Skip to main content
SpringerLink
Log in

Liver Enzymes and Ultrastructure in Rabbit Haemorrhagic Disease (RHD)

  • Published:
Veterinary Research Communications Aims and scope Submit manuscript

Abstract

Rabbit haemorrhagic disease (RHD) is caused by a calicivirus infection that kills most adult rabbits 24–72 h after viral inoculation. Two liver enzymes (AST, aspartate aminotransferase, and ALT, alanine aminotransferase) were monitored in blood samples of calicivirus-infected rabbits during the short course of RHD. Values of AST were used to differentiate three stages of hepatocellular degeneration in RHD: mild (up to 20-fold increase in AST), moderate (150–200-fold elevation of AST) and severe (more than 1000-fold elevation in AST). Liver samples of rabbits from these three biochemical stages of hepatocellular degeneration of RHD were studied by transmission electron microscopy to define the fine structure of the hepatocytes. In the mild hepatocellular degeneration there was proliferation (microvesiculation) of the smooth endoplasmic reticulum and swelling of mitochondria into spheroid bodies with loss of cristae. In moderate hepatocellular degeneration, vacuolization of cytoplasm and mitochondrial damage continued to be present, and there was also formation of autophagic vesicles. In the severe hepatocellular degeneration of RHD, the altered mitochondria also showed loss of density of their matrix; rupture of cytoplasmic vacuoles led to the formation of large vesicles. Marked depletion of liver glycogen was also found in this late stage of RHD. These data offer a correlation between biochemical and cytological features of the liver during the hepatocellular degeneration of RHD.

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

Similar content being viewed by others

Abbreviations

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

RHD:

rabbit haemorrhagic disease

SER:

smooth endoplasmic reticulum

TEM:

transmission electron microscopy

References

  • Águas, A.P., 1982. The use of the osmium teroxide-potassium ferrocyanide as an extracellular marker in electron microscopy. Stain Technology, 57, 69–73

    PubMed  Google Scholar 

  • Águas, A.P., Grande N.R. and Carvalho, E., 1991. Inflammatory macrophages contain high amounts of intravesicular ferritin and are associated with pouches of connective tissue. American Journal of Anatomy, 189, 89–96

    Google Scholar 

  • Alonso, C., Oviedo, J.M., Martin-Alonso J.M., Diaz, E., Boga, J.A. and Parra, F., 1998. Programmed cell death in the pathogenesis of rabbit hemorrhagic disease. Archives of Virology, 143, 321–332

    Article  CAS  PubMed  Google Scholar 

  • Boobis, A.R., Fawthrop, D.J. and Davies, D.S., 1992. Oxford Textbook of Pathology, (Oxford University Press, Oxford)

    Google Scholar 

  • Capucci, L., Fallacara, F., Grazioli, S., Lavazza, A., Pacciarini, M.L. and Brocchi, E., 1998. A further step in the evolution of rabbit hemorrhagic disease virus: the appearance of the first consistent antigenic variant. Virus Research, 58, 115–126

    Article  CAS  PubMed  Google Scholar 

  • Chasey, D., 1997. Rabbit haemorrhagic disease: the new scourge of Oryctolagus cuniculus. Laboratory Animals, 31, 33–44

    CAS  PubMed  Google Scholar 

  • Ciminale, V., Zotti, L., D'Agostino, D.M., Ferro, T., Casareto, L., Franchini, G., Bernardi, P. and Chieco-Bianchi, L., 1999. Mitochondrial targeting of the p13II protein coded by the x-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I). Oncogene, 18, 4505–4514

    Article  CAS  PubMed  Google Scholar 

  • Coen, M., Lenz, E.M., Nicholson, J.K., Wilson, I.D., Pognan, F. and Lindon, J.C., 2003. An integrated metabonomic investigation of acetaminophen toxicity in the mouse using NMR spectroscopy. Chemical Research in Toxicology, 16, 295–303

    Article  CAS  PubMed  Google Scholar 

  • Cooke, B.D. and Fenner, F., 2002. Rabbit haemorrhagic disease and the biological control of wild Oryctolagus cuniculus, in Australia and New Zealand, Wildlife Research, 29, 689–706

    Google Scholar 

  • Cornelius, C.E., 1989. Clinical Biochemistry of Domestic Animals, (Academic Press, New York)

    Google Scholar 

  • D'Agostino, D.M., Zotti, L., Ferro, T., Franchini, G., Chieco-Bianchi, L. and Ciminale, V., 2000. The p13II protein of HTLV type 1: comparasion with mitochondrial proteins coded by other human viruses. AIDS Research and Human Retroviruses, 16, 1765–1770.

    Article  PubMed  Google Scholar 

  • Ferreira, P.G., Costa-e-Silva, A., Monteiro, E., Oliveira, M.J.R. and Aguas, A.P., 2004. Transient decrease in blood heterophils and sustained liver damage caused by calicivirus infection of young rabbits that are naturally resistant to rabbit haemorrhagic disease. Research in Veterinary Science, 76, 83–94

    Article  CAS  PubMed  Google Scholar 

  • Ferreira, P.G., Costa-e-Silva, A., Monteiro, E., and Águas, A.P., 2005. Leukocyte hepatocyte interaction in calicivirus infection: differences between rabbits that are resistant or susceptible to rabbit haemorrhagic disease (RHD). Veterinary Immunology and Immunopathology, 10, 217–221

    Google Scholar 

  • Gelmetti, D., Grieco, V., Rossi, C., Capucci, L. and Lavazza, A., 1998. Detection of rabbit haemorrhagic disease virus (RHDV) by in situ hybridisation with a digoxigenin labelled RNA probe. Journal of Virological Methods, 72, 219–226

