Related Experiment Video
Updated: Jul 28, 2025
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Silymarin protects against doxorubicin induced cardiotoxicity by down-regulating topoisomerase IIβ expression in mice
1Department of Pathology, Faculty of Veterinary Medicine, Adnan Menderes University, Aydın, Turkey.
Abstract:
We investigated the potential protective effects of silymarin (SLY) on doxorubicin (DOX) induced chronic cardiotoxicity in mice. We used 30 male BALB/c mice assigned randomly to four experimental groups: control group administered normal saline orally daily and intraperitoneally (i.p.) twice/week during weeks 1, 2, 5 and 6; SLY group (was administered 100 mg/kg SLY daily by oral gavage for 6 weeks; DOX group was administered 3 mg/kg DOX i.p. twice/week during weeks 1, 2, 5 and 6; DOX + SLY group administered DOX and SLY corresponding to the DOX and SLY groups. At the end of the experiment, heart tissues were collected for analysis. Cardiomyopathy was observed in the DOX group; this damage was reduced by SLY treatment. SLY administration in DOX treated mice decreased topoisomerase IIβ (TopIIβ) expression as indicated by qPCR and immunostaining. Immunohistochemistry and western blot analysis revealed decreased phosphorylated histone-2AX (γH2Ax) expression in the SLY + DOX group. SLY administration combined with DOX increased cardiac troponin T and I (cTnT and cTnI) expression based on immunohistochemical and western blot analyses. SLY administration with DOX was cardioprotective by reducing double-strand DNA breakage by blocking the DOX-TopIIβ-DNA cleavage complex in response to down-regulation of TopIIβ expression. SLY also preserved the contractility of the heart by decreasing DOX related loss of cTnT and cTnI expression.
Insights
Silymarin (SLY) protects against doxorubicin (DOX)-induced heart damage by reducing DNA breaks and preserving cardiac function. This study shows SLY as a potential therapeutic agent against chemotherapy-related cardiotoxicity.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Toxicology
Background:
- Doxorubicin (DOX) is a potent chemotherapy agent with significant cardiotoxicity.
- Chronic cardiotoxicity induced by DOX poses a major clinical challenge.
- Silymarin (SLY), a natural flavonoid, has shown potential antioxidant and anti-inflammatory properties.
Purpose of the Study:
- To investigate the cardioprotective effects of silymarin (SLY) against doxorubicin (DOX)-induced chronic cardiotoxicity in a mouse model.
- To elucidate the molecular mechanisms underlying SLY's protective effects against DOX-induced cardiac damage.
Main Methods:
- Male BALB/c mice were divided into four groups: control, SLY, DOX, and DOX + SLY.
- DOX was administered intraperitoneally (i.p.) twice weekly during specific periods.
- SLY was administered orally daily for 6 weeks.
- Heart tissues were analyzed using qPCR, immunostaining, immunohistochemistry, and western blot.
Main Results:
- DOX administration induced significant cardiomyopathy, which was ameliorated by SLY treatment.
- SLY treatment reduced topoisomerase IIβ (TopIIβ) expression and decreased phosphorylated histone-2AX (γH2Ax) levels in DOX-treated mice.
- SLY administration increased cardiac troponin T (cTnT) and I (cTnI) expression, preserving cardiac contractility.
Conclusions:
- Silymarin exhibits significant cardioprotective effects against doxorubicin-induced cardiotoxicity.
- SLY functions by reducing double-strand DNA breaks through the downregulation of TopIIβ and protecting cardiac troponin expression.
- SLY represents a promising therapeutic strategy to mitigate chemotherapy-induced heart damage.
