An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin.

Autor:	Dyer PD; Department of Life and Sports Science, University of Greenwich, Central Avenue, Chatham, Kent ME4 4TB, UK., Kotha AK; Department of Life and Sports Science, University of Greenwich, Central Avenue, Chatham, Kent ME4 4TB, UK., Gollings AS; Department of Life and Sports Science, University of Greenwich, Central Avenue, Chatham, Kent ME4 4TB, UK., Shorter SA; Department of Life and Sports Science, University of Greenwich, Central Avenue, Chatham, Kent ME4 4TB, UK., Shepherd TR; Department of Life and Sports Science, University of Greenwich, Central Avenue, Chatham, Kent ME4 4TB, UK., Pettit MW; Department of Life and Sports Science, University of Greenwich, Central Avenue, Chatham, Kent ME4 4TB, UK., Alexander BD; Department of Pharmaceutical, Chemical and Environmental Science, University of Greenwich, Central Avenue, Chatham, Kent ME4 4TB, UK., Getti GT; Department of Life and Sports Science, University of Greenwich, Central Avenue, Chatham, Kent ME4 4TB, UK., El-Daher S; Department of Life and Sports Science, University of Greenwich, Central Avenue, Chatham, Kent ME4 4TB, UK., Baillie L; School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3AX, UK., Richardson SC; Department of Life and Sports Science, University of Greenwich, Central Avenue, Chatham, Kent ME4 4TB, UK. Electronic address: S.C.W.Richardson@Greenwich.ac.uk.
Jazyk:	angličtina
Zdroj:	Biochimica et biophysica acta [Biochim Biophys Acta] 2016 Jul; Vol. 1860 (7), pp. 1541-50. Date of Electronic Publication: 2016 Mar 23.
DOI:	10.1016/j.bbagen.2016.03.024
Abstrakt:	The catechin, epigallocatechin gallate (eGCG), found in green tea, has inhibitory activity against a number of protein toxins and was investigated in relation to its impact upon ricin toxin (RT) in vitro. The IC(50) for RT was 0.08±0.004 ng/mL whereas the IC(50) for RT+100 μM eGCG was 3.02±0.572 ng/mL, indicating that eGCG mediated a significant (p<0.0001) reduction in ricin toxicity. This experiment was repeated in the human macrophage cell line THP-1 and IC(50) values were obtained for RT (0.54±0.024 ng/mL) and RT+100 μM eGCG (0.68±0.235 ng/mL) again using 100 μM eGCG and was significant (p=0.0013). The documented reduction in ricin toxicity mediated by eGCG was found to be eGCG concentration dependent, with 80 and 100 μg/mL (i.e. 178 and 223 μM respectively) of eGCG mediating a significant (p=0.0472 and 0.0232) reduction in ricin toxicity at 20 and 4 ng/ml of RT in Vero and THP-1 cells (respectively). When viability was measured in THP-1 cells by propidium iodide exclusion (as opposed to the MTT assays used previously) 10 ng/mL and 5 ng/mL of RT was used. The addition of 1000 μM and 100 μM eGCG mediated a significant (p=0.0015 and <0.0001 respectively) reduction in ricin toxicity relative to an identical concentration of ricin with 1 μg eGCG. Further, eGCG (100 μM) was found to reduce the binding of RT B chain to lactose-conjugated Sepharose as well as significantly (p=0.0039) reduce the uptake of RT B chain in Vero cells. This data suggests that eGCG may provide a starting point to refine biocompatible substances that can reduce the lethality of ricin. (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu