Investigation of glibenclamide distribution in animal organs by acute intoxication modeling

Authors

DOI:

https://doi.org/10.15587/2519-4852.2016.79660

Keywords:

glibenclamide, acute intoxication, biological objects, distribution, chromatographic methods, solid phase extraction

Abstract

Modeling of the effects of chemical compounds toxic influence, including drugs is an important information source for forensic toxicological studies. Cases of fatal poisoning with glibenclamide, mainly at suicidal overdose, are known. Considering that the substance is being actively metabolised, the information about its distribution in organs and tissues after administration to an organism admission at lethal doses can be useful for selecting of biological objects.

Aim. This study is aimed to describe the glibenclamide distribution in organs of laboratory animals using the model of acute intoxication.

Methods. The model of the glibenclamide acute intoxication was reproduced using albino rats receiving the drug with tween-80 in suspension orally, considering on their body weight and LD50 of toxicant. For the further studies, liver, kidneys, stomach, intestinal content, heart, and blood of the experimental animals were taken after decapitation. Glibenclamide was isolated from the biological objects by acidulated acetonitrile. The extracts obtained from the organs were purified by TLC, and plasma – by solid-phase extraction on Oasis HLB cartridges. TLC and HPLC methods were applied for identification and quantification of glibenclamide.

Results. The study revealed that glibenclamide in the extracts obtained from the biological objects was determined in concentrations 2,2–19,8 µg/ml in sample. The highest concentrations of toxicant were found in the extracts obtained from blood and stomach, lower – in the extract from liver and intestinal contents. The given toxicant was found in the extract obtained from heart at concentration of 4,2 µg/ml in sample, that explains its selective toxicity on myocardium. Considering this data, the directed forensic toxicological studies at case of glibenclamide overdose can be carried out by determination of its native substance. Also, it has been proposed to use the heart as an alternative object for chemico-toxicological analysis of toxicants (besides biological objects recommended by TIAFT).

Conclusion. Glibenclamide distribution in animal organs and tissues after administration at lethal doses (the model of acute intoxication) has been established. This modeling allowed to determine biological objects, which can be used for forensic toxicological studies in cases of acute overdose with this toxicant, namely: liver, kidneys, stomach and intestinal contents, heart and blood

Author Biographies

Тетяна Володимирівна Кучер, National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002

Senior laboratory assistant, applicant

Department of drug and analytical toxicology

Сергій Іванович Мерзлікін, National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002

Doctor of Pharmaceutical Science, professor

Department of Drug and analytical toxicology

Сергій Юрійович Штриголь, National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002

