PLANT BIOLOGY
ANIMAL BIOLOGY
SUBSCRIPTION
E-SUBSCRIPTION
 
MAP
MAIN PAGE

 

 

 

 

doi: 10.15389/agrobiology.2022.2.371reng

UDC: 636.4:619:615.9:591.1

 

EXPERIMENTAL COMBINED MYCOTOXICOSIS IN PIGS AS AFFECTED BY INFECTION LOAD

E.I. Semenov, L.E. Matrosova, S.A. Tanaseva, A.R. Valiev,
R.M. Potekhina, E.Yu. Tarasova, G.N. Spiridonov, E.G. Gubeeva,
N.N. Mishina

Federal Center for Toxicological, Radiation and Biological Safety, Nauchnyi gorodok 2, Kazan, Republic of Tatarstan, 420075 Russia, e-mail semyonovei@bk.ru (✉ corresponding author), M.Lilia.Evg@yandex.ru,
vip.tanaseva2015@mail.ru, valalraf200@gmail.com, Evgenechka1885@gmail.com, RamziyaP@yandex.ru,
spiridonovkzn57@gmail.com, gubeevae@mail.ru, Mishinanailyan@yandex.ru

ORCID:
Semenov E.I. orcid.org/0000-0002-3029-7170
Potekhina R.M. orcid.org/0000-0002-9395-8327
Matrosova L.E. orcid.org/0000-0001-7428-7882
Spiridonov G.N. orcid.org/0000-0003-3558-3667
Tanaseva S.A. orcid.org/0000-0003-1295-6184
Gubeeva E.G. orcid.org/0000-0002-0505-2673
Valiev A.R. orcid.org/0000-0001-7187-4328
Mishina N.N. orcid.org/0000-0002-9312-0970
Tarasova E.Yu. orcid.org/0000-0002-9058-5798

Received February 25, 2021

 

Animal and human mycotoxicoses occur due to the ingestion of metabolites of toxicogenic microfungi. The effect increases in case of the co-ingestion of several mycotoxins, their mix with another ecotoxicants and biological agents. However, published research data only partially cover the nature of mixed mycotoxicoses in infectious diseases. This work shows for the first time the effect on pigs of the infection load of Clostridium perfringes and the combined effect of T-2 toxin, zearalenone, and deoxynivalenol in low doses. Our goal was to study the chronic form of combined mycotoxicosis in weaned pigs with a persistent infection in herd on the animal productivity, blood morpho-biochemical and immunological parameters, pathological changes in organs and tissues. Combined experimental mycotoxicosis with infectious load was modeled under the conditions of the vivarium complex (the Federal Center for Toxicological, Radiation and Biological Safety, 2018) on the weaning Large White piglets (Sus scrofa domesticus) divided into three groups 3 pigs each. Group I received no mycotoxins, group II received dietary T-2 toxin (70 mg/kg feed), group III received mixed dietary mycotoxins (DON 1000 mg/kg, ZEN 50 mg/kg and T-2 70 mg/kg). All animals were orally administered a suspension of Clostridium perfringes No. 392 type C (1×106 CFU/ml, 2 ml). On day 15, the animals were vaccinated intramuscularly in the posterior thigh with 1 ml of the associated vaccine against rota-, coronavirus and colorectal diarrhea of newborn piglets (FCTRB-VNIVI). Group I (control) was considered clinically healthy. Signs of intoxication, blood biochemical parameters (total protein, total bilirubin, glucose, malondialdehyde, alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase activity), blood morphology (counts of erythrocytes, leukocytes, the hemoglobin level) and immunological parameters (T- and B-lymphocytes, titer of antibodies to vaccine antigens) on day 10, 20 and 30. The antibody titers to the Escherichia coli vaccine strain were determined by the agglutination reaction, to the coronavirus vaccine antigen by the ELISA test using a Multiscan FC photometer (Thermo Scientific, USA), and to the rotavirus antigen by an indirect hemagglutination test. At the end of the experiment, pieces of organs were fixed in 10 % neutral formalin, followed by generally accepted pathomorphological processing for histological studies. Histopreparations were stained with hematoxylin and eosin. Feed contamination with mycotoxins combined with clostridiosis had an adverse effect on the clinical and immune status, blood morpho-biochemical parameters, and pathoanatomical patterns. The changes were more apparent in co-contamination with ecotoxicants. Average daily bodyweight gain in piglets of group II was lower by 20.5 % compared to the control (p ≥ 0.05), of group III by 39.2 % (p ≤0.05). In group III, by the end of the experiment, there was a decrease in the erythrocyte counts by 40 % (p ≤ 0.001), in the level of hemoglobin by 20 % (p ≤0.01), glucose by 57 % (p ≤ 0.001), and total protein by 13 % (p ≤ 0.05). The concentration of bilirubin increased 5.1-fold (p ≤ 0.001), the activity of alanine aminotransferase and aspartate aminotransferase 2.2- and 1.8-fold (p ≤ 0.001), respectively, the concentration of malondialdehyde 2.8-fold (p ≤ 0.001), the activity of alkaline phosphatase decrease by 41.5 % (p ≤ 0.001). Co-mycotoxicosis combined with an infectious load led to immunological changes. Titers of specific antibodies to rotavirus were 8 times lower, to coronavirus 6.4 times lower (p ≤ 0.05), to Escherichia 5 times lower (p ≤ 0.05) compared to the control. Marked pathological changes in the internal organs also occurred. Therefore, the co-mycotoxicosis due to T-2 toxin-, deoxynivalenol- and zearalenone-contaminated feed combined with the persistence of Clostridium perfringens, the causative agent of intestinal infection lead to suppression of immunological parameters (a decrease in the titer of specific protective antibodies, the number of T- and B-lymphocytes), activation of lipid peroxidation, and pathological changes in tissues and organs of the piglets.

