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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Gelofusine Ameliorates Colistin-Induced Nephrotoxicity
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Gelofusine Ameliorates Colistin-Induced Nephrotoxicity

机译：Gelofusine改善了Colistin诱导的肾毒性

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摘要

Colistin therapy is used as the last line of defense against life-threatening Gram-negative infections. Nephrotoxicity is the major dose-limiting side effect that impedes optimal dosing of patients. This study aims to examine the nephroprotective effect of the plasma volume expander gelofusine against colistin-induced nephrotoxicity. Renal protection was assessed in mice that were subcutaneously injected with colistin sulfate (14 mg/kg of body weight x 6 doses every 2 h; accumulated dose, 84 mg/kg) and simultaneously injected in the intraperitoneal region with gelofusine (75, 150, 300, or 600 mg/kg x 6). At 2 and 20 h after the last colistin dose, mice were euthanized, and the severity of renal alteration was examined histologically. Histological findings in mice revealed that colistin-induced nephrotoxicity was ameliorated by gelofusine in a dose-dependent manner, whereas significant histological abnormalities were detected in the kidneys of mice in the colistin-only group. The impact of coadministered gelofusine on colistin pharmacokinetics was investigated in rats. Rats were administered a single intravenous dose of gelofusine at 400 mg/kg 15 min prior to the intravenous administration of colistin (1 mg/kg). Gelofusine codosing did not alter the pharmacokinetics of colistin in rats; however, gelofusine did significantly lower the accumulation of colistin in the kidney tissue of mice. This is the first study demonstrating the protective effect of gelofusine against colistin-induced nephrotoxicity. These findings highlight the clinical potential of gelofusine as a safe adjunct for ameliorating the nephrotoxicity and increasing the therapeutic index of polymyxins.
机译：Colistin治疗被用作对危及生命的革命的革兰阴性感染的最后一系列防御。肾毒性是妨碍患者最佳给药的主要剂量限制副作用。本研究旨在检测血浆体积膨胀机胶质植物对菌霉素诱导的肾毒性的肾脏反应作用。在用硫酸钠（14mg / kg体重×6剂量每2小时14mg / kg体重x 6剂量的小鼠中评估肾保护剂。累积剂量，84mg / kg）并同时注射肠内区域（75,150， 300，或600 mg / kg x 6）。在最后一次Colistin剂量后2和20小时，对小鼠进行了安乐死，并在组织学上检查肾改变的严重程度。小鼠中的组织学发现显示，胶质素诱导的肾毒性以剂量依赖性方式改善，而仅在小鼠的小鼠肾脏中检测到显着的组织学异常。在大鼠中研究了CoDministeredGelofusine对Colistin药代动力学的影响。在静脉内给药在静脉内施用Colistin（1mg / kg）之前，将大鼠在400mg / kg下施用单个静脉注射剂量的胶茂剂。凝胶族母鸡的组织没有改变大鼠菌氨酸的药代动力学;然而，凝胶株在小鼠的肾组织中显着降低了Colistin的积累。这是第一项研究，证明凝胶蛋白酶对胚胎诱导的肾毒性的保护作用。这些发现突出了胶叶胺的临床潜力，作为改善肾毒性的安全辅助，并增加多态的治疗指数。

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  • 作者

    Sivanesan Sivashangarie S.; Azad Mohammad A. K.; Schneider Elena K.; Ahmed Maizbha U.; Huang Jiayuan; Wang Jiping; Li Jian; Nation Roger L.; Velkov Tony;

  • 作者单位

    Monash Univ Monash Inst Pharmaceut Sci Drug Delivery Disposit &

    Dynam Melbourne Vic Australia;

    Monash Univ Monash Biomed Discovery Inst Dept Microbiol Melbourne Vic Australia;

    Monash Univ Monash Inst Pharmaceut Sci Drug Delivery Disposit &

    Dynam Melbourne Vic Australia;

    Monash Univ Monash Inst Pharmaceut Sci Drug Delivery Disposit &

    Dynam Melbourne Vic Australia;

    Monash Univ Monash Inst Pharmaceut Sci Drug Delivery Disposit &

    Dynam Melbourne Vic Australia;

    Monash Univ Monash Inst Pharmaceut Sci Drug Delivery Disposit &

    Dynam Melbourne Vic Australia;

    Monash Univ Monash Biomed Discovery Inst Dept Microbiol Melbourne Vic Australia;

    Monash Univ Monash Inst Pharmaceut Sci Drug Delivery Disposit &

    Dynam Melbourne Vic Australia;

    Monash Univ Monash Inst Pharmaceut Sci Drug Delivery Disposit &

    Dynam Melbourne Vic Australia;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 治疗学;
  • 关键词

    colistin; nephrotoxicity; gelofusine;

    机译：Colistin;肾毒性;凝胶;

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