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 purpo...

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Main Authors: Anish Sharma, Mihir Parikh, Hital Shah, Tejal Gandhi
Format: Article
Language:English
Published: Elsevier 2020-04-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844020306484
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author Anish Sharma
Mihir Parikh
Hital Shah
Tejal Gandhi
author_facet Anish Sharma
Mihir Parikh
Hital Shah
Tejal Gandhi
author_sort Anish Sharma
collection DOAJ
description 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 11 Anish Sharma et al., MODULATION OF NRF2 BY QUERCETIN IN DOXORUBICIN TREATED RATS.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.
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spelling doaj.art-e2f92b1babf14a0e843187a24942a6232022-12-22T02:36:33ZengElsevierHeliyon2405-84402020-04-0164e03803Modulation of Nrf2 by quercetin in doxorubicin-treated ratsAnish Sharma0Mihir Parikh1Hital Shah2Tejal Gandhi3Corresponding author.; Pharmacology Department, Anand Pharmacy College, Anand, 388001, Gujarat, IndiaPharmacology Department, Anand Pharmacy College, Anand, 388001, Gujarat, IndiaPharmacology Department, Anand Pharmacy College, Anand, 388001, Gujarat, IndiaPharmacology Department, Anand Pharmacy College, Anand, 388001, Gujarat, IndiaDoxorubicin (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 11 Anish Sharma et al., MODULATION OF NRF2 BY QUERCETIN IN DOXORUBICIN TREATED RATS.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.http://www.sciencedirect.com/science/article/pii/S2405844020306484DoxorubicinCardiomyopathyQuercetinNRF2SD ratsAntioxidant parameters
spellingShingle Anish Sharma
Mihir Parikh
Hital Shah
Tejal Gandhi
Modulation of Nrf2 by quercetin in doxorubicin-treated rats
Heliyon
Doxorubicin
Cardiomyopathy
Quercetin
NRF2
SD rats
Antioxidant parameters
title Modulation of Nrf2 by quercetin in doxorubicin-treated rats
title_full Modulation of Nrf2 by quercetin in doxorubicin-treated rats
title_fullStr Modulation of Nrf2 by quercetin in doxorubicin-treated rats
title_full_unstemmed Modulation of Nrf2 by quercetin in doxorubicin-treated rats
title_short Modulation of Nrf2 by quercetin in doxorubicin-treated rats
title_sort modulation of nrf2 by quercetin in doxorubicin treated rats
topic Doxorubicin
Cardiomyopathy
Quercetin
NRF2
SD rats
Antioxidant parameters
url http://www.sciencedirect.com/science/article/pii/S2405844020306484
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