Autophagy alleviates amiodarone-induced hepatotoxicity

Area of Science:

• Hepatology
• Pharmacology
• Cellular Biology

Background:

• Amiodarone, an antiarrhythmic drug, is known to cause liver injury, including steatohepatitis, fibrosis, and cirrhosis.
• The precise molecular mechanisms underlying amiodarone-induced liver injury are not well understood.

Purpose of the Study:

• To investigate the mechanisms of amiodarone-mediated hepatocellular injury.
• To explore the role of lipid accumulation, ER stress, and autophagy in amiodarone toxicity.

Main Methods:

• Analysis of serum caspase-cleaved keratin-18 levels in amiodarone-treated patients and controls.
• In vitro studies using primary hepatocytes and HepG2 cells treated with amiodarone.
• Assessment of apoptosis, lipid accumulation, ER stress, and autophagy markers.

Main Results:

• Amiodarone-treated patients showed elevated serum levels of the apoptosis biomarker caspase-cleaved keratin-18.
• Amiodarone induced apoptosis, lipid accumulation, and ER stress in hepatocytes.
• Protective autophagy was induced in response to amiodarone-induced lipotoxicity, and its inhibition exacerbated liver injury.

Conclusions:

• Amiodarone induces hepatocellular injury via lipid accumulation, ER stress, and apoptosis.
• Serum keratin-18 fragments reflect amiodarone-induced liver cell apoptosis.
• Autophagy plays a protective role against amiodarone-mediated liver toxicity and represents a potential therapeutic target.