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Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity.

Abstract：

:Doxorubicin (DOX) is an efficient chemotherapeutic agent, but its clinical application is limited by its cardiotoxicity associated with increased oxidative stress. Thus, the combination of DOX and antioxidants has been encouraged. In this study, we evaluated (I) the chemical composition and antioxidant capacity of aqueous extracts from Guazuma ulmifolia stem bark (GUEsb) and leaves (GUEl) in 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, 2,2'-azobis(2-amidinopropane) dihydrochloride- (AAPH-) or DOX-induced lipid peroxidation inhibition in human blood cells, and intracellular reactive oxygen species (ROS) quantification using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) in K562 erythroleukemia cells incubated with GUEsb and stimulated with hydrogen peroxide; (II) the viability of K562 cells and human leukocytes treated with GUEsb in the absence or presence of DOX using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; (III) the acute toxicity of GUEsb; and (IV) the cardioprotective effect of GUEsb in C57Bl/6 mice treated with DOX. The chemical composition indicated the presence of flavan-3-ol derivatives and condensed tannins in GUEsb and glycosylated flavonoids in GUEl. GUEsb and GUEl showed free-radical scavenging antioxidant activity, antihemolytic activity, and AAPH- as well as DOX-induced malondialdehyde content reduction in human erythrocytes. Based on its higher antioxidant potential, GUEsb was selected and subsequently showed intracellular ROS reduction without impairing the chemotherapeutic activity of DOX in K562 cells or inducing leukocyte cell death, but protected them against DOX-induced cell death. Yet, GUEsb did not show in vivo acute toxicity, and it prevented MDA generation in the cardiac tissue of DOX-treated mice, thus demonstrating its cardioprotective effect. Taken together, the results show that GUEsb and GUEl are natural alternatives to treat diseases associated with oxidative stress and that, in particular, GUEsb may play an adjuvant role in DOX chemotherapy.

journal_name

Oxid Med Cell Longev

journal_title

Oxidative medicine and cellular longevity

authors

Dos Santos JM,Alfredo TM,Antunes KÁ,da Cunha JDSM,Costa EMA,Lima ES,Silva DB,Carollo CA,Schmitz WO,Boleti APA,Dos Santos EL,de Picoli Souza K

doi

10.1155/2018/2935051

subject

Has Abstract

pub_date

2018-06-28 00:00:00

pages

2935051

eissn

1942-0900

issn

1942-0994

journal_volume

2018

pub_type

杂志文章

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Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity.