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Example:10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
CARDIOTOXIC EFFECTS OF THE ANTINEOPLASTIC DOXORUBICIN IN A MODEL OF METABOLIC SYNDROME: OXIDATIVE STRESS AND TRANSPORTERS EXPRESSION IN THE HEART.
Journal of Cardiovascular Pharmacology  (IF3.105),  Pub Date : 2021-09-08, DOI: 10.1097/fjc.0000000000001137
Natalia Ogonowski, Natalia Lucía Rukavina Mikusic, Nicolás Martín Kouyoumdzian, Marcelo Roberto Choi, Andrea Fellet, Ana María Balaszczuk, Stella Maris Celuch

The aim of the present work was to examine whether metabolic syndrome-like conditions in rats with fructose (F) overload modify the cardiotoxic effects induced by doxorubicin (DOX) and whether the treatment altered the expression of P-gp, BCRP and OCTN transporters in the heart. Male Sprague-Dawley rats received either tap water (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 F-VEH groups) (n=8 per group). F overload enhanced thiobarbituric acid-reactive substances (TBARS) levels in the left ventricle, and DOX injection further increased those values. DOX did not alter TBARS production in C animals. DOX caused a decrease of 30% in the ejection fraction and a nearly 40% reduction in the fractional shortening in F animals, but not in C rats. Cardiac tissue levels of P-gp decreased by about 30% in F rats compared to the C groups. DOX did not modify cardiac P-gp expression. 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, probably due to enhanced cardiac lipid peroxidation and lower expression of cardiac P-gp. These results support the hypothesis that the cardiotoxicity of DOX could be increased under metabolic syndrome-like conditions or in other health disorders that involve cardiovascular risk factors.