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ECPB 2022, 94(1): 53–60
https://doi.org/10.25040/ecpb2022.01-02.053
Research articles

Effects of mitomycin C on pro-/antioxidant system of blood lymphocytes

D.R. SHEREMETA, O.P. SVERDAN, D.Z. VOROBETS, R.V. FAFULA, Z.D. VOROBETS
Abstract

Mitomycin С is an antibiotic obtained from natural sources, mechanism of action is related to the formation of cross-links with DNA that prevents the action of helicase and consequently cell proliferation. Mitomycin is given intravenously, intravesically, intraperitoneally, also can be used topically to treat or prevent scarring in the postoperative period, in particular urethral strictures. Mitomycin C has anti-fibroblastic properties and prevents the collagen formation in tissues. However, it is known that a wide range of antibiotics and cytostatics can also cause oxidative stress. And lipid peroxidation is the universal mechanism of cell membrane damage in various pathologies. The gluthatione antiperoxide system plays a leading role in the disposal of secondary peroxidation products and other oxidized substances. Lymphocytes are the heterogeneous cell population and a central link in specific immune response, they rapidly respond to oxidative stress and according to various research studies, activity of antioxidant enzyme defense system can serve as a marker for pathological conditions and adaptive mechanisms. Based on this, the purpose of this research, which was conducted on peripheral blood lymphocytes, was to elucidate the link between the action of mitomycin C and the state of pro-/ antioxidant system. We conducted a comparative study of the action of mitomycin C on the lipid peroxidation process and glutathione system in peripheral blood lymphocytes. The growth of lipid peroxidation process with action of different mitomycin concentrations has been shown, which was evaluated by determining the malonic dialdehyde concentrations. Under the action of mitomycin C glutathione peroxidase activity dose-dependently increases at all its concentrations and reaches its highest value at 10 -3 М concentration, however, reduced glutathione concetration at drug concentrations of 10 -6 –10 -4 М does not change concerning control values. Glutathione reductase activity reliably increases under the action of mitomycin C at 10 -6 М and 10 -5 М concentrations and reliably reduces at higher concentrations (10 -3 М). At all investigated mitomycin C concentrations glutathione-S-transferase activity reduces reliably and dose-dependently. Thus, in addition to the main mechanism of action of mitomycin C that is the formation of cross-links with DNA, inhibition of fibroblast proliferation and prevention of postoperative scarring, this drug significantly affects pro-/ antioxidant status of blood lymphocytes.

Received: 18.04.2022

Keywords: Mitomycin C, lymphocytes, oxidative stress, lipid peroxidation, glutathione system

Full text: PDF (Ukr) 491K

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