Melatonin ameliorates bupivacaine-induced spinal neurotoxicity in rats by suppressing neuronal NLRP3 inflammasome activation

Neurosci Lett. 2022 Feb 16:772:136472. doi: 10.1016/j.neulet.2022.136472. Epub 2022 Jan 20.

Abstract

Bupivacaine is a common local anesthetic that causes neurotoxicity when used at clinical concentrations. Melatonin (MT), is a potent neuroprotective molecule. The study aimed to characterize the neuroprotective effects of MT on spinal neurotoxicity induced by bupivacaine in rats. It showed that bupivacaine, by intrathecal injection, induced spinal injury, and that the protein levels of Nod-like receptor protein 3 (NLRP3), cleaved caspase-1, and the N-terminal region of gasdermin D (GSDMD-N) were significantly increased. NLRP3 was expressed mainly in neurons and microglia. MT treatment ameliorated bupivacaine-induced spinal cord injury in rats by suppressing activation of neuronal NLRP3 inflammasomes.

Keywords: Bupivacaine; Inflammasome; Melatonin; Neurotoxicity; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Bupivacaine / toxicity
  • Male
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • Microglia / drug effects
  • Microglia / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurotoxicity Syndromes / drug therapy*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / cytology
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Melatonin
  • Bupivacaine