Allylamine cardiotoxicity: III. Protection by semicarbazide and in vivo derangements of monoamine oxidase

We hypothesized that inhibition of monoamine oxidase (MAO) might protect the myocardium from the necrosis and fibrosis induced by allylamine consumption; therefore, we gave rats several MAO inhibitors simultaneously with allylamine (10.7 mM) in drinking water for 3 weeks. Semicarbazide (1.4 mM) prevented histopathologic cardiac lesions, while hydroxylamine (2.2 mM) decreased their severity. Other inhibitors tested - tranylcypromine (20 μM) and pargyline (15 μM) - did not decrease lesion incidence or severity. Weight gain and fluid consumption varied depending on treatment: these parameters resembled control values in rats protected by semicarbazide and in rats consuming tranylcypromine, but were decreased in rats consuming other inhibitors or only allylamine. We repeated the experiment, measuring MAO activity (toward 3 substrates) of brain, liver, and heart homogenate in rats given only the inhibitors, only allylamine, or allylamine combined with the inhbitors. Brain and liver MAO activities were not greatly affected by semicarbazide or hydrodxyalmine but were decreased as much as 60% by tranylcypromine and by pargyline. Cardiac MAO was significantly inhibited only by tranylcypromine. Allylamine also inhibited brain and liver MAO, but caused by anomalous, marked increase in cardiac MAO. Further study showed that this high cardiac MAO activity followed an initial decrease during the first day of the experiment, became manifest after 10 days, and was directly proportional to the histopathologic severity of cardiac lesions at 21 days. In rats given allylamine plus the MAO inhibitors, brain and liver MAO activity generally decreased. Cardiac MAO activity, however, increased in rats given allylamine plus tranylcypromine or pargyline, but did not differ from control activity in hearts protected from allylamine-induced lesions by semicarbazide or hydroxylamine. A single dose of allylamine (50-150 mg/kg body wt) given by gavage induced dose-dependent inhibition of MAO activity toward β-phenylethylamine in all 3 organs at 24 h. We conclude that the mechanism of protection from allylamine-induced cardiac injury is not MAO inhibition. Our studies, however, show marked systemic aberrations in MAO activity during allylamine intoxication, and complex cardiac MAO changes which probably results from the myocellular damage.