Allylamine cardiovascular toxicity

TY - JOUR

T1 - Allylamine cardiovascular toxicity

T2 - V. tissue distribution and toxicokinetics after oral administration

AU - Boor, Paul J.

PY - 1985/6/14

Y1 - 1985/6/14

N2 - We studied the uptake, tissue distribution, toxicokinetics, and excretion of allylamine by giving rats [14C] allylamine (1.5 μCi/kg; 150 mg/kg) by gavage. Rats were killed at intervals up to 2 h, and multiple tissues were sampled. Aorta showed the highest counts of 14C-label at most times (5-10-fold higher than most other organs, 100-fold higher than blood), although a minority of aortas had very low counts. Coronary arteries dissected from the hearts showed consistently higher 14C-label than myocardium. Liver counts, which were high at 5 min, decreased rapidly; kidney counts slowly increased until 45 min, then decreased rapidly, consistent with an excretory function for this organ. Counts of 14C-label were lower in all other organs, including lung, skeletal, muscle, brain, testes, pancreas, adrenal, spleen, fat, and blood. Toxicokinetic study showed a very rapid absorption rate and short half-lives (less than 1 h) for those organs which reasonably fit a toxicokinetic one-compartment model. 14C-label was rapidly excreted in the urine; approximately 60% of the dose given was recovered by 24 h. No counts were found in feces. These studies indicate that allylamine - or its metabolite(s) - has a unique predilection for elastic and muscular arteries, such as aorta and coronary arteries. This relatively specific cardiovascular toxin acts as a highly polar, highly water soluble substance, which is rapidly absorbed from the gastrointestinal tract, has a short half-life in most tissues, and is rapidly excreted in the urine. The actual mechanisms by which allylamine injures tissue, especially in view of its rapid sequestration in vascular tissue, remain to be uncovered.

AB - We studied the uptake, tissue distribution, toxicokinetics, and excretion of allylamine by giving rats [14C] allylamine (1.5 μCi/kg; 150 mg/kg) by gavage. Rats were killed at intervals up to 2 h, and multiple tissues were sampled. Aorta showed the highest counts of 14C-label at most times (5-10-fold higher than most other organs, 100-fold higher than blood), although a minority of aortas had very low counts. Coronary arteries dissected from the hearts showed consistently higher 14C-label than myocardium. Liver counts, which were high at 5 min, decreased rapidly; kidney counts slowly increased until 45 min, then decreased rapidly, consistent with an excretory function for this organ. Counts of 14C-label were lower in all other organs, including lung, skeletal, muscle, brain, testes, pancreas, adrenal, spleen, fat, and blood. Toxicokinetic study showed a very rapid absorption rate and short half-lives (less than 1 h) for those organs which reasonably fit a toxicokinetic one-compartment model. 14C-label was rapidly excreted in the urine; approximately 60% of the dose given was recovered by 24 h. No counts were found in feces. These studies indicate that allylamine - or its metabolite(s) - has a unique predilection for elastic and muscular arteries, such as aorta and coronary arteries. This relatively specific cardiovascular toxin acts as a highly polar, highly water soluble substance, which is rapidly absorbed from the gastrointestinal tract, has a short half-life in most tissues, and is rapidly excreted in the urine. The actual mechanisms by which allylamine injures tissue, especially in view of its rapid sequestration in vascular tissue, remain to be uncovered.

KW - Allylamine

KW - Aorta

KW - Tissue distribution

KW - Toxicokinetics

KW - Vascular tissue

UR - http://www.scopus.com/inward/record.url?scp=0021794379&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021794379&partnerID=8YFLogxK

U2 - 10.1016/0300-483X(85)90013-7

DO - 10.1016/0300-483X(85)90013-7

M3 - Article

VL - 35

SP - 167

EP - 177

JO - Toxicology

JF - Toxicology

SN - 0300-483X

IS - 3

ER -