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.
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 DPNdecreased 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.
Authors: P J Kushner; D A Agard; G L Greene; T S Scanlan; A K Shiau; R M Uht; P Webb Journal: J Steroid Biochem Mol Biol Date: 2000-11-30 Impact factor: 4.292
Authors: John M Menezes; Chris Hierholzer; Simon C Watkins; Timothy R Billiar; Andrew B Peitzman; Brian G Harbrecht Journal: Shock Date: 2002-01 Impact factor: 3.454
Authors: Y Mizushima; P Wang; D Jarrar; W G Cioffi; K I Bland; I H Chaudry Journal: Am J Physiol Regul Integr Comp Physiol Date: 2000-02 Impact factor: 3.619
Authors: Hauke Rensing; Inge Bauer; Jian X Zhang; Markus Paxian; Benedikt H J Pannen; Yukihiro Yokoyama; Mark G Clemens; Michael Bauer Journal: Hepatology Date: 2002-12 Impact factor: 17.425
Authors: Hirohisa Harada; Kevin P Pavlick; Ian N Hines; David J Lefer; Jason M Hoffman; Sulaiman Bharwani; Robert E Wolf; Matthew B Grisham Journal: Proc Natl Acad Sci U S A Date: 2003-01-09 Impact factor: 11.205
Authors: Chi-Hsun Hsieh; Eike A Nickel; Jianguo Chen; Martin G Schwacha; Mashkoor A Choudhry; Kirby I Bland; Irshad H Chaudry Journal: J Immunol Date: 2009-04-01 Impact factor: 5.422
Authors: Ikenna C Nweze; Jason W Smith; Baochun Zhang; Carolyn M Klinge; Jaganathan Lakshmanan; Brian G Harbrecht Journal: J Trauma Acute Care Surg Date: 2012-08 Impact factor: 3.313