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  • Title: Evaluation of cholesterol depletion as a marker of nephrotoxicity in vitro for novel β-cyclodextrin derivatives.
    Author: Wang H, Xie X, Zhang F, Zhou Q, Tao Q, Zou Y, Chen C, Zhou C, Yu S.
    Journal: Food Chem Toxicol; 2011 Jun; 49(6):1387-93. PubMed ID: 21426923.
    Abstract:
    Cyclodextrins (CDs) have been shown to improve physicochemical and biopharmaceutical properties of drugs when low solubility and low safety limit their use in the pharmaceutical field. Recently, we have developed new multi-substituted-β-CDs, hydroxypropyl-sulfobutyl ether-β-cyclodextrin (HPn-SBEm-β-CD). HPn-SBEm-β-CD exhibit low hemolysis, good solubility, strong inclusion ability, and an appropriate average molecular weight. In this study, we chose two products of HPn-SBEm-β-CD (HP(3)-SBE(2)-β-CD and HP(2)-SBE(3)-β-CD) and compared their effects to sulfobutyl ether-β-cyclodextrin (SBE(7)-β-CD), methyl-β-cyclodextrin (M-β-CD) and 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD). We evaluated viability, membrane damage, induction of apoptosis and necrosis, cholesterol depletion, and morphological changes in human embryonic kidney 293A cells (HEK293A) in vitro. CDs caused a reduction of cell viability and increased LDH levels in a concentration-dependent manner. The effect of HP(3)-SBE(2)-β-CD or HP(2)-SBE(3)-β-CD on cell viability, membrane damage, and the induction of apoptosis and necrosis resembled that of SBE(7)-β-CD, whereas the effects were significantly lower for M-β-CD or DM-β-CD. HP(3)-SBE(2)-β-CD and HP(2)-SBE(3)-β-CD exhibited morphological changes at high concentrations. In conclusion, the results showed that cholesterol depletion may be as a marker for evaluating the cytotoxicity of novel β-CD derivatives. These results will provide useful information for HPn-SBEm-β-CD as a promising safe adjuvant for intravenous administration in the future.
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