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生物二肽和两种卟啉衍生物对金属对人淋巴细胞细胞毒性的动力学研究及保护作用比较

Comparison of Kinetic Study and Protective Effects of Biological Dipeptide and Two Porphyrin Derivatives on Metal Cytotoxicity Toward Human Lymphocytes.

作者信息

Khosravi Maryam, Rahimi Rahmatollah, Pourahmad Jalal, Zarei Mohammad Hadi, Rabbani Mahboubeh

机构信息

Bionorganic Chemistry Research Laboratory, Chemistry Department, Iran University of Science and Technology, Narmak, Tehran, Iran.

School of Pharmacy, Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Pharm Res. 2017 Summer;16(3):1059-1070.

Abstract

In this research, dipeptide (his--alanine) and porphyrin derivatives were choosen for comparing chelating ability of toxic metals such as Al, Cu, Hg and Pb. The reason for choosing these two compounds is that both of them are naturally present in biological systems and comparison of chelating ability of these two compounds has not yet been done. Synthesis and comparison of kinetic study of dipeptide (his--alanine), meso-tetrakis(4-trimethylanilinium) porphyrin (TAPP) and Tetrakis(4-sulfonatophenyl)porphyrin (TPPS) were carried out by our team. In addition, cytotoxicity assays of metals and chelators were also performed using methylthiazoletetrazolium (MTT) test. Furthermore we investigated the protective effect of chelators against cytotoxicity, induced by differenrt toxic metals such as Al, Cu, Hg and Pb on human lymphocytes. EC values on human lymphocytes obtained after 12 h. incubation for Al, Cu and Hg were 30, 51, 3 µM respectively and for Pb no cytotoxicity was observed on human lymphocyte up to 1000 µM concentration. EC obtained for chelators dipeptide, TPPS and TAPP were 948, 472 and 175 µM respectively. Pretreatment of human lymphocyte with subtoxic concentations of chelators reduced toxicity of the metals against human blood lymphocytes.

摘要

在本研究中,选择二肽(组氨酸-丙氨酸)和卟啉衍生物来比较铝、铜、汞和铅等有毒金属的螯合能力。选择这两种化合物的原因是它们都天然存在于生物系统中,且尚未对这两种化合物的螯合能力进行比较。我们团队进行了二肽(组氨酸-丙氨酸)、中-四(4-三甲基苯胺基)卟啉(TAPP)和四(4-磺基苯基)卟啉(TPPS)的合成及动力学研究比较。此外,还使用甲基噻唑基四唑(MTT)试验对金属和螯合剂进行了细胞毒性测定。此外,我们研究了螯合剂对铝、铜、汞和铅等不同有毒金属诱导的人淋巴细胞细胞毒性的保护作用。铝、铜和汞在孵育12小时后在人淋巴细胞上获得的EC值分别为30、51、3μM,而铅在浓度高达1000μM时在人淋巴细胞上未观察到细胞毒性。二肽、TPPS和TAPP等螯合剂获得的EC值分别为948、472和175μM。用亚毒性浓度的螯合剂对人淋巴细胞进行预处理可降低金属对人血淋巴细胞的毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88b7/5610760/c9ca9da0c6a9/ijpr-16-1059-g001.jpg

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