Skip to main content

Advertisement

SpringerLink
Log in

The effect of estrogen on hepatic microcirculation after ischemia/reperfusion

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

Gender dimorphism in clinical manifestation of sepsis, hemorrhage, and trauma is still under investigation. Several experimental studies have indicated a protective effect of estrogen. Nonetheless, the effect of gender on hepatic ischemia/reperfusion remains controversially discussed, and the influence of estrogen is still unclear. In the present study, we investigated whether hepatic ischemia/reperfusion (I/R) injury is gender-dependent and if hepatic microvascular reperfusion injury can be prevented by estrogen.

Materials and methods

Eight female and eight male Sprague-Dawley rats were subjected to 90 min left lobar ischemia followed by 60 min reperfusion. Additional six males were pretreated with 17β-estradiol 24 h before I/R. Six female and six male rats served as nonischemic sham animals. By means of intravital microscopy, sinusoidal perfusion, leukocyte–endothelial cell interaction, and Kupffer cell activity were analyzed. Finally, arterial blood and liver tissue samples were taken for histomorphological analysis and liver enzyme determination.

Results

After hepatic ischemia/reperfusion, animals revealed a significant gender-specific impairment of hepatic microcirculation, whereas Kupffer cell depression, sinusoidal perfusion failure, leukocyte–endothelial cell interaction within post sinusoidal venules, and parenchymal liver cell damage were more pronounced in male animals. Pretreatment with estrogen caused a normalization of Kupffer cell dysfunction and an amelioration of sinusoidal perfusion failure and venular leukocyte–endothelial cell interaction. However, estrogen did not protect from manifestation of post ischemic parenchymal cell damage.

Conclusion

Hepatic ischemia and reperfusion generate a gender-specific occurrence of microvascular injury, which seems to be partially mediated by estrogen. However, additional factors may contribute to the initial post ischemic parenchymal cell damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Kahn D, Gavaler JS, Makowka L, van Thiel DH (1993) Gender of donor influences outcome after orthotopic liver transplantation in adults. Dig Dis Sci 38(8):1485–1488

    Article  PubMed  CAS  Google Scholar 

  2. Zeier M, Döhler B, Opelz G, Ritz E (2002) The effect of donor gender on graft survival. J Am Soc Nephrol 13:2570–2576

    Article  PubMed  Google Scholar 

  3. Ng IO, Ng M, Fan ST (1997) Better survival in women with resected hepatocellular carcinoma is not related to tumor proliferation or expression of hormone receptors. Am J Gastroenterol 92:1355–1358

    PubMed  CAS  Google Scholar 

  4. Lee CC, Chau GY, Lui WY, Tsay SH, King KL, Loong CC, Hshia CY, Wu CW (2000) Better post-resectional survival in female cirrhotic patients with hepatocellular carcinoma. Hepatogastroenterology 47:446–449

    PubMed  CAS  Google Scholar 

  5. Jain A, Reyes J, Kashyap R, Dodson SF, Demetris AJ, Ruppert K, Abu-Elmagd K, Marsh W, Madariaga J, Mazariegos G, Geller D, Bonham CA, Gayowski T, Cacciarelli T, Fontes P, Starzl TE, Fung JJ (2000) Long-term survival after liver transplantation in 4,000 consecutive patients at a single center. Ann Surg 232:490–500

    Article  PubMed  CAS  Google Scholar 

  6. Colantoni A, De Maria N, Caraceni P, Bernardi M, Van Thiel DH (1999) Gender influences cold preservation-reoxygenation injury in the liver. Transplant Proc 31(1–2):1052–1053

    Article  PubMed  CAS  Google Scholar 

  7. Gasbarrini A, Addolorato G, Di Campli C, Simoncini M, Montemagno S, Castagneto M, Padalino C, Pola P, Gasbarrini G (2001) Gender affects reperfusion injury in rat liver. Dig Dis Sci 46(6):1305–1312

    Article  PubMed  CAS  Google Scholar 

  8. Harada H, Pavlick KP, Hines IN, Hoffman JM, Bharwani S, Gray L, Wolf RE, Grisham MB (2001) Selected contribution: effects of gender on reduced-size liver ischemia and reperfusion injury. J Appl Physiol 91(6):2816–22

    PubMed  CAS  Google Scholar 

  9. Eckhoff DE, Bilbao G, Frenette L, Thompson JA, Contreras JL (2002) 17-Beta-estradiol protects the liver against warm ischemia/reperfusion injury and is associated with increased serum nitric oxide and decreased tumor necrosis factor-alpha. Surgery 132(2):302–309

    Article  PubMed  Google Scholar 

  10. Jarrar D, Wang P, Knoferl MW, Kuebler JF, Cioffi WG, Bland KI, Chaudry IH (2000) Insight into the mechanism by which estradiol improves organ functions after trauma-hemorrhage. Surgery 128(2):246–252

