title: Creatine supplementation reduces doxorubicin-induced cardiomyocellular injury.
abstract: Heart failure is a common complication of doxorubicin (DOX) therapy. Previous studies have shown that DOX adversely impacts cardiac energy metabolism, and the ensuing energy deficiencies antedate clinical manifestations of cardiac toxicity. Brief exposure of cultured cardiomyocytes to DOX significantly decreases creatine transport, which is the cell's sole source of creatine. We present the results of a study performed to determine if physiological creatine supplementation (5 mmol/L) could protect cardiomyocytes in culture from cellular injury resulting from exposure to therapeutic levels of DOX. Creatine supplementation significantly decreased cytotoxicity, apoptosis, and reactive oxygen species production caused by DOX. The protective effect was specific to creatine and depended on its transport into the cell.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA, lasantac@utmb.edu.
authors.forename: Lucia
authors.initials: L
authors.lastname: Santacruz
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Darrabie
authors.forename: Jose Gabriel
authors.initials: JG
authors.lastname: Mantilla
authors.forename: Rajashree
authors.initials: R
authors.lastname: Mishra
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Feger
authors.forename: Danny O
authors.initials: DO
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003401:Creatine / Q000008:administration & dosage*; D004317:Doxorubicin / Q000633:toxicity*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D003401:Creatine