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The influence of proteasome inhibitor on the expression of cardiomyocytes damage markers after incubation with doxorubicin

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Tereszkiewicz S., Matysiak W., Mandziuk S., Korga A., Oleksiejuk M., Hejna M., Korobowicz-Markiewicz A., Iwan M., Dudka J.
Current Issues in Pharmacy and Medical Sciences
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2014
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vol. 27
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issue 2
88-91
EN
The aim of the study was to verify the thesis that the cardiotoxic effects of doxorubicin are connected with activation of the ubiquitin - proteasome pathway followed by protein degradation. The expression of myocardial damage markers - fatty acid binding protein (H-FABP) and brain natriuretic peptide (BNP) was evaluated in rat fetal cardiomyocytes simultaneously treated with doxorubicin and the proteasome inhibitor - bortezomib. The level of H-FABP and BNP protein under the influence of doxorubicin was decreased below the detection threshold with unchanged (H-FABP) or elevated (BNP) mRNA expression level. Against the expectations, the inhibitor of proteasome did not abolish this effect. The observed abnormal expression of BNP and H-FABP protein after doxorubicin treatment makes their diagnostic significance in anthracycline cardiotoxicity questionable.
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The effect of one-electron reduced drugs on hepatic aconitase activity and triglycerides level

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Wnukowska M., Mandziuk S., Korga A., Jodlowska-Jedrych B., Matysiak W., Halasa J., Burdan F., Iwan M., Gieroba R., Dudka J.
Current Issues in Pharmacy and Medical Sciences
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2015
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vol. 28
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issue 1
5-7
EN
The redox cycle triggered by one electron reduction of doxorubicin and tirapazamine - both anticancer agents - leads to superoxide production. This superoxide production itself removes one iron atom from the [4Fe-4S] cluster, being an active center of aconitase. In addition, the incurred changes in cell redox equilibrium may affect lipid metabolism. The aim of the study was to evaluate a concomitant effect of both drugs on hepatic aconitase activity and triglycerides level. In our study, doxorubicin (1.8 mg/kg b.w.) was administered intraperitoneal (i.p.) six times, once a week, within male Wistar rats, to achieve a cumulative dose of 10.8 mg/kg b.w. Two hours before every doxorubicin administration, tirapazamine in the dose of either 5 or 10 mg/kg b.w. was also i.p. injected. A week after withdrawing drug administration, the liver was taken for biochemical analysis. Therein, an increase in aconitase activity and a decrease in triglycerides level was seen in all groups exposed to doxorubicin. Our work demonstrated that tirapazamine administration had no influence on both tested parameters, but its higher dose rate normalized aconitase activity affected by doxorubicin.
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