Myocyte injury by hemin.
Effects of free hemin on myocardium were investigated using a model of neonatal myocyte primary cultures. Cells were subjected to free hemin at concentrations up to 20 microM and equilibrated for 5 h at 37 degrees C. Distribution of hemin in media, cell sarcolemma, and cell interior was evaluated. Time-dependent reduction in beating rate was monitored throughout the entire concentration range of administrated hemin. With time and in a hemin concentration-dependent manner, arrhythmic beatings which were followed by loss of contractility were observed. In parallel, morphologic changes appeared from granulation to complete loss of cell integrity. At the concentration range studied, hemin also induced a biphasic release of cytosolic enzymes. In the first phase, the fraction of enzyme released was dependent of the ratio of hemin:cells and was correlated with the amount of nonviable cells as monitored by a trypan blue test. In the second phase, the fraction of released enzyme was much larger than that of nonviable cells. The data are interpreted as an indication of complete loss of cytosolic content due to sarcolemma damage in first phase and partial damage to cell interior in the prolonged second phase. It is concluded that in similarity with other amphipathic molecules, free hemin is toxic to the myocardium.
Sackler Institute of Molecular Medicine, Tel-Aviv University Sackler School of Medicine, Israel.
V
V
Bhoite-Solomon
G
G
Kessler-Icekson
N
N
Shaklai
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000032:analysis; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D006427:Hemin / Q000378:metabolism / Q000633:toxicity*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D006427:Hemin; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase