OXIDATIVE STRESS AND ENDOGENOUS INTOXICATION IN RATS UNDER CONDITIONS OF EXPERIMENTAL CARCINOGENESIS AND AFTER THE USE OF CYTOSTATICS

Grytcishin L. E., Fira L. S., Lykhatskyi P. H.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

The development of malignant tumors, including the correct ones, is accompanied by oxidative stress, which manifests itself at all stages of carcinogenesis. A significant number of people with cancer die from the socalled endogenous intoxication, which occurs with this pathology. To suppress tumor growth, cytostatic agents are used, which often show a side effect and cause disorders in the body. The aim of the work was to elucidate the features of the course of oxidative stress and endogenous intoxication in rats with simulated carcinogenesis against the background of the use of cytostatics. The experiments were performed on white male rats, which were colon cancer modeled by weekly subcutaneous administration of 1,2-dimethylhydrazine at a dose of 7.2 mg/kg body weight for 30 weeks. As components of cytostatic therapy, Xeloda was used in a dose of 134 mg/kg body weight of the animal for 21 days after modeling of colon adenocarcinoma. In the serum of blood and liver, the content of TBA-active products and the oxidative modification of proteins were studied. The degree of endogenous intoxication was evaluated for the content of medium weight molecules in blood serum. Under experimental carcinogenesis, there was a progressive increase in the content of TBA-active products in the blood serum and liver, and the oxidative modification of proteins and medium-weight molecules in the blood serum, the rates of which by the end of the experiment (7 months) were the highest. The use of the chemotherapeutic drug Xeloda led to an even greater increase in oxidative stress and endogenous intoxication in the affected body, which indicates a side effect when used. This leads to the search for drugs that would eliminate the negative impact of cytostatic.

oxidative stress, endogenous intoxication, carcinogenesis, cytostatic therapy.

1. Kancer-reestr Ukrainy. Dostupno: www.health.gov.ua [in Ukrainian].
2. Karjakina EV. Molekuly srednei massy kak integralnyi pokazatel metabolicheskih narushenii: (obzor. let.). Klinicheskaja laboratornaja diagnostica. 2004;3:3-7. [in Russian].
3. Nikolskaja VA. Biohimicheskii aspect rassmotrenija roli molekul srednei massy v organizme. Uchyonye zapiski Tavricheskogo nacionalnogo universiteta im. V. I. Vernadskogo Ser.: Biologia, himia. 2013;1(65):139-45. [in Russian].
4. Bendardaf R. Prognostic and predictive molecular markers in colorectal carcinoma. Anticancer Res. 2004;4:2519-30.
5. Gunina LM. Oksydatyvnyi stress i jogo rol v kancerogenezi. Phiziologichnyi zhurnal. 2006;4:78-88. [in Ukrainian].
6. Dimant II, Sharipov RK, Murathodzhaev NK. Okislitelnii procesy i opuholevyi rost. Tashkent: Izd.-poligraf. Obedinenie im. Ibn. Siny; 2012. 155 s. [in Russian].
7. Reuter S. Oxidative stress, inflammation, and cancer: How are they linked? Free Radic Biol Med. 2010;11:1603-16.
8. Sánchez-Pérez Y. Oxidative stress in carcinogenesis. Correlation between lipid peroxidation and induction of preneoplastic lesions in rat hepatocarcinogenesis. Cancer Letters. 2005;1:25-32.
9. Skrzydlewska E, Sulkowski S, Koda M. Lipid peroxidation and antioxidant status in colorectal cancer. World J Gastroenterol. 2005;3:403-6.
10. Seyfried T, Shelton L. Cancer as a metabolic disease. Nutrition & Metabolism. 2010;7:1-22.
11. Bhagat S, Ghone R, Suryakar A. Lipid peroxidation and antioxidant vitamin status in colorectal cancer patients. Indian J Physiol Pharmacol. 2011;1:72-6.
12. Viganò L. Liver surgery for colorectal metastases: results after 10 years of follow-up. Long-term survivors, late recurrences, and prognostic role of morbidity. Ann. Surg. Oncol. 2008;15(9):2458-64.
13. Dubinina EE, Pustygina AV. Okysljuvalna modyfikacija proteiniv, ih rol pry patologichnyh stanah. Ukrainskyi biohimichnyi zhurnal. 2008;6:5-18. [in Ukrainian].
14. Gür T, Demir H, Cetin M. Tumor markers and biochemical parameters in colon cancer patients before and after hhemotherapy. Asian pacific journal of cancer prevention. 2011;12:3147-50.
15. Gross D, Tolba R. Ethics in Animal-Based Research. Eur. Surg. Res. 2015;55(1-2):43-57.
16. Derjagina VP, Ryzhova NI. Eksperimentalnoe izuchenie deistvia Lentinus Edodes (Shyitake) na rost opuholi u myshei na modeljah transplantacionnogo i himicheskogo kancerogeneza. Rosiiskii onkologicheskii zhurnal. 2009;1:33-8. [in Russian].
17. Dobrova NV. Priminenie kselody v lechenii pacientov s metastaticheskim kolorektalnym rakom. Onkologia. 2011;1:41-5. [in Russian].
18. Muravjova LE. Okislitelnaja modifikacia belkov: problem i perspektivy issledovania. Phundamentalnye issledovania. 2010;1:74-8. [in Russian].
19. Panina LV, Terlecka OI. Ocinka endogennoi intoksykacii organizmu za umov eksperymentalnoi gemichnoi gipoksii. Zdobutky klinichnoi I eksperymentalnoi medycyny. 2008;2:72-6. [in Ukrainian].
20. Okeh U. Statistical problems in medical research. East. Afr. J. Public. Health. 2009;6(1):1-7.
21. Banyra OB, Stroi AA, Shuljak AV. Markery opuholevogo rosta v diagnostike raka. Eksperimentalnaja I klinicheskaja urologija. 2011;4:72-8. [in Russian].
22. Luschak VI. Pokaznyky oksydatyvnogo stresu. Tiobarbituratni produkty i karbonilni grupy bilkiv. Ukrainskyi biohimichnyi zhurnal. 2004;6:136- 41. [in Ukrainian].

«Bulletin of problems biology and medicine» Issue 1 (155), 2020 year, 112-116 pages, index UDK 612.186:599.32+615.9-085]- 092.4

10.29254/2077-4214-2020-1-155-112-116