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

Area of Science:

• Environmental Toxicology
• Cell Biology
• Biochemistry

Background:

• Methyl-triclosan (MTCS) is a persistent environmental transformation product of triclosan (TCS).
• The toxicological mechanisms of MTCS are not well understood.
• TCS and its derivatives are increasingly detected in the environment due to widespread use.

Purpose of the Study:

• To investigate the cytotoxic effects of MTCS on HepG2 cells.
• To elucidate the underlying toxicological mechanisms of MTCS.
• To analyze MTCS-induced alterations in cellular functions and gene expression.

Main Methods:

• Exposure of HepG2 cells to varying concentrations of MTCS.
• Assessment of cell viability, apoptosis, reactive oxygen species (ROS) production, glutathione (GSH/GSSG) levels, mitochondrial membrane potential (MMP), lactate dehydrogenase (LDH) release, glucose uptake, and ATP production.
• Quantitative real-time PCR (RT-qPCR) analysis of relevant gene transcripts.

Main Results:

• MTCS exposure significantly decreased cell viability, increased apoptosis, reduced MMP, and elevated LDH release.
• MTCS-induced toxicity was linked to increased ROS production and a decreased GSH/GSSG ratio.
• Elevated glucose uptake and ATP production suggested membrane damage due to oxidative stress, not mitochondrial uncoupling.

Conclusions:

• MTCS exhibits significant cytotoxicity in HepG2 cells at micromolar levels.
• Oxidative stress and subsequent membrane damage play a key role in MTCS toxicity.
• The caspase-dependent mitochondrial apoptosis pathway is implicated in MTCS-induced cytotoxicity.