Mechanism of hepatoprotection in proestrus female rats following trauma-hemorrhage: heme oxygenase-1-derived normalization of hepatic inflammatory responses

• DOI: 10.1189/jlb.0508288
• Publication Date: 2009-02-25T04:08:17Z
• Authors: Shaolong Yang; Shunhua Hu; Jianguo Chen; Mashkoor A Choudhry; Loring W Rue; Kirby I Bland; Irshad H Chaudry
• Keywords: Hepatoprotection; Proinflammatory cytokine; Zinc protoporphyrin

Abstract Hepatic damage occurs in males and ovariectomized (OVX), not proestrus (PE), females following trauma-hemorrhage (T-H). The mechanism responsible for hepatoprotection remains unknown. We hypothesized protection PE is a result of enhanced heme oxygenase-1 (HO-1)-derived down-regulation liver inflammatory responses. OVX rats underwent T-H (midline laparotomy, 60% blood loss). received vehicle (Veh; saline), HO-1 inhibitor chromium mesoporphyrin IX chloride (CrMP; 2.5 mg/kg), zinc protoporphyrin (ZnPP; 25 or Akt/PI-3K Wortmannin (Wort; 1 mg/kg) 30 min prior to resuscitation sham operation i.p. Veh 17β-estradiol (E2; before hemorrhage. Rats were killed 2 h thereafter. Following T-H, left ventricular performance was maintained E2 but depressed CrMP-, ZnPP-, Wort-treated rats; evident rats, CrMP, ZnPP, Wort abrogated protection; HO-1, p38 MAPK, Akt/PI3K, Bcl-2 expression increased which by Wort, ICAM-1, caspase-3, phospho-IκB-α, NF-κB Wort-PE myeloperoxidase, DNA-binding activity, TNF-α, IL-6, plasma proinflammatory cytokines, cytokine-induced neutrophil chemoattractants estradiol levels hepatic estrogen receptor-α -β decreased unaltered Wort. Thus, modulates responses protects T-H.