ENDOGENIC INTOXICATION IN RATS WITH EXPERIMENTAL CARCINOGENESIS AFTER APPLICATION OF CYTOSTATICS ON THE BACKGROUND OF SORPTION THERAPY
DOI:
https://doi.org/10.11603/mcch.2410-681X.2020.v.i2.11356Keywords:
oxidative stress, antioxidant system, dimethylhydrazine, enterosorbent AUT, cytostatic VincristineAbstract
Introduction. Every year the number of cancer patients with colorectal cancer is growing. The severity of the condition of patients is often due to hyperfunction of reactive oxygen species with subsequent violation of the body's antioxidant defenses. Therefore, it is important to study the effectiveness of cytostatics on the background of enterosorption therapy in conditions of endogenous intoxication.
The aim of the study – to evaluate the effectiveness of the use of the cytostatic Vincristine on the background of enterosorption therapy under conditions of oxidative stress in the body of rats affected by 1,2-dimethylhydrazine
Research Methods. The experiments were performed on white male rats simulated for colon cancer by weekly subcutaneous administration of 1,2-dimethylhydrazine at a dose of 7.2 mg/kg body weight for 30 weeks. Enterosorbent AUT was administered intragastrically daily for 21 days after modeling carcinogenesis at a dose of 1 ml of suspension (corresponding to 0.2 g of net weight of the drug) per 100 g of body weight of the animal. The cytostatic Vincristine was administered intragastrically daily to animals with induced carcinogenesis after 21 days of detoxification therapy for 14 days at a dose of 0.23 mg/kg body weight. The development of oxidative stress was studied by the activity of oxidative modification of proteins (OMB), the concentration of lipid peroxidation products (LPO) by the activity of superoxide dismutase (SOD), catalase.
Results and Discussion. The results of the study indicate that a 30-week administration of the xenobiotic 1,2-DMG promotes the development of oxidative stress. In experimental animals, the peroxidant and antioxidant balance is disturbed, which is accompanied by a decrease in the antioxidant system. The use of enterosorbent AUT contributed to the normalization of these parameters, and the cytostatic therapy had a negligible effect on the course of oxidative processes in the body of experimental animals.
Conclusion. The obtained results indicate the absence of a pronounced side effect of the cytostatic Vincristine and confirm the positive dynamics of the use of detoxification therapy with AUR sorbent during the progressive development of oxidative stress under the conditions of simulated carcinogenesis.
References
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R., Torre, L., & Jemal, A. (2018). Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 68, 394-424. DOI: https://doi.org/10.3322/caac.21492
Arigesavan, K., & Sudhandiran, G. (2015). Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1, 2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats. Biochem. Biophys. Res. Communю, 461 (2), 314-320. DOI: https://doi.org/10.1016/j.bbrc.2015.04.030
Hamiza, O.O., Rehman, M.U., & Tahir, M. (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 (9), 4393-4402.
Mikhalovsky, S.V. Sandeman, S.R., Howell, C.A., Phillips, G.J., & Nikolaev, V.G. (2012). Biomedical applications of carbon adsorbents. In Novel Carbon Adsorbents, 21, 639-669. DOI: https://doi.org/10.1016/B978-0-08-097744-7.00021-1
Nikolaev, V.G. Sakhno, L.A., & Snezhkova, E.A. (2011). Carbon adsorbents in oncology: achievements and perspectives. Exp. Oncol., 33, 2-8.
Madsen, M.L., Due, Н., Ejskjær, N., Jensen, Р., Madsen, J., & Dybkær, К. (2019). Aspects of Vincristine-induced neuropathy in hematologic malignancies: A systematic review. Cancer Chemother. Pharmacol., 84, 471-485. DOI: https://doi.org/10.1007/s00280-019-03884-5
Kozhemiakin, Yu.M., Khromov, O.S., Filonenko, M.A., & Saifetdinova, H.A. (2002). Naukovo-praktychni rekomen- datsii z utrymannia laboratornykh tvaryn ta roboty z nymy [Scientific and practical recommendations for the mainte- nance of laboratory animals and work with them]. Kyiv: Avitsena [in Ukrainian].
Deryagina, V.P., Ryzhova, N.I., & Razin, A.N. (2009). Eksperimentalnoye izucheniye deystviya LentinusEdodes (Shiitake) na rost opukholi u myshey na modelyakh trans plantatsionnogo i khimicheskogo kantserogeneza [Experimental study of the effect of LentinusEdodes (Shiitake) on tumor growth in mice on models of transplantation and chemical carcinogenesis]. Rossiyskiy onkologicheskiy zhurnal – Russian Journal of Oncology, 1, 33-38 [in Russian].
