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Tetracaine hydrochloride induces macrophage pyroptosis through caspase‑1/11‑GSDMD signaling pathways

  • Authors:
    • Ran Zhang
    • Wanrong Gou
    • Peng Yi
    • Zhengshan Qin
    • Danli Zhu
    • Jing Jia
    • Li Liu
    • Xian Jiang
    • Jianguo Feng
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 428
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    Published online on: July 19, 2023
       https://doi.org/10.3892/etm.2023.12127
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Abstract

Tetracaine hydrochloride (TTC) is a long‑lasting local anesthetic commonly used for topical anesthesia. Inappropriate dosage or allergic reactions to TTC can lead to local anesthetic toxicity. TTC exerts cytotoxic effects on certain cell types by inducing apoptosis and necrosis; however, the effects of TTC on macrophages are currently unclear. In the present study, the RAW 264.7 and BV2 cell lines, and murine peritoneal macrophages, were used to evaluate the cytotoxicity of TTC. The present study demonstrated that TTC caused a decrease in cell viability according to a Cell Counting Kit‑8 assay, increased lactate dehydrogenase and IL‑1β secretion according to ELISA, and induced morphological changes characteristic of pyroptosis according to western blotting. Moreover, TTC‑induced macrophage pyroptosis was mediated by gasdermin (GSDM)D, and the cleavage of GSDMD was modulated by both caspase‑1 and caspase‑11. These results were experimentally validated using caspase‑1 and caspase‑11 inhibitors. Furthermore, it was observed that TTC and lipopolysaccharide (LPS) exerted similar effects on macrophages. However, the mechanism of induction of pyroptosis by TTC was different from that of LPS. The present study demonstrated that TTC alone could induce macrophage pyroptosis mediated by canonical and non‑canonical inflammatory caspases. Therapies targeting pyroptosis may potentially provide a promising future strategy for the prevention and treatment of local anesthetic toxicity induced by TTC.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang R, Gou W, Yi P, Qin Z, Zhu D, Jia J, Liu L, Jiang X and Feng J: Tetracaine hydrochloride induces macrophage pyroptosis through caspase‑1/11‑GSDMD signaling pathways. Exp Ther Med 26: 428, 2023.
APA
Zhang, R., Gou, W., Yi, P., Qin, Z., Zhu, D., Jia, J. ... Feng, J. (2023). Tetracaine hydrochloride induces macrophage pyroptosis through caspase‑1/11‑GSDMD signaling pathways. Experimental and Therapeutic Medicine, 26, 428. https://doi.org/10.3892/etm.2023.12127
MLA
Zhang, R., Gou, W., Yi, P., Qin, Z., Zhu, D., Jia, J., Liu, L., Jiang, X., Feng, J."Tetracaine hydrochloride induces macrophage pyroptosis through caspase‑1/11‑GSDMD signaling pathways". Experimental and Therapeutic Medicine 26.3 (2023): 428.
Chicago
Zhang, R., Gou, W., Yi, P., Qin, Z., Zhu, D., Jia, J., Liu, L., Jiang, X., Feng, J."Tetracaine hydrochloride induces macrophage pyroptosis through caspase‑1/11‑GSDMD signaling pathways". Experimental and Therapeutic Medicine 26, no. 3 (2023): 428. https://doi.org/10.3892/etm.2023.12127
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang R, Gou W, Yi P, Qin Z, Zhu D, Jia J, Liu L, Jiang X and Feng J: Tetracaine hydrochloride induces macrophage pyroptosis through caspase‑1/11‑GSDMD signaling pathways. Exp Ther Med 26: 428, 2023.
APA
Zhang, R., Gou, W., Yi, P., Qin, Z., Zhu, D., Jia, J. ... Feng, J. (2023). Tetracaine hydrochloride induces macrophage pyroptosis through caspase‑1/11‑GSDMD signaling pathways. Experimental and Therapeutic Medicine, 26, 428. https://doi.org/10.3892/etm.2023.12127
MLA
Zhang, R., Gou, W., Yi, P., Qin, Z., Zhu, D., Jia, J., Liu, L., Jiang, X., Feng, J."Tetracaine hydrochloride induces macrophage pyroptosis through caspase‑1/11‑GSDMD signaling pathways". Experimental and Therapeutic Medicine 26.3 (2023): 428.
Chicago
Zhang, R., Gou, W., Yi, P., Qin, Z., Zhu, D., Jia, J., Liu, L., Jiang, X., Feng, J."Tetracaine hydrochloride induces macrophage pyroptosis through caspase‑1/11‑GSDMD signaling pathways". Experimental and Therapeutic Medicine 26, no. 3 (2023): 428. https://doi.org/10.3892/etm.2023.12127
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