Digestive Diseases and Sciences

, Volume 46, Issue 6, pp 1305–1312 | Cite as

Gender Affects Reperfusion Injury in Rat Liver

  • Antonio Gasbarrini
  • Giovanni Addolorato
  • Cristiana Di Campli
  • Mara Simoncini
  • Salvatore Montemagno
  • Marco Castagneto
  • Cristiano Padalino
  • Paolo Pola
  • Giovanni Gasbarrini

Abstract

Sex mismatch is a well-known risk factor for chronic rejection of liver allografts, but the mechanisms involved remain unclear. Since experimental observations suggest that female liver is more sensitive to reperfusion injury than male liver, we assessed the influence of gender on oxidative stress. Livers from male and female rats were exposed to warm ischemia and reperfused by an oxygenated buffer. Chemiluminescence was continuously recorded. Reduced and oxidized glutathione and malondialdheyde lactic dehydrogenase values were also determined. Chemiluminescence increased during reperfusion in both groups, but was significantly greater in livers from female rats. Malondyaldheide and lactic dehydrogenase progressively increased in all animals, reaching significantly greater values in female rats. Livers from female rats showed an increase in all the parameters of oxidative stress compared to male animals. A greater susceptibility to reperfusion injury may be evoked as an alternative mechanism to explain the poor outcome of female organ after liver transplantation.

