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

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.

Effects of aspirin on the expression of nuclear factor-κB in a rat model of acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (APE) is a disorder involving the pulmonary circulation resulting from a blockage of the pulmonary artery. The present study aimed to investigate the effects of aspirin on the nuclear factor-κB (NF-κB) activity in a rat model of APE. METHODS: A total of 108 healthy male Sprague-Dawley rats were randomly assigned into six groups (n=18 rats per group): control group, sham operation group, APE model group, and low-, medium- and high-dose aspirin groups. Six, 24, and 72 hours after the induction of APE, rats in the low-, medium- and high-dose aspirin groups were given aspirin at a respective daily dose of 150, 300, and 600 mg/kg by gavage for three consecutive days. Rats in the other groups were treated with equal volumes of normal saline. Six rats in each group were anesthetized with 10% chloral hydrate solution at each time point, and then the lung tissues were collected and analyzed using immunohistochemical staining. RESULTS: Positive immunohistochemical staining was present in the bronchial epithelial cells, alveolar cells, macrophages, and surrounding bronchial smooth muscle cells. When compared with the APE model group, the number of positive cells was significantly lower in the other groups at each time point (P<0.001). Statistically significant differences were also observed among the aspirin-treated groups at 6 hours (P<0.05, P<0.001). Compared with the APE model group, NF-κB protein expression was reduced in the other groups at each time point (P<0.05, P<0.001). Rats from the APE model group had thrombosis, damaged alveolar walls, and pulmonary hemorrhage, along with different degrees of inflammatory cellular infiltration at each time point. However, pathological changes such as pulmonary hemorrhage and infiltration of inflammatory cells were attenuated after the aspirin treatment. CONCLUSION: Aspirin can significantly inhibit NF-κB activity in the lung of rats with APE in a dose-dependent manner, and can alleviate lung injury after APE.