Vazin Afsaneh, Heidari Reza, Khodami Zahra
Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
J Exp Pharmacol. 2020 Jun 4;12:129-136. doi: 10.2147/JEP.S255861. eCollection 2020.
The last-line agent for gram-negative bacteria that have developed resistance towards commonly used antibiotics is polymyxin E (PolyE). The renal toxicity attributed to this agent limits its use, proper dosing, and eventually its clinical efficacy. Although the exact mechanism of PolyE-induced nephrotoxicity is not obvious, some investigations suggest the role of oxidative stress and its associated events in this complication. Curcumin (CUR) is a potent antioxidant molecule. The aim of the current investigation was the evaluation of the potential nephroprotective properties of CUR in PolyE-treated mice.
Mice were randomly allocated into five groups (n = 8 per group). PolyE (15 mg/kg/day, i.v, for 7 days) alone or in combination with CUR (10, 100 and 200 mg/kg, i.p) were administered to mice. Renal injury biomarkers, in addition to markers of oxidative stress and kidney histopathological alterations, were evaluated.
Plasma creatinine (Cr) and blood urine nitrogen (BUN) significantly raised in PolyE group. Oxidative stress biomarkers consisting of reactive oxygen species (ROS) and lipid peroxidation (LPO) also increased, and concomitantly GSH and antioxidant capacity of renal cells significantly decreased following the use of PolyE. Interstitial nephritis, tissue necrosis, and glomerular atrophy were all induced by the use of PolyE in the mice kidney. CUR (10, 100, and 200 mg/kg, i.p) treatment alleviated PolyE-induced oxidative stress and histopathological alterations in the kidney tissue significantly.
According to the results of this study, CUR has a protective role against renal toxicity induced by PolyE. Hence, more research is necessary until this compound could be clinically applicable to alleviate PolyE-induced renal injury.
对常用抗生素产生耐药性的革兰氏阴性菌的最后一线治疗药物是多粘菌素E（PolyE）。该药物所致的肾毒性限制了其使用、合适的剂量，最终也限制了其临床疗效。尽管PolyE诱导肾毒性的确切机制尚不明确，但一些研究表明氧化应激及其相关事件在这一并发症中发挥作用。姜黄素（CUR）是一种有效的抗氧化分子。本研究的目的是评估CUR对PolyE处理小鼠潜在的肾保护特性。
将小鼠随机分为五组（每组n = 8）。单独给予PolyE（15 mg/kg/天，静脉注射，共7天）或联合给予CUR（10、100和200 mg/kg，腹腔注射）。除了评估氧化应激标志物和肾脏组织病理学改变外，还对肾损伤生物标志物进行了评估。
PolyE组血浆肌酐（Cr）和血尿素氮（BUN）显著升高。使用PolyE后，由活性氧（ROS）和脂质过氧化（LPO）组成的氧化应激生物标志物也增加，同时肾细胞中的谷胱甘肽（GSH）和抗氧化能力显著降低。使用PolyE诱导了小鼠肾脏的间质性肾炎、组织坏死和肾小球萎缩。CUR（10、100和200 mg/kg，腹腔注射）治疗显著减轻了PolyE诱导的肾脏组织氧化应激和组织病理学改变。
根据本研究结果，CUR对PolyE诱导的肾毒性具有保护作用。因此，在该化合物能够临床应用以减轻PolyE诱导的肾损伤之前，还需要进行更多的研究。
