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.

Acrocomia aculeata(Jacq.) Lodd. ex Mart. Leaves Increase SIRT1 Levels and Improve Stress Resistance

“…Oxidative Medicine and Cellular Longevity to the potential of A. aculeata extracts in the antioxidant assays, as already reported in some studies with other plants [36,48,[53][54][55]. GC-MS analysis also identified campesterol, stigmasterol, and β-sitosterol, as well as the triterpenes lupeol and lupeol acetate, which are known to possess antioxidant properties [56] and anti-inflammatory effects [57].…”

“…In this way, the protection against oxidation is considered beneficial for the maintenance of health and prevention against the development of several diseases [53]. Similar results were also obtained in Cerrado plants [36,63]. The prooxidant effect showed by EE-Aa and EM-Aa in high concentrations is probably caused by the generation of free radicals, same as reported with AA [64].…”

“…Hence, the same conditions and concentrations of the prior assay were repeated and 50 mM of 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) was used to induce lipid peroxidation of erythrocytes membrane. Hemolysis was determined as the previous assay [36].…”

“…The absorbance of the supernatant was performed in a spectrophotometer at 532 nm. The generation of the lipid peroxidation product, MDA, was expressed by the following [36]:…”

The ethanol extract of the bastard cedar (Guazuma ulmifolia L.) as antioxidants

“…The antioxidant activities potentially contribute to the polyphenol contents found in the plant extracts. G. ulmifolia stem bark and leaves extracts exhibited DPPH scavenger activity at IC 50 of 25.2 µg/mL and 39.3 µg/mL (dos Santos et al, 2018). There have been some previous studies examining the antioxidant activities of EEGU using different assays, namely, FRAP, DPPH, MDA dosage, human erythrocyte suspension, hemolytic activity, and inhibition of oxidative hemolysis in human erythrocytes by 2,2′-Azobis(2-amidinopropane) dihydrochlorideinduced (AAPH) or DOX (Duraiswamy et al, 2018;dos Santos et al, 2018;Kaneria et al, 2009).…”