Keywords: mycotoxins, pigs, blood, morpho-biochemical parameters, immune suppression, histological study.

 

REFERENCES

  1. Ivanov A.V., Fisinin V.I., Tremasov M.YA., Papunidi K.Kh. Mikotoksikozy (biologicheskie i veterinarnye aspekty) [Mycotoxicoses (biological and veterinary aspects)]. Moscow, 2010 (in Russ.).
  2. Bryden W.L. Mycotoxin contamination of the feed supply chain: implications for animal productivity and feed security. Animal Feed Science and Technology, 2012, 173(1-2): 134-158 CrossRef
  3. Ferrigo D., Raiola A., Causin R. Fusarium toxins in cereals: occurrence, legislation, factors promoting the appearance and their management. Molecules, 2016, 21(5): 627 CrossRef
  4. Schiefer H.B., Beasley V.R. Effects on the digestive system and energy metabolism. In: Trichothecene mycotoxicosis: pathophysiologic effects. V.R. Beasley (eds.). CRC Press, 2017 CrossRef
  5. Rosenstein Y., Lafarge-Fraysinnet C. Inhibitory effect of Fusarium T-2 toxin on lymphoid DNA and protein synthesis. Toxicology and Applied Pharmacology, 1983, 70(2): 283-290 CrossRef
  6. Taylor M.J., Pang V.F., Beasley V.R. The Immunotoxicity of trichothecene mycotoxins. In: Trichothecene mycotoxicosis: pathophysiologic effects. Val Richard Beasley (eds.). CRC Press, 2017 CrossRef
  7. Sun Y., Li S., Chen R, Wu P., Liang J. Ultrasensitive and rapid detection of T-2 toxin using a target-responsive DNA hydrogel. Sensors and Actuators, B: Chemical,2020, 311: 127912 CrossRef
  8. Lin R., Sun Y., Ye W., Zheng T., Wen J., Deng Y. T-2 toxin inhibits the production of mucin via activating the IRE1/XBP1 pathway. Toxicology, 2019, 424: 152230 CrossRef
  9. Minervini F., Dell’Aquila M.E. Zearalenone and reproductive function in farm animals. International Journal of Molecular Sciences, 2008, 9(12): 2570-2584 CrossRef
  10. Akbari P., Braber S., Gremmels H., Koelink P.J., Verheijden K.A.T., Garssen J., Fink-Gremmels J. Deoxynivalenol: a trigger for intestinal integrity breakdown. FASEB Journal, 2014, 28(6): 2414-2429 CrossRef
  11. Escrivá L., Font G., Manyes L. In vivo toxicity studies of fusarium mycotoxins in the last decade: a review. Food and Chemical Toxicology, 2015, 78: 185-206 CrossRef
  12. Przybylska-Gornowicz B., Tarasiuk M., Lewczuk B., Prusik M., Ziółkowska N., Zielonka Ł., Gajęcki M., Gajęcka M. The effects of low doses of two Fusarium toxins, zearalenone and deoxynivalenol, on the pig jejunum. A light and electron microscopic study. Toxins, 2015, 7(11): 4684-4705 CrossRef
  13. Smith M.-C., Madec S., Coton E., Hymery N. Natural co-occurrence of mycotoxins in foods and feeds and their in vitro combined toxicological effects. Toxins, 2016, 8(4): 94 CrossRef
