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Updated: Apr 29, 2026
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
Antiapoptotic effect of aminoguanidine on doxorubicin-induced apoptosis
1Department of Toxicology, Faculty of Pharmacy, Hacettepe University, 06100, Sihhiye, Ankara, Turkey, sunaatasayar@hotmail.com.
Abstract:
Doxorubicin (DOX) is a broad-spectrum anthracycline that has cardiotoxicity as a major side effect. Reactive oxygen species (ROS) and reactive nitrogen species generations have been proposed to be an important mechanism of DOX-induced cardiotoxicity and cardiomyocyte apoptosis, which may be mediated by p53 protein. Aminoguanidine (AG) is an effective antioxidant due to its free radical scavenger activity. A549 lung cell line was incubated with various concentrations of AG (100-1,000 μM) wit/without 0.25 μM DOX for 24 h. The expression of p53 and its transcriptional target p21 were analyzed by Western blot. Apoptosis was analyzed with Annexin V assay. JC1 and H2AX immunofluorescence were used to assess mitochondrial and nuclear DNA damage, respectively. This study demonstrated that AG has a dose-dependent antiapoptotic effect on DOX-induced apoptosis. Thus, these data further identify AG as a potential chemopreventive agent to reduce ROS and nitric oxide synthase damage generated by DOX.
Insights
Aminoguanidine (AG) protects against Doxorubicin (DOX)-induced cardiotoxicity by reducing oxidative stress and apoptosis. This antioxidant demonstrates a dose-dependent protective effect, suggesting its potential as a chemopreventive agent.
Area of Science:
- Biochemistry
- Pharmacology
- Cell Biology
Background:
- Doxorubicin (DOX), an anthracycline chemotherapy, causes cardiotoxicity, a significant clinical limitation.
- DOX-induced cardiotoxicity is linked to reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation, potentially involving p53.
- Aminoguanidine (AG) is an antioxidant with free radical scavenging properties.
Purpose of the Study:
- To investigate the protective effects of Aminoguanidine (AG) against Doxorubicin (DOX)-induced cardiotoxicity in vitro.
- To evaluate the impact of AG on apoptosis, oxidative stress markers, and DNA damage in cells exposed to DOX.
Main Methods:
- A549 lung cells were treated with varying concentrations of AG and DOX.
- Western blot analysis assessed p53 and p21 expression.
- Annexin V assay measured apoptosis; JC1 and H2AX immunofluorescence evaluated mitochondrial and nuclear DNA damage.
Main Results:
- AG exhibited a dose-dependent antiapoptotic effect on DOX-induced apoptosis.
- AG treatment modulated p53 and p21 expression.
- AG reduced markers of mitochondrial and nuclear DNA damage.
Conclusions:
- Aminoguanidine (AG) demonstrates significant protective effects against Doxorubicin (DOX)-induced cellular damage and apoptosis.
- AG's antioxidant and free radical scavenging activities contribute to its cardioprotective potential.
- These findings position AG as a promising chemopreventive agent for mitigating DOX-related cardiotoxicity.
