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A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
The Effects of Mangiferin (Mangifera indica L) in Doxorubicin-induced Cardiotoxicity in Rats
W Arozal1, F D Suyatna1, V Juniantito2
1Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
Aim:
The cardiotoxicity effect of doxorubicin (DOX), a widely used antitumor agent has restricted its clinical application. The aim of the current study was to explore the potential protective effect of mangiferin, a naturally occurring glucosylxanthone, that have antioxidant activity by its iron-complexing ability in mitochondria, against DOX-induced cardiac toxicity in rats in comparison with other antioxidants namely Sylimarin (SYL) and Vitamin E (VitE).
Methods:
Mangiferin was given orally to rats at a dose of 50, and 100 mg/kg for 5 weeks, and DOX was injected at a total dose of 15 mg/kg. Cardiac toxicity was evaluated by lactate dehydrogenase and creatine kinase in the serum, malondialdehyde (MDA) level in plasma and cardiac tissue, and antioxidant enzyme superoxide dismutase (SOD) in cardiac tissue.
Results:
Mangiferin protected against DOX-induced increased mortality and electrocardiogram abnormality and decreased biochemical markers of cardiac toxicity i. e., lactate dehydrogenase and creatine phosphokinase isoenzyme. In addition, elevation of plasma and cardiac tissue levels of MDA in response to DOX treatment were significantly attenuated. The reduction of cardiac activity of SOD was significantly reduced in contrast with the other antioxidant SYL and Vit E. Histopathologically, mangiferin treatment showed significant reduction in inflammatory cell number, fibrotic area, and necrotic foci as compared with DOX only-treated rats.
Conclusion:
These results suggested that mangiferin had better protective effect against DOX-induced cardiac toxicity in comparison with SYL and VitE, thus besides the antioxidant activity, different mechanism may be involved in the action of mangiferin and need to be clarified in the future studies.
Insights
Mangiferin demonstrated superior protection against doxorubicin-induced cardiotoxicity in rats compared to Sylimarin and Vitamin E. This natural compound effectively mitigated cardiac damage and improved survival rates.
Area of Science:
- Pharmacology
- Toxicology
- Biochemistry
Background:
- Doxorubicin (DOX) is a vital chemotherapy drug, but its clinical use is limited by cardiotoxicity.
- Natural compounds with antioxidant properties are explored for mitigating drug-induced toxicities.
Purpose of the Study:
- To investigate the protective effects of mangiferin against doxorubicin-induced cardiotoxicity in a rat model.
- To compare mangiferin's efficacy with other antioxidants, Sylimarin (SYL) and Vitamin E (VitE).
Main Methods:
- Rats received oral mangiferin (50, 100 mg/kg) for 5 weeks, followed by doxorubicin injection.
- Cardiac toxicity was assessed via serum enzymes (LDH, CK), plasma/tissue malondialdehyde (MDA), and cardiac superoxide dismutase (SOD) activity.
- Histopathological examination evaluated cardiac tissue damage.
Main Results:
- Mangiferin reduced doxorubicin-induced mortality, ECG abnormalities, and elevated cardiac enzyme levels.
- It significantly attenuated increased MDA levels and preserved SOD activity in cardiac tissue.
- Histopathology revealed reduced inflammation, fibrosis, and necrosis in mangiferin-treated rats.
Conclusions:
- Mangiferin exhibits a potent protective effect against doxorubicin-induced cardiotoxicity, surpassing Sylimarin and Vitamin E.
- Potential mechanisms beyond antioxidant activity may contribute to mangiferin's cardioprotective effects, warranting further investigation.
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