Comparative toxicity of allylamine and acrolein in cultured myocytes and fibroblasts from neonatal rat heart.
Allylamine is toxic to the cardiovascular system causing aortic, valvular and myocardial lesions. Acute toxicity is believed to involve metabolism of allylamine to highly reactive acrolein. Comparative toxicity of allylamine and acrolein was evaluated in cardiac fibroblasts and myocytes, which were obtained from neonatal rat hearts by a differential plating technique. Allylamine and acrolein were added directly to serum supplemented culture media (M199). Toxicity was assessed by measuring lactate dehydrogenase (LDH) release as an indicator of cell lysis. Spontaneous beating activity of myocytes, and adenosine 5' triphosphate (ATP) levels of myocytes and fibroblasts were also assessed. Cell lysis occurred 4 h after treatment of myocytes with 0.5 mM allylamine, whereas 20 mM allylamine was required to lyse fibroblasts. Acrolein, at a concentration of 0.05 mM, was equally toxic to fibroblasts and myocytes. Semicarbazide, a benzylamine oxidase inhibitor, protected myocytes from allylamine toxicity, but clorgyline, a monoamine oxidase inhibitor, was ineffective. Semicarbazide was ineffective against acrolein toxicity. Beating activity of myocytes was arrested by 0.05 mM acrolein and 0.5 mM allylamine, although 0.05-0.1 mM allylamine reduced beating activity. Myocyte ATP levels were reduced 4 h after exposure to 0.01 mM acrolein. Allylamine at 0.05 mM reduced ATP in myocytes, but 10 mM allylamine was required to reduce ATP in fibroblasts. ATP levels remained normal in myocytes exposed to 1 mM allylamine in the presence of 0.1 mM semicarbazide. The findings support the hypothesis that the toxicity of allylamine in cultured myocytes is dependent on its metabolism to acrolein, and that cytotoxicity may result from interference with energy production.
Toraason
M
M
Centers for Disease Control, Robert A. Taft Laboratories, Cincinnati, OH 45226.
Luken
M E
ME
Breitenstein
M
M
Krueger
J A
JA
Biagini
R E
RE
D000171:Acrolein / Q000633:toxicity*; D000255:Adenosine Triphosphate / Q000032:analysis; D000447:Aldehydes / Q000633:toxicity*; D000499:Allylamine / Q000633:toxicity*; D000588:Amines / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured / Q000187:drug effects; D003010:Clorgyline / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009206:Myocardium / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D012663:Semicarbazides / Q000494:pharmacology
D000447:Aldehydes; D000588:Amines; D012663:Semicarbazides; C010059:carbamylhydrazine; D000499:Allylamine; D000171:Acrolein; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D003010:Clorgyline