Download full text in PDF

Bìol. Tvarin. 2023; 25 (3): 3–7.
https://doi.org/10.15407/animbiol25.03.003
Received 23.05.2023 ▪ Revision 13.07.2023 ▪ Accepted 20.09.2023 ▪ Published online 02.10.2023

---

Activity of antioxidant enzymes in hepatocytes of mice with lymphoma under the action of thiazole derivative in complex with polymeric nanocarrier

B. Omeliukh¹, Ya. Shalai¹, M. Bura¹, M. Ilkiv¹, Yu. Ostapiuk¹, N. Mitina², O. Zaichenko², A. Babsky¹

This email address is being protected from spambots. You need JavaScript enabled to view it.

¹Ivan Franko National University of Lviv, 4 Hrushevsky str., Lviv 79005, Ukraine
²Lviv Polytechnic National University, 9 St. Yura sq., Lviv 79013, Ukraine

---

Many chemotherapeutics drugs have low water solubility, which potentially can decrease their anticancer potential. The use of drug delivery systems has proven to be highly effective in addressing the challenges associated with delivering hydrophobic chemotherapy drugs to tumor tissues. However, two major issues that arise in the clinical nanoparticle-based treatment of cancer are hepatotoxicity and suppression of the hematopoietic system, which can limit their medical applicability. As previously established, thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide in complex with polymeric nanocarriers (nanomicelles) based on polyethylene glycol exhibited a greater level of cytotoxicity towards specific tumor cell lines melanoma, glioblastoma, hepatocarcinoma, leukemia, etc. This compound and its complexes with polymeric nanomicelle significantly changed the activity of antioxidant enzymes in lymphoma cells. Therefore, the purpose of this study was to examine the impact of a thiazole derivative with polymeric nanomicelles based on polyethylene glycol on the hepatocytes (liver cells) of mice that had been implanted with Nemet-Kelner lymphoma. The investigated compounds thiazole derivative, polymeric nanomicelle, and combination of thiazole derivative with nanomicelle at a final concentration of 10 μM were added to the liver samples and incubated for 10 min. The activity of antioxidant defense system enzymes such as superoxiddismutase, catalase, glutathionperoxidase was determined in liver homogenate under the action of studied compounds in vitro. It was reported that neither thiazole derivative, nanomicelle, nor their complex changed the activity of antioxidant enzymes in hepatocytes from mice with lymphoma. Thiazole derivative and it complex with nanomicelle had limited negative side effects in the mice with lymphoma. The investigated compounds were not hepatotoxic toward murine liver cells.

