肾毒性
多粘菌素
药理学
多粘菌素B
氧化应激
内质网
线粒体
肾
化学
医学
抗生素
生物化学
内分泌学
作者
Mohammad Azad Malik,Roger L. Nation,Tony Velkov,Jian Li
标识
DOI:10.1007/978-3-030-16373-0_18
摘要
Polymyxin-induced nephrotoxicity is the major dose-limiting factor and can occur in up to 60% of patients after intravenous administration. This chapter reviews the latest literature on the mechanisms of polymyxin-induced nephrotoxicity and its amelioration. After filtration by glomeruli, polymyxins substantially accumulate in renal proximal tubules via receptor-mediated endocytosis mainly by megalin and PEPT2. It is believed that subsequently, a cascade of interconnected events occur, including the activation of death receptor and mitochondrial apoptotic pathways, mitochondrial damage, endoplasmic reticulum stress, oxidative stress and cell cycle arrest. The current literature shows that oxidative stress plays a key role in polymyxin-induced kidney damage. Use of antioxidants have a potential in the attenuation of polymyxin-induced nephrotoxicity, thereby widening the therapeutic window. Mechanistic findings on polymyxin-induced nephrotoxicity are critical for the optimization of their use in the clinic and the discovery of safer polymyxin-like antibiotics.
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