    Article  CAS  PubMed  Google Scholar 

  • Jaeschke, H., Gores, G.J., Cederbaum, A.I., Hinson, J.A., Pessayre, D. and Lemasters, J.J., 2002. Mechanisms of hepatotoxicity. Toxicological Sciences, 65, 166–176

    Article  CAS  PubMed  Google Scholar 

  • Jones, T.C., Hunt, R.C. and King, N.W., 1997. Veterinary Pathology, (Williams & Wilkins, Baltimore)

    Google Scholar 

  • Jung, J.Y., Lee, B.J., Tai, J.H., Park, J.H. and Lee, Y.S., 2000. Apoptosis in rabbit haemorrhagic disease. Journal of Comparative Pathology, 123, 135–140

    Article  CAS  PubMed  Google Scholar 

  • Kanno, T., Fujita, H., Muranaka, S., Yano, H., Utsumi, T., Yoshioka, T., Inoue, M. and Utsumi, K., 2002. Mitochondrial swelling and cytochrome c release: sensitivity to cyclosporine A and calcium. Physiological Chemistry and Physics and Medical NMR, 34, 91–102

    CAS  PubMed  Google Scholar 

  • Kimura, T., Mitsui, I., Okada, Y., Furuya, T., Ochiai, K., Umemura, T. and Itakura, C., 2001. Distribution of rabbit haemorrhagic disease virus RNA in experimentally infected rabbits. Journal of Comparative Pathology, 124, 134–141

    Article  CAS  PubMed  Google Scholar 

  • Meyer, D.J., Coles, E.H. and Rich, L.J., 1992. Veterinary Laboratory Medicine: Interpretation and Diagnosis, (W.B. Saunders, Philadelphia)

    Google Scholar 

  • Mikami, O., Park, J.H., Kimura, T., Ochiai, K. and Itakura, C., 1999. Hepatic lesions in young rabbits experimentally infected with rabbit haemorrhagic disease virus. Research in Veterinary Science, 66, 237–242

    Article  CAS  PubMed  Google Scholar 

  • Nepomnyashchikh, L.M., Lushnikova, E.L. and Semenov, D.E., 2001. Ultrastructural changes in cardiomyocyte mitochondria during regenerative and plastic insufficiency of the myocardium. Bulletin of Experimental Biology and Medicine, 131, 181–185

    CAS  PubMed  Google Scholar 

  • Parra, F. and Prieto, M., 1990. Purification and characterization of a calicivirus as the causative agent of a lethal hemorrhagic disease in rabbits. Journal of Virology, 64, 4013–4015

    CAS  PubMed  Google Scholar 

  • Pessayre, D., Mansouri, A., Haouzi, D. and Fromenty, B., 1999. Hepatotoxicity due to mitochondrial dysfunction. Cell Biology and Toxicology, 15, 367–373

    Article  CAS  PubMed  Google Scholar 

  • Prieto, J.M., Fernandez, F., Alvarez, V., Espi, A., Garcia Marín, J.F., Alvarez, M., Martin, J.M. and Parra, F., 2000. Immunohistochemical localisation of rabbit haemorrhagic disease virus VP-60 antigen in early infection of young and adult rabbits. Research in Veterinary Science, 68, 181–187

    Article  CAS  PubMed  Google Scholar 

  • Rej, R., 1983. Immunochemical quantification of isoenzymes of aspartate aminotransferase and lactate dehydrogenase. Clinical Biochemistry, 16, 17–19

    Article  CAS  PubMed  Google Scholar 

  • Shien, J.H., Shien, H.K. and Lee, L.H., 2000. Experimental infections of rabbits with rabbit haemorrhagic disease virus monitored by polymerase chain reaction. Research in Veterinary Science, 68, 255–259

    Article  CAS  PubMed  Google Scholar 

  • Teifke, J.P., Reimann, I. and Schirrmeier, H., 2002. Subacute liver necrosis after experimental infection with rabbit haemorrhagic disease virus (RHDV). Journal of Comparative Pathology, 126, 231–234

    Article  CAS  PubMed  Google Scholar 

  • Ulrich, R.G., Bacon, J.A., Brass, E.P., Cramer, C.T., Petrella, D.K. and Sun, E.L., 2001. Metabolic, idiosyncratic toxicity of drugs: overview of the hepatic toxicity induced by the anxiolytic, panadiplon. Chemico-Biological Interactions, 134, 251–270

    Article  CAS  PubMed  Google Scholar 

  • Valicek, L., Smid, B. and Rodak, L., 1992. Immunoelectron microscopy of rabbit haemorrhagic disease virus using monoclonal antibodies. Acta Virologica, 36, 589–591

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, ICBAS (Abel Salazar Institute for Biomedical Sciences), UMIB (Unit for Multidisciplinary for Biomedical Research), University of Porto, Porto, Portugal

    P. G. Ferreira, A. Costa-e-Silva, E. Monteiro, M. J. R. Oliveira & A. P. Águas

  2. Department of Anatomy – ICBAS/UP, Largo Prof. Abel Salazar, 2, 4099-003, Porto, Portugal

    P. G. Ferreira

Authors
  1. P. G. Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Costa-e-Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Monteiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. J. R. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. P. Águas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. G. Ferreira.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferreira, P.G., Costa-e-Silva, A., Monteiro, E. et al. Liver Enzymes and Ultrastructure in Rabbit Haemorrhagic Disease (RHD). Vet Res Commun 30, 393–401 (2006). https://doi.org/10.1007/s11259-006-3297-1

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11259-006-3297-1

Keywords

Search

Navigation