The Role of Estrogen Receptor Subtypes in Ameliorating Hepatic Injury Following Trauma-hemorrhage

Overview

Journal J Hepatol

Publisher Elsevier

Specialty Gastroenterology

Date 2007 Mar 6

PMID 17336418

Citations 14

Authors

Tomoharu Shimizu

Huang-Ping Yu

Takao Suzuki

Laszlo Szalay

Ya-Ching Hsieh

Mashkoor A Choudhry

Kirby I Bland

Irshad H Chaudry

Affiliations

Soon will be listed here.

Abstract

Background/aims: The aim of this study was to determine which of the estrogen receptor (ER) subtypes plays a predominant role in ameliorating hepatic damage following trauma-hemorrhage.

Methods: Adult male rats were subjected to hemorrhagic shock (40 mmHg for 90 min) and resuscitation. ER-alpha agonist (PPT) or ER-beta agonist (DPN) was administered during resuscitation; rats were sacrificed 24h thereafter.

Results: PPT or DPN decreased elevated plasma alpha-glutathione S-transferase levels; however, PPT was more effective. PPT or DPN increased hepatic heat shock protein 32 (Hsp32) mRNA/protein expressions above levels observed after trauma-hemorrhage. PPT reduced hepatic NF-kappaB and AP-1 activity and iNOS expression. Although DPN reduced hepatic NF-kappaB activity, AP-1 activity remained higher than in shams; hepatic iNOS induction remained elevated. PPT/DPN reduced nitrate/nitrite production and iNOS mRNA in Kupffer cells following trauma-hemorrhage; however, these levels in DPN-treated animals remained higher than sham.

Conclusions: Although both PPT and DPN decreased hepatic injury following trauma-hemorrhage, ER-alpha agonist PPT appears to be more effective in downregulating NF-kappaB and AP-1 activity, and iNOS induction. Thus, ER-alpha appears to play a predominant role in mediating the salutary effects of E2 in ameliorating hepatic damage following trauma-hemorrhage.

Citing Articles

Spontaneous idiopathic liver hemorrhage: a systematic review of a rare entity.

Giannone F, Cinelli L, Bellissard A, Cherkaoui Z, Felli E, Saviano A Eur J Trauma Emerg Surg. 2024; 50(6):2765-2774.

PMID: 38502311 DOI: 10.1007/s00068-024-02500-3.

Gender differences in trauma, shock and sepsis.

Bosch F, Angele M, Chaudry I Mil Med Res. 2018; 5(1):35.

PMID: 30360757 PMC: 6203206. DOI: 10.1186/s40779-018-0182-5.

Sexual dimorphism in bacterial infections.

Vazquez-Martinez E, Garcia-Gomez E, Camacho-Arroyo I, Gonzalez-Pedrajo B Biol Sex Differ. 2018; 9(1):27.

PMID: 29925409 PMC: 6011518. DOI: 10.1186/s13293-018-0187-5.

Differential Relevance of NF-κB and JNK in the Pathophysiology of Hemorrhage/Resususcitation-Induced Liver Injury after Chronic Ethanol Feeding.

Relja B, Weber R, Maraslioglu M, Wagner N, Borsello T, Jobin C PLoS One. 2015; 10(9):e0137875.

PMID: 26367181 PMC: 4569329. DOI: 10.1371/journal.pone.0137875.

Anti-Inflammatory and Organ-Protective Effects of Resveratrol in Trauma-Hemorrhagic Injury.

Liu F, Tsai Y, Tsai H, Yu H Mediators Inflamm. 2015; 2015:643763.

PMID: 26273141 PMC: 4529946. DOI: 10.1155/2015/643763.

References

Menezes J, Hierholzer C, Watkins S, Billiar T, Peitzman A, Harbrecht B . The modulation of hepatic injury and heat shock expression by inhibition of inducible nitric oxide synthase after hemorrhagic shock. Shock. 2002; 17(1):13-8. DOI: 10.1097/00024382-200201000-00003. View

Yu H, Shimizu T, Hsieh Y, Suzuki T, Choudhry M, Schwacha M . Tissue-specific expression of estrogen receptors and their role in the regulation of neutrophil infiltration in various organs following trauma-hemorrhage. J Leukoc Biol. 2006; 79(5):963-70. DOI: 10.1189/jlb.1005596. View

Rensing H, Bauer I, Zhang J, Paxian M, Pannen B, Yokoyama Y . Endothelin-1 and heme oxygenase-1 as modulators of sinusoidal tone in the stress-exposed rat liver. Hepatology. 2002; 36(6):1453-65. DOI: 10.1053/jhep.2002.36934. View

Harada H, Pavlick K, Hines I, Lefer D, Hoffman J, Bharwani S . Sexual dimorphism in reduced-size liver ischemia and reperfusion injury in mice: role of endothelial cell nitric oxide synthase. Proc Natl Acad Sci U S A. 2003; 100(2):739-44. PMC: 141066. DOI: 10.1073/pnas.0235680100. View

