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Aggravation of pathogenesis mediated by ochratoxin A in mice infected with Trypanosoma brucei rhodesiense

Published online by Cambridge University Press:  21 January 2009

J. K. KIBUGU*
Affiliation:
Kenya Agricultural Research Institute, Trypanosomiasis Research Centre, P. O. Box 362, Kikuyu, Kenya Kenyatta University, Department of Biochemistry and Biotechnology, P. O. Box 43844, Nairobi, Kenya
J. J. N. NGERANWA
Affiliation:
Kenyatta University, Department of Biochemistry and Biotechnology, P. O. Box 43844, Nairobi, Kenya
J. N. MAKUMI
Affiliation:
Kenyatta University, Department of Biochemistry and Biotechnology, P. O. Box 43844, Nairobi, Kenya
J. K. GATHUMBI
Affiliation:
University of Nairobi, Department of Veterinary Pathology, Microbiology and Parasitology, P. O. Box 29053, Nairobi, Kenya
J. M. KAGIRA
Affiliation:
Kenya Agricultural Research Institute, Trypanosomiasis Research Centre, P. O. Box 362, Kikuyu, Kenya
J. N. MWANGI
Affiliation:
Kenya Agricultural Research Institute, Social Economics and Biometrics Division, P. O. Box 00200-57811, Nairobi, Kenya
M. W. MUCHIRI
Affiliation:
Kenya Agricultural Research Institute, Trypanosomiasis Research Centre, P. O. Box 362, Kikuyu, Kenya
R. E. MDACHI
Affiliation:
Kenya Agricultural Research Institute, Trypanosomiasis Research Centre, P. O. Box 362, Kikuyu, Kenya
*
*Corresponding author: Kenya Agricultural Research Institute, Trypanosomiasis Research Centre, P. O. Box 362, Kikuyu, Kenya. E-mail: jkkibugu@yahoo.com

Summary

Mice fed 1·5 mg ochratoxin A (OTA) per kg body weight and infected with Trypanosoma brucei rhodesiense were compared with trypanosome-infected placebo-fed and uninfected OTA-fed controls. Uninfected OTA-fed mice showed fever, lethargy, facial and eyelid oedemas, mild hepatitis and nephritis, and high survival. Infected placebo-fed controls had mean pre-patent period (PPP) of 3·26 days, lethargy, dyspnoea, fever, facial and scrotal oedema, survival of 33–65 days, reduced red cell counts (RCC: 10·96–6·87×106 cells/μl of blood), packed cell volume (PCV: 43·19–26·36%), haemoglobin levels (Hb: 13·37–7·92 g/dL) and mean corpuscular volume (MCV) of 37·96–41·31 fL, hepatosplenomegaly, generalized oedemas, heart congestion, hepatitis and nephritis. Compared to infected placebo-fed controls, infected OTA-fed mice had significantly (P<0·05) shorter mean PPP (2·58 days), reduced survival (6–47 days), more pronounced fever and dyspnoea. The latter had significantly (P<0·05) reduced RCC (10·74–4·56×106 cells/μl of blood), PCV (43·90–20·78%), Hb (13·06–5·74 g/dL), increased MCV (39·10–43·97 fL), severe generalized oedemas, haemorrhages, congestion, hepatic haemosiderosis, hepatitis, nephritis, endocarditis, pericarditis and exclusively, splenic macrophage and giant cell hyperplasia, expanded red pulp and splenic erythrophagocytosis. It was concluded that OTA aggravated the pathogenesis of T. b. rhodesiense infection in mice, and should therefore be taken into consideration during trypanosomosis control programmes.

