The effect of N-acetylcysteine on the neurotoxicity of sevoflurane in developing hippocampus cells

Neurotoxicology. 2024 Jul:103:96-104. doi: 10.1016/j.neuro.2024.05.006. Epub 2024 Jun 4.

Abstract

Sevoflurane, a common pediatric anesthetic, has been linked to neurodegeneration, raising safety concerns. This study explored N-acetylcysteine's protective potential against sevoflurane-induced neurotoxicity in rat hippocampi. Four groups were examined: Control: Received 6 hours of 3 l/min gas (air and 30 % O2) and intraperitoneal saline. NAC: Received 6 hours of 3 l/min gas and 150 mg/kg NAC intraperitoneally. Sev: Exposed to 6 hours of 3 l/min gas and 3 % sevoflurane. Sev+NAC: Received 6 hours of 3 l/min gas, 3 % sevoflurane, and 150 mg/kg NAC. Protein levels of NRF-2, NLRP3, IL-1β, caspase-1, Beclin 1, p62, LC3A, and apoptosis markers were assessed. Sevoflurane and NAC alone reduced autophagy, while Sev+NAC group maintained autophagy levels. Sev group had elevated NRF-2, NLRP3, pNRF2, Caspase-1, and IL-1β, which were reduced in Sev+NAC. Apoptosis was higher in Sev, but Sev+NAC showed reduced apoptosis compared to the control. In summary, sevoflurane induced neurotoxicity in developing hippocampus, which was mitigated by N-acetylcysteine administration.

Keywords: Apoptosis; Autophagy; N-acetylcysteine; Neuroinflammation; Neurotoxicity; Sevoflurane.

MeSH terms

  • Acetylcysteine* / pharmacology
  • Anesthetics, Inhalation* / toxicity
  • Animals
  • Apoptosis* / drug effects
  • Autophagy / drug effects
  • Hippocampus* / drug effects
  • Hippocampus* / metabolism
  • Hippocampus* / pathology
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sevoflurane* / toxicity

Substances

  • Sevoflurane
  • Acetylcysteine
  • Anesthetics, Inhalation
  • Neuroprotective Agents