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Updated: May 15, 2025
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and
Bamaprasad Dutta1,2, Shining Loo1,3, Antony Kam1,4
1School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Abstract:
(1) Background: Doxorubicin (DOX) is a frontline chemotherapeutic, but its side-effects from oxidative stress, leading to cardiotoxicity, pose significant challenges to its clinical use. We recently discovered a novel family of proteolysis-resistant, cystine-dense, and cell-penetrating microproteins from Panax ginseng that we term ginsentides. Ginsentides, such as the 31-residue TP1, coordinate multiple biological systems to prevent vascular dysfunction and endoplasmic reticulum stress induced by internal and external stressors. (2) Methods: We assessed the protective effects of ginsentide TP1 on DOX-induced cardiotoxicity using both in vitro functional studies on H9c2 cardiomyocytes and in vivo animal models by zebrafish and ICR mouse models. In these models, we examined oxidative stress, apoptosis, intracellular calcium levels, mitochondrial function, inflammatory responses, and cardiac function. (3) Results: We show that ginsentide TP1 protects against DOX-induced cytotoxicity in the mitochondria-rich H9c2 cardiomyocytes and reduces myocardial injury in zebrafish and mice by mitigating oxidative stress, inflammation, calcium, and mitochondrial dysfunction, as well as apoptosis-mediated cell death. Importantly, TP1 preserves cellular homeostasis without compromising the anticancer potency of DOX in breast cancer cells. (4) Conclusions: our findings highlight a specific antioxidative function of ginsentide TP1 in managing DOX-induced cardiotoxicity during cancer treatment and provide a promising lead for developing cardioprotective peptides and microproteins against oxidative stress.
Insights
Ginsentide TP1, a novel microprotein, effectively protects the heart from Doxorubicin-induced cardiotoxicity by reducing oxidative stress and inflammation. This peptide maintains heart function without hindering chemotherapy
Area of Science:
- Biochemistry
- Cardiology
- Pharmacology
Background:
- Doxorubicin (DOX) is a vital chemotherapy drug, but its use is limited by cardiotoxicity driven by oxidative stress.
- A new class of microproteins, ginsentides, derived from Panax ginseng, exhibit resistance to proteolysis and cell penetration.
- Ginsentide TP1, a specific ginsentide, has shown potential in mitigating stress-induced biological system dysfunctions.
Purpose of the Study:
- To evaluate the cardioprotective efficacy of ginsentide TP1 against Doxorubicin-induced cardiotoxicity.
- To investigate the underlying mechanisms of TP1's protective effects in vitro and in vivo.
Main Methods:
- In vitro studies using H9c2 cardiomyocytes to assess cytotoxicity.
- In vivo studies utilizing zebrafish and ICR mouse models to evaluate cardiac function.
- Analysis of oxidative stress, apoptosis, calcium levels, mitochondrial function, and inflammation.
Main Results:
- Ginsentide TP1 demonstrated significant protection against DOX-induced cytotoxicity in cardiomyocytes.
- TP1 mitigated myocardial injury in zebrafish and mice by reducing oxidative stress, inflammation, and mitochondrial dysfunction.
- TP1 preserved cellular homeostasis and did not compromise the anticancer efficacy of DOX in breast cancer cells.
Conclusions:
- Ginsentide TP1 possesses a specific antioxidative function beneficial for managing DOX-induced cardiotoxicity.
- TP1 represents a promising therapeutic lead for developing novel cardioprotective peptides against oxidative stress.
- This research supports the development of strategies to mitigate chemotherapy side effects while maintaining treatment efficacy.
