The methyl-triclosan induced caspase-dependent mitochondrial apoptosis in HepG2 cells mediated through oxidative stress

Abstract

Methyl-triclosan (MTCS) is a dominant transformation product of triclosan (TCS), which has been widely used as an effective antimicrobial ingredient with increasing concentrations in the environment. MTCS shows higher persistence in environment than its parent chemical TCS. The toxic effects of MTCS and toxicological mechanism are not well understood up to now. This study investigated the cytotoxic effects of MTCS in HepG2 cells in terms of cell viability, apoptosis induction, ROS production, GSH/GSSG levels, Mitochondrial Membrane Potential (MMP) reduction, LDH release, glucose uptake and ATP production. Moreover, the related gene transcripts were measured with RT-qPCR assay. Cytotoxic experiments in HepG2 cells revealed that MTCS exposure at micromol per liter levels had toxic effects as evidenced by decreased cell survival, elevated cell apoptosis, reduced MMP and increased LDH release. These toxic effects were associated with increased ROS production and reduced GSH/GSSG ratio. Meanwhile, elevated glucose uptake and ATP production indicated that MTCS induced membrane damages resulted not from a typical mitochondrial uncoupler, but from oxidative stress. Analysis of gene transcripts showed that MTCS exposure induced mRNA expressions alterations associated with oxidative stress response, energy production, cell cycle regulation and cell apoptosis. In general, the caspase-dependent mitochondrial apoptosis pathway might play a role in MTCS induced cytotoxicity in HepG2 cells.