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首页> 外文学位 >Doxorubicin Cytotoxicity in a Human Proximal Tubular Epithelial Cell Line was Attenuated by the Natural Product Resveratrol
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Doxorubicin Cytotoxicity in a Human Proximal Tubular Epithelial Cell Line was Attenuated by the Natural Product Resveratrol

机译：天然产物白藜芦醇可减轻人近端肾小管上皮细胞系中的阿霉素细胞毒性

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摘要

The cancer chemotherapeutic agent doxorubicin (DOX), Adriamycin, is part of the treatment regimen for breast, ovarian, small cell lung cancer and acute/chronic lymphoid leukemia. Adverse effects associated with DOX are cardiotoxicity and nephrotoxicity. Interventions are needed to reduce DOX nephrotoxicity. Resveratrol (RES) is a phytochemical contained in grapes, berries and nuts, which possesses antioxidant and anticancer properties. This study tested the hypothesis that RES will attenuate DOX renal cytotoxicity in human noncancerous renal proximal tubular epithelial (HK-2) cells and that RES will reduce DOX mediated changes in mitochondrial function. HK-2 cells were plated and grown for 48 hours (h). Cells were next pre- incubated for 1h with 0 (DMSO), 5 or 7.5 microM RES followed by a 24 h co-incubation with 0--5 microM DOX. RES did not alter cell growth or viability at the concentrations tested as indicated by comparable MTT values between DMSO and RES groups (p > 0.05). Cell viability was further assessed by cell count using Trypan blue exclusion. DOX produced a concentration dependent decline in viability within a 24 h exposure. Pretreatment for 1h with RES was sufficient to reduce DOX loss of cell viability. Studies were initiated to investigate the cellular mechanism of RES attenuation of DOX cytotoxicity. Western blot of cells following 24 h exposure examined increased protein carbonylation as an indicator of oxidative stress. Initial studies were begun to examine the DOX effects on mitochondrial oxygen consumption using a Seahorse platform. In summary, RES did not diminish cell viability at the concentrations tested in our HK-2 cells. DOX diminished cell viability within 24 h relative to vehicle control. A 1 h pretreatment with RES reduced DOX cytotoxicity in HK-2 cells. Prevention of mitochondrial impairment and oxidative stress by DOX are potential mechanisms for RES protection in HK-2 cells.
机译：癌症化疗药物阿霉素（DOX），阿霉素是乳腺癌，卵巢癌，小细胞肺癌和急性/慢性淋巴白血病治疗方案的一部分。与DOX相关的不良反应是心脏毒性和肾毒性。需要进行干预以减少DOX的肾毒性。白藜芦醇（RES）是葡萄，浆果和坚果中的一种植物化学物质，具有抗氧化和抗癌特性。这项研究检验了以下假设：RES将减弱人非癌性肾近端肾小管上皮（HK-2）细胞中DOX肾细胞毒性，并且RES将减少DOX介导的线粒体功能变化。将HK-2细胞铺板并生长48小时（h）。接下来，将细胞与0（DMSO），5或7.5 microM RES预孵育1小时，然后与0--5 microM DOX共同孵育24 h。在DMSO和RES组之间可比较的MTT值表明，在所测试的浓度下RES不会改变细胞生长或生存能力（p> 0.05）。使用台盼蓝排除法通过细胞计数进一步评估细胞活力。 DOX在24小时内产生了浓度依赖性的生存力下降。用RES预处理1h足以减少DOX细胞活力的损失。开始研究以研究RES减弱DOX细胞毒性的细胞机制。暴露24小时后细胞的蛋白质印迹检查了蛋白质羰基化的增加，作为氧化应激的指标。开始初步研究以使用Seahorse平台研究DOX对线粒体耗氧量的影响。总之，在我们的HK-2细胞中测试的浓度下，RES不会降低细胞活力。相对于媒介物对照，DOX降低了24小时内的细胞活力。 RES预处理1小时可降低HK-2细胞中DOX的细胞毒性。 DOX预防线粒体损伤和氧化应激是HK-2细胞中RES保护的潜在机制。

著录项

  • 作者

    Getty, Morghan Schuyler.;

  • 作者单位

    Marshall University.;

  • 授予单位 Marshall University.;
  • 学科 Toxicology.;Pharmacology.
  • 学位 M.S.
  • 年度 2017
  • 页码 78 p.
  • 总页数 78
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 植物学;
  • 关键词

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