Fatty acids ameliorate doxorubicin-induced intracellular ca2+ increase and apoptosis in rat cardiomyocytes.
Doxorubicin (Dox) is a highly effective anticancer drug but exhibits cumulative dose-dependent cardiomyopathy. In this study, we investigated effects of Magnolia seed extract (MagS) on the Dox-induced cardiotoxicity. The results showed that MagS significantly reduces doxorubicin (Dox)-induced increase in intracellular Ca2+ concentration ([Ca2+]i), generation of reactive oxygen species (ROS), and apoptosis in rat cardiomyocytes. Analyses of the bioactive compounds in MagS by thin layer chromatography and gas chromatography/mass spectroscopy revealed that bioactive compounds in MagS are linoleic acid, oleic acid, and palmitic acid. All three fatty acids were able to inhibit the Dox-induced increase in [Ca2+]i, ROS generation, and apoptosis with a similar potency. Efficacy of MagS was examined in in vivo using a murine Dox-induced cardiomyopathy model. Dox (12 mg/kg, intravenously) was administered to mice and treated with the MagS (2 mg/kg/d, intraperitoneally) or saline for three weeks. Dox-treated mice showed structural disarray in heart tissue, including lymphocyte infiltration and loss of body weight. In contrast, treatment of the MagS substantially attenuated the Dox-induced cardiac damages including the loss of body weight. These results indicate that fatty acids in MagS and other seeds may ameliorate cardiotoxicity of the anticancer drug.
Park
Kwang-Hyun
KH
College of Pharmacy, Medicinal Resources Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. khpark@wonkwang.ac.kr
Kim
Seon-Young
SY
Gul
Rukhsana
R
Kim
Byung-Ju
BJ
Jang
Kyu Yun
KY
Chung
Hun-Taeg
HT
Sohn
Dong-Hwan
DH
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D031566:Magnolia / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D000903:Antibiotics, Antineoplastic; D005227:Fatty Acids; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D053148:Caspase 3; D002118:Calcium