Ropivacaine impairs mitochondrial biogenesis by reducing PGC-1α

Area of Science:

• Biochemistry
• Neuroscience
• Cell Biology

Background:

• Ropivacaine is a widely used local anesthetic.
• Preclinical studies suggest ropivacaine may cause neurotoxicity.
• The safety of ropivacaine, particularly its cellular effects, requires further investigation.

Purpose of the Study:

• To investigate the impact of ropivacaine on mitochondrial biogenesis and function in neuronal cells.
• To elucidate the molecular mechanisms underlying ropivacaine-induced neurotoxicity.

Main Methods:

• Neuronal cells were exposed to clinically relevant doses of ropivacaine.
• Mitochondrial biogenesis markers (PGC-1α, NRF1, TFAM), mitochondrial mass, mtDNA/nDNA ratio, and COX-1 expression were assessed.
• Mitochondrial function was evaluated by measuring respiratory rate and ATP production.
• The role of CREB and PGC-1α in ropivacaine's effects was examined.

Main Results:

• Ropivacaine exposure reduced PGC-1α, NRF1, and TFAM expression.
• Mitochondrial biogenesis was impaired, evidenced by decreased mitochondrial mass, mtDNA/nDNA ratio, and COX-1 expression.
• Mitochondrial function was compromised, with reduced respiratory rate and ATP production.
• Ropivacaine-induced PGC-1α reduction involved CREB inactivation; PGC-1α reintroduction rescued mitochondrial abnormalities.

Conclusions:

• Mitochondrial impairment is a critical factor in ropivacaine-mediated neurotoxicity.
• Reduced PGC-1α and its downstream signaling pathways are likely molecular mechanisms of ropivacaine's cellular toxicity.
• These findings highlight potential safety concerns associated with ropivacaine use.