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

Dyer, Paul D.R., Kotha, Arun K., Gollings, Alex S., Shorter, Susan A., Shepherd, Thomas R., Pettit, Marie W., Alexander, Bruce D., Getti, Giulia T.M., El-Daher, Samer, Baillie, Les and Richardson, Simon C.W. 2016. An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin. Biochimica et Biophysica Acta (BBA) - General Subjects 1860 (7) , pp. 1541-1550. 10.1016/j.bbagen.2016.03.024

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Abstract

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 IC50 for RT was 0.08 ± 0.004 ng/mL whereas the IC50 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 IC50 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

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Additional Information: Available online 23 March 2016
Publisher: Elsevier
ISSN: 0304-4165
Date of First Compliant Deposit: 1 April 2016
Date of Acceptance: 20 March 2016
Last Modified: 04 Jun 2017 08:58
URI: http://orca-mwe.cf.ac.uk/id/eprint/88520

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