Crocin alleviates neurotoxicity induced by bupivacaine in SH-SY5Y cells with inhibition of PI3K/AKT signaling.

Abstract

BACKGROUND:

Bupivacaine, a common local anesthetic, can cause neurotoxicity and permanent neurological disorders. Crocin has been widely reported as a potential neuroprotective agent in neural injury models.

OBJECTIVE:

The aim of this study was to investigate the role and regulatory mechanism of crocin underlying bupivacaine-induced neurotoxicity.

METHOD:

Human neuroblastoma SH-SY5Y cells were treated with bupivacaine and/or crocin for 24 h, followed by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effect of crocin or bupivacaine on SH-SY5Y cell proliferation was measured by Ki67 immunofluorescence assay. The levels of apoptosis-related proteins and the markers in the PI3K/Akt signaling pathway were examined using western blot analysis. The activities of caspase 3, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were tested using respective commercial assay kits. Flow cytometry analysis was executed for detecting SH-SY5Y cell apoptosis.

RESULT:

Crocin attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells. Meanwhile, crocin inhibited SH-SY5Y cell apoptosis induced by bupivacaine via repressing the activity of caspase-3, reducing Bax expression, and elevating Bcl-2 expression. Moreover, crocin mitigated oxidative stress in SH-SY5Y cells by increasing the content of CAT, SOD, GSH-Px and reducing the content of MDA. Additionally, crocin protected against bupivacaine-induced dephosphorylation of Akt and GSK-3β. The protective effects of crocin against bupivacaine-induced neurotoxicity in SH-SY5Y cells were counteracted by the Akt inhibitor.

CONCLUSION:

These results suggested that crocin may exert a neuroprotective function by promoting cell proliferation and suppressing apoptosis and oxidative stress in SH-SY5Y cells. Thus, crocin might become a promising drug for the treatment of bupivacaine-induced neurotoxicity.

• Authors: Lili Lin, Zhen Chen, Jun Li, Jianye Peng, Jian Wang, Mingjun Feng, Tiancheng Liu, Mengli Zhang, Xian Wu, Fen Ai, Caijie Shen
• Journal: Genes & genomics (Genes Genomics) Vol. 46 Issue 1 Pg. 149-160 (Jan 2024) ISSN: 2092-9293 [Electronic] Korea (South)
• PMID: 37523128 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s) under exclusive licence to The Genetics Society of Korea.

Chemical References

• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• crocin
• Bupivacaine
• Glycogen Synthase Kinase 3 beta
• Superoxide Dismutase
• Carotenoids

Topics

• Humans
• Proto-Oncogene Proteins c-akt (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Bupivacaine (toxicity)
• Glycogen Synthase Kinase 3 beta (metabolism, pharmacology)
• Cell Line, Tumor
• Neuroblastoma
• Signal Transduction
• Superoxide Dismutase (metabolism)
• Carotenoids