gender ischemia–reperfusion liver injury chemiluminescence 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Eghtesad B, Bronsther O, Irish W, Casavilla A, Abu-Elmagd K, Van Thiel DH, Tzakis A, Fung JJ, Starzl TE: Disease gravity and urgency of need as guidelines for liver allocation. Hepatology 20:56S–62S, 1994Google Scholar
  2. 2.
    Mor E, Klintmalm GB, Gonwa TA, Solomon H, Holman MJ, Gibbs JF, Watemberg I, Goldstein RM, Husberg BS: The use of marginal donors for liver transplantation: A retrospective study of 365 liver donors. Transplantation 53:383–386, 1992Google Scholar
  3. 3.
    Marino IR, Doyle HR, Aldrighetti L, Doria C, McMichael J, Gayowski T, Fung JJ, Tzakis AG, Starzl TE: Effect of donor age and sex on the outcome of liver transplantation. Hepatology 22:1754–1762, 1995Google Scholar
  4. 4.
    Brooks BK, Levy MF, Jennings LW, Abbasoglu O, Vodapally M, Goldstein RM, Husberg BS, Gonwa TA, Klintmalm GB: Influence of donor and recipient gender on the outcome of liver transplantation. Transplantation 62:1784–1787, 1996Google Scholar
  5. 5.
    Berrevoet F, Hesse UJ, de-Laere S, Jacobs B, Pattyn P, de-Hemptinne B: Impact of donor and recipient gender on liver transplantation. Transplantation Proc 29:3431–3432, 1997Google Scholar
  6. 6.
    Grande L, Rull A, Rimola A, Manyalic M, Cabrer C, Garcia-Valdecasas JC, Navasa M, Fuster J, Lacy AM, Gonzalez FX, Lopez-Boado MA, Visa J: Impact of donor gender on graft survival after liver transplantation. Transplantation Proc 29:3373–3374, 1997Google Scholar
  7. 7.
    Kahn D, Gavaler JS, Makowka L, Van Thiel DH: Gender of donor influences outcome after orthotopic liver transplantation in adults. Dig Dis Sci 38:1485–1488, 1993Google Scholar
  8. 8.
    Jaeschke H: Reactive oxygen and ischemia/reperfusion injury of the liver. Chem Biol Interact 79:115–136, 1991Google Scholar
  9. 9.
    Gonzalez-Flecha B, Cutrin JC, Boveris A: Time course and mechanism of oxidative stress and tissue damage in rat liver subjected to in vivo ischemia-reperfusion. J Clin Invest 91:456–464, 1993Google Scholar
  10. 10.
    Caraceni P, Gasbarrini A, Van Thiel DH, Borle AB: Oxygen free radical formation by rat hepatocytes during postanoxic reoxygenation: Scavenging effect of albumin. Am J Physiol 266:G451–G458, 1994Google Scholar
  11. 11.
    Caraceni P, Rosemblum ER, Van Thiel DH, Borle AB: Reoxygenation injury in isolated rat hepatocytes: Relation to oxygen free radicals and lipid peroxidation. Am J Physiol 66:G799–G806, 1994Google Scholar
  12. 12.
    Nunes FA, Kumar C, Chance B, Brass C: Chemiluminescent measurement of increased free radical formation after ischemia/ reperfusion. Dig Dis Sci 40:1045–1053, 1995Google Scholar
  13. 13.
    Gasbarrini A, Pasini P, Nardo B, De Notariis S, Simoncini M, Cavallari A, Roda E, Bernardi M, Roda A: Chemiluminescent real time imaging of post-ischemic oxygen free radicals formation in livers isolated from young and old rats. Free Radi. Biol Med 24:211–216, 1998Google Scholar
  14. 14.
    Buege JA, Aust SD: Microsomial lipid peroxidation. Methods Enzymol 52:302–310, 1978Google Scholar
  15. 15.
    Guarnieri C, Flamigni F, Rossoni Caldarera C: Glutathione peroxidase activity and release of glutathione from oxygendeficient perfused rat heart. Biochem Biophys Res Commun 89:678–684, 1979Google Scholar
  16. 16.
    Lowry HO, Rosebrough NJ, Farr AL, Randell RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951Google Scholar
  17. 17.
    Rembish SJ, Trush MA: Further evidence that lucigeninderived chemiluminescence monitors mitochondrial superoxide generation in rat alveolar macrophages. Free Radic Biol Med 17:117–126, 1994Google Scholar
  18. 18.
    Jaeschke H, Mitchell JR: Mitochondria and xanthine oxydase both generate reactive oxygen species in isolated perfused rat liver after hypoxic injury. Biochem Biophys Res Commun 160:140–147, 1989Google Scholar
  19. 19.
    Caldwell-Kenkel JC, Currin RT, Tanaka Y, Thurman RG, Lemasters JJ: Kupffer cell activation and endothelial cell dam-age after storage of rat livers: effect of reperfusion. Hepatology 13:83–95, 1991Google Scholar
  20. 20.
    Kukan M, Vajdava K, Horecky J, Nagyova A, Mehendale HM, Trnovec T: Effects of blockade of Kupffer cells by gadolinium chloride on hepatobiliary function in cold ischemia- reperfusion injury of rat liver. Hepatology 26:1250–1257, 1997Google Scholar
  21. 21.
    Norton R, Batey R, Dwyer T, McMahon S: Alcohol consumption and the risk of alcohol related cirrhosis in women. Br Med J 295:80–82, 1987Google Scholar
  22. 22.
    Guattery JM, Faloon WW: Effect of estradiol upon serum enzymes in primary liver cirrhosis. Hepatology 7:737–742, 1987Google Scholar
  23. 23.
    Becker U: The influence of ethanol and liver disease on sex hormones and hepatic estrogen receptors in women. Dan Med Bull 40:447–459, 1993.Google Scholar
  24. 24.
    Ikejima K, Enomoto N, Iimuro Y, Ikejima A, Fang D, Xu J, et al: Estrogen increase sensitivity of Kupffer cells to endotoxin. Am J Physiol 274:G669–G676, 1998Google Scholar
  25. 25.
    Neugarten J, Silbiger SR: The impact of gender on renal transplantation. Transplantation 58:1145–1152, 1994Google Scholar
  26. 26.
    Candinas D, Gunson BK, Nightingale P, Hubscher S, McMaster P, Neuberger JM: Sex mismatch as a risk factor for chronic rejection of liver allografts. Lancet 346:1117–1121, 1995Google Scholar
  27. 27.
    Jaeschke H, Farhood A: Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver. Am J Physiol 260:G355–G362, 1991Google Scholar
  28. 28.
    Rymsa B, Wang JF, De Groot H: O2 - release by activated Kupffer cells upon hypoxia-reoxygenation. Am J Physiol 260:G602–G607, 1991Google Scholar
  29. 29.
    Chao TC, Van Alten PJ, Walter RJ: Steroid sex hormones and macrophage function: modulation of reactive oxygen intermediates and nitrite release. Am J Reprod Immunol 32:43–52, 1994Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Antonio Gasbarrini
    • 1
  • Giovanni Addolorato
    • 2
  • Cristiana Di Campli
    • 2
  • Mara Simoncini
    • 2
  • Salvatore Montemagno
    • 3
  • Marco Castagneto
    • 3
  • Cristiano Padalino
    • 2
  • Paolo Pola
    • 1
  • Giovanni Gasbarrini
    • 2
  1. 1.Patologia MedicaCatholic University of RomeRomeItaly
  2. 2.Medicina InternaCatholic University of RomeRomeItaly
  3. 3.Chirurgia dei TrapiantiCatholic University of RomeRomeItaly

Personalised recommendations