The majority of residents of the United States, Canada, and Europe are exposed to pyrethroids, the most commonly used class of insecticides. Surprisingly little is known about key aspects of their pharmacokinetics, including their mode of transport in the systemic circulation. This study tested the hypothesis that pyrethroids are transported by both plasma lipoproteins and proteins, similarly to other highly lipophilic environmental contaminants. Other aims were to characterize the binding of representative type I and II pyrethroids, and to compare their binding to rat versus human plasma. Binding of 14 C-labeled cis-permethrin (CIS), trans-permethrin (TRANS) and deltamethrin (DLM) to proteins and lipoproteins was measured by sequential extraction of spiked plasma with isooctane, 2-octanol, and acetonitrile. Binding of DLM, CIS, and TRANS to plasma proteins and lipoproteins was linear from 250 to 750 nM; concentrations present in the plasma of orally dosed rats. Binding of DLM to high-density lipoprotein was twice that to low-density lipoprotein. Binding of DLM, CIS, and TRANS was ∼2-fold greater to proteins than to lipoproteins of rat and human plasma; albumin was primarily responsible for protein binding. Higher total binding of each pyrethroid to human (∼90%) than to rat (∼80%) plasma resulted from higher protein binding in human plasma. This was attributable in part to the higher albumin/protein content of human plasma. Rat albumin exhibited lower pyrethroid binding capacity than did human albumin. The results of this investigation indicate that albumin and lipoproteins play a major role in binding and transport of pyrethroids in the systemic circulation of both rats and humans.
An investigation was conducted to study insulin-like growth factor (IGF)-I, IGF-II, insulin, glucagon, leptin, triiodothyronine (T(3)), and thyroxine (T(4)) levels in a chicken population divergently selected for P bioavailability (PBA). There were differences in growth and feed efficiency between the 2 lines. Concentrations of IGF-I, IGF-II, and T(3) were significantly greater in the high PBA line compared with the low PBA line, whereas the reverse was true for glucagon. There were no correlations between IGF-I and II and PBA in either line, suggesting that the line differences may be the result of factors other than PBA. Glucagon and IGF-I have different relationships with feed conversion ratio in the high PBA line compared with the low PBA line. There was a significant correlation between PBA and T(3) in the low line and between PBA and T(4) in the high PBA line. Thyroid hormone levels may be an indirect indicator of PBA in growing chickens. The genes in the thyroid hormone pathway may be key in the identification of genes associated with PBA.
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