Zingarelli B, Sheehan M, Wong H . Nuclear factor-kappaB as a therapeutic target in critical care medicine. Crit Care Med. 2003; 31(1 Suppl):S105-11. DOI: 10.1097/00003246-200301001-00015. View

Jarrar D, Chaudry I, Wang P . Organ dysfunction following hemorrhage and sepsis: mechanisms and therapeutic approaches (Review). Int J Mol Med. 1999; 4(6):575-83. DOI: 10.3892/ijmm.4.6.575. View

Mizushima Y, Wang P, Jarrar D, Cioffi W, Bland K, Chaudry I . Preinduction of heat shock proteins protects cardiac and hepatic functions following trauma and hemorrhage. Am J Physiol Regul Integr Comp Physiol. 2000; 278(2):R352-9. DOI: 10.1152/ajpregu.2000.278.2.R352. View

Mizushima Y, Wang P, Jarrar D, Cioffi W, Bland K, Chaudry I . Estradiol administration after trauma-hemorrhage improves cardiovascular and hepatocellular functions in male animals. Ann Surg. 2000; 232(5):673-9. PMC: 1421221. DOI: 10.1097/00000658-200011000-00009. View

Kushner P, Agard D, Greene G, Scanlan T, Shiau A, Uht R . Estrogen receptor pathways to AP-1. J Steroid Biochem Mol Biol. 2001; 74(5):311-7. DOI: 10.1016/s0960-0760(00)00108-4. View

10.

Harbrecht B, Doyle H, Clancy K, Townsend R, Billiar T, Peitzman A . The impact of liver dysfunction on outcome in patients with multiple injuries. Am Surg. 2001; 67(2):122-6. View

11.

Nuedling S, Karas R, Mendelsohn M, Katzenellenbogen J, Katzenellenbogen B, Meyer R . Activation of estrogen receptor beta is a prerequisite for estrogen-dependent upregulation of nitric oxide synthases in neonatal rat cardiac myocytes. FEBS Lett. 2001; 502(3):103-8. DOI: 10.1016/s0014-5793(01)02675-8. View

12.

Tamion F, Richard V, Bonmarchand G, Leroy J, Lebreton J, Thuillez C . Induction of heme-oxygenase-1 prevents the systemic responses to hemorrhagic shock. Am J Respir Crit Care Med. 2001; 164(10 Pt 1):1933-8. DOI: 10.1164/ajrccm.164.10.2010074. View

13.

You H, Kim J, Jeong H . 17 beta-estradiol increases inducible nitric oxide synthase expression in macrophages. Biochem Biophys Res Commun. 2003; 303(4):1129-34. DOI: 10.1016/s0006-291x(03)00477-7. View

14.

Chaudry I, Samy T, Schwacha M, Wang P, Rue 3rd L, Bland K . Endocrine targets in experimental shock. J Trauma. 2003; 54(5 Suppl):S118-25. DOI: 10.1097/01.TA.0000064511.14322.F1. View

15.

Voss M, Stallone J, Li M, Cornelussen R, Knuefermann P, Knowlton A . Gender differences in the expression of heat shock proteins: the effect of estrogen. Am J Physiol Heart Circ Physiol. 2003; 285(2):H687-92. DOI: 10.1152/ajpheart.01000.2002. View

16.

Chen T, Zamora R, Zuckerbraun B, Billiar T . Role of nitric oxide in liver injury. Curr Mol Med. 2003; 3(6):519-26. DOI: 10.2174/1566524033479582. View

17.

Yokoyama Y, Toth B, Kitchens W, Schwacha M, Bland K, Chaudry I . Role of thromboxane in producing portal hypertension following trauma-hemorrhage. Am J Physiol Gastrointest Liver Physiol. 2003; 285(6):G1293-9. DOI: 10.1152/ajpgi.00268.2003. View

18.

Toth B, Yokoyama Y, Kuebler J, Schwacha M, Rue 3rd L, Bland K . Sex differences in hepatic heme oxygenase expression and activity following trauma and hemorrhagic shock. Arch Surg. 2003; 138(12):1375-82. DOI: 10.1001/archsurg.138.12.1375. View

19.

Harada H, Bharwani S, Pavlick K, Korach K, Grisham M . Estrogen receptor-alpha, sexual dimorphism and reduced-size liver ischemia and reperfusion injury in mice. Pediatr Res. 2004; 55(3):450-6. DOI: 10.1203/01.PDR.0000110524.88784.DD. View

20.

Matthews J, Gustafsson J . Estrogen signaling: a subtle balance between ER alpha and ER beta. Mol Interv. 2004; 3(5):281-92. DOI: 10.1124/mi.3.5.281. View