The nephroprotective properties of taurine in colistin-treated mice is mediated through the regulation of mitochondrial function and mitigation of oxidative stress
The nephroprotective properties of taurine in colistin-treated mice is mediated through the regulation of mitochondrial function and mitigation of oxidative stress
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DOI：
10.1016/j.biopha.2018.10.093
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发表时间：
2019-01-01
影响因子：
7.5
通讯作者：
Vazin, Afsaneh
中科院分区：
文献类型：
--
作者：
Heidari, Reza;Behnamrad, Shima;Vazin, Afsaneh
粘菌素 (COL) 属于多粘菌素类抗生素，用作对抗耐药感染的最后一线抗生素。然而，肾毒性是与 COL 治疗相关的主要有害和剂量限制副作用。氧化应激和线粒体损伤被怀疑是 COL 诱导肾毒性的机制。牛磺酸是人体内最丰富的氨基酸之一，具有抗氧化和线粒体保护特性。目前的研究旨在评估牛磺酸对 COL 相关肾毒性的潜在肾保护特性。小鼠单独使用 COL（15 毫克/公斤/天，静脉注射，连续 7 天）或与牛磺酸（500 和 1000 毫克/公斤，静脉注射）联合治疗。除了氧化应激的肾组织标记物之外，还评估了肾毒性的血浆生物标记物。此外，分离了肾线粒体，并评估了一些线粒体指数。 COL 相关的肾损伤通过肾损伤的血浆标志物显着增加而明显增加，包括肌酐 (Cr) 和血尿氮 (BUN)。 COL 治疗还导致肾脏活性氧 (ROS) 和脂质过氧化 (LPO) 显着增加。在 COL 治疗的动物中，肾脏 GSH 储存和抗氧化能力也有所下降。 COL 治疗小鼠肾脏中的线粒体参数，包括线粒体脱氢酶活性、膜电位、GSH 和 ATP 显着降低，而线粒体 LPO、通透性和 GSSG 含量则增加。研究发现，牛磺酸（500 和 1000 mg/kg，腹膜内注射）治疗可减轻 COL 诱导的肾组织氧化应激和线粒体功能障碍。当前研究获得的数据表明线粒体功能障碍和氧化应激是 COL 引起肾损伤的基本机制。另一方面，补充牛磺酸通过减少氧化应激和调节线粒体功能来保护肾脏。
Colistin (COL) belongs to the polymixin class of antibiotics used as the last line antibiotic against drug-resistant infections. However, nephrotoxicity is the major deleterious and dose-limiting side effect associated with COL therapy. Oxidative stress and mitochondrial impairment are suspected mechanisms involved in COL-induced nephrotoxicity. Taurine is one of the most abundant amino acids in the human body with antioxidant and mitochondria protecting properties. The current study was designed to evaluate the potential nephroprotective properties of taurine against COL-associated nephrotoxicity. Mice were treated with COL (15 mg/kg/day, i.v, for 7 consecutive days) alone or in combination with taurine (500 and 1000 mg/kg, i. p). Plasma biomarkers of nephrotoxicity in addition of kidney tissue markers of oxidative stress were evaluated. Additionally, kidney mitochondria were isolated, and several mitochondrial indices were assessed. The COL-associated renal injury was evident by a significant increase in plasma markers of renal injury including creatinine (Cr), and blood urine nitrogen (BUN). COL treatment also caused a significant increase in kidney reactive oxygen species (ROS) and lipid peroxidation (LPO). Renal GSH reservoirs and antioxidant capacity were also decreased in COL-treated animals. Mitochondrial parameters including mitochondrial dehydrogenase activity, membrane potential, GSH, and ATP were significantly decreased while mitochondrial LPO, permeabilization, and GSSG content were increased in the kidney of COL-treated mice. It was found that taurine (500 and 1000 mg/kg, i.p) treatment alleviated COL-induced oxidative stress and mitochondrial dysfunction in the kidney tissue. The data obtained from the current study suggest mitochondrial dysfunction and oxidative stress as fundamental mechanisms of renal injury induced by COL. On the other hand, taurine supplementation protected kidney through decreasing oxidative stress and regulating mitochondrial function.