Krassimira UZUNOVA, Rumen Georgiev BINEV, Lazarin LAZAROV, Tsanko HRISTOV, Nely GROSEVA, Ivan VALCHEV

Morphological ınvestigations of experimental acute ıntoxication with the anticoagulant rodenticide bromadiolone in pheasants

Sülünlerde antikoagülan rodentisit bromadiolone kullanılarak geliştirilen deneysel akut intoksikasyondan sonra değişimleri gözlemlemek amacıyla morfolojik incelemeler yapılmıştır. Çalışmada 8 grup sülün artan dozlarda incelemeye alındı: 5 mg/kg (Grup 1), 10 mg/kg (Grup 2), 20 mg/kg (Grup 3), 30 mg/kg (Grup 4), 40 mg/kg (Grup 5), 50 mg/kg (Grup 6), 60 mg/kg (Grup 7) ve 70 mg/kg (Grup 8). Birinci ve 5. gruplar arasındaki kuş gruplarının hepsi intoksikasyondan hayatta kalırken; 6., 7. ve 8. grupların öldüğü saptanmıştır. İntoksikasyon sırasında, iştahsızlık, hızlı solunum ve solunum güçlüğü, bitkinlik, gagadan sulu kan geldiği gözlenmiştir. Deney sonucunda (20 gün) ötenazi yapılarak nekropsisi yapılan hayatta kalan sülünlerin ve ölen sülünlerin nekropsilerinde dalak, akciğer ve böbreklerde değişiklikler saptandı. Dalakta şiddetli hiperemi ve monositik-makrofaj sisteminin aktivasyonu sonucu diffuz vakuoler ya da granüler parenkimal distrofi, intra ve inter lobuler hemorajiler, perivasküler mononükleer proliferasyonlar ve safra kanalı hiperplazisi görülmüştür. Akciğerlerde konjestif hiperemi, interstitiyum, bronş ve parabronşların mukoz membranlarında ödem, bronşiollerde bulunan epitel hücrelerde deskuamasyon ve parenkimal hemorajiler görülmüştür. Böbrek parenkiminde, konjestif hiperemi ve hemorajiler görülmüş, epitelyal tubuler hücrelerinde değişen derecelerde karyolizis ve karyopiknozis alanları, hücresel deskuamasyon ve parçalanma ve nekroz odakları görülmüştür. Parenkimal organlarda gözlenen tüm değişiklikler doza bağlı olarak değişmekle birlikte, rodentisitin yüksek dozda uygulandığı sülünlerde değişimler daha belirgin olarak seyretmiştir.

Sülünlerde antikoagülan rodentisit bromadiolone ile oluşturulan deneysel akut intoksikasyonun morfolojik incelenmesi

Morphological investigations were performed to observe the changes after experimental acute intoxication with the anticoagulant rodenticide bromadiolone in pheasants. The study was performed with 8 groups of pheasants treated with increasing doses of the tested preparation: 5 mg/kg (group I), 10 mg/kg (group II), 20 mg/kg (group III), 30 mg/kg (group IV), 40 mg/kg (group V), 50 mg/kg (group VI), 60 mg/kg (group VII) and 70 mg/kg (group VIII). All birds from groups I to V have survived the intoxication whereas those from groups VI, VII and VIII have died. During the intoxication, inappetence, accelerated and difficult breathing, adynamia, watery blood discharge from the beak were observed. All pheasants with fatal outcome and the survivors, which were euthanized after the experiment (day 20) were necropsied and gross changes in the liver, the lungs and kidneys were described. Liver alterations varied from strong hyperaemia and activation of the monocytic-macrophageal system to diffuse vacuolar or granular parenchymal dystrophy, as well as necrobiotic to necrotic changes, intra- and inter-lobular haemorrhages, perivascular mononuclear proliferations and bile duct hyperplasia. Lungs exhibited congestive hyperaemia, oedema in the interstitium and the mucous coats of bronchi and parabronchi, desquamation of epithelial cells in bronchioles and lung parenchymal haemorrhages. In the kidney parenchyma, congestive hyperaemia and haemorrhages were seen, varying within a broad range from karyolysis and karyopyknosis in epithelial tubular cells to cellular desquamation and disintegration and necrosis. All observed changes in parenchymal organs were dose-related, being more pronounced in pheasants treated with higher doses of the tested rodenticide.

