Randjelovic Pavle, Veljkovic Slavimir, Stojiljkovic Nenad, Sokolovic Dušan, Ilic Ivan
University of Niš, Faculty of Medicine, Department of Physiology, Niš, Serbia.
University of Niš, Faculty of Medicine, Department of Biochemistry, Niš, Serbia.
EXCLI J. 2017 Mar 24;16:388-399. doi: 10.17179/excli2017-165. eCollection 2017.
Due to high relative blood flow the kidney is prone to drug-induced damage. Aminoglycoside type antibiotic gentamicin is one of the leading cause of drug-induced nephrotoxicity. In recent years gentamicin nephrotoxicity is significantly reduced by shifting to once daily dosage as well as by eliminating known risk factors. Application of gentamicin is still related to serious side effects which are reported more often compared to other antibiotics. Because gentamicin is still heavily used and is highly efficient in treating infections, it is important to find mechanisms to reduce its nephrotoxicity. This aim can only be achieved through better understanding of kidney metabolism of gentamicin. This problem has been extensively researched in the last 20 years. The experimental results have provided evidence for almost complete understanding of mechanisms responsible for gentamicin nephrotoxicity. We now have well described morphological, biochemical and functional changes in kidney due to gentamicin application. During the years, this model has become so popular that now it is used as an experimental model for nephrotoxicity per se. This situation can mislead an ordinary reader of scientific literature that we know everything about it and there is nothing new to discover here. But quite opposite is true. The precise and complete mechanism of gentamicin nephrotoxicity is still point of speculation and an unfinished story. With emerge of new and versatile technics in biomedicine we have an opportunity to reexamine old beliefs and discover new facts. This review focuses on current knowledge in this area and gives some future perspectives.
由于相对血流量较高,肾脏容易受到药物诱导的损伤。氨基糖苷类抗生素庆大霉素是药物性肾毒性的主要原因之一。近年来,通过改为每日一次给药以及消除已知风险因素,庆大霉素肾毒性显著降低。与其他抗生素相比,庆大霉素的应用仍与更常报道的严重副作用相关。由于庆大霉素仍被大量使用且在治疗感染方面高效,找到降低其肾毒性的机制很重要。这一目标只能通过更好地了解庆大霉素在肾脏中的代谢来实现。在过去20年里,这个问题已经得到了广泛研究。实验结果为几乎完全理解庆大霉素肾毒性的机制提供了证据。我们现在已经很好地描述了由于应用庆大霉素导致的肾脏形态、生化和功能变化。多年来,这个模型变得非常流行,现在它本身被用作肾毒性的实验模型。这种情况可能会误导科学文献的普通读者,让他们认为我们对它了如指掌,没有什么新东西可发现了。但事实恰恰相反。庆大霉素肾毒性的确切和完整机制仍然是猜测的焦点,是一个未完成的故事。随着生物医学中新型多功能技术的出现,我们有机会重新审视旧观念并发现新事实。这篇综述聚焦于该领域的当前知识,并给出了一些未来展望。