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

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