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ASSA13-03-37 Adriamycin Induced Cardiac Dysfunction is Attenuated by Selenium Via Restoring Oxidative Stress Mediated Expression of ATP Sensitive Potassium Channels in Rats
  1. Liu Zhongwei1,
  2. Zhu Haitao2,
  3. Chen Kunlun2,
  4. Niu Xiaolin1,
  5. Yang Guang1,
  6. Meng Zhe1,
  7. Qiu Chuan3,
  8. Gao Dengfeng1
  1. 1Department of Cardiology, Second Affiliated Hospital, Xian Jiaotong University
  2. 2School of Medicine, Xian Jiaotong University
  3. 3Department of Biostatistics & Bioinformatics, School of Public Health & Tropical Medicine, Tulane University

Abstract

Objective Cardiac toxicity is an important complication of chemotherapy. Selenium (Se) acts as antioxidant agent to protect myocytes from oxidative damage. Lack of Se would lead to enhancement of oxidative stress. It has been mentioned that impairment of ATP sensitive potassium channels (KATP) which are expressed in myocytes are correlated with oxidative mediated cardiac dysfunction. The possible mechanism of adriamycin (ADR) and/or Se deficiency induced cardiac dysfunction, and cardioprotective effects of Se against ADR induced cardiac toxicity were investigated in this study.

Methods Animal model of cardiac dysfunction was induced by adriamycin inraperitoneal injection or/and Se deficit diet. Then by intraperitoneal injections, Se supplementation was applied to rats. We assessed cardiac function by serum brain natriuretic peptide (BNP) level, echocardiographic and hemodynamic parameters. Cardiac glutathione peroxidase (GPx) activity which mirrors oxidative stress indirectly was measured spectrophotometrically. Expression levels of KATP channels were evaluated by real-time polymerase chain reaction (PCR) and western blotting.

Results The results showed that cardiac function and cardiac GPx activity decreased remarkably after administration of ADR or Se deficiency; more dramatic impairment of cardiac function and cardiac GPx activity were observed after co-administration of ADR and Se deficiency. Mechanically, down-regulation of KATP subunits gene expression in cardiac tissue was found after administration of ADR or Se deficiency; more significant inhibition of KATP subunits gene expression was identified after co-administration of ADR and Se deficiency. However, cardiac toxicity of ADR was alleviated by Se supplementation, accompanied by restoring of cardiac GPx activity and KATP subunits gene expression.

Conclusions These results indicate that decreased oxidative mediated expression of KATP is involved in adriamycin and/or Se deficiency induced cardiac dysfunction; Se deficiency exacerbates adriamycin induced cardiac dysfunction by future inhibition of oxidative mediated KATP expression; Se supplementation seems to protect against adriamycin induced cardiac dysfunction by alleviating oxidative stress and then restoring KATP expression, showing potential clinical application in cancer chemotherapy.

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