Butorphanol inhibits ferroptosis to attenuate PC12 cell injury by blocking JNK/p38 signaling

Ji,Lulu; She,Qing; Zhou,Ping; Qin,Yibin

doi:10.3892/etm.2023.12295

Butorphanol inhibits ferroptosis to attenuate PC12 cell injury by blocking JNK/p38 signaling

Authors:
- Lulu Ji
- Qing She
- Ping Zhou
- Yibin Qin
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Affiliations: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: November 10, 2023 https://doi.org/10.3892/etm.2023.12295
Article Number: 8
Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Butorphanol is a synthetic selective opioid receptor antagonist that exhibits substantial analgesic effects. The present study aimed to explore the effects of butorphanol on a neurodegenerative disease cell model and to investigate its specific regulatory mechanism. Cell viability of PC12 cells was assessed using the Cell Counting Kit‑8 assay. Oxidative stress levels were measured by the corresponding kits and western blotting of specific protein markers. Apoptosis was determined using the terminal‑deoxynucleoitidyl transferase mediated nick end labeling assay and by western blotting. Western blotting was used to analyze the expression levels of c‑Jun NH2‑terminal kinase (JNK)/p38 signaling pathway‑related proteins. Thiobarbituric acid‑reactive substances and Fe⁺² content were detected using the corresponding assay kits and the expression levels of ferroptosis‑associated proteins were assessed by western blotting following the addition of the JNK activator anisomycin (ANI). Oxidative stress and apoptosis were examined with the aforementioned assays following the supplementation of ANI or the ferroptosis inducer erastin (ERA). It was revealed that butorphanol dose‑dependently enhanced the viability and suppressed the oxidative stress and apoptosis of H₂O₂‑treated PC12 cells. In addition, butorphanol blocked JNK/p38 signaling and hampered ferroptosis, while this effect was reversed by ANI. ANI or ERA reversed the effects of butorphanol on oxidative stress and apoptosis of H₂O₂‑treated PC12 cells. In summary, butorphanol suppressed ferroptosis by blocking JNK/p38 signaling to impart inhibitory effects on oxidative stress and apoptosis in a neurodegenerative disease cell model.

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