Sex differences in hepatic heme oxygenase expression and activity following trauma and hemorrhagic shock.
OBJECTIVE
Sex differentially influences heme oxygenase (HO) expression following trauma and hemorrhagic shock.


METHODS
Prospective controlled animal study.


METHODS
A university laboratory.


METHODS
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 x the shed blood volume). In another group of animals, tin protoporphyrin IX was used to block HO activity.


METHODS
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.
Toth
Balazs
B
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 35294-0019, USA.
Yokoyama
Yukihiro
Y
Kuebler
Joachim F
JF
Schwacha
Martin G
MG
Rue
Loring W
LW
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000704:Analysis of Variance; D000818:Animals; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D012771:Shock, Hemorrhagic / Q000201:enzymology*; D014947:Wounds and Injuries / Q000201:enzymology*
D006419:Heme Oxygenase (Decyclizing)