  14. Trufanov O.V., Kotik A.N., Trufanova V.A. Zhivotnovodstvo Rossii, 2017, 7: 5-7 (in Russ.).
  15. Yang Y., Yu S., Tan Y., Liu N., Wu A. Individual and combined cytotoxic effects of co-occurring deoxynivalenol family mycotoxins on human gastric epithelial cells. Toxins, 2017, 9(3): 96 CrossRef
  16. Tremasov M.Ya., Smetov P.K. Veterinariya, 1995, 3: 20-22 (in Russ.).
  17. Kryukov V.C. Kombikorma, 2013, 10: 59-63 (in Russ.).
  18. Semenenko M.P., Tyapkina E.V., Kuz'minova E.V., Koshchaev A.G. Manifestations of chronic feed mycotoxicosis in laboratory rats under experimental conditions. Sel'skokhozyaistvennaya biologiya [Agricultural Biology], 2019, 4: 777-786 CrossRef
  19. Mishina N.N., Semenov E.I., Papunidi K.Kh., Potekhina R.M., Tanaseva S.A., Ermolaeva O.K., Sagdeeva Z.Kh., Gataullin D.Kh. Veterinarnyi vrach, 2018, 6: 3-9 (in Russ.).
  20. Papunidi K.Kh., Konyukhov G.V., Nizamov R.N., Semenov E.I., Kadikov I.R. Kombinirovannye porazheniya zhivotnykh i razrabotka sredstv profilaktiki i lecheniya [Combined lesions in animals and the means of prevention and treatment]. Kazan', 2019 (in Russ.).
  21. Burdov L.G., Matrosova L.E. Veterinarnyi vrach, 2011, 2: 7-9 (in Russ.).
  22. Gagkaeva T.Yu., Gavrilova O.P., Levitin M.M., Novozhilova K.V. Zashchita i karantin rastenii, 2011, 5: 2-3 (in Russ.).
  23. Meurens F., Summerfield A., Nauwynck H., Saif L., Gerdts V. The pig: A model for human infectious diseases. Trends in Microbiology, 2012, 20(1): 50-57 CrossRef
  24. Obremski K., Zielonka Ł., Gajęcka M., Jakimiuk E., Bakuła T., Baranowski M., Gajęcki M. Histological estimation of the small intestine wall after administration of feed containing deoxynivalenol, T-2 toxin and zearalenone in the pig. Polish Journal of Veterinary Sciences, 2008, 11(4): 339-345.
  25. Zielonka Ł., Jakimiuk E., Obremski K., Gajęcka M., Dąbrowski M., Gajęcki M. Evaluation of the proliferative activity of immunocompetent cells in the jejunal and iliac lymph nodes of prepubertal female wild boars diagnosed with mixed mycotoxicosis. Bulletin of the Veterinary Institute in Pulawy, 2015, 59(2): 197-203 CrossRef
  26. Miroshnichenko P.V. Veterinarnyi vrach, 2007, 2: 16-17 (in Russ.).
  27. Antonissen G., Martel A., Pasmans F., Ducatelle R., Verbrugghe E., Vandenbroucke V., Li S., Haesebrouck F., Van Immerseel F., Croubels S. The impact of Fusarium mycotoxins on human and animal host susceptibility to infectious diseases. Toxins,2014, 6(2): 430-452 CrossRef
  28. Park S.-H., Kim D., Kim J., Moon Y. Effects of mycotoxins on mucosal microbial infection and related pathogenesis. Toxins, 2015, 7(11): 4484-4502 CrossRef
