MITOMYCIN C IN THE TREATMENT OF URETHRIC STRICTURE AND ITS EFFECT ON ARGINASE/NO-SYNTHASE SYSTEM

Sheremeta D.R., Sverdan O.P., Vorobets D.Z., Fafula R.V., Vorobets Z.D.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Mitomycin C is used to treat or prevent scar formation, urethral strictures in particular, in the postoperative period. Depending on the location of operating field, it is administered intravenously, intravesically, intraperitoneally, and topically. Cicatricial changes are one of the postoperative complications. Mitomycin C has significant anti-fibroblastic properties and prevents collagen production in tissues. However, it is known that a wide range of antibiotics and cytostatics can also affect the cell regulatory systems. The nitric oxide system is an important regulatory system, which includes enzymes such as arginase and certain nitric oxide synthase isoforms. The objective of the study is to determine the effect of mitomycin C on the enzymes of arginase/ NO synthase system activity. The research was performed on peripheral blood lymphocytes obtained from practically healthy men as they are considered as «metabolic mirror» of organism and they respond quickly to all external and internal influences on the body. It has been shown that mitomycin C at concentrations of 10–6–10–3 M caused a dose-dependent increase in arginase activity in peripheral blood lymphocytes. At drug concentration of 10–6 М – by 1.2 times, at drug concentration of 10–3M – by 1.5 times compared to the control values. In parallel with the increase in arginase activity, the corresponding changes in the activity of constitutive isoform of nitric oxide synthase were revealed. It has been shown that activity in control lymphocytes is (71.4±6.9), and the inducible isoform activity is (1.58±0.18) nmol NADPH/(H+ )/min per 1 mg of protein. Under effect of mitomycin C at concentration of 10–6 М cNOS activity was decreasing by 1.4 times concerning control values, iNOS activity is almost undetectable. When studying the effect of mitomycin C on iNOS activity in lymphocytes, isolated from the blood of practically healthy men, we did not observe its activity, and the inhibitory effect could not be determined due to its low activity. Oxidative stress was used to induce iNOS activity in blood lymphocytes with Н2 О2 lymphocytes preincubation. Lymphocytes preincubation with 0.2 mM Н2 О2 leads to an increase in iNOS by 22.4 times. By activation of iNOS with hydrogen peroxide, 10–6 М concentration of mitomycin C leads to inhibition of enzyme activity by 1.4 times. Thus, the results we obtained concerning the mechanism of action of mitomycin C, that is used to treat urethral strictures, indicate an additional effect on the cell regulatory systems in particular a disorder of arginase/NO-synthase system of blood lymphocytes that leads to disbalance of lymphocytes regulatory system and the regulatory function of NO. Presumably, one of the mechanisms of action of mitomycin C is the decrease in NO hyperproduction.

urethral stricture, mitomycin C, arginase, NO synthase.

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«Bulletin of problems biology and medicine» Issue 2 Part 1 (164), 2022 year, 276-287 pages, index UDK 615.273.3:616.62:577.151.042]-055.1

10.29254/2077-4214-2022-2-1-164-276-287