Ukr.Biochem.J. 2016; Volume 88, Issue 1, Jan-Feb, pp. 51-60


Biochemical indicators of nephrotoxicity in blood serum of rats treated with novel 4-thiazolidinone derivatives or their complexes with polyethylene glycol-containing nanoscale polymeric carrier

L. I. Kоbylinska1, D. Ya. Havrylyuk1, N. E. Mitina2, A. S. Zаichenko2,
R. B. Lesyk1, B. S. Zіmenkovsky1, R. S. Stoika3

 1Danylo Halytsky Lviv National Medical University, Ukraine;
2Lviv Polytechnic National University, Ukraine;
3Іnstitute of Cell Biology, National Academy of Sciences of Ukraine, Lviv

The aim of this study was to compare the effect of new synthetic 4-thiazolidinone derivatives (potential anticancer compounds denoted as 3882, 3288 and 3833) and doxorubicin (positive control) in free form and in their complexes with synthetic polyethylene glycol-containing nanoscale polymeric carrier on the biochemical indicators of nephrotoxicity in blood serum of rats. The concentration of total protein, urea, creatinine, glucose, ions of sodium, potassium, calcium, iron and chloride was measured. It was found that after injection of the investigated compounds, the concentration of sodium cations and chloride anions in blood serum was increased compared with control (untreated animals). Doxorubicin’s injection was accompanied by a decrease in the concentration of iron cations. The concentration of total protein, urea and creatinine decreased under the influence of the studied compounds. Complexation of these аntineoplastic substances with a synthetic polymeric nanocarrier lowered the concentration of the investigated metabolites substantially compared to the effect of these compounds in free form. The normalization of concentration of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with the polymeric carrier comparing with increased concentration of these indicators at the introduction of such compounds in free form was found.

Keywords: , , , , ,


  1. Perry MC, Doll DC, Freter CE. The Chemotherapy Source Book. Philadelphia: Walters Kluwer, Lippincott Williams & Wilkins, 2012. 248 p.
  2. Zimmerman HJ. Hepatotoxicity: The Adverse Effects of Drugs and Other Chemicals on the Liver. Lippincott Williams&Wilkins, 1999. 789 p.
  3. оbylinska LI, Havrylyuk DYa, Ryabtseva АО, Mitina NE, Zаichenko ОS, Zіmenkovsky BS, Stoika RS. Study of rat blood serum biochemical indicators of cardiotoxic action of novel 4-thiazolidone derivatives and doxorubicin in complexes with polyethylenglycol-containing polymeric carrier. Ukr Biochem J. 2014 Nov-Dec;86(6):84-95. (In Ukrainian). PubMedCrossRef
  4. Kоbylinska LI, Havrylyuk DYa, Ryabtseva АО, Mitina NE, Zаichenko ОS, Lesyk RB, Zіmenkovsky BS, Stoika RS. Biochemical indicators of hepatotoxicity in blood serum of rats under the effect of novel 4-thiazolidinone derivatives and doxorubicin and their complexes with polyethyleneglycol-containing nanoscale polymeric carrier. Ukr Biochem J. 2015 Mar-Apr;87(2):122-32. PubMed, CrossRef
  5. Naughton CA. Drug-induced nephrotoxicity. Am Fam Physician. 2008 Sep 15;78(6):743-50. PubMed
  6. Pentiuk AA, Voloshchuk NI, Mashevska OV. Nephrotoxicity drugs: clinical manifestations, pathophysiological mechanisms and approaches to treatment. Rational Pharmacotherapy. 2009; (1(10)): 55-62. (In Ukrainian).
  7. Derymedvid’ LV, Drogovoz SM, Matveeva EV, Kireyev IV, Vereitinova VP. Nephrotoxicity as the manifestation of drugs side effect. Ukr Biopharm J. 2014; 5(34): 59-61. (In Ukrainian).
  8. Boiko NM, Klyuchivska OYu, Kobylinska LI, Havrylyuk DYa, Mitina NYe, Lesyk RB, Zaichenko OS, Stoika RS. Vitality and morphology of tumor cells treated with 4-thiazolidinone derivatives immobilized on nanoscale polymer carrier. Biotechnologia Acta. 2015;8(1):39-48. CrossRef
  9. Chumak VV, Panchuk RR, Manko NO, Havrylyuk D, Kobylinska L, Lesyk R, Zіmenkovsky BS, Stoika RS. Comparative study of the cytotoxic properties of isatin-containing derivatives of 4-thiazolidinone with different structure toward human tumor cells in vitro. Studia Biologica. 2014;8(2):29-42. (In Ukrainian).
  10. Havrylyuk D, Zimenkovsky B, Vasylenko O, Gzella A, Lesyk R. Synthesis of new 4-thiazolidinone-, pyrazoline-, and isatin-based conjugates with promising antitumor activity. J Med Chem. 2012 Oct 25;55(20):8630-41. PubMed, CrossRef
  11. Kobylinska L, Patereha I, Ryabtseva АО, Mitina NE, Zаichenko ОS, Kotsyumbas I, Zіmenkovsky BS, Stoika R. Study of acute toxicity of nanosized drug delivery system based on PEG comb-like carriers in white laboratory rats and mice. Modern  Toxicol Food Chem Safety. 2014;(3/4(66/67)):43-48. (In Ukrainian).
  12. Kobylinska L, Havrylyuk D, Patereha I, Kotsyumbas I, Lesyk R, Stoika R. Study of acute toxicity and cumulative properties in rats of novel synthetic 4-tiazolidone derivatives with potential antineoplastic activity. Modern Probl Toxicol Food  Chem Safety.  2013;4(63):38-43. (In Ukrainian).
  13. Bharali DJ, Khalil M, Gurbuz M, Simone TM, Mousa SA.Nanoparticles and cancer therapy: a concise review with emphasis on dendrimers. Int J Nanomedicine. 2009;4:1-7. PubMed, PubMed, CrossRef
  14. Stefanov OV. Preclinical Studies of Medicines. Methodological Recommendations. Kyiv, 2001. 527 p. (In Ukrainian).
  15. European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes (Strasbourg, March 18, 1986). Availableat (In Ukrainian).
  16. Establishing the order of conduct for preclinical studies of pharmaceutical substances and expert evaluation of materials from preclinical studies of pharmaceutical substances: Decree No 944 by Ministry of Health of Ukraine issued on 14.12.2009. Available at
  17. Arzamastsev EV, Gouscova TA, Bere­zovskaya IV. Methodological Instructions on research of general toxicity of pharmaceuticals. Manual on experimental (preclinical) study of new pharmacological substances. Moscow, 2000. P. 18-26. (In Russian).
  18. Riabtseva A, Mitina N, Boiko N, Garasevich S, Yanchuk I, Stoika R, Slobodyanyuk O, Zaichenko A. Structural and colloidal-chemical characteristics of nanosized drug delivery systems based on pegylated comb-like carriers. Chem Chem Technol. 2012;6(3):291-295.
  19. Senkiv YuV, Ryabtseva AR, Heffeter P, Boyko NM, Shlyakhtina EA, Mitina NE, Berger W, Zaichenko OS, Stoika RS. Immobilization of doxorubicin on the olygoeleсtrolytic polymeric carrier VEP-GMA-PEG increases its and anticancer activity cellular uptake. Studia Biologica. 2012;6(2):5-16. (In Ukrainian).
  20. Kamyshnikov VS. Manual on Clinical Biochemical Investigations and Laboratory Diagnostics. Moscow: MEDpress-inform, 2004. 911 p. (In Russian).

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