INFLAMMATION AND IMPACT OF VINCRISTINE AND ENTEROSORPTION USE IN CHEMICALLY INDUCED COLON CARCER IN RATS
Keywords:inflammatory processes, proinflammatory interleukins, anti-inflammatory interleukins, AUT-M sorbent, cytostatic Vincristine
Background. The increasing incidence of colon malignant tumors is one of the most urgent matters of contemporary medicine. In the study of carcinogenesis of the colon the attention is paid to the state of the body’s immune system and activation of inflammatory processes in experimental animals.
Objective. The aim of the study was to estimate the level of markers of inflammation in the serum of experimental animals with chemically induced carcinogenesis and their dynamics in case of administration of the cytostatic Vincristine secondary to AUT-M carbon enterosorbent.
Methods. The study was performed on white male rats. Animals were modeled for colon cancer by administration of 1.2-dimethylhydrazine hydrochloride at a dose of 7.2 mg/kg body weight for 30 weeks. AUT-M enterosorbent was administered intragastrically daily during 7 and 21 days after modeling of carcinogenesis at a dose of 1 ml of suspension (corresponding to 0.2 g of drug weight) per 100 g of animal body weight. The antitumor drug was administered to the animals with induced carcinogenesis intragastrically daily during 14 days at a dose of 0.23 mg/kg of body weight after a 21-day detoxification therapy. The activity of inflammatory processes was evaluated by the content of pro-inflammatory interleukin 6 and anti-inflammatory interleukin 4, C-reactive protein in the serum of experimental animals.
Results. It was established that introduction of 1.2-dimethylhydrazine hydrochloride in the rats caused changes in the cytokine profile and the content of C-reactive protein. In the affected animals an increase in the content of pro-inflammatory interleukin 6, C-reactive protein, as well as a decrease in the content of anti-inflammatory interleukin 4 was evidenced in all periods of the study. AUT-M enterosorbent contributed to normalization of these parameters. The cytostatic Vincristine had a negligible effect on development of inflammatory processes in the studied animals.
Conclusions. In cases of induced carcinogenesis, an imbalance in the content of pro- and anti-inflammatory cytokines, an increase in the content of acute-phase C-reactive protein was established. The positive effect of the cytostatic Vincristine secondary to a previous detoxification therapy with AUТ-M sorbent during a progressive development of inflammatory processes in the presence of modeled carcinogenesis was evidenced.
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424.
Karmazina IS, Kulinich VA. Correlation analysis of protein metabolism indices at carcinogenesis and inflammation. Natural Almanac.2015;12: 112-8.
Zhang X, Liu S, Zhou Y. Circulating levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α and risk of colorectal adenomas: a meta-analysis. Oncotarget. 2016 Sep 27;7(39):64371-79.
Gross D, Tolba R. Ethics in animal-based research. Eur. Surg. Res. 2015;55(1-2):43–57. doi: 10.1159/000377721
Zhou B, Shu B, Yang J, et al. C-reactive protein, interleukin-6 and the risk of colorectal cancer: a meta-analysis. Cancer Causes Control, 2014;25(10): 1397-1405.
Madsen ML, Due H, Ejskaer N, et al. Aspects of Vincristineinduced neuropathy in hematologic malignancies: A systematic review. Cancer Chemother Pharmacol. 2019; 84:471–85.
Nikolaev VG, Sakhno LA, Snezhkova EA, Yushko LA. Саrbon adsorbents: achievements and perspec- tives. Experimental Oncology, 2011;1: 2-8.
Howell CA, Sandeman SR, Zheng Y, et al. New dextran coated activated carbons for medical use. Carbon N. Y. 2016;97:134-46.
Deryagina VP, Ryzhova NI, Razin AN. Experimental study of the action of Lentinus edodes (Shiitake) on tumor growth in mouse models of transplantation and chemical carcinogenesis. Rossijskij onkologicheskij zhurnal. 2009(1):33-8.
Mikhalovsky SV., Sandeman SR, Howell CA, et al. Biomedical Applications of Carbon Adsorbents. In Novel Carbon Adsorbents,2012;21:639-69.
Rybolovlev YuR. Dosing of substances for mammals according to the constants of biological activity. Reports of the Academy of Sciences of the USSR, 1979; 247(6): 1513-6.
Kozhemiakin YuM, Khromov OS, Filonenko MA, et al.: Scientific and practical recommendations for the maintenance of laboratory animals and work with them. Kyiv - State Pharmacological Center of the Ministry of Health of Ukraine. Kiev, 2002.
Gaber W, Azkalany GS, Gheita TA, Mohey A, Sabry R. Clinical significance of serum interleukin-6 and− 174 G/C promoter polymorphism in Rheumatoid arthritis patients. The Egyptian Rheumatologist. 2013 Apr 1;35(2):107-13.
Alybaeva KM, Berdyyarova NA, Mukhamed-zhanova NK, et al. Analysis of the quantitative determination of the level of C-reactive protein and procalcitonin in patients with infectious diseases. Bulletin of AGIUV. 2015;1-2:36-40.
Okeh U. Statistical problems in medical research. East. Afr. J. Public. Health. 2009;6 (1):1-7.
Andreichyn SM, Lototska SV, Meretskyi VM. Changes in the indices of cytokine immunity in patients with COPD when using enterosorption. Infectious Diseases, 2015; 3:44-7.
Gaber W, Azkalany GS, Gheita TA, Mohey A, Sabry R. Clinical significance of serum interleukin-6 and 174 G/C promoter polymorphism in Rheumatoid arthritis patients. The Egyptian Rheumatologist. 2013 Apr 1;35(2):107-13.
Godos J, Biondi A, Galvano F, et al. Markers of systemic inflammation and colorectal adenoma risk: Meta-analysis of observational studies. World journal of gastroenterology. 2017 Mar 14;23(10):1909-19.
Kim MH, Moon HS, Kwon IS, et al. The incidence and risk factors of sessile serrated adenomas in left side colon cancer patients after curative surgery. Medicine. 2020 Jul 17;99(29).
How to Cite
Authors who sent their manuscript to International Journal of Medicine and Medical Research agree to the following terms:
1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License CC-BY-NC that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
2. Authors able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).