Butorphanol reduces the neuronal inflammatory response and apoptosis via inhibition of p38/JNK/ATF2/p53 signaling

Abstract

Neuronal cell apoptosis is a complex pathophysiological change that occurs following spinal cord injury (SCI) and affects self-repair. Therefore, preventing neuronal cell apoptosis can promote the recovery of nerve function. The present study aimed to investigate the effects of butorphanol on neuronal inflammatory response and apoptosis. The effects of butorphanol on cell viability and pathway-related protein expression were first assessed using the CCK8 and western blot assays, respectively. Lipopolysaccharide (LPS) was used to establish models. The influences of additional anisomycin, an agonist of MAPK pathway, on cell viability, pathway-related protein expression and lactate dehydrogenase level were determined using the CCK8 assay, western blotting and assay kits, respectively. In addition, the roles of butorphanol and anisomycin in inflammatory factor levels and cell apoptosis were determined using reverse transcription-quantitative PCR, TUNEL and western blot assays. Butorphanol was found to protect PC12 cells from the action of LPS on viability and effectively upregulated the p38/JNK/activation of transcription factor 2 (ATF2)/p53 protein expression levels. In addition, anisomycin could break the protective role of butorphanol in cell viability and the inhibitory roles in inflammatory response and apoptosis. To sum up, butorphanol reduces neuronal inflammatory response and apoptosis via inhibiting p38/JNK/ATF2/p53 signaling. The present findings may provide a new direction for the treatment for SCI.

Protective effects of butorphanol in oleic acid-endotoxin “two-hit” induced rat lung injury by suppression of inflammation and apoptosis

“…( ## p < 0.01 or # p < 0.05). The results were in accordance with these previous reports that butorphanol reduced brain and neurological damage and relieved the expression of in ammatory cytokines 12,19 . Arterial blood gas analysis was also one of the important criteria to assess the gas exchange extent and destruction of the alveolar wall 20,21 .…”

“…Butorphanol is widely used in the clinic as a lipid-soluble anesthetic drug with e cient analgesic effects 12,16,17 . In recent years, a series of reports have shown that butorphanol decreases the levels of proin ammatory cytokines or increases the levels of antiin ammatory cytokines to reduce organ injury and cell apoptosis [11][12][13]18 . However, the underlying anti-in ammatory mechanism of butorphanol has not been fully demonstrated.…”

“…1A) is a new opioid receptor anesthetic drug that is a strong κ-receptor agonist and a weak µ-receptor agonist-antagonist 10 . Butorphanol is widely applied in the clinic as an analgesic, while many studies have established the protective effect of κ-receptors on the heart, lung, brain, and other important organs [11][12][13] . Huang et al 11 reported that butorphanol attenuates myocardial ischemia reperfusion injury by inhibiting mitochondriamediated apoptosis in mice.…”

“…Huang et al 11 reported that butorphanol attenuates myocardial ischemia reperfusion injury by inhibiting mitochondriamediated apoptosis in mice. Huang et al 12 butorphanol reduces the neuronal in ammatory response and apoptosis. Luan et al 13 shown that butorphanol promotes macrophage phenotypic transition to inhibit in ammatory lung injury.…”

S100A1 expression is increased in spinal cord injury and promotes inflammation, oxidative stress and apoptosis of PC12 cells induced by LPS via ERK signaling

“…on the whole, these results suggested that S100a1 expression was upregulated in the Pc12 cell model of LPS-induced inflammation. Subsequently, 5 µg/ml lPS was used for Pc12 cell model establishment to explore the biological function of S00a1 in lPS induced Sci model in vitro as the reported studies (30)(31)(32).…”