Differential effects of Cu(II) and Fe(III) on the binding of omeprazole and pantoprazole to bovine serum albumin: toxic effect of metal ions on drugs.

Differential effects of Cu(II) and Fe(III) on the binding of omeprazole and pantoprazole to bovine serum albumin: toxic effect of metal ions on drugs.
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DOI:
10.1016/j.jpba.2011.08.012
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发表时间:
2011-12
影响因子:
3.4
通讯作者:
Yuping Zhang;S. Shi;You-nian Liu;Xiaoqing Chen;Mijun Peng
Yuping Zhang;S. Shi;You-nian Liu;Xiaoqing Chen;Mijun Peng
中科院分区:
医学3区
文献类型:
--
作者:
Yuping Zhang;S. Shi;You-nian Liu;Xiaoqing Chen;Mijun Peng

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通过荧光光谱法研究了奥美拉唑或泮托拉唑与牛血清白蛋白(BSA)在铜(II)或铁(III)存在和不存在下的相互作用。加入奥美拉唑或泮托拉唑后,BSA的荧光强度明显降低,并有轻微的蓝移。在Cu(II)或Fe(III)存在下,随着奥美拉唑或泮托拉唑浓度的增加,观察到BSA具有较大猝灭程度的类似蓝移和荧光形状。Cu(II)和Fe(III)的存在使奥美拉唑与BSA的亲和力分别提高了12.0%和3.9%,而Cu(II)的存在使泮托拉唑与BSA的亲和力降低了25.7%,Fe(III)的存在使泮托拉唑与BSA的亲和力提高了16.3%。在金属离子的存在下,可变的亲和力和增加的结合距离可能是由于在不同的白蛋白位点的非竞争性结合。结果表明,奥美拉唑和泮托拉唑的结构以及金属离子的种类共同影响其与BSA的结合作用,这可能对胃溃疡患者合理用药具有重要意义。
The interaction between omeprazole or pantoprazole and bovine serum albumin (BSA) has been investigated in the absence and presence of Cu(II) or Fe(III) by means of fluorescence spectroscopy. The fluorescence intensity of BSA decreased remarkably with slight blue shifts by adding omeprazole or pantoprazole. Similar blue shifts and fluorescence shape with larger quenching extent of BSA were observed with increasing concentrations of omeprazole or pantoprazole in the presence of Cu(II) or Fe(III). The presence of Cu(II) and Fe(III) increased the affinities of omeprazole with BSA about 12.0% and 3.9%, while the presence of Cu(II) decreased the affinity of pantoprazole with BSA about 25.7%, and the presence of Fe(III) improved the affinity of pantoprazole with BSA about 16.3%. The changeable affinity and increased binding distance in the presence of metal ions may result from a noncompetitive binding in different albumin sites. The results indicated that the structures of omeprazole or pantoprazole and kinds of metal ions together affected the binding interaction with BSA, which may have relevant consequence in rationalizing dosage for patients with gastric ulcer.