Chlorfenapyr Induces Hepatotoxicity Associated With Oxidative Stress and Mitochondrial Dysfunction Involving...

Area of Science:

• Toxicology
• Molecular Biology
• Biochemistry

Background:

• Chlorfenapyr (CHL) is a widely used insecticide with known but incompletely understood hepatotoxic effects.
• The underlying mechanisms of CHL-induced liver injury, particularly involving cellular signaling pathways, require further investigation.

Purpose of the Study:

• To investigate the toxic effects of CHL on rat liver and BRL-3A hepatocytes.
• To explore the involvement of the Keap1/Nrf2 signaling pathway in CHL-induced hepatotoxicity.

Main Methods:

• Rats and BRL-3A hepatocytes were exposed to varying doses of CHL.
• Biochemical markers, oxidative stress indicators (ROS, MDA, SOD, GSH), mitochondrial function (ATP, protein expression), apoptosis, and Keap1/Nrf2 pathway activation were assessed.
• The effect of Nrf2 activator tBHQ was evaluated.

Main Results:

• CHL exposure significantly increased liver damage markers, oxidative stress, and apoptosis, while reducing mitochondrial function in both rats and hepatocytes.
• CHL suppressed the Keap1/Nrf2 signaling pathway by increasing Keap1 and decreasing Nrf2 and its downstream targets (HO-1, NQO1).
• Nrf2 activation by tBHQ partially reversed CHL-induced toxicity, mitigating oxidative stress, mitochondrial dysfunction, and apoptosis.

Conclusions:

• CHL induces hepatotoxicity through oxidative stress, mitochondrial dysfunction, and apoptosis, partly via Keap1/Nrf2 pathway disruption.
• Activation of the Nrf2 pathway presents a potential therapeutic strategy for mitigating Chlorfenapyr-induced liver injury.