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Tytuł pozycji:

P53 inhibitor pifithrin-α inhibits ropivacaine-induced neuronal apoptosis via the mitochondrial apoptosis pathway.

Tytuł:
P53 inhibitor pifithrin-α inhibits ropivacaine-induced neuronal apoptosis via the mitochondrial apoptosis pathway.
Autorzy:
Zeng L; Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.; Hubei Clinical Research Center of Parkinson's disease, Xiangyang No.1 People s Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Zhang F; Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Zhang Z; Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Xu M; Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Xu Y; Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Liu Y; Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Xu H; Central Laboratory, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.; Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Sun X; Hubei Clinical Research Center of Parkinson's disease, Xiangyang No.1 People s Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.; Central Laboratory, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.; Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Sang M; Hubei Clinical Research Center of Parkinson's disease, Xiangyang No.1 People s Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.; Central Laboratory, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.; Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Luo H; Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Źródło:
Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2021 Aug; Vol. 35 (8), pp. e22822. Date of Electronic Publication: 2021 Jun 06.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: New York, NY : Wiley, c1998-
MeSH Terms:
Apoptosis/*drug effects
Benzothiazoles/*pharmacology
Mitochondria/*metabolism
Ropivacaine/*adverse effects
Spinal Cord Injuries/*metabolism
Toluene/*analogs & derivatives
Tumor Suppressor Protein p53/*antagonists & inhibitors
Animals ; PC12 Cells ; Rats ; Rats, Sprague-Dawley ; Ropivacaine/pharmacology ; Spinal Cord Injuries/drug therapy ; Spinal Cord Injuries/pathology ; Toluene/pharmacology ; Tumor Suppressor Protein p53/metabolism
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Grant Information:
81903005 the National Natural Science Foundation of China; YC2020029 the Innovative Research Program for Graduates of Hubei University of medicine
Contributed Indexing:
Keywords: PC12; apoptosis; pifithrin-α; ropivacaine; spinal cord
Substance Nomenclature:
0 (Benzothiazoles)
0 (Tp53 protein, rat)
0 (Tumor Suppressor Protein p53)
3FPU23BG52 (Toluene)
7IO5LYA57N (Ropivacaine)
D213B92S1Y (pifithrin)
Entry Date(s):
Date Created: 20210606 Date Completed: 20210901 Latest Revision: 20210901
Update Code:
20240105
DOI:
10.1002/jbt.22822
PMID:
34091999
Czasopismo naukowe
The neurotoxicity of local anesthetics (LAs) has attracted more and more attention, However, they lack preventive and therapeutic measures. Many studies have shown that apoptosis plays an important role in the process of LA-induced neurotoxicity. As an important signaling molecule to activate apoptosis, p53 has been proved to be involved in the neurotoxicity induced by LAs, but the mechanism is unclear. In this study, we explored the effect of pifithrin-α (PFT-α), a p53 inhibitor, on apoptosis by ropivacaine (Rop) in vivo and in vitro. Cell viability and apoptosis detected by CCK-8 and a JC-1 apoptosis detection kit, the changes of spinal cord structure observed after hematoxylin and eosin staining, apoptosis of the spinal cord measured by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, behavioral assessment of the nerve Injury evaluated by the detection of sciatic nerve conduction velocity (SNCV) andmechanical withdrawal threshold (MWT), the expression of p53 and many apoptosis-related genes included Bax, Bcl-2, and caspase-3 detected by quantitative real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. Results showed that PC12 cell viability decreased because of Rop, but the pretreatment of PFT-α could protect it. And PFT-α reduced the injuries in the spinal cord by Rop included vacuoles or edema. The results of immunofluorescence and immunohistochemistry testing showed that PFT-α inhibited the p53 protein upregulated by Rop. Apoptosis rate and many proapoptotic genes include p53, Bax, caspase-3 messenger RNA, and proteins were increased by Rop, but PFT-α could decrease it. In conclusion, PFT-α inhibited cell apoptosis and spinal cord injuries induced by Rop.
(© 2021 Wiley Periodicals LLC.)

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