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01-08-2019

Micheliolide Protects Against Doxorubicin-Induced Cardiotoxicity in Mice by Regulating PI3K/Akt/NF-kB Signaling Pathway

Authors: Ashkan Kalantary-Charvadeh, Davoud Sanajou, Mohsen Hemmati-Dinarvand, Yasser Marandi, Mehran Khojastehfard, Hamed Hajipour, Mehran Mesgari-Abbasi, Leila Roshangar, Saeed Nazari Soltan Ahmad

Published in: Cardiovascular Toxicology | Issue 4/2019

Abstract

Micheliolide (MCL) is a naturally derived anti-inflammatory agent. In the present investigation, we examined the protective potential of MCL against doxorubicin (DOX)-induced cardiotoxicity in mice. Mice were injected with a single 15-mg/kg intraperitoneal dose of DOX at day 1 and the study groups received daily 12.5, 25, and 50 mg/kg doses of MCL for 7 days. Cardiac histopathology, cardiac function, serum markers of cardiac injury, and tissue markers of inflammation, and oxidative stress were examined. MCL decreased serum levels of creatinine kinase MB (CK-MB) and cardiac troponin I (cTnI) levels, ameliorated cardiac tissue architecture, and improved cardiac stroke volume. Apart from reducing the activities of NF-kB p65 subunit, MCL attenuated the cardiac levels of PI3K, phosphorylated (p)-Akt, p-Bad, and caspase-3 levels and simultaneously elevated p-PTEN levels. While the gene expressions of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) were decreased, the tissue activities of superoxide dismutase (SOD) as well as gene expressions of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase-1 (NQO1) were increased after treatment with MCL. Furthermore, tissue levels of malondialdehyde (MDA) were also decreased. Collectively, these findings point to the protective effects of MCL against DOX-induced cardiotoxicity by regulating PI3K/Akt/NF-kB signaling pathway in mice.

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Title: Micheliolide Protects Against Doxorubicin-Induced Cardiotoxicity in Mice by Regulating PI3K/Akt/NF-kB Signaling Pathway
Authors: Ashkan Kalantary-Charvadeh
Davoud Sanajou
Mohsen Hemmati-Dinarvand
Yasser Marandi
Mehran Khojastehfard
Hamed Hajipour
Mehran Mesgari-Abbasi
Leila Roshangar
Saeed Nazari Soltan Ahmad
Publication date: 01-08-2019
Publisher: Springer US
Published in: Cardiovascular Toxicology / Issue 4/2019
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-019-09511-2

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Micheliolide Protects Against Doxorubicin-Induced Cardiotoxicity in Mice by Regulating PI3K/Akt/NF-kB Signaling Pathway

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