Transport of L-[ 125 I]Thyroxine bY iN Situ Perfused Ovine Choroid Plexus: Inhibition by Lead Exposure

• Published in: Journal of Toxicology and Environmental Health, Part A Part A, 2003-03, Vol.66 (5), p.435-451
• Main Authors: Zheng, Wei, Deane, Rashid, Redzic, Zoran, Preston, Jane, Segal, Malcolm
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Choroid Plexus - physiology; Disease Models, Animal; Injections, Intraperitoneal; Iodine Radioisotopes; Kinetics; Lead - administration & dosage; Lead - adverse effects; Medical sciences; Metals and various inorganic compounds; Organometallic Compounds - administration & dosage; Organometallic Compounds - adverse effects; Sheep; Thyroxine - pharmacokinetics; Toxicology
• ISSN: 1528-7394; 1087-2620; 2381-3504
• DOI: 10.1080/15287390306451

Lead (Pb) exposure hinders brain development in children by mechanisms that remain unknown. Previous evidence shows that sequestration of Pb in the choroid plexus lowers the production and secretion of transthyretin (TTR), a thyroxine (T 4 ) transport protein, from the choroid plexus into the cerebrospinal fluid (CSF). This study was undertaken to characterize the uptake kinetics of T 4 by the choroid plexus and to determine if in vivo Pb exposure altered the T 4 uptake in an in situ perfused ovine choroid plexus model. Sheep received ip injections of Pb acetate (20 mg Pb/kg) or Na acetate (as the controls) every 48 h for a period of 16 d. The [ 125 I]T 4 uptake was determined by a paired-tracer perfusion method using 0.5 w Ci [ 125 I]T 4 and 2 w Ci [ 14 C]mannitol at various concentrations of unlabeled T 4 (trace to 20 w M). The flux of [ 125 I]T 4 into the choroid plexus followed Michaelis-Menten kinetics with the maximum flux (V max ) of 56.6 nmol/min/g and half-saturation constant (K m ) of 10.7 w mol/L, suggesting an evident saturable influx of T 4 into the choroid epithelium. In vivo Pb exposure in these sheep resulted in a significant accumulation of Pb in the choroid plexus and hippocampus. Pb treatment diminished the V max by 63.7% of control, but did not alter K m . The maximal cellular uptake (U max ) and net uptake (U net ) in Pb-treated animals were 2.1-fold and 1.9-fold, respectively, lower than those of control. Exposure to Pb, however, did not significantly change the flow rate through the choroid plexus. Data suggest that the choroid plexus may serve as a significant site for T 4 transport into the CSF, and Pb exposure may hinder the influx of T 4 from the blood into the choroid plexus.