of carbon monoxide.

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