Toxicity Mechanisms of Amphotericin B and Its Neutralization by Conjugation with Arabinogalactan
作者： Sarah Kagan , Diana Ickowicz , Miriam Shmuel , Yoram Altschuler , Edward Sionov
DOI: 10.1128/AAC.00612-12
关键词:
摘要: Amphotericin B (AMB) is an effective antifungal agent. However, its therapeutic use hampered by toxicity, mainly due to channel formation across kidney cell membranes and the disruption of postendocytic trafficking. We previously described a safe injectable AMB-arabinogalactan (AG) conjugate with neutralized toxicity. Here we studied mechanism toxicity free AMB neutralization conjugation AG. treatment line modulated trafficking three receptors (C-X-C chemokine receptor type 4 [CXCR4], M1 receptor, human transferrin [hTfnR]) increase in endosomal pH. Similar data were also obtained yeast but vacuolar pH perturbation Hxt2-green fluorescent protein (GFP) The AG all elements toxic activity mammalian not fungal cells. Based on these results, provide explanation how neutralizes cells add knowledge action both
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