    Article  PubMed  CAS  Google Scholar 

  11. Kuebler JF, Jarrar D, Toth B, Bland KI, Rue LW 3rd, Wang P, Chaudry IH (2002) Estradiol administration improves splanchnic perfusion following trauma-hemorrhage and sepsis. Arch Surg 137(1):74–79

    Article  PubMed  CAS  Google Scholar 

  12. Yokoyama Y, Toth B, Kitchens WC, Schwacha MG, Rue LW 3rd, Bland KI, Chaudry IH (2004) Estradiol’s effect on portal response to endothelin-1 after trauma-hemorrhage. J Surg Res 121(1):25–30

    Article  PubMed  CAS  Google Scholar 

  13. Vollmar B, Glasz J, Leiderer R, Post S, Menger MD (1994) Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia–reperfusion. Am J Pathol 145(6):1421–1431

    PubMed  CAS  Google Scholar 

  14. Vollmar B, Menger MD, Glasz J, Leiderer R, Messmer K (1994) Impact of leukocyte–endothelial cell interaction in hepatic ischemia–reperfusion injury. Am J Physiol 267:G786–G793

    PubMed  CAS  Google Scholar 

  15. Vollmar B, Glasz J, Post S, Menger MD (1994) Depressed phagocytic activity of Kupffer cells after warm ischemia–reperfusion of the liver. J Hepatol 20:301–304

    Article  PubMed  CAS  Google Scholar 

  16. Majno G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146(1):3–15

    PubMed  CAS  Google Scholar 

  17. Levin S, Bucci TJ, Cohen SM, Fix AS, Hardisty JF, LeGrand EK, Maronpot RR, Trump BF (1999) The nomenclature of cell death: recommendations of an ad hoc Committee of the Society of Toxicologic Pathologists. Toxicol Pathol 27(4):484–490

    PubMed  CAS  Google Scholar 

  18. Yokoyama Y, Nimura Y, Nagino M, Bland KI, Chaudry IH (2005) Current understanding of gender dimorphism in hepatic pathophysiology. J Surg Res 128:147–156

    PubMed  CAS  Google Scholar 

  19. Lentsch AB, Kato A, Yoshidome H, McMasters KM, Edwards MJ (2000) Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury. Hepatology 32(2):169–173

    Article  PubMed  CAS  Google Scholar 

  20. Harada H, Bharwani S, Pavlick KP, Korach KS, Grisham MB (2004) Estrogen receptor-alpha, sexual dimorphism and reduced-size liver ischemia and reperfusion injury in mice. Pediatr Res 55(3):450–456

    Article  PubMed  CAS  Google Scholar 

  21. Lü P, Liu F, Wang CY, Chen DD, Yao Z, Tian Y, Zhang JH, Wu YH (2005) Gender differences in hepatic ischemic reperfusion injury in rats are associated with endothelial cell nitric oxide synthase-derived nitric oxide. World J Gastroenterol 11(22):3441–3445

    PubMed  Google Scholar 

  22. Jaeschke H, Farhood A (1991) Neutrophil and Kupffer cell-induced oxidant stress and ischemia–reperfusion injury in rat liver. Am J Physiol 260:G355–G362

    PubMed  CAS  Google Scholar 

  23. Menger MD, Richter S, Yamauchi J, Vollmar B (1999) Role of microcirculation in hepatic ischemia/reperfusion injury. Hepatogastroenterology 46(Suppl 2):1452–1457

    PubMed  Google Scholar 

  24. Yokoyama Y, Kuebler JF, Matsutani T, Schwacha MG, Bland KI, Chaudry IH (2003) Mechanism of the salutary effects of 17beta-estradiol following trauma-hemorrhage: direct downregulation of Kupffer cell proinflammatory cytokine production. Cytokine 21:91–97

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Trauma, Hand and Reconstructive Surgery, Saarland University Hospital, Kirrberger Straße, 66421, Homburg/Saar, Germany

    M. Burkhardt, P. Garcia & T. Pohlemann

  2. Institute for Clinical and Experimental Surgery, University of Saarland, 66421, Homburg/Saar, Germany

    J. E. Slotta & M. D. Menger

  3. Department of Orthopedic Surgery, Schleswig-Holstein University Hospital, 24105, Kiel, Germany

    A. Seekamp

Authors
  1. M. Burkhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. E. Slotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Seekamp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. D. Menger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. Pohlemann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Burkhardt.

Additional information

M. Burkhardt and J.E. Slotta equally contributed to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burkhardt, M., Slotta, J.E., Garcia, P. et al. The effect of estrogen on hepatic microcirculation after ischemia/reperfusion. Int J Colorectal Dis 23, 113–119 (2008). https://doi.org/10.1007/s00384-007-0360-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-007-0360-5

Keywords

Search

Navigation