Impact of Terminalia ivorensis on drug metabolising and antioxidant enzyme activities, hepatotoxicity and genotoxicity in human liver cells in vitro

1.Introduction We previously reported the effects of Terminalia ivorensis on the proliferation, genomic instability and migration of human colon cancer cells. This study assessed the effect of T. ivorensis on hepatotoxicity, genotoxicity and drug metabolising and antioxidant enzymes (DMAEs) in human liver which remains unknown.2.Methods T. ivorensis sample was extracted sequentially with petroleum ether (TIPE), chloroform (TICE), ethyl acetate (TIEaE) and ethanol (TIEE) and the phytochemicals analysed. Effects of T. ivorensis extracts on HepG2 cell viability and growth, and DNA damage, and the activities of DMAEs were investigated.3.Results T. ivorensis extracts decreased cell viability, cell growth and increased DNA damage (IC50 ≥3.5mg/ml for viability and growth; and LC50=1.1–2mg/ml DNA damage). TIEE was both the most cytotoxic (IC50=1.6mg/ml) and genotoxic (LC50=1.1mg/ml). TICE significantly (p < 0.05) inhibited the activities of cytochrome P450, reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GSR). TIEE significantly (p < 0.05) induced the activities of cytochrome P450, catalase, GSH, GPx and GSR.4.Conclusions T. ivorenesis extracts were equally cyto- and genotoxic to human liver cells at high concentrations and were well-tolerated at lower concentrations. T. ivorensis also showed a significant and differential time-dependent ability to alter several key DMAEs which may impact subsequent metabolism in human liver.