Toxicity of Palicourea marcgravii: combined effects of fluoroacetate, N-methyltyramine and 2-methyltetrahydro-beta-carboline.

This research investigates the toxicity of Palicourea marcgravii, a common plant species, on cattle and horses. The study identified two substances, N-methyltyramine and 2-methyltetrahydro-beta-carboline, that contribute to the plant’s toxic effects, explaining why the plant can cause sudden death in ruminants such as cattle. Both substances inhibit certain body processes, leading to increased blood pressure and rapid distribution of another toxin, fluoroacetate, resulting in potentially lethal effects.

Detailed Explanation of the Research

• The researchers conducted feeding experiments on cattle and horses using Palicourea marcgravii, a plant species from the Rubiaceae family. They observed consistent toxic effects in all experimental cases. Interestingly, only ruminants (like cattle) exhibited “sudden death syndrome,” a symptom with an until-now unexplained cause.
• The researchers discovered that apart from fluoroacetate, a known toxic substance, two additional toxins—N-methyltyramine and 2-methyltetrahydro-beta-carboline (2-Me THBC)—were also present in P. marcgravii. These compounds were identified using techniques such as 1H-NMR, 13C-NMR, and MS.
• Despite the relatively minor concentration of fluoroacetate (5.4 micrograms/g of the plant), the main toxic effects appear to be due to N-methyltyramine and 2-Me THBC. This finding was particularly influential in explaining “sudden death syndrome” in cattle, which results from their higher gastrointestinal absorption of these substances compared to horses.
• When ingested, N-methyltyramine and 2-Me THBC disrupt the function of monoamine oxidase type A (MAO-A), an enzyme involved in neurotransmitter regulation. N-methyltyramine competes with natural substrates, while 2-Me THBC acts as an inhibitor of MAO-A. Consequentially, the breakdown of certain substrates—including noradrenaline, adrenaline, and N-methyltyramine—is blocked.
• This enzymatic obstruction leads to an over-stimulation of the sympathetic nervous system’s alpha- and beta-receptors. This heightened activity subsequently causes a dramatic rise in blood pressure, which facilitates a speedier distribution of fluoroacetate within the body.
• The increased circulation of fluoroacetate means more of the toxin is delivered to the body’s active organs (like the heart). As a result, even small quantities can have lethal effects, thereby providing an explanation for “sudden death syndrome” in cattle. The researchers suggest that the toxicity of P. marcgravii comes from the combined effects of fluoroacetate, N-methyltyramine, and 2-Me THBC.