کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5853453 | 1130860 | 2011 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Evaluation of cholesterol depletion as a marker of nephrotoxicity in vitro for novel β-cyclodextrin derivatives Evaluation of cholesterol depletion as a marker of nephrotoxicity in vitro for novel β-cyclodextrin derivatives](/preview/png/5853453.png)
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 (HP3-SBE2-β-CD and HP2-SBE3-β-CD) and compared their effects to sulfobutyl ether-β-cyclodextrin (SBE7-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 HP3-SBE2-β-CD or HP2-SBE3-β-CD on cell viability, membrane damage, and the induction of apoptosis and necrosis resembled that of SBE7-β-CD, whereas the effects were significantly lower for M-β-CD or DM-β-CD. HP3-SBE2-β-CD and HP2-SBE3-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.
Journal: Food and Chemical Toxicology - Volume 49, Issue 6, June 2011, Pages 1387-1393