title: Protective effects of deep sea water against doxorubicin‑induced cardiotoxicity in H9c2 cardiac muscle cells.
abstract: Doxorubicin (DOX) is one of the most effective chemotherapeutic agents in the treatment of a variety of tumors. However, its clinical use has been compromised by the risk of cardiotoxicity. Thus, many efforts have been focused on exploring new strategies to prevent or reverse DOX-induced cardiotoxicity. Recently, deep sea water (DSW) has drawn much scientific interest for therapeutic intervention due to its enrichment in nutrients and minerals. In this study, we investigated whether DSW has protective effects against DOX-induced cardiotoxicity. Pre-treatment with DSW significantly increased the viability of DOX-treated rat H9c2 cardiac muscle cells. This protective effect of DSW appears to be mediated through the inhibition of DNA damage rather than suppression of reactive oxygen species (ROS) production in DOX‑treated H9c2 cardiac muscle cells. The inhibitory effect of DSW on DOX-induced DNA damage subsequently attenuated apoptotic signaling such as activation of cysteine-aspartic acid protease-3 (caspase-3) and fragmentation of poly(ADP-ribose) polymerase (PARP), whereas the expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-xL) was increased. Moreover, DSW treatment rescued the activation of protein kinase B (Akt) to protect cells from DOX-triggered apoptosis. Taken together, our data showed that DSW has protective effects against DOX-induced cardiotoxicity, suggesting that DSW has some promise as a novel protective supplement for promoting the successful use of DOX in clinical regimen.
authors.affiliation: Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University, Gyeongju, Gyeongsangbuk-do 780‑714, Republic of Korea.
authors.forename: Do-Hyung
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University, Gyeongju, Gyeongsangbuk-do 780‑714, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University, Gyeongju, Gyeongsangbuk-do 780‑714, Republic of Korea.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Nam
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D066126:Cardiotoxicity / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012623:Seawater
chemical_list: D017382:Reactive Oxygen Species; D004317:Doxorubicin; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3