Type
Research Article
Copyright
Copyright © 2009 Cambridge University Press

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References

REFERENCES

Al-Anati, L. and Petzinger, E. (2006). Immunotoxicity of ochratoxin A. Journal of Veterinary Pharmacology and Therapeutics 29, 7990.CrossRefGoogle ScholarPubMed
Albassam, M. A., Yong, S. I., Bhatnagar, R., Sharma, A. K. and Prior, M. G. (1987). Histopathologic and electron microscopic studies on the acute toxicity of ochratoxin A in rats. Veterinary Pathology 24, 427435.CrossRefGoogle ScholarPubMed
Anderson, J. R. (1985). Muir's Textbook of Pathology, 12th Edn. Edward Arnold, London, New York, Melbourne, Auckland.Google Scholar
Anyanwu, E. C., Morad, M and Campbell, A. W. (2004). Metabolism of mycotoxins, intracellular functions of vitamin B12 and neurological manifestations in patients with chronic toxigenic mold exposures: A Review. The Scientific World Journal 4, 736745.CrossRefGoogle ScholarPubMed
Assaf, H., Azouri, H. and Pallardy, M. (2004). Ochratoxin A induces apoptosis in human lymphocytes through down regulation of Bcl-xL. Toxicological Sciences 79, 335344.CrossRefGoogle ScholarPubMed
Azziz-Baumgartner, E., Lindblade, K., Gieseker, K., Rogers, H. S., Kieszak, S., Njapau, H., Schleicher, R., McCoy, L. F., Misore, A., DeCock, K., Rubin, C., Slutsker, L. and the Aflatoxin Investigative Group (2005). Case-control study of an acute aflatoxicosis outbreak, Kenya, 2004. Environmental Health Perspectives 113, 17791783.CrossRefGoogle ScholarPubMed
Bain, B. J. and Bates, I. (2001). Basic haematological techniques. In Dacie and Lewis Practical Haematology, 9th Edn. (ed. Lewis, E. M., Bain, B. J. and Bates, I.), pp. 1946. Churchill Livingstone, London, UK.Google Scholar
Baker, F. J., Silverton, R. E. and Pallister, C. J. (2001). Introduction to Medical Laboratory Technology, 7th Edn. Oxford University Press, London, New York, New Delhi.Google Scholar
Balber, A. E. (1974). Trypanosoma brucei: Attenuation by corticosteroids of anaemia of infected mice. Experimental Parasitology 35, 209218.CrossRefGoogle ScholarPubMed
Ben-Rashed, M., Ingram, G. A. and Pentreath, V. W. (2003). Mast cells, histamine and the pathogenesis of intestinal damage in experimental Trypanosoma brucei brucei infections. Annals of Tropical Medicine and Parasitology 97, 803809.CrossRefGoogle ScholarPubMed
Bondy, G. S. and Pestka, J. J. (2000). Immunomodulation by fungal toxins. Journal of Toxicology and Environmental Health 3, 109143.Google ScholarPubMed
Budovsky, A., Prinsloo, I. and El-On, J. (2006). Pathological developments mediated by cyclophosphamide in rats infected with Trypanosoma lewesi. Parasitology International 55, 237242.CrossRefGoogle Scholar
Carlson, M. P. and Ensley, S. M. (2003). Understanding fungal (mold) toxins (mycotoxins). NebGuide published http:www.fda.gov/cvm/.Google Scholar
Cukrova, V., Longrova, E. and Akao, M. (1991). Effects of aflatoxin B1 on myelopoiesis in vivo. Toxicology 70, 203211.CrossRefGoogle Scholar
Drury, R. A. B. and Wallington, E. A. (1980). Carleton's Histological Technique, 5th Edn. Oxford University Press, Oxford New York Toronto.Google Scholar
Dwivedi, P. and Burns, R. B. (1984). Effects of ochratoxin A on immunoglobulin in broiler chicks. Research in Veterinary Science 36, 117121.CrossRefGoogle ScholarPubMed
