Lipid peroxidation and oxidative stress during acute allylamine-induced cardiovascular toxicity

Allylamine is an aliphatic amine that causes vascular lesions in aorta and medium-sized arteries. This primary amine has been shown to be metabolized to acrolein both in vivo and in vitro. Acrolein may cause allylamine's toxic effects, since it acts as a strong peroxidizing agent itself; in addition, deamination of allylamine is accompanied by production of hydrogen peroxide. To investigate the relative roles of oxidative stress and lipid peroxidation in allylamine intoxication, we conducted an acute in vivo time-course study following administration of allylamine (150 mg/kg) to rats by gavage. Animals were sacrificed at 1, 3 and 5 h after allylamine treatment, and subcellular fractions of aorta, epicardium and endocardium were assayed for enzymes of the oxidant defense system and thiol (-SH) status, capacity for lipid peroxidation, and .OH radical generation. Results suggest that in vivo treatment with allylamine causes preferential damage to aortic mitochondria. A marked depletion of total and free -SH content was found in aorta, epicardium and endocardium, with a striking increase in the formation of thiobarbiturate-reactive substance by aortic mitochondria at all time points. A significant increase in the capacity to generate .OH was found in aorta (with lesser increases in epicardium and endocardium) after allylamine treatment. Levels of defense system enzymes were not consistently altered, however. In a totally in vitro experiment, liposomes incubated with acrolein (0.2-2 mM) showed a proportional increase in lipid peroxidation of liposomal membrane. A likely basis of allylamine's cardiovascular toxicity is acrolein-induced lipid peroxidation, especially in mitochondria.