  29. Papunidi K.Kh., Tremasov M.YA., Fisinin V.I., Nikitin A.I., Semenov E.I. Mikotoksiny (v pishchevoi tsepi) [Mycotoxins (in the food chain)]. Kazan', 2017 (in Russ.).
  30. Frimel' G. Immunologicheskie metody [Immunological methods]. Moscow, 1987 (in Russ.).
  31. Metody veterinarnoi klinicheskoi laboratornoi diagnostiki. Spravochnik /Pod redaktsiei I.P. Kondrakhina [Methods of veterinary clinical laboratory diagnostics. Handbook. I.P. Kondrakhin (ed.)]. Moscow, 2004 (in Russ.).
  32. Bonnet M.S., Roux J., Mounien L., Dallaporta M., Troadec J.D. Advances in deoxynivalenol toxicity mechanisms: the brain as a target. Toxins, 2012, 4(11): 1120-1138 CrossRef
  33. Schoevers E.J., Santos R.R., Colenbrander B., Fink-Gremmels J., Roelen B.A.J. Transgenerational toxicity of Zearalenone in pigs. Reproductive Toxicology, 2012, 34(1): 110-119 CrossRef
  34. Döll S., Dänicke S. The Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) in animal feeding. Preventive Veterinary Medicine, 2011, 102(2): 132-145 CrossRef
  35. McDonald E., Cavan K.R., Smith T.K. Effect of acute oral doses of T-2 toxin on tissue concentrations of biogenic amines in the rat. Journal of Animal Science, 1998, 66(2): 434-441 CrossRef
  36. Dąbrowski M., Obremski K., Gajęcka M., Gajęcki M.T., Zielonka Ł. Changes in the subpopulations of porcine peripheral blood lymphocytes induced by exposure to low doses of zearalenone (ZEN) and deoxynivalenol (DON). Molecules, 2016, 21(5): 557 CrossRef
  37. Dinu D., Bodea G.O., Ceapa C.D., Munteanu M.C., Roming F.I., Serban A.I., Hermenean A., Costache M., Zarnescu O., Dinischiotu A. Adapted response of the antioxidant defense system to oxidative stress induced by deoxynivalenol in Hek-293 cells. Toxicon, 2011, 57(7-8): 1023-1032 CrossRef
  38. Tarasova E.Yu., Tremasov M.Ya. Uchenye zapiski Kazanskoi gosudarstvennoi akademii veterinarnoi meditsiny im. N.E. Baumana, 2013, 213: 278-282 (in Russ.).
  39. Valiev A.R., Semenov E.I., Akhmetov F.G. Veterinarnyi vrach, 2011, 2: 4-6 (in Russ.).
  40. Kuchenbuch H.S., Cramer B., Humpf H.U. Matrix binding of T-2 toxin: structure elucidation of reaction products and indications on the fate of a relevant food-borne toxin during heating. Mycotoxin Research, 2019, 35(3): 261-270 CrossRef
  41. Pinton P., Guzylack-Piriou L., Kolf-Clauw M., Oswald I.P. The effect on the intestine of some fungal toxins: the trichothecenes. Current Immunology Reviews, 2012, 8(3): 193-208 CrossRef
  42. Waśkiewicz A., Beszterda M., Kostecki M., Zielonka Ł., Goliński P., Gajęcki M. Deoxynivalenol in gastrointestinal tract of immature gilts under per os toxin application. Toxins, 2014, 6(3): 973-987 CrossRef
