title: Effects of Adrenomedullin on Doxorubicin-Induced Cardiac Damage in Mice.
abstract: Doxorubicin (DOX) is one of the best known anticancer drugs, and is used in the treatment of lymphoma, lung cancer, stomach cancer, and a number of other cancers. However, DOX has some serious side effects, the worst being lethal heart failure. Occasionally, its side effects result in the cessation of the anticancer treatment, thus having a serious adverse influence on prognosis. Agents that can be administered as alternative prophylactics or to ameliorate the side effects of DOX will be useful in increasing the safety and efficacy of anticancer therapy. Adrenomedullin (AM) is a peptide hormone secreted by many organs, including the heart; it has an organ-protective effect, including antiapoptotic, anti-inflammatory, and antioxidative stress. Blood AM levels increase with heart failure; endogenic AM has been suggested in order to protect the heart. Furthermore, exogenous AM administration has shown therapeutic effects for heart failure in patients. However, it is unclear whether AM can protect the heart against drug-induced cardiac injury in vivo. The present study was performed in order to investigate the effects of AM on DOX-induced cardiac damage. Male BALB/c mice were treated with DOX and/or AM. Exogenous AM improved the survival ratio of DOX-treated mice. In addition, AM reduced serum lactate dehydrogenase (LDH) levels following DOX treatment. On pathological examination, AM was shown to inhibit DOX-induced cardiac tissue damage, mitochondrial abnormality, and cell death. These findings suggest that AM has a protective effect against DOX-induced cardiac damage.
authors.affiliation: Research Center for Human and Environmental Sciences, Shinshu University.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yoshizawa
authors.forename: Sho
authors.initials: S
authors.lastname: Takizawa
authors.forename: Shin
authors.initials: S
authors.lastname: Shimada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokudome
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shindo
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D053607:Adrenomedullin / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects*; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008807:Mice, Inbred BALB C; D008929:Mitochondria, Heart / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D002316:Cardiotonic Agents; D053607:Adrenomedullin; D004317:Doxorubicin; D019255:NADPH Oxidases