Doctor of Medical Sciences, professor, Head of department

Department of pharmacology

References

  1. Karkischenko, N. N. (2007). Alternativyi biomeditsinyi [Biomedicine alternatives] Vol. 1. Osnovyi biomeditsinyi i farmakomodelirovaniya. Kyiv: VPK, 320.
  2. Apihtina, O. L. (2011). Pravovi aspekti pri roboti z eksperimentalnimi tvarinami [Legal aspects by working with experimental animals]. Nowadays and bioethics. Kyiv: VD «Avicena», 244–250.
  3. Nedosugova, L. V. (2011). Glibenklamid – profil effektivnosti i bezopasnosti [Glibenclamide – profile of effectiveness and safety]. Diabetes mellitus, 3, 85–90.
  4. Reshedko, G. K., Haykina, E. V. (2012). Klinicheskoe primenenie glibenklamida: voprosyi bezopasnosti i effektivnosti [Clinical application of glibenclamide: safety and efficiency]. Problems of Endocrinology, 3, 65–69.
  5. Schulz, M., Schmoldt, A. (2003). Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics. Pharmazie, 58 (7), 447–474.
  6. Kucher, T. V., Merzlikin, S. I. (2015). Vibir ta standartizatsiya umov selektivnogo rozdilennya glibenklamidu, gliklazidu ta glimepiridu v tonkomu shari sorbentu [The сhoice and standardization of the conditions for selective separation of glibenclamide, gliclazide and glimepiride in a thin layer]. Management, economics and quality assurance in Pharmacy, 1, 8–13.
  7. Ibragimova, M. M. (2014). K voprosu himiko-toksikologicheskogo analiza gliklazida i metformina pri ih sovmestnom primenenii [On the issue of chemical-toxicological analysis of gliclazide and metformin in their mutually application]. Astana medical journal, 2, 152–158.
  8. Ibragimova, M. M. (2016). Himiko-toksikologicheskie svoystva nekotoryih antidiabeticheskih preparatov proizvodnyih sulfonilmochevinyi [Chemico-toxicological properties of some antidiabetic sulfonylureas derivatives]. Tashkent, 39.
  9. Ayyappan, J., Umapathi, P., Quine, S. (2011). Validated HPLC method for the fast and sensitive determination of few anti-diabetic drugs residues in support of cleaning validation in formulation area. International journal of pharmacy and pharmaceutical sciences, 3, 371–374.
  10. Rayanm, V., Lakshman, A., Ramana, M. (2011). Validated RP – HPLC method for the estimation of glibenclamide in formulation and serum. International journal of research in pharmaceutical and biomedical sciences, 2, 856–862.
  11. Albu, F., Georgiţă, C., David, V., Medvedovici, A. (2007). Determination of glibenclamide in human plasma by liquid chromatography and atmospheric pressure chemical ionization/MS-MS detection. Journal of Chromatography B, 846 (1-2), 222–229. doi: 10.1016/j.jchromb.2006.09.005
  12. Dastmalchi, S., Garjani, A., Maleki, N. et. al. (2005). Enhancing dissolution, serum concentrations and hypoglycemic effect of glibenclamide using solvent deposition technique. Pharm. Pharmaceut. Sci, 8 (2), 175–181.
  13. Treherne, J. M., Ashford, M. L. J. (1991). The regional distribution of sulphonylurea binding sites in rat brain. Neuroscience, 40 (2), 523–531. doi: 10.1016/0306-4522(91)90138-e
  14. Adaramoye, O., Akanni, O., Adesanoye, O., Labo-Popoola, O., Olaremi, O. (2012). Evaluation of toxic effects of metformin hydrochloride and glibenclamide on some organs of male rats. Niger J Physiol Sci., 27 (2), 137–144.
  15. Vanelli, G., Hussain, S., Dimori, M., Aguggini, G. (1997). Cardiovascular responses to glibenclamide during endotoxaemia in the pig. Veterinary Research Communications, 21 (3), 187–200. doi: 10.1023/a:1005880228344
  16. Takahashi, N., Ooie, T., Saikawa, T., Iwao, T., Yoshimatsu, H., Sakata, T. (2003). Long-term treatment with glibenclamide increases susceptibility of streptozotocin-induced diabetic rat heart to reperfusion-induced ventricular tachycardia. Exp Biol Med., 228 (10), 1234–1238.
  17. Ji, M.-H., Yang, J.-J., Ju, L.-S., Zhu, S.-H., Yang, J.-J. (2014). Glibenclamide pretreatment attenuates acute lung injury by inhibiting the inflammatory responses and oxidative stress in a polymicrobial sepsis animal model. J Anesth Perioper Med., 1 (1), 36–43. doi: japm006TBD
  18. Council Directive 2010/63/EU of 22 September 2010 on the protection of animals used for scientific purposes (2010). Official Journal of the European Communities, L 276, 33–79.
  19. Reznikov, O. G., Solovyov, A. I., Dobrelya, N. V., Stefanov, O. V. (2007). Bioetichna ekspertiza doklinichnih ta inshih naukovih doslidzhen, scho vikonuyutsya na tvarinah [Bioethical expertise preclinical and other research performed in animals]. Journal of Pharmacology and Pharmacy, 7, 47–61.
  20. Nedosugova, L. V. (2013). Rol preparatov sulfonilmochevinyi v razvitii serdechno-sosudistyih oslozhneniy pri saharnom diabete 2 tipa [The role of sulphonylurea drugs in development of cardiovascular complications by type 2diabetes]. Diabetes mellitus, 2, 26–35.
  21. Kucher, T. V., Merzlikin, S. I. (2015). Hromatografichne doslidzhennya viluchen glibenklamidu, gliklazidu ta glimepiridu iz biologichnih ob’ektiv [The chromatographic study of the extracts of glibenclamide, gliclazide and glimepiride obtained from biological objects]. News of pharmacy, 4, 3–7.
  22. Kucher, T. V., Merzlikin, S. I., Kovalenko, E. V. (2016). Hromatograficheskoe obnaruzhenie glibenklamida v biologicheskih ob'ektah pri modelirovanii kombinirovannyih otravleniy lekarstvennyimi veschestvami [Chromatographic detection of glibenclamide in biological objects by modeling the combined poisoning of drugs]. Vestnik pharmacy, 1, 28–33.

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Published

2016-10-30

How to Cite

Кучер, Т. В., Мерзлікін, С. І., & Штриголь, С. Ю. (2016). Investigation of glibenclamide distribution in animal organs by acute intoxication modeling. ScienceRise: Pharmaceutical Science, (3 (3), 7–12. https://doi.org/10.15587/2519-4852.2016.79660

Issue

No. 3 (3) (2016)

Section

Pharmaceutical Science

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Copyright (c) 2016 Тетяна Володимирівна Кучер, Сергій Іванович Мерзлікін, Сергій Юрійович Штриголь

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