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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Melatonin synergistically enhances protective effect of atorvastatin against gentamicin-induced nephrotoxicity in rat kidney
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Melatonin synergistically enhances protective effect of atorvastatin against gentamicin-induced nephrotoxicity in rat kidney

机译：褪黑素协同增强阿托伐他汀对庆大霉素诱导的大鼠肾脏肾毒性的保护作用

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摘要

The risk of serious side-effects such as nephrotoxicity is the principal limitation of gentamicin (GEN) therapeutic efficacy. Oxidative stress is considered to be an important mediator of GEN-induced nephrotoxicity. The present study was designed to evaluate the efficacy of the combination of melatonin (MT) plus atorvastatin (ATO) against GEN-induced nephrotoxicity in rats. We utilized 30 male Wistar albino rats allocated in 5 groups, each containing 6 rats: control, GEN (100 mg/kg/day), ATO (10 mg/kg/day) + GEN, MT (20 mg/kg/day) + GEN, and ATO (10 mg/kg/day) plus MT (20 mg/kg/day) + GEN. Kidney weight, serum creatinine and urea concentration, renal ROS, MDA, GSH levels, SOD, and CAT activity were determined. GEN-induced nephrotoxicity was evidenced by marked elevations in serum urea and creatinine, kidney weight, renal ROS, and MDA levels and reduction in renal GSH level, SOD and CAT activity. MT pretreatment significantly lowered the elevated serum creatinine concentration, kidney weight, renal ROS and MDA levels. However ATO could not reduce these parameters, but similarly to MT, it was able to enhance the renal GSH level, CAT and SOD activity. In addition, a combination therapy of MT plus ATO enhanced the beneficial effects of ATO, while not changing the effects of MT effects or even improving them. The present study indicates that a combination therapy of MT plus ATO can attenuate renal injury in rats treated with GEN, possibly by reducing oxidative stress, and it seems that MT can enhance the beneficial effects of ATO.
机译：诸如肾毒性之类的严重副作用的风险是庆大霉素（GEN）治疗功效的主要限制。氧化应激被认为是GEN诱导的肾毒性的重要介质。本研究旨在评估褪黑激素（MT）加阿托伐他汀（ATO）联合使用对GEN诱导的大鼠肾毒性的功效。我们使用了30只雄性Wistar白化病大鼠，分为5组，每组包含6只大鼠：对照，GEN（100 mg / kg /天），ATO（10 mg / kg /天）+ GEN，MT（20 mg / kg /天） + GEN，以及ATO（10 mg / kg /天）加MT（20 mg / kg /天）+ GEN。测定肾脏重量，血清肌酐和尿素浓度，肾ROS，MDA，GSH水平，SOD和CAT活性。血清尿素和肌酐，肾脏重量，肾脏ROS和MDA水平显着升高以及肾脏GSH水平，SOD和CAT活性降低证明了GEN诱导的肾毒性。 MT预处理可显着降低血清肌酐浓度，肾脏重量，肾脏ROS和MDA水平升高。但是，ATO不能降低这些参数，但是与MT相似，它可以增强肾脏GSH水平，CAT和SOD活性。另外，MT加ATO的组合疗法增强了ATO的有益作用，而没有改变MT作用的作用或什至没有改善它们。本研究表明，MT加ATO的联合治疗可以减轻GEN所致大鼠的肾脏损伤，可能是通过降低氧化应激，并且看来MT可以增强ATO的有益作用。

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