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. ORCID: https://orcid.org/0000-0003-1402-8496, El-Daher, Samer, Baillie, Les and Richardson, Simon C. W. ORCID: https://orcid.org/0000-0002-7927-0649 (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. ISSN 0304-4165 (doi: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±0.004ng/mL where as the IC50 for RT + 100μM eGCG was 3.02±0.572ng/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±0.024ng/mL) and RT + 100μM eGCG (0.68±0.235ng/mL) again using 100μM 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 100μg/mL (i.e. 178 and 223μM respectively) of eGCG mediating a significant (p=0.0472 and 0.0232) reduction in ricin toxicity at 20 and 4ng/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) 10ng/mL and 5ng/mL of RT was used. The addition of 1000μM and 100μM eGCG mediated a significant (p=0.0015 and <0.0001 respectively) reduction in ricin toxicity relative to an identical concentration of ricin with 1μg eGCG. Further, eGCG (100μM) was found to reduce the binding of RT B chain to lactoseconjugated 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
Additional Information:	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords:	Ricin toxin; Endocytosis; Polyphenol; Epigallocatechin gallate; eGCG; Tea
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Education, Health & Human Sciences > School of Human Sciences (HUM)
Last Modified:	09 Oct 2021 04:45
URI:	http://gala.gre.ac.uk/id/eprint/14755

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