---

Key words: antitumor drugs, nanomicelle, hepatotoxicity, antioxidant system

1. AlAsmari AF, Ali N, AlAsmari F, AlAnazi WA, Alqahtani F, Alharbi M, Alotaibi FM, Aldossari AA, AlSwayyed M, Alanazi MM, Alshamrani AA. Elucidation of the molecular mechanisms underlying sorafenib-induced hepatotoxicity. Med. Cell. Longev. 2020; 2020: 7453406. DOI: 10.1155/2020/7453406.
2. Bose A, Roy Burman D, Sikdar B, Patra P. Nanomicelles: Types, properties and applications in drug delivery. IET Nanobiotechnol. 2021; 15 (1): 19–27. DOI: 10.1049/nbt2.12018.
3. Chmielewski PP, Strzelec B. Elevated leukocyte count as a harbinger of systemic inflammation, disease progression, and poor prognosis: a review. Folia Morphologica. 2018; 77 (2): 171–178. DOI: 10.5603/FM.a2017.0101.
4. Cornu R, Béduneau A, Martin H. Influence of nanoparticles on liver tissue and hepatic functions: A review. Toxicol. 2020; 430: 152344. DOI: 10.1016/j.tox.2019.152344.
5. Cui Y, Liu H, Zhou M, Duan Y, Li N, Gong X, Hu R, Hong M, Hong F. Signaling pathway of inflammatory responses in the mouse liver caused by TiO₂ J. Biomed. Mat. Res. A. 2010; 96A (1): 221–229. DOI: 10.1002/jbm.a.32976.
6. Hadwan MH, Ahmed AY. A validated method to assess glutathione peroxidase enzyme activity. Preprint. 2021: v. 1. DOI: 10.21203/rs.3.rs-526347/v1.
7. Hamza TA, Hadwan MH. New spectrophotometric method for the assessment of catalase enzyme activity in biological tissues. Preprint. 2019: v. 1. DOI: 10.20944/preprints201910.0323.v1.
8. Finiuk NS, Hreniuh VP, Ostapiuk YV, Matiychuk VS, Frolov DA, Obushak MD, Stoika RS, Babsky AM. Antineoplastic activity of novel thiazole derivatives. Cell. 2017; 33 (2): 135–146. DOI: 10.7124/bc.00094B.
9. Finiuk NS, Popovych MV, Shalai YR, Mandzynets SM, Hreniuh VP, Ostapiuk YV, Obushak MD, Mitina NE, Zaichenko OS, Stoika RS, Babsky AM. Antineoplastic activity in vitro of 2-amino-5-benzylthiasol derivative in the complex with nanoscale polymeric carriers. Gen. 2021; 55 (1): 19–27. DOI: 10.3103/S0095452721010084.
10. Harrington KJ. Chemotherapy and targeted agents. Surg. 2017; 1: 339–354. DOI: 10.1016/B978-0-7020-6056-4.00022-8.
11. Ilkiv MV, Shalai YR, Manko BO, Ostapiuk YV, Mitina NE, Zaichenko AS, Babsky AM. Generation of ROS under the influence of thiazole derivative and its complexes with PEG-based polymeric nanoparticles. Cell. 2022; 38 (3): 158–168. DOI: 10.7124/bc.000A7D.
12. Kiss M, Caro AA, Raes G, Laoui D. Systemic reprogramming of monocytes in cancer. Oncol. 2020; 10: 1399. DOI: 10.3389/fonc.2020.01399.
13. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. Biol. Chem. 1951; 193 (1): 265–275. DOI: 10.1016/S0021-9258(19)52451-6.
14. Mandaliya H, Baghi P, Prawira A, George MK. A Rare case of paclitaxel and/or trastuzumab induced acute hepatic necrosis. Case Rep. Oncol. Med. 2015; 2015: 825603. DOI: 10.1155/2015/825603.
15. Mitina NY, Riabtseva AO, Garamus VM, Lesyk RB, Volyanyuk KA, Izhyk OM, Zaichenko OS. Morphology of the micelles formed by a comb-like PEG-containing copolymer loaded with antitumor substances with different water solubilities. J. Phys. 2020; 65 (8): 670. DOI: 10.15407/ujpe65.8.670.
16. Navya PN, Kaphle A, Srinivas SP, Bhargava SK, Rotello VM, Daima HK. Current trends and challenges in cancer management and therapy using designer nanomaterials. Nano Converg. 2019; 6 (1): 23. DOI: 10.1186/s40580-019-0193-2.
17. Paoletti F, Aldinucci D, Mocali A, Caparrini A. A sensitive spectrophotometric method for the determination of superoxide dismutase activity in tissue extracts. Biochem. 1986; 154 (2): 536–541. DOI: 10.1016/0003-2697(86)90026-6.
18. Ramadori G, Cameron S. Effects of systemic chemotherapy on the liver. Hepatol. 2010; 9 (2): 133–143. DOI: 10.1016/S1665-2681(19)31651-5.
19. Shalai YR, Popovych MV, Mandzynets SM, Hreniukh VP, Finiuk NS, Babsky AM. Prooxidant and antioxidant processes in the liver homogenate of healthy and tumor-bearing mice under the action of thiazole derivatives. Biochem. J. 2021; 93 (3): 61–67. DOI: 10.15407/ubj93.03.061.
20. Tawfik SM, Azizov S, Elmasry MR, Sharipov M, Lee YI. Recent advances in nanomicelles delivery systems. Nanomaterials. 2020; 11 (1): 70. https://doi.org/10.3390/nano11010070.
21. Vincenzi B, Armento G, Spalato Ceruso M, Catania G, Leakos M, Santini D, Minotti G, Tonini G. Drug-induced hepatotoxicity in cancer patients — implication for treatment. Expert Opin. Drug Saf. 2016; 15 (9): 1219–1238. DOI: 10.1080/14740338.2016.1194824.