online ISSN 2415-3176
print ISSN 1609-6371
logoExperimental and Clinical Physiology and Biochemistry
  • 5 of 12
ECPB 2018, 82(2): 38–42
Research articles

The Level of Activity of Key Antioxidant Enzymes in Lymphoma and Liver Cells Under the Effect of New Thiazole Derivative


A pronounced cytotoxic action of the newly synthesized thiazole derivative N-(5-Benzyl-1,3- thiazole-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (compound 1) on the tumour cells has been found in vitro earlier, but cytotoxicity of this substance has not been detected in relation to non-cancerous cells. In addition, it has been determined that the scavengers of active forms of oxygen significantly reduce the cytotoxic effect of the compound 1. In this study the influence of compound 1 on the activity of superoxide dismutase and catalase in the mouse Nemeth-Kellner lymphoma (NK/Ly) cells and hepatocytes has been studied in order to evaluate the possible role of the antioxidant activity during the action of a substance. The experiments have been performed using two groups of nonlinear male rats weighing 20-30 g. Rats from the first group have had grafted lymphoma and rats from the second group have been healthy. The ascites form of lymphoma has been caused by the intraperitoneal inoculation of 10-15 million cancer cells in the rats. Thiazole derivative (compound 1) has been dissolved in dimethyl sulfoxide and added to the test sample (lymphoma or liver homogenate) in final concentrations of 1, 10 and 50 ƒÊM. The activities of superoxide dismutase and catalase have been determined spectrophotometrically in a homogenate of the lymphoma cells and homogenate of a liver (from both the grafted lymphoma and the healthy rats) after incubation with the drug for 10 minutes.

The baseline level of superoxide dismutase activity in the lymphoma of the rats has been 0.33 } 0.02 activity units/min~protein. Compound 1 significantly has increased the enzyme activity by 35% and 29% at concentrations of 10 and 50 ƒÊM, respectively. The baseline level of catalase activity has been 4.61 } 0.17 nmoles H2O2/min~mg protein and has significantly decreased by 15% with the action of the thiazole derivative at a concentration of 10 ƒÊM. The increase of superoxide dismutase activity in the case of decrease or absence of the changes in catalase activity have to be cytotoxic to cancer cells.

Since a liver is the main detoxification organ for most of drugs, including chemotherapeutic chemicals, hepatocytes have been selected in order to study the effects of substance 1 on healthy cells. It is known that the process of carcinogenesis not only causes the metastases in other organs (very often in a liver), but can also affect tissues in which metastases are not detected, that happens because of biologically active substances released by tumors to develop cancer. The state of the antioxidant defense system in normal liver of rats with grafted NK/Ly has been compared with the liver of the healthy rats without lymphoma. Superoxide dismutase activity have not differ in these two types of livers, while catalase activity has been drastically higher in the liver of rats with grafted lymphoma. The studied thiazole derivative has not affect the activity of the enzymes of the antioxidant system in the both type of livers.

In summary, the investigated thiazole derivative increases activity of superoxide dismutase in the lymphoma and does not affect the activity of the catalase (in doses 1 and 50 ƒÊM) or even reduces it (in 10 ƒÊM), that must increase the accumulation of H2O2 in the cancer cells. At the same time, compound 1 does not affect the activity of enzymes in the antioxidant system of the liver indicating the specificity of the action of this thiazole derivative in relation to cancer cells. Thus, these results show that cytotoxicity of newly synthetized thiazole derivative is related to the antioxidant system in lymphoma and can be used for further preclinical tests as a potential chemotherapeutic drug with the minimal effects on a liver.

Article recieved: 22.05.2018

Keywords: lymphoma, thiazole derivatives, antioxidant system, cytotoxicity

Full text: PDF (Ukr) 365K

  1. 1. Belenichev I, Levitskiy Ye, Gubskiy Yu. Antioxidant defense system. Mod Toxic Probl. 2002;3:21-31.
  2. 2. Bondar GV, Dumansky YuV, Popovich OYu. Oncology. K.: Medicine; 2013.542.
  3. 3. Korolyuk МА, Ivanova LI, Mayorova IH, Tokaryev VYe. Method for determination of catalase activity. Lab. Work. 1988;1:16-9.
  4. 4. Kostyuk VA, Potapovich AI, Kovaleva ZnV. A simple, sensitive assay for determination of superoxide dismutase activity based on reaction of quercetin oxidation. Problems of Medical Chemistry. 1990;2:88-91.
  5. 5. Menshchikova EB, Lankin VZ, Bondar NK, Krugovykh NF, Trufakin VA. Oxidative stress. Prooxidants and antioxidants. Мoscow: Slovo; 2006. 556.
  6. 6. Turov KV, Krupskaya TV, Barvinchenko VM. Antiradical Properties of Thiazole Derivatives. Influence on metabolic activity of yeast. Biotechnologia Acta. 2012;5(3):75-83.
  7. 7. Shalai YaR, Mandzynets SM, Hreniukh VP, Finiuk NS, Babsky AM. Free-radical processes in NK/Ly lymphoma cells and hepatocytes under the effect of thiazole derivative. Bulletin of Probl Biol and Med. 2018; 2(143):234-8.
  8. 8. Casado A1, de la Torre R, López-Fernández ME, Carrascosa D, Casado MC, Ramírez MV. Superoxide dismutase and catalase blood levels in patients with malignant diseases. Send to Cancer Lett. 1995;93(2):187-92.
  9. 9. Finiuk NS, Hreniuh VP, Ostapiuk YuV, Matiychuk VS, Frolov DA, Obushak MD, Stoika RS, Babsky AM. Antineoplastic activity of novel thiazole derivatives. Biopolym Cell. 2017;33(2):135-46
  10. 10. Finiuk NS, Ostapiuk YuV, Hreniuh VP, Shalai YaR, Matiychuk VS, Obushak MD, Stoika RS, Babsky AM. Evaluation of antiproliferative activity of pyrazolothiazolopyrimidine derivatives. Ukr Biochem J. 2018;90(2):16- 23.
  11. 11. Коbylinska LI, Klyuchivska OY, Grytsyna II, Finiuk NS, Panchuk RR, Starykovych MO, Lehka LV, Lesyk RB, Zіmenkovsky BS, Stoika RS. Differential pro-apoptotic effects of synthetic 4-thiazolidinone derivative Les-3288, doxorubicin and temozolomide in human glioma U251 cells. Croat Med J 2017;58(2):150-59.
  12. 12. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265-75.
  13. 13. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem Cell Biol. 2007;39(1):44-84.
  14. 14. Wag YH, Yang XL, Han X, Zhang LF, Li HL. Mimic of manganese superoxide dismutase to induce apoptosis of human non-Hodgkin lymphoma Raji cells through mitochondrial pathways. International Immunopharmacology. 2012;14(4):620-8. 15. Zhou CH, Wang Y. Recent researches in triazole compounds as medicinal drugs. Curr Med Chem. 2012; 19(2)

Програмування -