Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, P. R. China.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
J Antimicrob Chemother. 2017 Sep 1;72(9):2562-2569. doi: 10.1093/jac/dkx185.
Nephrotoxicity is the major adverse effect patients experience during colistin therapy. The development of effective nephroprotective agents that can be co-administered during polymyxin therapy remains a priority area in antimicrobial chemotherapy.
To investigate the nephroprotective effect of baicalein, a component of the root of Scutellaria baicalensis, against colistin-induced nephrotoxicity using a mouse model.
C57BL/6 mice were randomly divided into the following groups: control, baicalein 100 mg/kg/day (administered orally), colistin (18 mg/kg/day administered intraperitoneally) and colistin (18 mg/kg/day) plus baicalein (25, 50 and 100 mg/kg/day). After 7 day treatments, histopathological damage, the markers of renal functions, oxidative stress and inflammation were examined. The expressions of Nrf2, HO-1 and NF-κB mRNAs were also further examined using quantitative RT-PCR examination.
Baicalein co-administration markedly attenuated colistin-induced oxidative and nitrative stress, apoptosis, the infiltration of inflammatory cells, and caused decreases in IL-1β and TNF-α levels (all P < 0.05 or 0.01) in the kidney tissues. Baicalein co-administration up-regulated expression of Nrf2 and HO-1 mRNAs and down-regulated the expression of NF-κB mRNA, compared with those in the colistin alone group.
To the best of our knowledge, this is the first study demonstrating the protective effect of baicalein on colistin-induced nephrotoxicity and apoptosis by activating the antioxidant defence mechanism in kidneys and down-regulating the inflammatory response. Our study highlights that oral baicalein could potentially ameliorate nephrotoxicity in patients undergoing polymyxin therapy.
肾毒性是患者在黏菌素治疗过程中经历的主要不良反应。开发可与多黏菌素治疗同时使用的有效肾保护剂仍然是抗菌化疗的优先领域。
使用小鼠模型研究黄芩素（黄芩根的一种成分）对黏菌素诱导的肾毒性的肾保护作用。
将 C57BL/6 小鼠随机分为以下几组：对照组、黄芩素 100mg/kg/天（口服）组、黏菌素（18mg/kg/天腹腔注射）组和黏菌素（18mg/kg/天）加黄芩素（25、50 和 100mg/kg/天）组。治疗 7 天后，检查组织病理学损伤、肾功能标志物、氧化应激和炎症。还通过定量 RT-PCR 检查进一步检查 Nrf2、HO-1 和 NF-κB mRNA 的表达。
黄芩素共给药显著减轻了黏菌素诱导的氧化和硝化应激、细胞凋亡、炎症细胞浸润，并降低了肾脏组织中 IL-1β 和 TNF-α 水平（均 P<0.05 或 0.01）。与单独使用黏菌素组相比，黄芩素共给药上调了 Nrf2 和 HO-1 mRNA 的表达，并下调了 NF-κB mRNA 的表达。
据我们所知，这是第一项研究表明，黄芩素通过激活肾脏抗氧化防御机制和下调炎症反应，对黏菌素诱导的肾毒性和细胞凋亡具有保护作用。我们的研究强调，口服黄芩素可能改善接受多黏菌素治疗的患者的肾毒性。
