title: Quercetin augments the protective effect of losartan against chronic doxorubicin cardiotoxicity in rats.
abstract: The present study aimed to examine whether the co-administration of quercetin (QRN) and losartan (LOS) can produce additional protective effects against chronic DOX cardiotoxicity. Cardiotoxicity in rats was induced by intraperitoneal injection of doxorubicin (DOX) in a cumulative dose of 15mg/kg for two weeks. Results revealed that DOX administration exhibited elevated serum levels of TNF-α, creatine kinase (CK-MB), lactate dehydrogenase (LDH) in addition to increased myocardial lipid peroxide (MDA) and nitric oxide (NO) alongside attenuating cardiac antioxidant defense system of superoxide dismutase (SOD) and catalase (CAT) activities. DOX produced leukocyte infiltration and myocardial lesions. Pretreatment with QRN (10mg/kg, orally) solely or in combination with LOS (0.7mg/kg, orally) for 6 weeks markedly ameliorated all these biochemical characteristics, and substantially reduced the myocardium peroxidative damage. The protective effects obtained by LOS were more pronounced by its combination with QRN. Our results suggest that quercetin potentially augmented the cardioprotective effect of losartan against chronic DOX cardiotoxicity via its antioxidant and anti-inflammatory properties.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt.
authors.forename: Asmaa I
authors.initials: AI
authors.lastname: Matouk
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt. Electronic address: Ashraf_taye70@yahoo.com.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Taye
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt.
authors.forename: Gehan H
authors.initials: GH
authors.lastname: Heeba
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El-Moselhy
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002374:Catalase / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D004317:Doxorubicin; D004359:Drug Therapy, Combination; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D008054:Lipid Peroxides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D004317:Doxorubicin; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D052279:Creatine Kinase, MB Form; D019808:Losartan
keywords: Cardiotoxicity; Doxorubicin; Losartan; Oxidative stress; Quercetin; TNF-α