Modulation of Nrf2 by quercetin in doxorubicin-treated rats

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.