CARDIOTOXIC EFFECTS OF THE ANTINEOPLA- SIC DOXORUBICIN IN A MODEL OF METABOLIC SYN- DROME: OXIDATIVE STRESS AND TRANSPORTERS EXPRESSION IN THE LEFT VENTRICLE

NICOLÁS KOUYOUMDZIAN, NATALIA OGONOWSKI, NATALIA RUKAVINA MIKUSIC, ANDREA FELLET, MARÍA INÉS ROSÓN, MARCELO CHOI, ANA BALASZCZUK, STELLA MARIS CELUCH.

Congreso; LXII Reunión Anual de la Sociedad de Investigación Clínica; 2018

Doxorubicin (DOX) clinical use as chemotherapeutic agent is limited due to the development of cardiomyopathies and heart failure. In the present study we aimed to examine whether Metabolic Syndrome-like conditions in rats, generated by administration of 10% fructose in the drinking water, modify the adverse effects induced by a single dose of DOX and whether the treatment modifies the expression of P-glycoprotein (P-gp) and organic cation/carnitine transporter OCT-N2 in the heart. Male Sprague-Dawley rats receiving either tap water (C, control) or water with 10% fructose (F) during 8 weeks were treated with DOX (6 mg/kg, ip, md) or vehicle (V) (n=4/group). Three days after injection, echocardiographic monitoring was performed and then rats were sacrificed. Left ventricles were excised to measure oxidative stress markers and protein expression of P-gp and OCTN1/2/3 by western blot. F increased TBARS tissue levels and decreased the activity of the antioxidant enzyme SOD (p