Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

22 October 2019 : Animal Research  

MD-1 Deficiency Accelerates Myocardial Inflammation and Apoptosis in Doxorubicin-Induced Cardiotoxicity by Activating the TLR4/MAPKs/Nuclear Factor kappa B (NF-κB) Signaling Pathway

Ying-Jun Zhang123ACE, He Huang123AE*, Yu Liu123BE, Bin Kong123BD, Guangji Wang123BCD

DOI: 10.12659/MSM.919861

Med Sci Monit 2019; 25:7898-7907


BACKGROUND: Myocardial apoptosis and inflammation play important roles in doxorubicin (DOX)-caused cardiotoxicity. Our prior studies have characterized the effects of myeloid differentiation protein 1(MD-1) in pathological cardiac remodeling and myocardial ischemia/reperfusion (I/R) injury, but its participations and potential molecular mechanisms in DOX-caused cardiotoxicity remain unknown.

MATERIAL AND METHODS: In the present study, MD-1 knockout mice were generated, and a single intraperitoneal injection of DOX (15 mg/kg) was performed to elicit DOX-induced cardiotoxicity. Cardiac function, histological change, mitochondrial structure, myocardial death, apoptosis, inflammation, and molecular alterations were measured systemically.

RESULTS: The results showed that the protein and mRNA levels of MD-1 were dramatically downregulated in DOX-treated cardiomyocytes. DOX insult markedly accelerated cardiac dysfunction and injury, followed by enhancements of apoptosis and inflammation, all of which were further aggravated in MD-1 knockout mice. Mechanistically, the TLR4/MAPKs/NF-κB pathways, which were over-activated in MD-1-deficient mice, were significantly increased in DOX-damaged cardiomyocytes. Moreover, the abolishment of TLR4 or NF-κB via a specific inhibitor exerted protective effects against the adverse effects of MD-1 loss on DOX-caused cardiotoxicity.

CONCLUSIONS: Collectively, these findings suggest that MD-1 is a novel target for the treatment of DOX-induced cardiotoxicity.

Keywords: Cardiotoxins, Doxorubicin, Antigens, Surface, cardiotoxicity, Membrane Glycoproteins, Mice, Knockout, Myocardial Reperfusion Injury, Myocardium, Myocytes, Cardiac, Toll-Like Receptor 4

Add Comment 0 Comments

1209 14


01 September 2023 : Editorial  

Editorial: A Rapid Global Increase in COVID-19 is Due to the Emergence of the EG.5 (Eris) Subvariant of Omicron SARS-CoV-2

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.942244

Med Sci Monit 2023; 29:e942244


In Press

22 Sep 2023 : Clinical Research  

Comparative Analysis of Symptomatology in Hospitalized Children with RSV, COVID-19, and Influenza Infections

Med Sci Monit In Press; DOI: 10.12659/MSM.941229  

21 Sep 2023 : Clinical Research  

The Impact of Implementing the Vortex Approach on Airway Management Performance in Stressed Medical Student...

Med Sci Monit In Press; DOI: 10.12659/MSM.940372  

20 Sep 2023 : Clinical Research  

Changes in Upper Airway Anatomy Following Orthodontic Treatment for Malocclusion: A Comparative Retrospecti...

Med Sci Monit In Press; DOI: 10.12659/MSM.941749  

20 Sep 2023 : Database Analysis  

Comparative Finite Element Analysis of Endocrowns and Traditional Restorations for Endodontically Treated M...

Med Sci Monit In Press; DOI: 10.12659/MSM.941314  

Most Viewed Current Articles

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788


30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750