7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Functional Redox Proteomics Reveal That Salvia miltiorrhiza Aqueous Extract Alleviates Adriamycin-Induced Cardiomyopathy via Inhibiting ROS-Dependent Apoptosis

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The anticancer agent adriamycin (ADR) has long been recognized to induce a dose-limiting cardiotoxicity, while Salvia miltiorrhiza (SM) is a Chinese herb widely used for the treatment of cardiovascular disorders and its aqueous extract (SMAE) has shown anticancer as well as antioxidant effects. In the current study, we aimed at investigating the synergistic effect and potent molecular mechanisms of SMAE with a focus on the cardioprotective benefit observed under ADR adoption. Histopathological analysis indicated that SMAE could substantially alleviate cardiomyopathy and cell apoptosis caused by ADR. Meanwhile, the two-dimensional electrophoresis (2-DE) oxyblots demonstrated that SMAE treatment could effectively reduce carbonylation of specific proteins associated with oxidative stress response and various metabolic pathways in the presence of ADR. SMAE application also showed protective efficacy against ADR-mediated H9c2 cell death in a dose-dependent manner without causing any cytotoxicity and significantly attenuated the reactive oxygen species production. Particularly, the simultaneous administration of ADR and SMAE could remarkably suppress the growth of breast cancer cells. We also noticed that there was a marked upregulation of detoxifying enzyme system in the presence of SMAE, and its exposure also contributed to an increase in Nrf2 and HO-1 content as well. SMAE also amended the ERK/p53/Bcl-xL/caspase-3 signaling pathways and the mitochondrial dysfunction, which eventually attribute to apoptotic cathepsin B/AIF cascades. Correspondingly, both the ERK1/2 inhibitor (U0126) and pan-caspase inhibitor (Z-VAD-FMK) could at least partially abolish the ADR-associated cytotoxicity in H9c2 cells. Collectively, these results support that ROS apoptosis-inducing molecule release is closely involved in ADR-induced cardiotoxicity while SMAE could prevent or mitigate the causative cardiomyopathy through controlling multiple targets without compromising the efficacy of chemotherapy.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          Molecular mechanism of doxorubicin-induced cardiomyopathy – An update

          Doxorubicin is utilized for anti-neoplastic treatment for several decades. The utility of this drug is limited due to its side effects. Generally, doxorubicin toxicity is originated from the myocardium and then other organs are also ruined. The mechanism of doxorubicin is intercalated with the DNA and inhibits topoisomerase 2. There are various signalling mechanisms involved in doxorubicin cardiotoxicity. First and foremost, the doxorubicin-induced cardiotoxicity is due to oxidative stress. Cardiac mitochondrial damage is supposed after few hours following the revelation of doxorubicin. This has led important new uses for the mechanism of doxorubicin-induced cardiotoxicity and novel avenues of investigation to determine better pharmacotherapies and interventions for the impediment of cardiotoxicity. The idea of this review is to bring up to date the recent findings of the mechanism of doxorubicin cardiomyopathies such as calcium dysregulation, endoplasmic reticulum stress, impairment of progenitor cells, activation of immune, ubiquitous system and some other parameters.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Oxidative stress injury in doxorubicin-induced cardiotoxicity

            Doxorubicin (DOX) is widely used as a broad-spectrum anti-tumor anthracycline to treat various cancers. The serious adverse effects of DOX on cardiotoxicity limit its clinical application. There are several different mechanisms involved in DOX-induced cardiotoxicity. Oxidative stress (OS) is caused by an imbalance between reactive oxygen species (ROS) and endogenous antioxidants in response to injury, which can lead to myocardial toxicity. The aim of this review was to investigate the mechanisms underlying the effects of oxidative stress injury on myocardial toxicity, from three different aspects: the increase in downstream oxidative stress products, the reduction in upstream antioxidative stress products, and subcellular organelles. Finally, there are some anti-oxidative drugs that show efficacy in limiting DOX-induced cardiotoxicity. It is necessary to fully understand the toxicity of DOX to the myocardium and achieve symptomatic treatment.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Drug-induced mitochondrial dysfunction and cardiotoxicity.

              Mitochondria has an essential role in myocardial tissue homeostasis; thus deterioration in mitochondrial function eventually leads to cardiomyocyte and endothelial cell death and consequent cardiovascular dysfunction. Several chemical compounds and drugs have been known to directly or indirectly modulate cardiac mitochondrial function, which can account both for the toxicological and pharmacological properties of these substances. In many cases, toxicity problems appear only in the presence of additional cardiovascular disease conditions or develop months/years following the exposure, making the diagnosis difficult. Cardiotoxic agents affecting mitochondria include several widely used anticancer drugs [anthracyclines (Doxorubicin/Adriamycin), cisplatin, trastuzumab (Herceptin), arsenic trioxide (Trisenox), mitoxantrone (Novantrone), imatinib (Gleevec), bevacizumab (Avastin), sunitinib (Sutent), and sorafenib (Nevaxar)], antiviral compound azidothymidine (AZT, Zidovudine) and several oral antidiabetics [e.g., rosiglitazone (Avandia)]. Illicit drugs such as alcohol, cocaine, methamphetamine, ecstasy, and synthetic cannabinoids (spice, K2) may also induce mitochondria-related cardiotoxicity. Mitochondrial toxicity develops due to various mechanisms involving interference with the mitochondrial respiratory chain (e.g., uncoupling) or inhibition of the important mitochondrial enzymes (oxidative phosphorylation, Szent-Györgyi-Krebs cycle, mitochondrial DNA replication, ADP/ATP translocator). The final phase of mitochondrial dysfunction induces loss of mitochondrial membrane potential and an increase in mitochondrial oxidative/nitrative stress, eventually culminating into cell death. This review aims to discuss the mechanisms of mitochondrion-mediated cardiotoxicity of commonly used drugs and some potential cardioprotective strategies to prevent these toxicities.
                Bookmark

                Author and article information

                Contributors
                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2020
                9 September 2020
                : 2020
                : 5136934
                Affiliations
                1Department of Chinese Medicine, College of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan
                2Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
                3Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan
                4TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan
                5Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
                6School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan
                7Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
                8Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
                Author notes

                Academic Editor: Peeter Karihtala

                Author information
                https://orcid.org/0000-0002-0937-3108
                https://orcid.org/0000-0002-0187-8689
                Article
                10.1155/2020/5136934
                7501560
                70f8e622-47b3-4759-8d7e-f350e5691eda
                Copyright © 2020 Yu-Chiang Hung et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 July 2020
                : 14 August 2020
                : 19 August 2020
                Funding
                Funded by: Chang Gung Memorial Hospital
                Award ID: BMRP445
                Award ID: CMRPD1J0191
                Funded by: Ministry of Science and Technology, Taiwan
                Award ID: MOST108-2320-B-182-024-MY3
                Award ID: MOST109-2320-B-039-040
                Award ID: MOST108-2320-B-182-022
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

                Comments

                Comment on this article