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J Appl Physiol 91: 2816-2822, 2001;
8750-7587/01 $5.00
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Vol. 91, Issue 6, 2816-2822, December 2001

HIGHLIGHTED TOPICS
Genome and Hormones: Gender Differences in Physiology
Selected Contribution: Effects of gender on reduced-size liver ischemia and reperfusion injury

Hirohisa Harada1,*, Kevin P. Pavlick1,*, Ian N. Hines1, Jason M. Hoffman1, Sulaiman Bharwani2, Laura Gray1, Robert E. Wolf2, and Matthew B. Grisham1

1 Department of Molecular and Cellular Physiology and 2 Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130

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.

inflammation; estrogen; ovariectomy; nitric oxide; reactive oxygen species

* H. Harada and K. P. Pavlick contributed equally to the study and to the preparation of the manuscript.




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