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.

中文翻译：

---

代谢综合征模型中抗肿瘤药阿霉素的心脏毒性作用：心脏中的氧化应激和转运蛋白表达。

本工作的目的是检查果糖（F）超载大鼠中的代谢综合征样病症是否会改变阿霉素（DOX）诱导的心脏毒性作用，以及治疗是否改变了果糖（F）超负荷大鼠中 P-gp、BCRP 和 OCTN 转运蛋白的表达。心脏。雄性 Sprague-Dawley 大鼠在八周内接受自来水（C，对照组；n=16）或含 F 10% w/v 的水（n=16）。处死前三天，动物接受单剂量 DOX（6 mg/kg，ip，md）（C-DOX 和 F-DOX 组）或媒介物（VEH；ISS 1ml/kg BW；ip）（C-VEH和 F-VEH 组）（每组 n=8）。F 超载会增加左心室中硫代巴比妥酸反应物质 (TBARS) 的水平，而注射 DOX 会进一步增加这些值。DOX 不会改变 C 动物中 TBARS 的产生。DOX 导致 F 组大鼠的射血分数降低 30%，缩短分数降低近 40%，但 C 组大鼠则不然。与 C 组相比，F 组大鼠心脏组织 P-gp 水平降低约 30%。DOX 不会改变心脏 P-gp 的表达。F 或 DOX 均未改变 BCRP 和 OCTN1/2/3 蛋白水平。表明 DOX 可能对接受 F 的大鼠造成更大的心脏毒性，可能是由于心脏脂质过氧化增强和心脏 P-gp 表达降低所致。这些结果支持这样的假设：在代谢综合征样条件下或涉及心血管危险因素的其他健康疾病中，DOX 的心脏毒性可能会增加。