Related Experiment Video

Updated: Apr 19, 2026

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
05:14

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

Published on: May 16, 2020

5.6K

Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase

Yan Liu1, Aarti Asnani1, Lin Zou2

  • 1Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Broad Institute, Cambridge, MA 02142, USA.

Science Translational Medicine
|December 16, 2014
PubMed

Insights

Visnagin and diphenylurea protect the heart from doxorubicin chemotherapy damage. These compounds target mitochondrial malate dehydrogenase (MDH2), offering a new strategy against cardiotoxicity.

Area of Science:

  • Biochemistry
  • Cardiology
  • Pharmacology

Background:

  • Doxorubicin is a vital chemotherapy drug, but its use is limited by severe cardiotoxicity.
  • Doxorubicin-induced cardiotoxicity involves cardiomyocyte apoptosis and impaired cardiac function, mirroring patient outcomes.
  • Developing cardioprotective strategies is crucial for optimizing cancer treatment.

Purpose of the Study:

  • To identify novel compounds that prevent doxorubicin-induced cardiotoxicity.
  • To investigate the mechanism underlying the cardioprotective effects of identified compounds.
  • To validate a zebrafish model for screening cardiotoxicity interventions.

Main Methods:

  • Established a doxorubicin-induced cardiomyopathy model in zebrafish.
  • Screened 3000 compounds for cardioprotective activity.
  • Assessed compound efficacy in cellular and animal models (zebrafish, mice).
  • Investigated drug-target interactions using affinity chromatography and enzyme assays.

Main Results:

  • Visnagin (VIS) and diphenylurea (DPU) were identified as potent cardioprotective agents.
  • VIS and DPU reduced doxorubicin-induced apoptosis in cardiomyocytes and in vivo.
  • VIS improved cardiac contractility in doxorubicin-treated mice without compromising chemotherapy efficacy.
  • VIS was found to bind to mitochondrial malate dehydrogenase (MDH2).
  • MDH2 inhibition or malate treatment mimicked the cardioprotective effects of VIS.

Conclusions:

  • Visnagin and diphenylurea are effective in preventing doxorubicin-induced cardiotoxicity.
  • Mitochondrial malate dehydrogenase (MDH2) is a novel, druggable target for mitigating doxorubicin cardiotoxicity.
  • The findings support the development of MDH2-modulating therapies to improve cancer patient outcomes.

More Related Videos

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish08:09

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

Published on: June 7, 2018

10.5K
Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment04:48

Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment

Published on: January 7, 2015

7.9K

Related Concept Videos

Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
939
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
811
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
812
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
19.8K
Cardiomyopathy VI: Nursing Management01:29

Cardiomyopathy VI: Nursing Management

Assessment: Nursing management of patients with cardiomyopathy begins with a thorough assessment of the patient's history, including a family history of cardiomyopathy or sudden cardiac death, personal history of heart disease, hypertension, diabetes, and any alcohol consumption or drug use.During the physical examination, assess vital signs, look for signs of heart failure (such as edema, jugular venous distention, and cyanosis), auscultate for abnormal heart sounds (like murmurs and gallops),...
473
Heart Failure Drugs: Inotropic Agents01:26

Heart Failure Drugs: Inotropic Agents

Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
2.0K