CARDIAC MARKERS IN THE BLOOD OF RATS EXPOSED TO FREE AND BOUND DOXORUBICIN

478 Volume 5, Issue 10: Special Issue (EJAR) ISSN: 2181-2020 MPHAPP THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE “MODERN PHARMACEUTICS: ACTUAL PROBLEMS AND PROSPECTS” TASHKENT, OCTOBER 17, 2025 in-academy.uz CARDIAC MARKERS IN THE BLOOD OF RATS EXPOSED TO FREE AND BOUND DOXORUBICIN Tagayalieva N.A., Usmonov Sh.T., Abdullaev A.A., Zaripova M.R., Baratov K.R., Yakubova R.A., Rakhmonova G.G., Mukhitdinov B.I., Kalonova M.A., Turaev A.S. Institute of Bioorganic Chemistry, AS of RUz, Tashkent, Republic of Uzbekistan e-mail: [email protected], tel: 97 723 44 54 https://doi.org/10.5281/zenodo.17342756 Background: The anthracycline antibiotic doxorubicin (DOX) is widely used in clinical practice for the treatment of cancer; however, its high cardiotoxicity limits its use. The development of targeted delivery systems for the cytostatic agent to the tumor site has significantly reduced DOX toxicity. Research in this area has also been conducted at the Institute of Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan, where various DOX derivatives have been obtained. Comprehensive studies are currently underway on the promising polysaccharideconjugated drug PGA-DOX. To assess the cardiotoxic effect of various drugs, levels of various cardiac markers are determined.Creatine kinase (CK), the biochemical "gold standard" in the diagnosis of acute cardiac muscle injury, is a cytosolic enzyme involved in the synthesis of the highenergy compound creatine phosphate, required during increased energy expenditure, and is present in the myocardium as CK-MB.Following myocardial injury, CK-MB is rapidly released from myocardial tissue into the serum, with levels increasing within 4 hours, peaking at 16-24 hours, and returning to normal within 3-4 days. Lactate dehydrogenase (LDH-1) is an important enzyme in anaerobic metabolism.In acute myocardial infarction, the level of the LDH-1 isoenzyme remains elevated from the second to the fourth day and even up to the 10th day after reaching its maximum value after 24-48 hours, although not always statistically significant. The aim of the study was to determine the activity of two cardiac marker enzymes – CK-MB and LDH-1 in the blood of rats exposed to free and bound forms of DOX. Materials and methods: Rats weighing 200±20 g (5 per group) were treated with a single intravenous injection of PGA-DOX at a dose of 94 mg/kg (group 1), DOX at a dose of 8 mg/kg (group 2), and control animals (group 3) were treated with water for injection in an equivalent volume. On days 1 and 10 after administration, blood was collected and the levels of CK-MB and LDH-1 were measured using standard test kits (Cypress Diagnostics, Belgium) on a Rayto-10 biochemical analyzer (China). Results: Against the background of the drugs, a statistically significant increase in the level of cardiac markers CK-MB and LDH-1 was observed from the first day of observation and was maintained on the 10th day of the study. After administration of DOX and PGA-DOX, the CK-MB indices increased 2-fold relative to the control from 0.198±0.002 U/ml, respectively, to 0.442±0.009 and 0.359±0.007 U/ml on the first day and to 0.411±0.004 and 0.429±0.016 U/ml on the 10th day of the experiment (p <0.0001 for all). On the first day, CK-MB activity was significantly higher (p<0.0001) with free DOX than with PGA-DOX, but this difference subsequently leveled out. The increase in LDH-1 in the blood of rats with DOX and PGA-DOX administration on days 1 and 10 of the experiment also reached a significant difference compared to the control level, but was less noticeable relative to CK-MB. On the 10th day of observation, with the introduction of PGA-DOX, a better normalization of the indicator relative to free DOX was noted (p = 0.007). 479 Volume 5, Issue 10: Special Issue (EJAR) ISSN: 2181-2020 MPHAPP THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE “MODERN PHARMACEUTICS: ACTUAL PROBLEMS AND PROSPECTS” TASHKENT, OCTOBER 17, 2025 in-academy.uz Conclusions: DOX and PGA-DOX, when administered intravenously to rats once in doses exceeding therapeutic doses by 1.6 times, lead to significant damage to cardiomyocytes, which is accompanied by functional disorders of the cardiovascular system within 10 days of observation, which is the cause of functional disorders of the cardiovascular system. When comparing the two drugs, a greater damaging effect on the heart muscle was revealed after DOX administration (8 mg/kg) relative to PGA-DOX (94 mg/kg) (p<0.05).