CARDIOTOXIC EFFECTS OF THE ANTINEOPLASTIC DOXORUBICIN IN A MODEL OF METABOLIC SYNDROME: OXIDATIVE STRESS AND TRANSPORTERS EXPRESSION IN THE HEART

OGONOWSKI N; RUKAVINA MIKUSIC NL; KOUYOUMDZIAN NM; CHOI MR; FELLET A; BALASZCZUK AM; CELUCH SM

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2021

0160-2446

The aim of the present work was to examine whether metabolic syndrome-likeconditions in rats with fructose (F) overload modify the cardiotoxic effects induced bydoxorubicin (DOX) and whether the treatment altered the expression of P-gp, BCRPand OCTN transporters in the heart. Male Sprague-Dawley rats received either tapwater (C, control group; n=16) or water with F 10% w/v (n=16) during eight weeks.Three days before sacrifice, the animals received a single dose of DOX (6 mg/kg, ip,md) (C-DOX and F-DOX groups) or vehicle (VEH; ISS 1ml/kg BW; ip) (C-VEH and FVEH groups) (n=8 per group). F overload enhanced thiobarbituric acid-reactivesubstances (TBARS) levels in the left ventricle, and DOX injection further increasedthose values. DOX did not alter TBARS production in C animals. DOX caused adecrease of 50% in the ejection fraction and a nearly 40% reduction in the fractionalshortening in F animals, but not in C rats. Cardiac tissue levels of P-gp decreased byabout 30% in F rats compared to the C groups. DOX did not modify cardiac P-gpexpression. BCRP and OCTN1/2/3 protein levels did not change with either F or DOX.It is suggested that DOX could cause greater cardiotoxicity in rats receiving F, probablydue to enhanced cardiac lipid peroxidation and lower expression of cardiac P-gp.These results support the hypothesis that the cardiotoxicity of DOX could be increasedunder metabolic syndrome-like conditions or in other health disorders that involvecardiovascular risk factors.