Acute cytotoxic effects of ethanol on cultured mouse myocardial cells in a monolayer--enzymatic, chronotropic and ultrastructural studies.
The cytotoxicity of ethanol was investigated by detecting the leakage of lactate dehydrogenase (LDH) from three types of cultured mouse cells--non-proliferative but spontaneously and synchronously contracting atrial and ventricular myocardial cells in monolayer sheets, and also proliferative non-muscle fibroblast-like cells--over a 24-hr period (1, 3, 6 and 24 hr) after exposure to ethanol (12.5, 50, 200 and 500 mM). The beat rate and ultrastructure were also investigated. Only a 24-hr exposure to 500 mM ethanol markedly increased LDH leakage from all three types of cells, and it made 20-50% of these cells dead. The rate of spontaneous contractions of ventricular cells transiently increased after a 1-hr exposure to 200 mM ethanol and a 3-hr exposure to 500 mM ethanol compared with the control, though that of atrial cells did not show any significant change but tended rather to dose-dependently cease contracting. Atrial cells exposed to 500 mM ethanol never contracted, while ventricular cells ceased contracting only at 24 hr. After a 24-hr exposure to 500 mM ethanol some cells were necrosed ultrastructually, and the surviving cells contained giant mitochondria being bizarre in shape and many lipid droplets. Thus, ethanol induced cytotoxic effects terminating in death in cultured mouse heart-derived cells at a concentration of 500 mM. However, this concentration of ethanol did not induce any fatal effects within a 6-hr period, and neither did ethanol concentrations of less than 200 mM over a 24-hr period, as confirmed by the continuance of spontaneous contractions and ultrastructural observations.
Mashimo
K
K
Department of Legal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Sato
S
S
Ohno
Y
Y
D000818:Animals; D002478:Cells, Cultured; D000431:Ethanol / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure*
D000431:Ethanol; D007770:L-Lactate Dehydrogenase