Bìol. Tvarin, 2018, volume 20, issue 1, pp. 28–39

STATUS OF PROOXIDATIVE-ANTIOXIDATIVE BALANCE AND ACTIVITY OF KREBS CYCLE ENZYMES IN LIVER, HEART AND KIDNEY TISSUES FOR ACTION OF VARIOUS CUMULATIVE DOSES OF DOXORUBICIN

V. O. Dziuba1, O. B. Kuchmenko1,2, O. V. Yakoviichuk1
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1Melitopol State Pedagogical University named after Bogdan Khmelnytsky,
20 Hetmanska str., Melitopol 72312, Ukraine

2National University “Kyiv-Mohyla Academy”,
2 Hryhoriya Skovorody str., Kyiv 04070, Ukraine

Doxorubicin is a powerful anthracycline antibiotic used to treat many human neoplasms. Doxorubicin may also cause cardiotoxicity, hepatotoxicity and nephrotoxicity when used for a prolonged period of time, thereby limiting its clinical use. The cytotoxic effect of doxorubicin is very dangerous, since it can lead to the development of irreversible chronic side effects.
30 male rats with an average body weight of 240 g were used in this study. Animals were randomly assigned to one of three groups (control, 3 weeks of therapy, or 5 weeks of therapy). Heart, liver and kidney tissues were used to study the biochemical markers of antioxidant and energy systems. The use of doxorubicin led to a growing number of TBA-active products in all experimental tissues, indicating the pro-oxidant properties of drug. Moreover, doxorubicin can directly affect the activity of antioxidant enzymes. In our study, it was found that doxorubicin caused an increase the activity of antioxidant enzymes in the tissues of heart and liver, and decreased it in kidneys. The activity of citric acid cycle enzymes increased in the liver and decreased in the kidneys after doxorubicin therapy. Activity of the enzymes of Krebs cycle in heart increased only for 3 first weeks of therapy and after that began to decrease. After treatment with doxorubicin, the activity of aspartate aminotransferase in rat tissues varied similar to the enzymatic activity of Krebs cycle dehydrogenases.
Increased activity of succinate dehydrogenase and alpha ketoglutarate dehydrogenase may represent a compensatory or survival response to the onset of functional defects. Assessment of the complex effect of doxorubicin on intracellular processes will help to develop new protecting systems from doxorubicin-induced cytotoxicity, but work in this direction requires more detailed research.

Keywords: ASPARTATE AMINOTRANSFERASE, CITRIC ACID CYCLE, TBA-ACTIVE PRODUCTS, CATALASE, SUPEROXIDE DISMUTASE, CYTOTOXICITY, ANTHRACYCLINE

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