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

• Published in: Cardiovascular toxicology Vol. 19; no. 4; pp. 297 - 305
• Main Authors: Kalantary-Charvadeh, Ashkan, Sanajou, Davoud, Hemmati-Dinarvand, Mohsen, Marandi, Yasser, Khojastehfard, Mehran, Hajipour, Hamed, Mesgari-Abbasi, Mehran, Roshangar, Leila, Nazari Soltan Ahmad, Saeed
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2019; Springer; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Anti-Inflammatory Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Calcium-binding protein; Cardiology; Cardiotoxicity; Caspase; Caspase-3; Creatine kinase; Creatinine; Disease Models, Animal; Doxorubicin; Gene expression; Heart; Heart Diseases - chemically induced; Heart Diseases - enzymology; Heart Diseases - pathology; Heart Diseases - prevention & control; Heme; Heme oxygenase (decyclizing); Histopathology; Inflammation; Inflammation Mediators - metabolism; Interleukin 1; Interleukins; Kinases; Male; Malondialdehyde; Markers; Mice; Mice, Inbred C57BL; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; NAD; NF-kappa B - metabolism; NF-κB protein; Oxidative stress; Oxidative Stress - drug effects; Oxygenase; Pharmacology/Toxicology; Phosphatidylinositol 3-Kinase - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; PTEN protein; Quinones; Serum levels; Sesquiterpenes, Guaiane - pharmacology; Signal Transduction; Stroke volume; Superoxide; Superoxide dismutase; Tissues; Troponin; Troponin I; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Doxorubicin-induced cardiotoxicity; Akt; PI3K; NF-kB; Micheliolide
• ISSN: 1530-7905; 1559-0259
• DOI: 10.1007/s12012-019-09511-2

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.