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Updated: Sep 12, 2025
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Ameliorative effects of agomelatine against doxorubicin-induced hepatotoxicity
Hasan Basri Savas1, Mehmet Enes Sozen2, Gokhan Cuce3
1School of Medicine, Department of Medical Biochemistry, Mardin Artuklu University, Mardin, Turkey.
Abstract:
Drug-induced hepatotoxicity is a significant impediment to the use of doxorubicin, a commonly employed chemotherapeutic agent with established efficacy in cancer treatment. The present study aimed to determine the potential protective effects of agomelatine against doxorubicin hepatotoxicity in rat toxicity models. Thirty-two rats were divided into four groups: control (with saline administration), Doxo (with 40 mg/kg doxorubicin administration), Doxo + Ago20, and Doxo + Ago40 (with 20 and 40 mg/kg agomelatine administration and 40 mg/kg doxorubicin administration). On the day of 14 rats were sacrificed, samples were collected for comparison of immunohistochemical, hematological, and biochemical analysis. There were statistically significant differences between the study groups in terms of immunohistochemical, hematological, and biochemical parameters. Agomelatine administration reduced the TNF-alpha, and caspase-3, which increased by doxorubicin, and reversed levels of oxidative stress markers altered by doxorubicin (p < 0.05). Doxorubicin induces oxidative stress, apoptosis, and hepatotoxicity. Agomelatine may be favored as a primary antidepressant to mitigate hepatic damage induced by doxorubicin.
Insights
Agomelatine demonstrates protective effects against doxorubicin-induced liver damage in rats. This study found agomelatine reduced key markers of oxidative stress and apoptosis, suggesting its potential to mitigate chemotherapy-related hepatotoxicity.
Area of Science:
- Pharmacology
- Toxicology
- Oncology
Background:
- Doxorubicin is a vital chemotherapeutic agent, but its use is limited by significant hepatotoxicity.
- Drug-induced liver injury remains a major clinical challenge, necessitating protective strategies.
Purpose of the Study:
- To investigate the potential hepatoprotective effects of agomelatine against doxorubicin-induced liver injury in a rat model.
- To evaluate agomelatine's impact on biochemical, hematological, and immunohistochemical markers of liver damage.
Main Methods:
- Thirty-two rats were divided into four groups: control, doxorubicin-only, and two groups receiving doxorubicin with varying doses of agomelatine.
- Rats were administered treatments, and samples were collected on day 14 for comprehensive analysis.
- Immunohistochemical, hematological, and biochemical assays were performed to assess liver injury and oxidative stress markers.
Main Results:
- Doxorubicin administration significantly increased TNF-alpha, caspase-3 levels, and oxidative stress markers.
- Agomelatine treatment, particularly at 40 mg/kg, significantly reduced elevated TNF-alpha and caspase-3 levels.
- Agomelatine administration reversed doxorubicin-induced alterations in oxidative stress markers, demonstrating a protective effect (p < 0.05).
Conclusions:
- Doxorubicin induces significant hepatotoxicity, oxidative stress, and apoptosis in rats.
- Agomelatine exhibits notable hepatoprotective properties against doxorubicin-induced liver damage.
- Agomelatine may be a beneficial adjunct therapy to mitigate doxorubicin-related hepatic injury.
