Lisovska V. S., Zhminko P. G., Shulyak V. G.

TOXIC EFFECT OF CARBENDAZIM ON BLOOD SYSTEM OF RATS IN ACUTE ORAL TOXICITY MODEL


About the author:

Lisovska V. S., Zhminko P. G., Shulyak V. G.

Heading:

HYGIENE AND ECOLOGY

Type of article:

Scentific article

Annotation:

Carbendazim is a systemic benzimidazole fungicide active against wide range of plant diseases. According to monitoring of pesticide residues in food, carbendazim is at the top 30 pollutants of plant production. Despite the strict standards and regulations of using pesticide safe, in some circumstances these substances can exceed the maximum acceptable levels and cause potential and actual risks for human health. It is known that the main mechanisms of carbendazim toxicity are aneugenic effects such as interruption of mitotic spindle formation. These effects can affect haematopoiesis and the whole organism. Evaluation of changes in blood system and under the influence of carbendazim and its effect on haematopoesis process is necessary to improve the understanding of mechanism of acute and chronic intoxications and preventing the negative toxic effects for humans and animals. Aim of this study is to determine the presence and character of carbendazim influence on rat blood system as a model of major regulatory system of organism. Object and methods. We investigated the effect of generic 98% technical carbendazim in dosage 750 mg/kg on peripheral blood of mature male Wister rats. Such blood parameters were studies as haemoglobin concentration with cyanmethemoglobin method, erythrocyte and leukocyte count with Goryaev chamber method, reticulocytes count after supravital stain with brilliant cresyl blue; platelet count with Fonio method; mean corpuscular hemoglobin concentration. There were also determined leukocyte differential count, morphologic analysis of blood cells, atypic cells count in Pappenheim–Kryukov stain. Cytochemical status of leukocytes was studied respectively to such parameters as neutrophil peroxidase activity with Löele method; neutrophil chloroacetate esterase activity with method of Moloney, McPherso, Fliegelman; neutrophil lipid content with Askerman method; lymphocyte succinate dehydrogenase activity with Narcissov method. Quantative and qualitative parameters were studies in dynamics in same rats on 1, 3, 7, 14 and 21 day after carbendazim treatment. Data were statistically analyzed using Student t-test; differences were considered reliable with Р≤0,05. Results. It was shown that carbendazim causes normochromic anaemia with decrease in reticulocytes and erythrocytes count and haemoglobin level; causes acanthocytosis in erythrocytes; causes leuko- and neutrophilopaenia with compensatory leukocytosis and appropriate lymphocytopaenia in terminal stages of research; causes appearance of atypic forms of lymphocytes, hypersegmented neutrophils, shadow cells; leads to thrombocytopenia. Carbendazim inhibits the activity of succinate dehydrogenase in lymphocytes, peroxidase, chloroacetate esterase and decreases lipid content in neutrophiles. These affects were accompanied by increase in atypic forms of lymphocytes and neutrophil stab cells count. Conclusions 1. Carbendazim in dosage 750 mg/kg in acute experiment conditions in Wistar rats causes anaemia and affects erythropoiesis due to its cytotoxic activity; 2. Carbendazim causes thrombocytopenia and affects thrombopoiesis; 3. Leukopenia, neutrophilopenia and morphological changes in leucocytes are linked with toxic effect of carbendazim on the process of granulocytopoiesis. Granulocytopoiesis is restored hereinafter due to compensatory reactions of blood system; 4. In abovementioned experimental conditions carbendazim inhibits the activity of succinate dehydrogenase, peroxidase, chloroacetate esterase and decreases lipid content in leucocytes. The revealed changes are reversible. Prospects for further research. Important question for future research is the study of interrelation of morphological and biochemical changes in blood and also in tissues and organs of mammals under influence of carbendazim.

Tags:

carbendazim, peripheric blood, acute oral toxicity, rats

Bibliography:

