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Title: Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury
Authors: Chotiros Daosukho
Yumin Chen
Teresa Noel
Pradoldej Sompol
Ramaneeya Nithipongvanitch
Joyce M. Velez
Terry D. Oberley
Daret K. St. Clair
University of Kentucky College of Medicine
Mahidol University
University of Wisconsin Madison
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 15-Jun-2007
Citation: Free Radical Biology and Medicine. Vol.42, No.12 (2007), 1818-1825
Abstract: Cardiac injury is a major complication for oxidative-stress-generating anticancer agents exemplified by Adriamycin (ADR). Recently, several histone deacetylase inhibitors (HDACIs) including phenylbutyrate (PBA) have shown promise in the treatment of cancer with little known toxicity to normal tissues. PBA has been shown to protect against oxidative stress in normal tissues. Here, we examined whether PBA might protect heart against ADR toxicity in a mouse model. The mice were i.p. injected with ADR (20 mg/kg). PBA (400 mg/kg/day) was i.p. injected 1 day before and daily after the ADR injection for 2 days. We found that PBA significantly decreased the ADR-associated elevation of serum lactate dehydrogenase and creatine kinase activities and diminished ADR-induced ultrastructual damages of cardiac tissue by more than 70%. Importantly, PBA completely rescued ADR-caused reduction of cardiac functions exemplified by ejection fraction and fraction shortening, and increased cardiac manganese superoxide dismutase (MnSOD) protein and activity. Our results reveal a previously unrecognized role of HDACIs in protecting against ADR-induced cardiac injury and suggest that PBA may exert its cardioprotective effect, in part, by the increase of MnSOD. Thus, combining HDACIs with ADR could add a new mechanism to fight cancer while simultaneously decrease ADR-induced cardiotoxicity. © 2007 Elsevier Inc. All rights reserved.
ISSN: 08915849
Appears in Collections:Scopus 2006-2010

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