Menadione-induced cardiotoxicity is associated with alteration in intracellular Ca2+ homeostasis.
Cardiotoxicity of menadione was elucidated in neonatal rat cardiomyocytes. When incubated with menadione, contraction of myocytes initially slowed down and eventually stopped. Later blebs appeared on the cell surface, leading to cell degeneration. During the time of diminished cellular contraction, a large portion of endogenous ATP was depleted whilst intracellular Ca2+ levels were increased. However, if menadione was washed out prior to termination of contraction, the myocytes survived and most of the cells resumed regular contraction. Preincubation of the cells with diltiazem (a Ca2+ antagonist), or fura-2 acetoxymethyl ester (a chelate for Ca2+), or antipain (a proteinase inhibitor) suppressed menadione's ability for cellular damage. These results indicate that menadione is toxic to cardiomyocytes, and that the increase of intracellular Ca2+ is related to the mechanism of cardiotoxicity of menadione.
Tzeng
W F
WF
Department of Biology, Fu Jen University, Taipei, Taiwan, Republic of China.
Chiou
T J
TJ
Huang
J Y
JY
Chen
Y H
YH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014812:Vitamin K / Q000494:pharmacology* / Q000633:toxicity
D014812:Vitamin K; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D002118:Calcium