Hydroxytyrosol Prevents Doxorubicin-Induced Oxidative Stress and Apoptosis in Cardiomyocytes

Abstract

Doxorubicin (Dox) is a highly effective chemotherapeutic agent employed in the handling of hematological and solid tumors. The effective use of Dox in cancer therapy has been seriously limited due to its well-known cardiotoxic side effects, mainly mediated by oxidative damage. Therefore, the identification of an effective and safe antagonist against Dox-induced cardiotoxicity remains a challenge. In this respect, as plant polyphenols have attracted considerable interest due to their antioxidant properties and good safety profile, hydroxytyrosol (HT), the major phenolic compound in olive oil, could be a potential candidate due to its remarkable antioxidant and anticancer powers. In this study, the effect of HT was tested on Dox-induced cardiotoxicity by using a combination of biochemical and cellular biology techniques. Interestingly, HT was able to counteract Dox-induced cytotoxicity in cardiomyocytes by acting on the SOD2 level and the oxidative response, as well as on apoptotic mechanisms mediated by Bcl-2/Bax. At the same time, HT did not to interfere with the antitumorigenic properties of Dox in osteosarcoma cells. This study identifies new, beneficial properties for HT and suggests that it might be a promising molecule for the development of additional therapeutic approaches aimed at preventing anthracycline-related cardiotoxicity and improving long-term outcomes in antineoplastic treatments.

Pregnenolone Inhibits Doxorubicin-Induced Cardiac Oxidative Stress, Inflammation, and Apoptosis—Role of Matrix Metalloproteinase 2 and NADPH Oxidase 1

“…The current findings showed that the damage caused by DOX was mostly due to the production of ROS, which destroy cell walls and trigger apoptosis. Many studies confirmed our findings that DOX-induced heart damage is primarily caused by increased oxidative/nitrosative stress linked with a reduced antioxidant defense state [ 12 , 40 , 43 , 44 , 45 , 46 ]. Increased cardiac lipid peroxidation and decreased cardiac cellular GSH content in DOX-treated rats are indicators of an imbalanced redox state in the cardiomyocyte.…”

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

“…Similarly, in 143B osteosarcoma cells, OLE showed a synergistic, antiproliferative, and anti-migratory effect in combination with estradiol metabolite 2-methoxyestradiol at all OLE concentrations tested (1–250 μM for proliferation, and 100 μM for wound healing assay) [ 89 ]. On the contrary, HT did not modify doxorubicin-mediated growth inhibition of human osteosarcoma cells U-2 OS [ 277 ]. In neuroblastoma cells T98G, 277.5 μM and 555 μM OLE showed a synergistic effect with alkylating agent temozolomide on cell viability, increasing the expression of miRNAs involved in tumor growth suppression, mainly Let-7d [ 95 ].…”

“…In vitro, 50 μM and 70 μM HT reduced doxorubicin-mediated toxicity in embryonic rat cardiomyoblasts H9c2(2-1) after 48 h incubation. Also, 24 and 48 h incubation with 50 μM HT reduced doxorubicin-dependent intracellular ROS accumulation, increasing SOD2 levels and protecting cells from doxorubicin-induced apoptosis [ 277 ].…”

Sophora interrupta bedd., ameliorates doxorubicin induced myocardial necrosis by attenuation of oxidative stress and structural cardiomyocyte alterations in rats

“…Numerous antioxidants, including flavonoids and polyphenols, have been employed in the past to combat DOX-induced cardiotoxicity, according to reports. 10 In cardiac tissues intoxicated with DOX, histopathology revealed myocardial atrophy, nuclear condensation of chromosomes, and cytoplasmic vacuoles. Significant fatty blockage in the blood vessel and foamy-looking cytoplasm were cleared after DOX treatment, along with nuclear deterioration.…”