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A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Polyphenol-Rich Citrullus lanatus Rind Extract Mitigates Doxorubicin-Induced Cardiotoxicity: HPLC Profiling and In
1Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia.
Insights
Polyphenol-rich Citrullus lanatus rind extract demonstrated significant cardioprotective effects against doxorubicin-induced cardiotoxicity in rats. The extract restored antioxidant biomarkers and protected cardiac tissue, suggesting its potential as a natural therapeutic agent.
Area of Science:
- Pharmacology and Toxicology
- Natural Product Chemistry
- Cardiovascular Research
Background:
- Cardiovascular diseases (CVDs) are a leading global cause of mortality, exacerbated by oxidative stress and inflammation.
- Doxorubicin, a common chemotherapy agent, is known to induce cardiotoxicity, necessitating the search for protective strategies.
Purpose of the Study:
- To investigate the cardioprotective potential of polyphenol-rich Citrullus lanatus (PRCL) rind extract against doxorubicin-induced cardiotoxicity in a rat model.
- To identify and quantify the major bioactive polyphenolic compounds in the PRCL rind extract.
Main Methods:
- High-performance liquid chromatography (HPLC) was used to analyze the phenolic and flavonoid composition of the PRCL extract.
- Cardiotoxicity was induced in Wistar Kyoto rats using doxorubicin (10 mg/kg).
- Rats were treated with varying doses of PRCL extract (250 and 500 mg/kg/day) or quercetin for 21 days, with various biochemical and histopathological analyses performed.
Main Results:
- HPLC analysis identified five phenolic acids and two flavonoids, with p-hydroxybenzoic acid (PHBA) being the most abundant.
- PRCL extract treatment significantly improved lipid profiles, reduced cardiovascular risk indices, restored antioxidant biomarkers (SOD, CAT, GPx, GSH), and decreased lipid peroxidation (MDA) and inflammatory cytokines (TNF-α, IL-6).
- The 500 mg/kg dose of PRCL extract showed superior efficacy, comparable to quercetin, and provided significant protection against cardiac tissue damage.
Conclusions:
- PRCL rind extract possesses significant antioxidant and cardioprotective properties due to its rich polyphenolic composition.
- The extract effectively mitigates doxorubicin-induced cardiotoxicity in rats by combating oxidative stress and inflammation.
- PRCL rind extract holds promise as a natural therapeutic agent for preventing or treating cardiotoxicity.
Abstract:
Background/Objectives: Cardiovascular diseases (CVDs) remain a major cause of mortality globally, driven in part by oxidative stress and inflammation. The present study investigated the polyphenolic composition and cardioprotective potential of polyphenol-rich Citrullus lanatus (PRCL) rind extract against doxorubicin-induced cardiotoxicity in rats; Methods: High-performance liquid chromatography (HPLC) was employed to identify and quantify the major bioactive compounds present in the extract. Total 30 healthy male Wistar Kyoto rats were recruited and divided into 6 groups and various cardiovascular markers and antioxidant were measured in vivo and in vitro methods; Results: Ethanolic extraction of Citrullus lanatus rind yielded 19.58 g extract per 100 g of dry plant material. HPLC analysis identified five phenolic acids, i.e., gallic acid, p-hydroxybenzoic acid (PHBA), chlorogenic acid, caffeic acid, and vanillic acid, and two flavonoids, i.e., catechin and hesperetin, with PHBA (163.66 mg/g of extract) being the most abundant. Total phenolic and flavonoid content was determined to be 35.6 mg GAE/g and 12.8 mg CE/g, respectively. In vitro antioxidant assays showed moderate free radical scavenging, reducing power, and 86.9% inhibition of linoleic acid peroxidation. In vivo, Wistar rats were treated with doxorubicin (10 mg/kg) to induce cardiotoxicity, followed by PRCL extract administration (21 days at 250 and 500 mg/kg/day). The extract significantly improved body weight, serum lipid profile, and reduced cardiovascular risk indices. Antioxidant biomarkers (SOD, CAT, GPx, GSH) were restored, while lipid peroxidation (MDA) and inflammatory cytokines (TNF-α, IL-6) were significantly reduced in treated groups. The 500 mg/kg dose demonstrated superior efficacy, comparable to the standard quercetin group. Histopathological examination revealed notable protection of cardiac tissue architecture in the high-dose PRCL-500 group; Conclusions: These findings suggest that PRCL rind extract contains potent compounds having antioxidant and cardioprotective properties and may be used as a natural therapeutic agent against cardiotoxicity.

