内源性物质对白内障患者房水中双氯芬酸与白蛋白结合的ii位到i位位移的影响。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2024-01-20 Epub Date: 2023-12-07 DOI:10.1248/bpb.b23-00301
Saya Ishii, Mineo Ozaki, Norito Takamura, Kenji Ogata, Jin Tokunaga, Ryuji Ikeda
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引用次数: 0

摘要

双氯芬酸滴注对预防白内障术后炎症引起的术中瞳孔缩小和黄斑水肿有效;然而,当输注双氯芬酸与患者房水中的白蛋白强烈结合时,并没有达到最佳疗效。因此,需要一种抑制双氯芬酸结合并增加其游离分数浓度的方法。我们进行了一项关于抑制剂对输注双氯芬酸与房水白蛋白和内源性物质结合的影响的基础研究。将16例患者的房水样本收集在一起进行分析。双氯芬酸的游离部分采用超滤方法在各种实验中与池和模拟房水。II位药物双氯芬酸在混合房水中的游离分数为0.363±0.013。双氯芬酸与I位抑制剂苯丁酮(PB)的结合明显受到抑制(游离分数= 0.496±0.013);而II位点抑制剂布洛芬无明显抑制作用(游离分数= 0.379±0.004)。这一意想不到的结果是由于游离脂肪酸[FFAs;棕榈酸(PA)和色氨酸(L-Trp)。在含有这些内源性物质的模拟房水中,PB对双氯芬酸结合的抑制表明,PA和L-Trp存在时,PB对双氯芬酸的结合有显著的抑制作用。双氯芬酸在房水中有游离脂肪酸和l -色氨酸存在时,会从II位强烈反弹到I位,这是因为游离脂肪酸和l -色氨酸会诱导白蛋白的构象改变。因此,PB显著抑制双氯芬酸与白蛋白的结合。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Influence of Endogenous Substances on Site-II to Site-I Displacement of Diclofenac Bound to Albumin in the Aqueous Humor of Patients with Cataract.

Diclofenac instillation is useful in preventing intraoperative miosis and macular edema caused by postoperative inflammation in cataract surgery; however, optimum efficacy is not attained when the instilled diclofenac strongly binds to albumin in patients' aqueous humor. Therefore, a method that inhibits diclofenac binding and increases the concentration of its free fraction is needed. We conducted a basic study regarding the effects of inhibitors on the binding of instilled diclofenac to albumin and endogenous substances in aqueous humor. Aqueous humor samples from 16 patients were pooled together for analysis. The free fraction of diclofenac was measured using ultrafiltration methods in various experiments with pooled and mimic aqueous humor. Free fraction of diclofenac, a site II drug, in pooled aqueous humor was 0.363 ± 0.013. The binding of diclofenac in the presence of phenylbutazone (PB), a site I inhibitor, was significantly inhibited (free fraction = 0.496 ± 0.013); however, no significant inhibition by ibuprofen, a site II inhibitor, (free fraction = 0.379 ± 0.004), was observed. The unexpected result was due to free fatty acids (FFAs; palmitic acid (PA)) and L-tryptophan (Trp). The inhibition of diclofenac binding by PB in the mimic aqueous humor containing these endogenous substances revealed significant binding inhibition in the presence of PA and Trp. Diclofenac is strongly rebound from site II to site I in the presence of FFAs and Trp in the aqueous humor because FFAs and Trp induce a conformational change in albumin. Therefore, PB significantly inhibits the binding of diclofenac to albumin.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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