Related Experiment Video
Updated: Jan 21, 2026
Sublingual Immunotherapy as an Alternative to Induce Protection Against Acute Respiratory Infections
Published on: August 30, 2014
Protective effects of dimethyl itaconate in mice acute cardiotoxicity induced by doxorubicin
Qing Shan1, Xiaoyu Li2, Mei Zheng3
1Department of Geriatrics, The Second Affilicated Hospital, Nanjing Medical University, Nanjing, 211166, People's Republic of China; Department of Geriatrics, Affilicated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, People's Republic of China.
Abstract:
Doxorubicin (DOX) is an antitumor drug widely used in hematological tumors and various solid tumors. However, the cardiotoxicity elicited by DOX severely limits its clinical treatment. Dimethyl itaconate (DI), a common form of itaconate, is found many potential targets for prevent heart injury. Here we employed wild type and Nrf2 knockout mice and induced a cardiotoxicity model by administration of DOX to clarify the effects of DI. After treatment with DI, we found that it could effectively alleviate the cardiotoxicity by analyzing morphology, LDH levels and heart weight/body weight ratio changes. Meanwhile we demonstrated that RIP3, a key protein of necrosis, was significantly decreased in DI treated group. Further we observed that treatment with DI could suppress oxidative stress by altering Nrf2/HO-1. Compared with vehicle group, DI could increase the tissue SOD and GSH, and reduce MDA levels, then DHE staining revealed that the level of ROS in DI group reduced by half. Finally, transmission electron microscope (TEM) data showed that treatment with DI obviously decreased the mitochondrial damage. While Nrf2 was ablated in mice, the protective effects of DI were vanished and SOD, GSH, MDA became unchanged related to vehicle group. This report provides the evidence for the protective effects of DI treatment in cardiotoxicity induced by DOX. On mechanisms, DI could reduce the oxidative stress by altering Nrf2/HO-1 pathway and prevent mitochondrial from damage. Taken together, these findings of this paper will afford the new therapeutic targets in DOX related cardiotoxicity.
Insights
Dimethyl itaconate (DI) protects against doxorubicin (DOX)-induced cardiotoxicity by reducing oxidative stress and mitochondrial damage. These protective effects are mediated through the Nrf2/HO-1 pathway and are dependent on Nrf2 presence.
Area of Science:
- Biomedical Science
- Pharmacology
- Cardiology
Background:
- Doxorubicin (DOX) is a vital chemotherapy agent but causes significant cardiotoxicity, limiting its use.
- Dimethyl itaconate (DI) shows potential in preventing heart injury.
- Understanding DI's protective mechanisms against DOX cardiotoxicity is crucial.
Purpose of the Study:
- To investigate the protective effects of Dimethyl itaconate (DI) against Doxorubicin (DOX)-induced cardiotoxicity in a mouse model.
- To elucidate the underlying molecular mechanisms, focusing on oxidative stress and mitochondrial function.
- To determine the role of the Nrf2 pathway in DI's cardioprotective effects.
Main Methods:
- Induction of DOX cardiotoxicity in wild-type and Nrf2 knockout mice.
- Administration of Dimethyl itaconate (DI) and assessment of cardiac morphology, LDH levels, and heart weight/body weight ratio.
- Measurement of oxidative stress markers (SOD, GSH, MDA, ROS) and key proteins (RIP3).
- Transmission electron microscopy (TEM) for mitochondrial damage evaluation.
- Comparison of effects in Nrf2 knockout versus wild-type mice.
Main Results:
- DI treatment significantly alleviated DOX-induced cardiotoxicity, improving cardiac morphology and reducing injury markers.
- DI administration decreased RIP3 levels, a key protein in necrosis.
- DI suppressed oxidative stress by increasing SOD and GSH, reducing MDA and ROS levels, and modulating the Nrf2/HO-1 pathway.
- Mitochondrial damage was significantly reduced in DI-treated mice.
- The cardioprotective effects of DI were abolished in Nrf2 knockout mice, with no significant changes in oxidative stress markers.
Conclusions:
- Dimethyl itaconate (DI) effectively mitigates Doxorubicin (DOX)-induced cardiotoxicity.
- DI exerts its protective effects by reducing oxidative stress via the Nrf2/HO-1 pathway and preventing mitochondrial damage.
- Nrf2 is essential for the cardioprotective action of DI, highlighting potential therapeutic targets for DOX cardiotoxicity.
Related Concept Videos
01:16Zones of Protection
Protective zones are defined by closed dashed lines, containing one or more components. A key characteristic of these zones is the strategic placement of...
02:31Protection of Alcohols
Protection
It defines a protecting group as the masking agent to make the more reactive species inert to a given set of conditions. This concept is depicted via the illustration of liquid flow through different outlets in an assembly of pipes. The analogy helps to understand the role...
01:27Protecting Self-Esteem
01:23Radial System Protection
In a radial system with a fault downstream of the third breaker, ideally, only the third breaker will open, isolating the fault and interrupting the load connected beyond it. The second breaker has a longer delay setting,...
01:27Line Protection with Impedance Relays
Under normal conditions, low load currents keep the measured...
01:20Personal Protective Equipment