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Modulation of Nrf2 by quercetin in doxorubicin-treated rats
Anish Sharma1, Mihir Parikh1, Hital Shah1
1Pharmacology Department, Anand Pharmacy College, Anand, 388001, Gujarat, India.
Abstract:
Doxorubicin (DOXO), a potent and widely used chemotherapeutic agent, causes irreversible heart failure by increasing oxidative stress, which limits its clinical utility. Nuclear factor erythroid-derived 2 -like 2 (Nrf2) is a prominent central regulator of cellular impenetrable to oxidants. The purpose of the study is to assess the ameliorative outcome of quercetin in cardiomyopathic rats induced by doxorubicin. Cardiomyopathy was produced in rats by single intraperitoneal weekly with DOXO (2 mg/kg) for 4 weeks. The rats were divided into five groups: (I) control group; (II) DOXO (2 mg/kg, i.p.) group; (III-V) DOXO + quercetin (10 mg/kg, 25 mg/kg and 50 mg/kg, orally), and were treated for 7 weeks. At the end of the treatment duration, cardiac function and biochemical parameters were assessed. Quercetin (10 mg/kg, 25 mg/kg and 50 mg/kg, orally) treatment reduced the raised blood pressure (BP) and left ventricular dysfunction. Withal, it prevented the rise in CKMB and LDH, suggesting the effect of quercetin in the maintaining the integrity of the cell membrane Besides, it also prevented the alteration in electrolyte levels, the activity of ATPase, and antioxidant status. Quercetin increased Nrf2 mRNA expression and reduced histological abnormalities compared to the DOXO control group. In conclusion, quercetin protected against DOXO- induced cardiomyopathy, by increasing expression of NRF2, and thereby increasing antioxidant defense and restoring biochemical and histological abnormalities.
Insights
Quercetin protects against doxorubicin-induced cardiomyopathy by enhancing the antioxidant defense system. This natural compound boosts Nuclear factor erythroid-derived 2 -like 2 (Nrf2) expression, improving heart function and reducing damage.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Doxorubicin (DOXO) is a chemotherapy drug that causes heart failure due to oxidative stress.
- Nuclear factor erythroid-derived 2 -like 2 (Nrf2) is a key regulator of cellular defense against oxidants.
Purpose of the Study:
- To evaluate the protective effects of quercetin against doxorubicin-induced cardiomyopathy in rats.
- To investigate the role of Nrf2 in quercetin's cardioprotective mechanism.
Main Methods:
- Cardiomyopathy was induced in rats using doxorubicin.
- Rats were treated with varying doses of quercetin (10, 25, 50 mg/kg) or vehicle for 7 weeks.
- Cardiac function, biochemical markers (CKMB, LDH, ATPase), electrolyte levels, antioxidant status, Nrf2 mRNA expression, and cardiac histology were assessed.
Main Results:
- Quercetin treatment significantly reduced blood pressure and improved left ventricular function in doxorubicin-treated rats.
- Quercetin prevented increases in cardiac enzyme levels (CKMB, LDH), maintained electrolyte balance, and preserved ATPase activity.
- Quercetin administration increased Nrf2 mRNA expression and ameliorated histological damage in the heart.
Conclusions:
- Quercetin demonstrates significant cardioprotective effects against doxorubicin-induced cardiomyopathy.
- The mechanism involves the upregulation of Nrf2, leading to enhanced antioxidant defense.
- Quercetin restores biochemical and histological abnormalities, offering a potential therapeutic strategy.