El-Arab, A. M. E., Girgis, S. M., Hegazy, E. M. and El-Khalek, A. B. A. (2006). Effect of dietary honey on intestinal microflora and toxicity of mycotoxins in mice. BMC Complemetary and Alternative Medicine 6, 113.Google Scholar
Everitt, B. S. and Der, G. (1998). A Handbook of Statistical Analysis Using SAS. Boca Raton, London, New York, Washington D. C.Google Scholar
FAO/UNEP (1977). Recommended practices for the prevention of mycotoxins in food, feed and their products. Draft of a Document for the Joint FAO/WHO/UNEP Conference on Mycotoxins, Nairobi, 19–27 September, 1977.Google Scholar
Fink, E. and Schmidt, H. (1979). Meningoencephalitis in chronic Trypanosoma brucei rhodesiense infection of the white mouse. Tropenmedizin und Parasitologie 30, 206211.Google ScholarPubMed
Fink, E. and Schmidt, H. (1980). Preclinical testing of potential trypanocidal drugs in primates: preliminary investigation of an experimental diamidine in vervets. In Recent Developments in Medical Research in East Africa (ed. Njogu, A. R., Tukei, P.M and Roberts, J. M. D.), pp. 173182. KETRI/KEMRI, Nairobi, Kenya.Google Scholar
Gichuki, C. and Brun, R. (1999). Animal models of CNS (second-stage) sleeping sickness. In Handbook of Animal Models of Infection, (ed. Zak, O and Sande, M.) pp. 795800. Academic Press, London, UK.CrossRefGoogle Scholar
Gupta, M., Sasmal, D., Bandyopadhyay, S., Bagchi, G.Chatterjee, T. and Dey, S. (1983). Hematological changes produced in mice by ochratoxin A and citrinin. Toxicology 26, 5562.CrossRefGoogle ScholarPubMed
Halliwell, R. E. W. and Gorman, N. T. (1989). Anti-inflammatory drugs, immuno-suppressive agents and immuno-modulators. In Veterinary Clinical Immunology 9th Edn. (ed. Pedersen, D.), pp. 493507. W.B. Saunders Company: Philadelphia, PA, USA.Google Scholar
Hendrickse, R. G., Lamplugh, S. M. and Maegraith, B. G. (1986). Influence of aflatoxin on nutrition and malaria in mice. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, 846847.CrossRefGoogle ScholarPubMed
Herbert, W. J. and Lumsden, W. H. R. (1976). Trypanosoma brucei: a rapid “Matching” method for estimating the host's parasitaemia. Experimental Parasitology 40, 427431.CrossRefGoogle Scholar
JECFA, 47 (2001). Evaluation of certain mycotoxins. WHO Food Additives Series No. 47/FAO Food and Nutrition Paper 74, 2001 nos. 1011–1020 Inchem.Google Scholar
Kagira, J. M., Ngotho, M. and Thuita, J. (2007 a). Development of a rodent model for late stage rhodesian sleeping sickness. Journal of Protozoology Research 17, 4856.Google Scholar
Kagira, J. M., Thuita, J. K., Ngotho, J. M., Mdachi, R. E., Mwangangi, D. M. and Ndung'u, J. M. (2007 b). Haematology of experimental Trypanosoma brucei rhodesiense infection in Vervet Monkeys. African Journal of Health Sciences 13, 5965. Available at Bioline International 1989–2007, last up-dated on 23/02/07.Google Scholar
Kimathi, G. M. and Siboe, G. M. (1994). Maize flour contaminated with toxigenic fungi and mycotoxins. Proceedings of the 15th Annual African Health Science Congress, KEMRI HQ, Nairobi, 7–11 February, 1994. KETRI/KEMRI, Nairobi, Kenya.Google Scholar
Kumar, A., Jindal, N., Shukla, C. L., Pal, Y., Ledoux, D. R. and Rottinghaus, G. E. (2003). Effect of ochratoxin A on Escherichia coli-challenged broiler chicks. Avian Diseases 47, 415424.CrossRefGoogle ScholarPubMed
