XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta
XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta
XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta
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Lectures<br />
effECTS of DOXOrUBICIN treaTMENT ON MatrIX<br />
METaLLOPrOTEINaSES IN raTS<br />
Miroslav Barančík, Petra Šimončíková and Monika Ivanová<br />
Institute for Heart Research CEKVY SAS, Bratislava<br />
The anthracycline doxorubicin (DOX) is an effective chemotherapeutic agent which is<br />
frequently used in the treatment of many types of malignancies. Limitation of its use is<br />
a cardiotoxicity associated with the development of cardiomyopathy and chronic heart<br />
failure. Matrix metalloproteinases (MMPs) are enzymes that play an important role in<br />
degradation and remodeling of extracellular matrix under physiological and pathological<br />
conditions. Especially MMP-2 and MMP-9 are suggested to play an important role also in<br />
pathogenesis of several cardiovascular diseases. The aim of the study was to investigate<br />
the involvement of MMPs in the responses of rats to prolonged doxorubicin treatment.<br />
In the study, male Wistar rats were used. DOX was administered to rats by intraperitoneal<br />
injections of 7 doses in 3-day’s intervals (total cumulative dose of DOX was 15 mg<br />
per kg of body weight). The control animals were treated with saline. The samples of<br />
tissue or plasma were collected 4, 8 and 12 weeks after application of last dose of DOX.<br />
The protein levels were determined by immunoblot assay and MMPs activities were<br />
measured by gelatin zymography. Determined were also blood pressure, body weight<br />
and weight of several organs (heart, brain, liver, kidney) and the parameters obtained<br />
in DOX-treated rats were compared with parameters of control animals. The investigation<br />
of changes associated with action of DOX revealed that prolonged exposure of rats<br />
to DOX led to changes in MMPs activation in heart tissue. Moreover, the effects of DOX<br />
were connected with time-dependent changes in plasma MMPs activities. Our results<br />
suggest that MMPs are involved in the responses of rat hearts to chronic DOX treatment.<br />
Acknowledgement: Supported by VEGA SR 2/0205/09, APVV 51-027404<br />
<strong>XXII</strong>. Biochemistry Congress, Martin<br />
43
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