The Intestinal Absorption of Lead:The importance of lead speciation

Abstract

Clinically evident lead poisoning often results from the absorption of lead across the gastrointestinal tract. The possibility of an active transport mechanism for lead in the duodenum was examined by studying the transport of lead in the everted sac against a concentration gradient. No active transport of lead was demonstrated. The effect of the presence of food in the rat gut on the absorption of an oral lead dose was studied in vivo. Fasted rats absorbed substantially more lead than fed rats. More of the administered lead dose was recovered in the blood four hours after dosing than in any other internal organ. Total recovery of lead was not achieved, suggesting that in both fed and fasted rats, an important lead reservoir had still not been taken into account. Reasons for the reduced lead absorption following feeding were examined by studying the lead species formed in the gut of fed and fasted rats. Gut washings from fed and fasted rats were incubated with lead in vitro, and the species formed were separated by gel filtration chromatography. Besides soluble lead carbonate and lead phosphate, lead was present as a number of lead-protein, lead-peptide and lead-amino acid complexes in both fed and fasted animals. In the fed animal the identity of the lead-protein complexes remains unknown. In fasted animals one of the proteins is thought to be metallothionein. The transport of the lead species elucidated was investigated in vivo. Lead, when administered orally with metallothionein, showed a slight although non-significant reduction in absorption. The presence of lead in the gut lumen as carbonate and phosphate ion pairs was also investigated using an in vivo perfusion technique. The presence of ion pairs reduced lead absorption. These studies indicate that the majority of lead is transported as the hydrated cation, (Pb(H20)42+), and the formation of strongly associated soluble lead complexes reduces cation availability and therefore reduces lead absorption.