Lejon, V., Sindic, C. J. M., Van Antwerpen, M. P., Doua, F., Dje, N., Solano, P., Jamonneau, V. and Buscher, P. (2003). Human African trypanosomiasis: quantitative and qualitative assessment of intrathecal immune response. European Journal of Neurology 10, 711719.CrossRefGoogle ScholarPubMed
Maina, N., Ngotho, J. M., Njiru, Z. K., Karanja, W. M., Gem, C. O., Karanja, S. M., Kibugu, J. K. and Ndung'u, J. M. (2003). Efficacy of Trypan® (Diminazene Di-aceturate) in camels infected with Trypanosoma evansi. Journal of Camel Practice and Research 10, 5155.Google Scholar
Minakshi, D. (2005). Pathological techniques in diagnosis of animal, bird and fish disease. Current Science 89, 605.Google Scholar
Naessens, J., Kitani, H., Nakamura, Y., Yagi, Y., Sekikawa, K. and Iraqi, F. (2005). TNF-α mediates the development of anaemia in a murine Trypanosoma brucei rhodesiense infection, but not the anaemia associated with a murine Trypanosoma congolense infection. Clinical and Experimental Immunology 139, 405410.CrossRefGoogle Scholar
Njiru, Z. K., Olaho-Mukani, W., Khaemba, B. M., Ochieng, R. S. and Ndung'u, J. M. (2000). Haematological and serological changes during acute Trypanosoma evansi infection in dromedary camels (Camelus dromedarius). Journal of Camel Practice and Research 7, 113116.Google Scholar
Oswald, I. P., Bouhet, S., Marin, D. E., Pinton, P. and Taranu, I. (2005). Mycotoxin effects on the pig immune system. http://www.engormix.com.Google Scholar
Pier, A. C. and McLoughlin, M. E. (1985). Mycotoxic suppression of immunity. In Trichothecenes and other mycotoxins: Proceedings of the International Mycotoxin Symposium, Sydney, Australia, 1984 (ed. Lacey, J.), pp. 507519. John Wiley and Sons, New York, USA.Google Scholar
Sacks, D. L., Selkirk, M., Ogilvie, B. M. and Askonas, B. A. (1980). Intrinsic immunosuppression activity of different trypanosome strains varies with parasite virulence. Nature, London 283, 476478.CrossRefGoogle ScholarPubMed
Sandhu, B. S., Singh, B. and Brar, R. S. (1998). Haematological and biochemical studies in broiler chicks fed ochratoxin A and inoculated with inclusion body hepatitis virus, singly and in concurrence. Veterinary Research Communications 22, 335346.CrossRefGoogle ScholarPubMed
Scott, P. M. (1995). Natural toxins: subchapter 1 -Mycotoxins. In Official Methods of Analysis (ed. Cunniff, P.), pp. 153Health Protection Branch, Canada. AOAC International.Google Scholar
Smith, J. E. and Moss, M. O. (1985). Mycotoxins: Formation, Analysis and Significance. John Wiley and Sons, New York, USA.Google Scholar
Stephen, L. E. (1986). Trypanosomiasis: a Veterinary Perspective. 1st Edn. Pergamon Press, Oxford, New York, Beijing, Frankfurt Sao Paulo, Sydney, Tokyo, Toronto.Google Scholar
World Health Organization (2004). Trypanosomiasis. WHO Division of Control of Tropical Diseases. Internet Homepage updated 29 October, 2004. URL:http://www.med.sc.edu.85/trypanosomiasis.htm. World Health Organization, Geneva, Switzerland.Google Scholar
Williams, J. H., Phillips, T. D., Jolly, P. E., Stiles, J. K., Jolly, C. M. and Aggarwal, D. (2004). Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences and interventions. American Journal of Clinical Nutrition 80, 11061122.CrossRefGoogle ScholarPubMed
Young, R. H., Hendrickse, R. G., Maxwell, S. M. and Maegraith, B. G. (1988). Influence of aflatoxin on malarial infection in mice. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 559560.CrossRefGoogle ScholarPubMed