Boucher F, Coudray C, Tirard V, Barandier C, Tresallet N, Favier A, de Leiris J
Groupe de Physiopathologie Cellulaire Cardiaque, URA CNRS 1287, Université Joseph Fourier, Grenoble, France.
Nutrition. 1995 Sep-Oct;11(5 Suppl):708-11.
The aim of the present study was to assess whether an 8-wk oral selenium supplementation (standard food enriched with 2500 micrograms Se/kg) in rats might prevent the cardiotoxicity of adriamycin (ADR) treatment. ADR was administered at a dose of 2.5 mg/kg body wt intraperitoneally twice weekly for 3 wk. One week after the end of ADR treatment, rats (n = 10 per group) were killed and their hearts were perfused on a Langendorff mode and subjected to a 30-min period of low-flow ischemia (residual flow = 0.1 ml/min) followed by reperfusion (15 min). The results were as follows: 1) selenium supplementation significantly increased the activity of cardiac mitochondrial glutathione peroxidase (GPx) in ADR-treated rats (control: 206 +/- 17.4 IU/g protein; Se: 277 +/- 24.5 IU/g protein, p < 0.05); 2) selenium supplementation reduced myocardial malondialdehyde content in ADR-treated rats (control: 1220 +/- 49.1 nmol/g protein; Se: 1010 +/- 75.9 nmol/g protein; p < 0.05); and 3) ADR treatment significantly increased the degree of reperfusion-induced structural alterations to sarcomeres compared to untreated hearts. Again, this phenomenon was abolished by selenium supplementation. In conclusion, this study demonstrates that selenium supplementation is able to limit ADR cardiotoxicity in isolated rat hearts submitted to a sequence of ischemia/reperfusion.
本研究的目的是评估在大鼠中进行为期8周的口服硒补充(标准食物中添加2500微克硒/千克)是否可以预防阿霉素(ADR)治疗的心脏毒性。ADR以2.5毫克/千克体重的剂量腹腔注射,每周两次,共3周。在ADR治疗结束后1周,处死大鼠(每组n = 10),并在Langendorff模式下对其心脏进行灌注,然后进行30分钟的低流量缺血(残余流量 = 0.1毫升/分钟),随后再灌注(15分钟)。结果如下:1)补充硒显著提高了ADR治疗大鼠心脏线粒体谷胱甘肽过氧化物酶(GPx)的活性(对照组:206±17.4国际单位/克蛋白质;硒组:277±24.5国际单位/克蛋白质,p < 0.05);2)补充硒降低了ADR治疗大鼠心肌丙二醛含量(对照组:1220±49.1纳摩尔/克蛋白质;硒组:1010±75.9纳摩尔/克蛋白质;p < 0.05);3)与未治疗的心脏相比,ADR治疗显著增加了再灌注诱导的肌节结构改变程度。同样,这种现象通过补充硒而消除。总之,本研究表明,补充硒能够限制经历缺血/再灌注序列的离体大鼠心脏中的ADR心脏毒性。