Rybolovlev, Yu.R., & Rybolovlev, R.S. (1979). Dozirovaniye veshchestv dlya mlekopitayushchikh po konstantam biologicheskoy aktivnosti [Dosing of substances for mammals according to the constants of biological activity]. Doklady AN SSSR – Reports of the Academy of Sciences of the USSR, 247 (6), 1513-1516 [in Russian].
Dubinina, E.E., & Pustyhina, A.V. (2008). Okislitelnaya modifikatsiya proteinov, yeye rol pripatologicheskikh sostoyaniyakh [Oxidative modification of proteins, its role in pathological conditions]. Ukr. biokhim. zhurn. – Ukrainian Biochemical Journal, 80 (6), 5-18 [in Russian].
Lushchak, V.I., Bahniukova, T.V. & Lushchak, O.V. (2004). Pokaznyky oksydatyvnoho stresu. Tiobarbituraktyvni produkty i karbonilni hrupy bilkiv [Indicators of oxi- dative stress. Thiobarbiturative products and carbonyl groups of proteins]. Ukrainskyi biokhimichnyi zhurnal – Ukrainian Biochemical Journal, 76 (6), 136-141 [in Ukrainian].
Koroliuk, M.A., Ivanova, L.I. & Maiorova, I.H. (1988). Metod opredeleniya aktivnosti katalazy [Method for determining the activity of catalase]. Lab. Delo – Lab. Business, 1, 16-19 [in Russian].
Chevari, S., Chaba, I. & Sekey, I. (1985). Rol super-oksiddismutazy v okislitelnykh protsessakh kletki i metod opredeleniya yeye v biologicheskikh materialakh [The role of superoxide dismutase in the oxidative processes of the cell and the method for determining it in biological materials]. Lab. delo – Lab. Business, 1, 678-681 [in Russian].
Okeh, U. (2009). Statistical problems in medical research. East. Afr. J. Public. Health., 6 (1), 1-7. DOI: https://doi.org/10.4314/eajph.v6i3.45762
Marushchak, M.I. (2012). Rol aktyvnykh form kysniu u rozvytku i prohresuvanni hostroho urazhennia lehen v eksperymenti [Role of reactive oxygen species in the development and progression of acute lung injury in experiment]. Med. khimiia – Med. Chemistry, 1 (50), 104-108 [in Ukrainian].
Perše, M., & Cerar, A. (2005). The dimethylhydrazine induced colorectal tumours in rat – experimental colorectal carcinogenesis. Radiology and Oncology, 39 (1), 61-70.
Zyn, A. (2012). Prooksydantno-antyoksydantnyi homeostaz i membrannyi transport u zhyvykh orhanizmakh [Prooxidant-antioxidant homeostasis and membrane transport in living organisms]. Visnyk Lvivskoho universytetu – Bulletin of Lviv National University, 60, 21-39 [in Ukrainian].
Harzallah, H.J., Grayaa, R., Kharoubi, W., Maaloul, A., Hammami, M., & Mahjoub, T. (2012). Thymoquinone, the Nigella sativa bioactive compound, prevents circulatory oxidative stress caused by 1,2-dimethylhydrazine in erythrocyte during colon postinitiation carcinogenesi. Oxid. Med. Cell Longev., 4, 1-6. DOI: https://doi.org/10.1155/2012/854065
Hamiza, O.O., Rehman, M.U., Tahir, M., Khan, R., Khan, A.Q., Lateef, A., Ali, F., et al. (2012). Amelioration of 1,2 dmethylhydrazine (DMH) induced colon oxidative stress, inflammation and tumor promotion response by tannic acid in Wistar rats. Asian Pacific Journal of Cancer Prevention, 13 (9), 4393-4402. DOI: https://doi.org/10.7314/APJCP.2012.13.9.4393
Poprac, P., Jomova, K., & Simunkova, M. (2017). Targeting free radicals in oxidative stress-related human diseases. Trends Pharmacol. Sci., 38 (7), 592-607. DOI: https://doi.org/10.1016/j.tips.2017.04.005
Mandal P. (2017). Potential biomarkers associated with oxidative stress for risk assessment of colorectal cancer. Naunyn Schmiedebergs Arch. Pharmacol., 390 (6), 557-565. DOI: https://doi.org/10.1007/s00210-017-1352-9