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

Tóth, Balázs; Yokoyama, Yukihiro; Kuebler, Joachim F.; Schwacha, Martin G.; Rue, Loring W.; Bland, Kirby I.; Chaudry, Irshad H.

doi:10.1001/archsurg.138.12.1375

Cited by 45 publications

(57 citation statements)

References 52 publications

(98 reference statements)

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“…In this regard, estrogen has been shown to be protective under ischemic conditions (34). Interestingly, estrogen can modulate HSP induction (29) and recent findings from our laboratory suggest that the attenuated liver injury in proestrus females after trauma-hemorrhage is, in part, due to the upregulation of HSP32 by estradiol (36). Whereas Lu et al (17) reported the estrogen-induced HSP production after ischemia, other investigators have observed a similar effect of estrogen under physiologic conditions (29).…”

mentioning

confidence: 78%

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression

Szalay

Shimizu

Suzuki

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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-Although studies indicate that 17␤-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats (ϳ300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for ϳ90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17␤-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-␣, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-␣, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17␤-estradiol on organ functions after T-H. heme oxygenase-1; organ dysfunction; tumor necrosis factor-␣; estrogen; injury THE DELETERIOUS EFFECTS OF hemorrhagic shock and septic shock on organ functions are well established (12,34,41). Nonetheless, studies have also shown that upregulation of heat shock protein (HSP) under the same conditions has protective effects (18,19,35,38). HSPs, sometimes termed molecular chaperones, are highly conserved intracellular proteins that play an important role in the folding of the newly synthesized proteins and prevent the aggregation of denatured proteins (9). In addition, a particular HSP, HSP32, also known as heme oxygenase-1, appears to act as a potent vasodilator and antioxidant-producing agent in many organs against insults, such as ischemia and oxidative stress (22). HSP upregulation was first observed with hyperthermia, but other stresses, such as ischemia, free radicals, or proinflammatory cytokines can also induce their expression (24). Furthermore, HSP induction appears to play a critical role in the protection against the pathophysiological effects of low-flow states, since its induction results in protection, whereas their inhibition leads to exacerbation of the injury (...

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confidence: 78%

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression

Szalay

Shimizu

Suzuki

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In line with these findings, our results indicate a significant increase in HO-1 expression in diestrus, estrus, and metestrus phases of the reproductive cycle and in ovariectomized rats after trauma-hemorrhage compared with sham-operated rats. Studies have also indicated that the markedly increased HO-1 expression found in proestrus females improves liver function, and blockade of HO abolished these protective effects after trauma-hemorrhage (31). Thus the higher levels of HO-1 in proestrus females compared with the other trauma-hemorrhage groups were effective in protecting the host under these conditions.…”

Section: Discussionmentioning

confidence: 98%

Maintenance of lung myeloperoxidase activity in proestrus females after trauma-hemorrhage: upregulation of heme oxygenase-1

Yang²,

Hsieh³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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. Maintenance of lung myeloperoxidase activity in proestrus females after trauma-hemorrhage: upregulation of heme oxygenase-1. Am J Physiol Lung Cell Mol Physiol 291: L400 -L406, 2006. First published March 23, 2006 doi:10.1152/ajplung.00537.2005.-Previous studies showed that females in the proestrus stage of the reproductive cycle maintain organ functions after trauma-hemorrhage. However, it remains unknown whether the female reproductive cycle is an important variable in the regulation of lung injury after trauma-hemorrhage and, if so, whether the effect is mediated via upregulation of heme oxygenase (HO)-1. To examine this, female Sprague-Dawley rats during diestrus, proestrus, estrus, and metestrus phases of the reproductive cycle or 14 days after ovariectomy underwent soft tissue trauma and then hemorrhage (mean blood pressure 40 mmHg for 90 min followed by fluid resuscitation). At 2 h after trauma-hemorrhage or sham operation, lung myeloperoxidase (MPO) activity and intercellular adhesion molecule (ICAM)-1, cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, and HO-1 protein levels were measured. Plasma 17␤-estradiol concentration was also determined. The results indicated that trauma-hemorrhage increased lung MPO activity and ICAM-1, CINC-1, and CINC-3 levels in ovariectomized females. These parameters were found to be similar to sham-operated animals in proestrus female rats subjected to trauma-hemorrhage. Lung HO-1 protein level in proestrus females was increased significantly compared with female rats subjected to trauma-hemorrhage during diestrus, estrus, and metestrus phases of the reproductive cycle and ovariectomized rats. Furthermore, plasma 17␤-estradiol level was highest in proestrus females. Administration of the HO inhibitor chromium mesoporphyrin prevented the attenuation of shock-induced lung damage in proestrus females. Thus these findings suggest that the female reproductive cycle is an important variable in the regulation of lung injury following trauma-hemorrhage and that the protective effect in proestrus females is likely mediated via upregulation of HO-1. hemorrhagic shock; cytokine-induced neutrophil chemoattractant-1; cytokine-induced neutrophil chemoattractant-3; intercellular adhesion molecule-1

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“…The basis for this difference is unclear. One possible mechanism is the gender difference of HO expression (Toth et al 2003). Another possible mechanism is the effect of sex hormones on bilirubin excretion.…”

Section: Discussionmentioning

confidence: 99%

High Serum Bilirubin Is Associated with the Reduced Risk of Diabetes Mellitus and Diabetic Nephropathy

Han

Chae

et al. 2010

Tohoku J. Exp. Med.

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

Abstract: Hypothesis: Sex differentially influences heme oxygenase (HO) expression following trauma and hemorrhagic shock.

Cited by 45 publications

References 52 publications

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression

Maintenance of lung myeloperoxidase activity in proestrus females after trauma-hemorrhage: upregulation of heme oxygenase-1

High Serum Bilirubin Is Associated with the Reduced Risk of Diabetes Mellitus and Diabetic Nephropathy

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