J Appl Biomed 12:291-299, 2014 | DOI: 10.1016/j.jab.2014.03.001

Possible hepatocellular toxicity of EGCG under the influence of an inflammagen

Ibrahim G. Saleh^a,b, Zulfiqar Ali^a, Naohito Abe^a, Farid M. Hamada^b, Mohamed F. Abd-Ellah^b, Larry A. Walker^a,c, Ikhlas A. Khan^a,d,e, Mohammad K. Ashfaq^a,*

^a National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA

^b Department of Pharmacology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt

^c Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS 38677, USA

^d Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677, USA

^e Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11557, Saudi Arabia

Epigallocatechin-3-gallate (EGCG) is widely used as a weight controlling supplement. Concerns about its safety evoked after cases of hepatotoxicity occurred upon its use. The underlying factors that could be involved in EGCG associated hepatotoxicity are not fully studied. In this study, we investigated the possible impact of lipopolysaccharide (LPS), as an inflammagen, on the effect of EGCG on hepatocytes. HepG2 cells were treated with different concentrations of EGCG (100, 200, 500 μM), with and without LPS (10 nM)-presensitization of the cells. Viability of HepG2 cells decreased with the increased concentrations of EGCG; the viability was even lesser in LPS-presensitized cells. Oxidative stress (Ox.LDL and CXCL16), the expression of nuclear retinoic receptors (RAR, RXR) and the biomarkers of hepatocellular injury (TNFα, TGFβ1) were all relatively higher in LPS-presensitized cells compared to non-sensitized cells upon treatment with EGCG. Sensitization of HepG2 cells with LPS alone did not affect the viability or any of the other biomarkers considered in this study. In conclusion, EGCG alone can be harmful to liver at high concentrations and this effect may become more pronounced under the influence of an inflammagen.

Keywords: Green tea; EGCG; LPS; Inflammation; Hepatotoxicity

Received: December 27, 2013; Revised: February 28, 2014; Accepted: March 17, 2014; Published: November 1, 2014  Show citation