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Albert, C.A., Mineau, L.K., Trudeau, S., Eliott, J.E., 2009. Anticoagulant rodenticides in three owl species from western Canada, 1988-2003. Archives of Environmental Contamination and Toxicology 14, 451-459.
Bachmann, K.A., Sullivan, T.J., 1983. Dispositional and pharmacodynamic characteristics of brodifacoum in warfarin-sensitive rats. Pharmacology 27 (5), 281-288.
Bailey, C., Fisher, P., Eason, C.T., 2005. Assessing anticoagulant resistence in rat and coagulation effects using small-volume blood samples. Science for Conservation 249, 1-22.
Beauchamp, C., Enache, I., Haskour, A., Martin, L., 2008. Acute interstitial nephritis of fluindione: about three cases. Néphrologie and Thérapeutique 4 (5), 273-282.
Binev, R., Petkov, P., Rusenov, A., 2005. Intoxication with anticoagulant rodenticide bromadiolone in a dog – a case report. Veterinarski Arhiv 75 (3), 273-282.
Brodsky, S.V., Satoskar, A., Chen, J., Nadasdy, G., Eagen, J.W., Hamirani, M., Hebert, L., Calomeni, E., Nadasky, T., 2009. Acute kidney injury during warfarin therapy associated with obstructive tubular red blood cell casts: a report of 9 cases. American Journal of Kidney Diseases 54 (6), 1121-1126.
Del Piero, F., Poppenga, R.H., 2006. Chlorophacinone exposure causing an epizootic of acute fatal hemorrhage in lambs. Journal of Veterinary Diagnostic Investigation 18 (5), 483-485.
Dorman, D.S., Simon, J., Harlin, K.A., Buck, W.B., 1990. Diagnosis of bromethalin toxicosis in the dog. Journal of Veterinary Diagnostic Investigation 2 (2), 123–128.
DuVall, M., Murphy, M., Ray, A., Reagor, J., 1989. Case studies on second-generation anticoagulant rodenticide toxicities in nontarget species. Journal of Veterinary Diagnostic Investigation 1, 66-68.
Eason, C.T., Murphy, E.C., Wright, G.R., Spurr, E.B., 2002. Assessment of risks of brodifacoum to non-target birds and mammals in New Zealand. Ecotoxicology 11 (1), 35-48.
Evans, J.G., Appleby, E.C., Lake, B.G., Conning, D.M., 1989. Studies on the induction of cholangiofibrosis by coumarin in the rat. Toxicology 55 (1-2), 207-224.
Fry, M.M., Forman, M.A., 2004. 5-fluorouracil toxicity with severe bone marrow suppression in a dog. Veterinary and Human Toxicology 46 (4), 178-180.
Godfrey, M.R., 1985. Non-target and secondary poisoning hazards of "second generation" anticoagulants. Acta Zoologica Fennica 173, 209-212.
Howald, G.R., 1997. The risk of non-taget species poisoning from Bradifacoum used to eradicate rats from langara island Britsh Columbia Canada. Ph.D Thesis department of animal science. University of British Columbia. Vancouver, British Columbia.
Huckle, K.R., Hutson, D.H., Warburton, P.A., 1988. Elimination and accumulation of the rodenticide flocoumafen in rats following repeated oral administration. Xenobiotica 18, 1465-1479.
Huckle, K.R., Hutson, D.H., Logan, C.J., Morrison, B.J., Warburton, P.A., 1989. The fate of the rodenticide flocoumafen in the rat: Retention and elimination of a single oral dose. Pesticide Science 25, 297-312.
Jack, K.R., Kho, K., Thomas, N.W., Fry, J.R., 1996. Further studies on the lobar heterogeneity in response to coumarin-mediated hepatotoxicity. International Journal of Experimental Pathology 77 (2), 79-82.
Jahad, M.Y., Saddiiq, A.A., 2010. Studies the effected microbiological biochemical analysis and histological exanamination of pendant coumarin thiocarboxydrazone and its cobalt (II) complex in rats. Global Journal of Molecular Science 5 (1), 18-29.
James, S.B., Raphael, B.L., Cook, R.A., 1998. Brodifacoum toxicity and treatment in a whitewinged wood duck (Cairina scutulata). Journal Zoo and Wildlife Medicine 29 (3), 324-327.
Jeanted, A.Y., Trucher, M., Naulleau, G., Martoja, R., 1991. Effects of bromadiolone on some organs and tissues (liver, kidney, spleen, blood) of coypu (Myocastor coypus). CR. Academic Science III 312 (4), 49-56.
Kapoor, K.G., Bekali-Saab, T., 2008. Warfarininduced allergic interstitial nephritis and leucocytoclastic vasculitis. Journal of Internal Medicine 38 (4), 281-283.
Karanth, S., Nayyar, V., 2003. Rodenticide-induced Hepatotoxicity. Journal of Association of Physicians India 51, 816-817.
