title: Selected contribution: Effects of gender on reduced-size liver ischemia and reperfusion injury.
abstract: Hepatic resection with concomitant periods of ischemia and reperfusion (I/R) is a common occurrence in resectional surgery as well as reduced-size liver transplantation (e.g., split liver or living donor transplantation). However, the I/R induced by these types of surgical manipulations may impair liver regeneration, ultimately leading to liver failure. The objectives of the study were to develop a murine model of reduced-size liver I/R and assess the role of gender in this model of hepatocellular injury. We found that 100% of female mice survived the surgery indefinitely, whereas all male mice had greater initial liver injury and died within 5 days after surgery. The protective effect observed in females appeared to be due to ovarian 17beta-estradiol, as ovariectomy of females or administration of a selective estrogen antagonist to female mice resulted in enhanced liver injury and greater mortality following reduced-size liver I/R. Conversely, 17beta-estradiol-treated male mice exhibited less hepatocellular damage and survived indefinitely. Taken together, these data demonstrate an estrogen-mediated protective pathway(s) that limits or attenuates hepatocellular injury induced by reduced-size liver I/R.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: H
authors.initials: H
authors.lastname: Harada
authors.forename: K P
authors.initials: KP
authors.lastname: Pavlick
authors.forename: I N
authors.initials: IN
authors.lastname: Hines
authors.forename: J M
authors.initials: JM
authors.lastname: Hoffman
authors.forename: S
authors.initials: S
authors.lastname: Bharwani
authors.forename: L
authors.initials: L
authors.lastname: Gray
authors.forename: R E
authors.initials: RE
authors.lastname: Wolf
authors.forename: M B
authors.initials: MB
authors.lastname: Grisham
mesh_terms: D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D007511:Ischemia / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D015427:Reperfusion Injury / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D012727:Sex Characteristics; D016019:Survival Analysis
chemical_list: D004965:Estrogen Antagonists; D000077267:Fulvestrant; D004958:Estradiol