  1. EFSA (European Food Safety Authority). The 2015 European Union report on pesticide residues in food. European Food Safety Authority Journal. 2017;15(4):4791, 134 p.
  2. Prodanchuk МG. Toxicologo-gigienichni osnovy bezpechnosti harchovyh productive. Zhurnal AMN Ukrainy. 2002;8(4):693-702. [in Ukrainian].
  3. Carbendazim Review Findings Report. Australian Pesticides and Veterinary Medicines Authority. 2012. Canberra: APVMA; 2012. 47 p.
  4. Shuljak VG, Zhminko PG. Gematotoksichnost' kak problema toksikologii himicheskih veshhestv i nekotorye podhody k ee resheniju. Sovremennye problemy toksikologii. 2017;1-2:80-5. [in Russian].
  5. Human health risk assessment of Carbendazim. Australian Pesticides and Veterinary Medicines Authority. Office of Chemical Safety and Environmental Health Office of Health Protection. Canberra: 2009. 143 p.
  6. EFSA. Conclusion on the peer review of the pesticide risk assessment of the active substance Carbendazim. EFSA Jornal. 2010;8(5):1598.
  7. Hashem MA, Mohamed WM, Attia ES. Assessment of protective potential of Nigella sativa oil against carbendazim- and/or mancozeb-induced hematotoxicity, hepatotoxicity, and genotoxicity. Environ. Sci. Pollut. Res. Int. 2018;25(2):1270-82.
  8. European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes. Strasbourg: Council of Europe; 1986. 51 p.
  9. Menshikov VV. Laboratornye metody issledovanija v klinike. Spravochnik. Moskva: Medicina; 1987. 365 p. [in Russian].
  10. Hejhou FG, Kvaglino D. Gistohimicheskaja himija. Moskva: Medicina; 1983. 320 p. [in Russian].
  11. Gavrilov OK, Kozinets GI, Chernyak NB. Kletki kostnogo mozga i perifericheskoy krovi: monographia. Moskva: Medicina; 1985. 288 p. [in Russian].
  12. Wei KL, Chen FY, Lin CY, Gao GL, Kao WY, Yeh CH, et al. Activation of aryl hydrocarbon receptor reduces carbendazim-induced cell death. Toxicol Appl Pharmacol. 2016;306:86-97.
  13. Laryea D, Gullbo J, Isaksson A, Larsson R, Nygren P. Characterization of the cytotoxic properties of the benzimidazole fungicides, benomyl and carbendazim, in human tumour cell lines and primary cultures of patient tumour cells. Anticancer Drugs. 2010;21(1):33-42.
  14. Lipunova EA, Skorkina MU. Sistema krasnoj krovi. Sravnitelnaja fiziologija:monografija Belgorod: BelGU; 2004. 216 p. [in Russian].
  15. Novik AA, Bogdanov AN. Anemii (ot A do Ja): (rukovodstvo dlja vrachej). Moskva: Niva; 2004. 320 p. [in Russian].
  16. Boldyrev AA. Vvedenie v biohimiju membran. Moskva: Vysshaya Shkola; 1986. 112 p. [in Russian].
  17. Shevchenko TM, Polushkіn PM. Elektronnij posіbnik do vivchennja kursu «Osnovi zagal'noi klіnіchnoi laboratornoi dіagnostiki». Dnipro: DNU; 2016.138 p. [in Ukrainian].
  18. Obshchiye predstavleniya o hemopoese. [Internet]. Dostupno: http://meddaily.info [in Russian].
  19. Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011;11(11):762-74.
  20. Lynch DT, Hall J, Foucar K. How I investigate monocytosis. Int J Lab Hematol. 2018;40(2):107-14.
  21. Mikhailova NN, Gorohova LG, Kazitskaya AS, Maslennykova EN, Shcherbakova DA. Otsenka biohimicheskih izmeneniy perifericheskoy krovi na rannih stadiyah eksperimentalnoy ftoristoy intoksikatsii. Bulleten VSNC SO RAMN. 2010;4(74):80-8. [in Russian].
  22. Abdulkadyirov K.M. Gematologiya: Noveyshiy spravochnik. Moskva: Eksmo; Sankt-Peterburg: Sova. 2004. 928 p. [in Russian].
  23. Kolot NV. Issledovanie kletok kostnogo mozga kryis v zavisimosti ot ih vozrasta i kaloriynosti pitaniya. Scientific Jornal «Science Rise: Biological Science». 2017;1(4):25-32. [in Russian].
  24. Kjeldsen E. A novel acquired in v(2)(p23.3q24.3) with concurrent submicroscopic deletions at 2p23.3, 2p22.1, 2q24.3 and 1p13.2 in a patient with chronic thrombocytopenia and anemia. MolCytogenet. 2015 Feb 1;8:7.
  25. Kamel WA, Al-Hashel JY, Alexander KJ, Massoud F, Shawaf FA, Huwaidi IE. Cerebral Venous Thrombosis in a Patient with Iron Deficiency Anemia and Thrombocytopenia: A Case Report. J MedSci. 2017;28;5(7):967-9.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 2 (144), 2018 year, 117-122 pages, index UDK 615.9:616.15:616-099:632.95.024

DOI: