EFFECTIVENESS OF THE USE OF GLUTARGINE TO ELIMINATE THE SIDE EFFECTS OF CYTOSTATICS IN THE CONDITIONS OF EXPERIMENTAL CARCINOGENESIS
DOI:
https://doi.org/10.11603/mcch.2410-681X.2022.i2.13201Keywords:
induced carcinogenesis, lipoperoxidation, oxidative modification of proteins, endogenous intoxication, Xeloda, GlutarginAbstract
Introduction. According to personalized data of the National Registry of Ukraine, colon cancer is one of the three most common types of cancer among Ukrainians of both sexes. Studying the mechanisms of the effect of cytostatic drugs on the development of colorectal cancer is an urgent problem today. Most of these agents cause side effects after their use, among which hepatotoxicity, cardiotoxicity and neurotoxicity are the most pronounced. In this case, it is advisable to use drugs that would eliminate the side effects of chemotherapy.
The aim of the study – to investigate the activity of free radical processes and the degree of endogenous intoxication in rats with induced colorectal cancer after the use of the cytostatic Xeloda and the hepatoprotector Glutargin.
Research Methods. The experiments were conducted on 72 white male rats in compliance with all the rules of the Convention on the Protection of Vertebrate Animals. Modeling of colorectal cancer was carried out with 1,2-dimethylhydrazine hydrochloride at a dose of 7.2 mg/kg of body weight. Some groups of animals against the background of the development of colorectal cancer received cytostatic Xelodu in a dose of 134 mg/kg of body weight. Several more groups of rats were exposed to the hepatoprotector Glutargin at a dose of 130 mg/kg of body weight to eliminate the side effect of Xeloda on the liver. Euthanasia was performed under thiopental anesthesia. The study was conducted every 30 days for 7 months. The content of products of lipoperoxidation and oxidative modification of proteins, as well as molecules of average mass in blood serum was determined.
Results and Discussion. Under the conditions of induced carcinogenesis, the content of TBA-active products increased in the blood serum and liver of rats, which reached a maximum at the 7th month of the study (in the blood serum it increased by 3.5 times, in the liver by 2.6 times). The use of Xeloda led to an even greater increase in this indicator. A similar increase during carcinogenesis and after the use of Xeloda was also noted for the products of oxidative modification of proteins of both neutral and basic nature. The introduction of the hepatoprotector Glutargin into the affected body caused a probable (p<0.05) decrease in these parameters. Along with an increase in oxidative processes in the liver of rats with induced carcinogenesis, an increase in the content of medium-mass molecules in blood serum was observed, as indicated by the distribution coefficient between both fractions (with a predominance of chain and aromatic amino acids). The use of Glutargin proved to be effective for this indicator as well.
Conclusions. The use of cytostatic Xeloda led to a more pronounced activation of lipoperoxidation processes and oxidative modification of proteins in the body of rats with experimental carcinogenesis. The effectiveness of the use of the hepatoprotector Glutargin to eliminate the side effect of Xeloda on the liver in rats with colorectal cancer has been confirmed, which makes it possible to recommend it for further research with the aim of introducing it into clinical practice.
References
Fedorenko, Z.P., Gulak, L.O., Mykhailovych, Yu.Y., Goroh, E.L., Ryzhov, A.Yu., Sumkina, O.V., & Kutsenko, L.B. (2017). Cancer in Ukraine, 2015–2016. Morbidity, mortality, performance indicators of the oncology service. Byul. national Chancery Registry of Ukraine, Kyiv, 18, 130. Retrieved from: http://www.ncru.inf.ua/publications/BULL_18/index.htm. [in Ukrainian].
American Cancer Society. Colorectal Cаncer Facts and Figures 2014-2016. Atlanta: American Cancer Society. Retrieved from: file:///C:/Users/admin/Downloads/colorectal-cancer-facts-and-figures-2014-2016.
Hameeza, Come O, Rehman, Munib U., Tahir, Mir, Khan, Rehan, Khan, Abdul Quayyum, Latif, Ali, Farrah, & Sultana, Sarwat (2012). Amelioration of 1,2 dimethylhydrazine (DMH) induced colon oxidative stress, inflammation and tumor promotion response by tannic acid in Wistar rats. Asian Pacific Journal of Cancer Prevention, 13, 4393-4402. PMID: 23167349 DOI: 10.7314/apjcp.2012.13.9.4393
Lynchak, O.V., Rybalchenko, V.K., Carpezo, N.O., Ostrovska G.V., & Babuta, O.M. (2012). Hepatotoxicity of 1,2-dimethylhydrazine in modeling colorectal cancer in rats. Modern Problems of Toxicology, 1 (2), 29-34. Retrieved from: http://library.zsmu.edu.ua/cgi/irbis64r_14/cgiirbis_64.exe [in Ukrainian].
Filinska, O.M., Yablonska, S.V., Mandryk, S.Ya., Kharchuk, I.V., Ostrovska, G.V., & Rybalchenko, V.K. (2010). The state of the antioxidant system of the liver and the content of matrix metalloproteinase-2 in the large intestine in the case of the action of a maleimide derivative during experimental colorectal carcinogenesis in rats. Ukr. biochem. Journal, 4 (82), 69-77. Retrieved from: http://ubj.biochemistry.org.ua/images/stories/pdf/ubj4. [in Ukrainian].
Soroka, Yu.V. (2013). Metabolic disorders in chronic neoplastic intoxication and the use of cytostatic therapy. Medicine and Education in Siberia, 2, 16-19 [in Ukrainian].
Dobrova, N.V. (2011). The use of xeloda in the treatment of patients with metastatic colorectal cancer. Oncology, 13 (1), 41-45. Retrieved from: http://dspace.nbuv.gov.ua/bitstream/handle/123456789/19685/41.pdf [in Ukrainian].
Karnabeda, O.A., Tkach, S.M., Perederiu, V.G., & Chichula, Yu.V. (2013). Toxic liver damage in patients with oncological pathology (treatment diagnostics). Clinical Oncology, 1 (9), 125-131. Retrieved from: https://www.clinicaloncology.com.ua/article/7342/ [in Ukrainian].
Hrytsyshyn, L.E., Fira, L.S., & Lykhatskyi, P.H. (2020). Oxidative stress and endogenous intoxication in rats under conditions of experimental carcinogenesis and after the use of cytostatics. Herald of Problems of Biology and Medicine, 1 (155), 112-116. Retrieved from: http://dx.doi.org/10.29254/2077-4214-2020-1-155-112-116[in Ukrainian].
Harmanchuk, L.V., Senchylo, N.V., Nikulina, V.V., Denis, E.O., Nikolayenko, T.V., & Ostapchenko L.I. (2011). Cytotoxic effect on tumor cells in vitro of agents with antitumor and antimetastatic effects. Physics of the Living,19 (2), 51-53. Retrieved from: https://cyberleninka.ru/article/n/tsitotoksichniy- [in Ukrainian].
Andreychyn, S.M., & Skirak, Z.S. (2014). The influence of glutargin on the binding function of serum albumin and other indicators of the functional state of the liver in acute toxic hydrazine hepatitis. Medical and Clinical Chemistry, 4 (16), 66-69. DOI: https://doi.org/10.11603/16812557.2014.v16.i4.4029[in Ukrainian].
Gross, D., & Tolba, R. (2015). Ethics in animal-based research. Eur. Surg. Res., 55 (1-2), 43-57. DOI: 10.1159/000377721
Rybolovlev, Y.R., & Rybolovlev R.S. (1979). Dosing of substances for mammals according to biological activity constants. Proceedings of the Academy of Sciences of the USSR, 247 (6), 1513-1516 [in Russian].
Lushchak, V.I., Bagniukova, T.V., & Lyzna, L.I. (2006). Indicators of oxidative stress. 2. Lipid peroxides. Ukr. biochem. Journal, 78 (5), 113-119. Retrieved from: http://ubj.biochemistry.org.ua/index.php/journal-archiveac/ww2006/5-nvx [in Ukrainian].
Dubinina, E.E., & Pustigina, A.V. (2008). Oxidative modification of proteins, their role in pathological conditions. Ukrainian Biochemical Journal, 80 (6), 5-18. Retrieved from: http://ubj.biochemistry.org.ua/index.php/journal-archiveac/[in Ukrainian].
Nikolskaya, V.A., Danilchenko, J.D, & Memetova, Z.N. (2013). Biochemical aspect of consideration of the role of molecules of average mass in the body in the body. Uchenye zapiski Tavricheskogo natsionalnogo universiteta im. V. I. Vernadsky. Ser.: Biology, Chemistry, 1 (65), 139-145. Retrieved from: https://cyberleninka.ru/article/n/biohimicheskiy- [in Russian].
Okeh, U. (2009). Statistical problems in medical research. East. Afr. J. Public. Health, 6 (1), 1-7. DOI: 10.4314/eajph.v6i3.45762
Ovsyannikova, L.M. (2007). [Methods of evaluating free radical oxidation and the state of the body’s antioxidant system in clinical practice]. Kyiv: Vyshcha shkola [in Ukrainian].
Bhagat, Sonali S., Ghoun, Rahul A., Suryakar, Adinath N., & Khundekar, Prakash S. (2011). Lipid peroxidation and antioxidant vitamin status in colorectal cancer patients. Indian J Physiol Pharmacol, 55 (1), 72–76. https://pubmed.ncbi.nlm.nih.gov/22315813/
Muravieva, L.E. (2010). Oxidative modification of proteins: problems and prospects of research. Fundamental research, 1, 74–78. https://fundamental-research.ru/ru/article/view?id=1617 [in Russian].
Cai, Z., & Liang-Jun, Yan (2013). Protein Oxidative Modifications: Beneficial Roles in Disease and Health. J. Biochem. Pharmacol. Res. 1(1),15–26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646577/
Kachur, O.I., Fira, L.S., & Lykhatskyi, P.H. (2020). Endogenous intoxication in rats with experimental carcinogenesis after the use of cytostatics against the background of sorption therapy. Medical and clinical chemistry, 2, 39-46. DOI 10.11603/mcch.2410-681X.2020.v.i2.11356 [in Ukrainian].
Zhukov, V.I., Perepadya, S.V., Barannikov, K.V., Vinnyk, Yu.O., Zaitseva, O.V., Kyzhavko, V.G., & Moiseyenko A.S. (2012). Conjugation of the metabolic activity of the intestinal microbiocenosis and its barrier function and the level of endogenous intoxication in patients with colorectal cancer. Experimental and Clinical Medicine, 2 (55), 58-65. http://www.irbis-nbuv.gov.ua/cgi-bin/irbis_nbuv/cgiirbis_64.exe [in Ukrainian].
Gromashevskaya, L.L. (2006). Metabolic intoxication in pathogenesis and diagnostics of pathological processes. Laboratory Diagnosis, 1 (35), 3-13 [in Ukrainian].
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Medical and Clinical Chemistry
This work is licensed under a Creative Commons Attribution 4.0 International License.
