Soroudi Setareh, Mousavi Ghazal, Jafari Fatemeh, Elyasi Sepideh
Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box, Mashhad, 91775-1365, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun;397(6):3709-3727. doi: 10.1007/s00210-023-02884-w. Epub 2023 Dec 13.
Polymyxin E or colistin is an effective antibiotic against MDR Gram-negative bacteria. Due to unwanted side effects, the use of this antibiotic has been limited for a long time, but in recent years, the widespread of MDR Gram-negative bacteria infections has led to its reintroduction. Neurotoxicity and nephrotoxicity are the significant dose-limiting adverse effects of colistin. Several agents with anti-inflammatory and antioxidant properties have been used for the prevention of colistin-induced neurotoxicity. This study aims to review the preclinical studies in this field to prepare guidance for future human studies. The data was achieved by searching PubMed, Scopus, and Google Scholar databases. All eligible pre-clinical studies performed on neuroprotective agents against colistin-induced neurotoxicity, which were published up to September 2023, were included. Finally, 16 studies (ten in vitro and eight in vivo) are reviewed. Apoptosis (in 13 studies), inflammatory (in four studies), and oxidative stress (in 14 studies) pathways are the most commonly reported pathways involved in colistin-induced neurotoxicity. The assessed compounds include non-herbal (e.g., ascorbic acid, rapamycin, and minocycline) and herbal (e.g., curcumin, rutin, baicalein, salidroside, and ginsenoside) agents. Besides these compounds, some other measures like transplantation of mitochondria and the use of nerve growth factor and mesenchymal stem cells could be motivating subjects for future research. Based on the data from experimental (in vitro and animal) studies, a combination of colistin with neuroprotective agents could prevent or decrease colistin-induced neurotoxicity. However, well-designed randomized clinical trials and human studies are essential for demonstrating efficacy.
多粘菌素E或黏菌素是一种针对多重耐药革兰氏阴性菌的有效抗生素。由于存在不良副作用，这种抗生素的使用长期受到限制，但近年来，多重耐药革兰氏阴性菌感染的广泛传播导致其重新被启用。神经毒性和肾毒性是黏菌素显著的剂量限制性不良反应。几种具有抗炎和抗氧化特性的药物已被用于预防黏菌素诱导的神经毒性。本研究旨在回顾该领域的临床前研究，为未来的人体研究提供指导。数据通过检索PubMed、Scopus和谷歌学术数据库获得。纳入了截至2023年9月发表的所有关于抗黏菌素诱导神经毒性神经保护剂的合格临床前研究。最后，回顾了16项研究（10项体外研究和8项体内研究）。细胞凋亡（13项研究）、炎症（4项研究）和氧化应激（14项研究）途径是黏菌素诱导神经毒性中最常报道的途径。评估的化合物包括非草药类（如抗坏血酸、雷帕霉素和米诺环素）和草药类（如姜黄素、芦丁、黄芩素、红景天苷和人参皂苷）药物。除了这些化合物外，一些其他措施，如线粒体移植以及使用神经生长因子和间充质干细胞，可能是未来研究的有吸引力的课题。基于实验（体外和动物）研究的数据，黏菌素与神经保护剂联合使用可以预防或降低黏菌素诱导的神经毒性。然而，精心设计的随机临床试验和人体研究对于证明疗效至关重要。
