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| GV1001 alleviates doxorubicin-induced cardiotoxicity by inhibiting cGAS/STING signaling pathway |
| Chen Jiming1, Lin Hui2, Meng Liping2, Yu Ziheng1, Lu Kongjie1. |
| 1.Department of Cardiology, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University (Huzhou Central Hospital), Huzhou 313099, China;2.Department of Cardiology, Shaoxing People’s Hospital, Shaoxing 312035, China |
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| Cite this article: |
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Chen Jiming,Lin Hui,Meng Liping, et al. GV1001 alleviates doxorubicin-induced cardiotoxicity by inhibiting cGAS/STING signaling pathway[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2024, 54(9): 718-724,731.
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Abstract Objective: To investigate the protective effect of telomerase-derived peptide GV1001 on doxorubicin (DOX)-induced cardiac toxicity in mice and its potential mechanisms. Methods: A DOX-induced cardiac toxicity animal model was established in C57BL/6 mice by administering DOX (20 mg/kg), which were divided as the control group, DOX group, GV1001 groups of different concentration (6, 30 and 60 μmol/kg).Mouse’s cardiac function was assessed, and markers of myocardial injury were detected in serum; heart tissues were subjected to HE staining and Masson staining; myocardial levels of MDA, T-SOD, and GSH-PX were measured using spectrophotometry; protein was extracted from heart tissue, and Western blot was performed to evaluate the expression levels of cyclic GMP-AMP synthase (cGAS), phosphorylated stimulator of interferon genes (STING), and IRF3. Changes in myocardial tissue damage and oxidative stress were also assessed after administration of STING agonist. Results: Compared with the control group, mice in the DOX group exhibited decreased LVIDd, LVEF, and LVFS, increased LVIDs, disrupted myocardial fiber arrangement, nuclear condensation, vacuolization, and increased collagen deposition (all P<0.05). Concurrently, serum myocardial enzyme cTnI, CK⁃MB and LDH were increased, and so did myocardial MDA levels, while SOD and GSH levels decreased (all P<0.05). Compared with the DOX group, mice in the GV1001 groups of different dose showed increased LVIDd, LVEF, and LVFS, reduced myocardial damage, mitigatory vacuolization, decreased collagen deposition, lower serum levels of cTnI, CK⁃MB and LDH, lower myocardial MDA level and increased T-SOD and GSH-PX levels (all P<0.05). Compared with the control group, the expressions of cGAS, p-STING, and p-IRF3 protein in the hearts of DOX-treated mice were all increased (P<0.05). After treatment with GV1001, the expressions of cGAS, p-STING, and p-IRF3 were decreased (P<0.05) in DOX-treated mice. The improvement of cardiac function by GV1001 in DOX-treated mice was attenuated, and the inhibition of oxidative stress in cardiac tissue was reduced after administration with STING agonist. Conclusion: GV1001 can alleviate DOX-induced myocardial damage in mice, possibly by reducing oxidative stress levels through the inhibition of the cGAS/STING pathway.
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Received: 07 November 2023
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