Kohn, B., Weingart, C., Giger, U., 2003. Haemorrhage in seven cats with suspected anticoagulant rodenticide intoxication. Journal of Feline Medicine and Surgery 5, 295-304.
Lake, B.G., Evans, J.G., 1993. Effect of pretreatment with some mixed-function oxidase enzyme inducers on the acute hepatotoxicity of coumarin in the rat. Food and Chemical Toxicology 31 (12), 963-970.
Lake, B.G., Grasso, P., 1996. Comparison of the hepatotoxicity of coumarin in the rat, mouse, and Syrian hamster: a dose and time response study. Fundamental and Applied Toxicology 34 (1), 105-117.
Massey, J.G., Valutis, L., Marzluff, J., Powers, L.V., 1997. The anticoagulant diphacinone effects of crow protrombin time. Proceedings effect of the annual conference of the association of Avian Veterinarians. Bedfort Texas pp. 97-98.
Mount, M., 1988. Diagnosis and therapy of anticoagulant rodenticide intoxicants. Veterinary Clinics North America Small Animal Practice 18, 115-129.
Munger, L.L., Su, J.J., Barnes, H.J., 1993. Coumafuril (fumarin) toxicity in chicks. Avian Diseases 37 (2), 622-624.
Murray, M., Tseng, F., 2008. Diagnosis and treatment of secondary anticoagulant rodenticide toxicosis in a red-tailed hawk (Buteo janaicosis). Journal of Animal Medicine and Surgery 22, 41-48.
Nikolov, Y., Binev, R., 2008. Texbook of Clinical Veterinary Toxicology. Kontrast Press, Stara Zagora.
Olmos, V., López, C.M., 2007. Brodifacoum poisoning with toxicokinetic data. Clinical Toxicology 45 (5), 487-489.
Palmer, R.B., Alakija, P., de Baca, J.E., Nolte, K.B., 1999. Fatal brodifacoum rodenticide poisoning: autopsy and toxicologic findings. Journal of Forensic Sciences 44, 851-855.
Petrus, D.J., Henik, R.A., 1999. Pericardial effusion and cardiac tamponade secondary to brodifacoum toxicosis in a dog. Journal of the American Veterinary Medicine Association 215 (5), 647-648.
Petterino, C., Paolo, B., 2001. Toxicology of various anticoagulant rodenticides in animals. Veterinary and Human. Toxicology 43, 353-360.
Rattner, B.A., Horak, K.F., Warner, S.E., Day, D.D., Meteyer, C.U., Volker, S.F., Eisemann, J.D., Johnston, J.J., 2011. Acute toxicity, histopathology, and coagulopathy in American kestrels (Falco sparverius) following administration of the rodenticide diphacinone. Environmental Toxicology and Chemistry 30 (5), 1213-1222.
Remkova, A., Milatova, E., Fuchsbergerova, M., 2010. A severe renal bleeding as a complication of coumarin therapy in Behcet's disease. Blood Coagulation and Fibrinolisis 21 (5), 487-490.
Revathi, K., Yogananda, M., 2006. Effect of bromadiolone on haematology, liver and kidney in Mus musculus. Journal of Environmental Biology 27 (1), 135-140.
Sheafor, S.E., Couto, C.G., 1999. Anticoagulant rodenticide toxicity in 21 dogs. Journal of the American Animal Hospital Association 35 (1), 38-46.
Sherley, M., 2004. The traditional categories of fluoroacetate poisoning signs and symptoms belie substantial underlying similarities. Toxicology Letters 151, 399-406.
Spurr, E.B., 1993. Feeding by captive rare birds on baits used in poisoning operations for control of brushtail possums. New Zealand Journal of Ecology 17, 13-18.
Stone, W.B., Okoniewski, J.C., Stedelin, J.R., 1999. Poisoning of wildlife with anticoagulant rodenticides in New York. Jornal Wildlife Diseases 35 (2), 187-193.
Тоdorov, Т., 2006. Intoxications with anticoagulat rodenticides in dogs – clinical challenges. Veterinarna Sbirka 9-10, 13-16.
Valchev, I., Binev, R., Yordanova, V., Nikolov, Y., 2008. Anticoagulant rodenticide intoxication in animals. A Review. Turkish Journal of Veterinary and Animal Sciences 32, 237-243.
Valchev, I., Lazarov, L., Hristov, T., Groseva, N., Binev, R., Nikolov, Y., 2009a. Investigation on clinical signs and some haematological parameters in experimental subchronic intoxication with anticoagulant rodenticide bromadialone in dogs. Scientific Woks of the Rousse University 48 (1.1), 44-49.
Valchev, I., Lazarov, L., Hristov, T., Binev, R., Yordanova, V., Nikiforov, I., Mihaylov, R., Nikolov, Y., 2009b. Investigation on intoxication with anticoagulant rodenticide bromadialone (Lanirat) in dogs. Bulgarian Journal of Veterinary Medicine 12 (1), 167-172.