Comparative toxicity of allylamine and acrolein in cultured myocytes and fibroblasts from neonatal rat heart.
Toraason-M; Luken-ME; Breitenstein-M; Biagini-JA
Toxicology 1989 May; 56(1):107-117
The direct myocardial effects of allylamine (107119) were investigated by comparing the toxicity of allylamine with acrolein (107028) in spontaneously contracting cardiac myocytes and cardiac fibroblasts from neonatal rats. Hearts were harvested from 2 to 4 day old Sprague-Dawley-rats. Cells were treated with chemicals by replacing culture media with fresh media containing the desired concentrations of chemicals or by adding concentrated aliquots to the culture dishes immediately after changing media. Measurement of lactate-dehydrogenase (LDH) was used as an assessment of the toxicity of the chemicals. Assessment was also made of the spontaneous beating activity of myocytes, and adenosine-5'- triphosphate (ATP) levels of myocytes and fibroblasts. Four hours after treatment of the myocytes with 0.5 millimolar (mM) allylamine, cell lysis occurred. A dose of 20mM allylamine was needed to lyse fibroblasts. A 0.05mM concentration of acrolein was equally toxic to fibroblasts and myocytes. Myocytes were protected by semicarbazide from allylamine toxicity. Clorgyline was ineffective as a protective agent. Semicarbazide was not effective against acrolein toxicity. Doses of 0.05mM acrolein and 0.5mM allylamine arrested the beating activity of myocytes. Doses of 0.05 to 0.1mM allylamine reduced beating activity. Four hours after exposure to reduce ATP in fibroblasts. Myocytes exposed to 1mM allylamine in the presence of 0.1mM semicarbazide maintained normal ATP levels. The authors suggest that the findings support the theory that allylamine toxicity depends on its metabolism to acrolein and that cytotoxicity may be a product of interference with energy production.
NIOSH-Author; Laboratory-animals; Amines; Comparative-toxicology; Cardiovascular-system-disorders; Pharmaceutical-industry; Drugs; Heart; In-vitro-studies