OXIDATIVE STRESS MARKERS AND TRANSPORTERS EXPRESSION IN THE HEART OF FRUCTOSE-FED RATS TREATED WITH THE CARDIOTOXIC ANTINEOPLASIC DOXORUBICIN

OGONOWSKI N; FELLET A; BALASZUC A; RUKAVINA MIKUSIC N; ROSON I; CELUCH SM; KOUYOUMDZIAN N; CHOI M

Mar del Plata

Congreso; SAIC-SAI-SAFE 2016; 2016

SAIC-SAI-SAFE

Oxidative stress markers andtransporterS EXPRESSION in the heart of FRUCTOSE-FED RATS TREATED WITH THECARDIOTOXIC ANTINEOPLASIC doxorubicin   1Natalia Ogonowski, 2NataliaLucía Rukavina Mikusic, 2Nicolás Kouyoumdzian, 1Andrea Fellet,  2Inés Rosón, 2Marcelo Choi, 1AnaBalaszuk, 3Stella Maris Celuch. 1Cát deFisiología (FFyB, UBA); 2ININCA (UBA-CONICET) 3ININFA(UBA-CONICET), CABA. Doxorubicin (DOX)clinical use as chemotherapeutic agent is limited due to the development ofcardiomyopathies and heart failure. Our interest is to study whether thecardiotoxicity of DOX could be increased in conditions with cardiovascular riskfactors. In this sense, we reported that in a model of metabolic syndromecaused by fructose-feeding (FRU) in rats, a single dose of DOX decreased theejection and shortening fractions in the left ventricle, suggesting greatercardiotoxicity than in control (C) animals. Both FRU and DOX produce oxidativestress. Moreover, DOX changes the expression of the plasma membrane transporterP-GP which extrudes DOX from cells . Also, a possible mechanism of its cardiotoxicityis the depletion of carnitine which is uptaken by transporters OCTNs. The aimof this study was to analyze the effects of DOX on oxidative stress markers andexpression of P-GP and OCTNs in cardiac tissue of C and FRU rats.   Male Sprague-Dawley rats receiving eithertap water or water with 10% fructose during 8 weeks were treated with DOX (6mg/kg, ip, md) or vehicle (ISS) (n=4/group). Three days after injection, ratswere sacrificed and left ventricles were excised to measure oxidative stressmarkers and perform western blot for P-GP and OCTN1/2/3. Both FRU and DOX enhancedTBARS production with a significant increase in the FRU+DOX group compared to C(1.71±0.27 vs 0.97±0.11 nmol/mg prot; p<0.05). There were not changes in superoxidedismutase and catalase activities. The expression of P=GP in FRU was 55% lowerthan in C (p<0.01). DOX showed a tendency to increase P=GP expression,although FRU+DOX values remained 35% lower than C (p<0.01). Similar resultswere obtained with OCTNs. It is suggested that a minor efflux of DOX due toreduced expression of P=GP and a possible depletion of carnitine related todecrease in OCTNs expression could contribute to the greater cardiotoxicity ofDOX in FRU rats. Supported by CONICET (PIP 112=201201=00425).