Tomoharu Shimizu, Huang-Ping Yu, Takao Suzuki, László Szalay, Ya-Ching Hsieh, Mashkoor A Choudhry, Kirby I Bland, Irshad H Chaudry
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Journal of hepatology 2007 JunThe 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. 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. 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. 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.
Tomoharu Shimizu, Huang-Ping Yu, Takao Suzuki, László Szalay, Ya-Ching Hsieh, Mashkoor A Choudhry, Kirby I Bland, Irshad H Chaudry. The role of estrogen receptor subtypes in ameliorating hepatic injury following trauma-hemorrhage. Journal of hepatology. 2007 Jun;46(6):1047-54
PMID: 17336418
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