  43. Diesing A.K., Nossol C., Panther P., Walk N., Post A., Kluess J., Kreutzmann P., Dänicke S., Rothkὅtter H.J., Kahlert S. Mycotoxin deoxynivalenol (DON) mediates biphasic cellular response in intestinal porcine epithelial cell lines IPEC-1 and IPEC-J2. Toxicology Letters, 2011, 200(1-2): 8-18 CrossRef
  44. Awad W.A., Ghareeb K., Zentek J. Mechanisms underlying the inhibitory effect of the feed contaminant deoxynivalenol on glucose absorption in broiler chickens. Veterinary Journal, 2014, 202(1): 188-190 CrossRef
  45. Obremski K., Gajęcka M., Zielonka Ł., Jakimiuk E., Gajęcki M. Morphology and ultrastructure of small intestine mucosa in gilts with zearalenone mycotoxicosis. Polish Journal of Veterinary Sciences, 2005, 8(4): 301-307.
  46. Verbrugghe E., Vandenbroucke V., Dhaenens M., Shearer N., Goossens J., De Saeger S., Eeckhout M., D’Herde K., Thompson A., Deforce D., Boyen F., Leuman B. T-2 toxin induced Salmonella Typhimurium intoxication results in decreased Salmonella numbers in the cecum contents of pigs, despite marked effects on Salmonella-host cell interactions. Veterinary Research, 2012, 43: 22 CrossRef
  47. Antonissen G., Van Immerseel F., Pasmans F., Ducatelle R., Haesebrouck F., Timbermont L., Verlinden M., Janssens G.P.J., Eeckhaut V., Eeckhout M., De Saeger S., Hessenberger S., Martel A., Croubels S. The mycotoxin deoxynivalenol predisposes for the development of Clostridium perfringens-induced necrotic enteritis in broiler chickens. PLoS ONE, 2014, 9(9): e108775 CrossRef
  48. Nurgaliev F.M., Semenov E.I., Pozdeev O.K., Sofronov P.V. Veterinarnyi vrach, 2020, 2: 31-38 (in Russ.).
  49. Grenier B., Applegate T.J. Modulation of intestinal functions following mycotoxin ingestion: Meta-analysis of published experiments in animals. Toxins, 2013, 5(2): 396-430 CrossRef
  50. Timbermont L., Haesebrouck F., Ducatelle R., Van Immerseel F. Necrotic enteritis in broilers: an updated review on the pathogenesis. Avian Pathology, 2011, 40(4): 341–347 CrossRef
  51. Gereza J.R., Pintonb P., Callud P., Grosjeand F., Oswaldb I.P., Bracarensea A.P.F.L. Deoxynivalenol alone or in combination with nivalenol and zearalenone induce systemic histological changes in pigs. Experimental and Toxicologic Pathology, 2015, 67(2): 89-98 CrossRef
  52. Grenier B., Oswald I.P. Mycotoxin co-contamination of food and feed. Meta-analysis of publications describing toxicological interactions. World Mycotoxin Journal, 2011, 4(3): 285-313 CrossRef
  53. Shakhov A.G., Vostroilova G.A., Shabunin S.V., Sashnina L.Yu., Kantorovich Yu.A., Chusova G.G. Problemy veterinarnoi sanitarii, gigieny i ekologii, 2017, 3(23): 91-97 (in Russ.).

 

back

 


CONTENTS

 

 

Full article PDF (Rus)

Full article PDF (Eng)