Effects of gender on reduced-size liver ischemia and reperfusion injury

Hirohisa Harada, Kevin P. Pavlick, Ian N. Hines, Jason M. Hoffman, Sulaiman Bharwani, Laura Gray, Robert E. Wolf, Matthew B. Grisham

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74 Citations (Scopus)


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 17β-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, 17β-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.

Original languageEnglish
Pages (from-to)2816-2822
Number of pages7
JournalJournal of Applied Physiology
Issue number6
Publication statusPublished - 2001
Externally publishedYes


  • Estrogen
  • Inflammation
  • Nitric oxide
  • Ovariectomy
  • Reactive oxygen species

ASJC Scopus subject areas

  • General Medicine


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