Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 15, Issue -, Pages 543-556Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S296405
Keywords
magnesium isoglycyrrhizinate; arsenic trioxide; cardiotoxicity; Nrf2; TLR4/NF-kappa B
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Funding
- Research Foundation of Administration of Traditional Chinese Medicine of Hebei Province, China [2019075]
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The study demonstrated that MgIG could significantly reduce ATO-induced cardiac toxicity through its anti-inflammation, anti-oxidation, and anti-apoptosis effects. Additionally, MgIG exerted its protective effects by modulating the Nrf2 pathway and suppressing the TLR4/NF-kappa B pathway.
Purpose: Magnesium isoglycyrrhizinate (MgIG), a single stereoisomer magnesium salt of glycyrrhizic acid, has beneficial effects on the cardiovascular system through antiinflammatory, anti-oxidation, and anti-apoptotic actions. However, MgIG has not been shown to provide protection against cardiotoxicity induced by arsenic trioxide (ATO). This study aims to demonstrate the protection of MgIG against ATO-induced cardiac toxicity in mice and to investigate the underlying mechanism. Methods: A mouse cardiotoxicity model was established by administering 5 mg/kg ATO for 7 days. MgIG used in conjunction with the ATO to assess its cardioprotection. Results: MgIG administration could significantly reduce reactive oxygen species generation and the changes in tissue morphology. Also, MgIG administration increased the activity of antioxidase, such as superoxide dismutase, catalase, and glutathione peroxidase, and reduced malondialdehyde content and pro-inflammatory cytokine levels. Western blotting showed decreased expression of Bcl-2 associated X protein and Caspase-3, with increased expression of B-cell lymphoma 2. Importantly, MgIG administration increased nuclear factor-erythroid -2-related factor 2 (Nrf2) expression, while the expressions of nuclear factor kappa-B (NF-kappa B) and toll-like receptor-4 (TLR4) were significantly decreased. Conclusion: Our data showed that MgIG alleviates ATO-induced cardiotoxicity, which is associated to the anti-inflammation, anti-oxidation, and anti-apoptosis action, potentially through activation of the Nrf2 pathway and suppression of the TLR4/NF-kappa B pathway.
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