Factors affecting the absorption and excretion of lead in the rat Original paper

What was studied?

This original experimental study examined lead absorption and excretion in the rat, quantifying where and how inorganic lead enters and leaves the body and which physiological and dietary variables modulate flux. Using radiotracers and whole-body counting, the authors mapped intestinal uptake (with surgical isolation of gut segments, bile-duct ligation when needed), characterized red-cell versus plasma transport, and measured renal, hepatic, osseous, and fecal/urinary clearance over minutes to weeks. The central mechanistic questions were whether uptake saturates at the mucosa, how bile and luminal chemistry shape bioavailability, and whether body burden feeds back to limit further absorption.

Who was studied?

Pathogen-free male Wistar rats (∼200–250 g) were fasted for standardized intervals and received defined intraluminal or intravenous lead doses while under ether or pentobarbital anesthesia. Intestinal segments (stomach, duodenum, jejunum, ileum, colon) were tested in vivo; some experiments manipulated bile flow, dietary protein, iron status (deficient, replete, iron-loaded), and co-administered solubilizing ligands (ascorbate; sulfur-containing amino acids) or competing cations (Fe, Zn, Ca). Serial sampling quantified carcass retention, organ deposition, and excretion in urine and stool.

Most important findings

Duodenum was the principal absorption site; radioautography localized lead to villus mucosal epithelial cells, and bile enhanced uptake, implicating enterohepatic factors in luminal bioavailability. Absorption showed a relative mucosal “block”: as intraluminal dose rose 100-fold, fractional uptake fell, yet absolute absorbed lead still increased—evidence for limited receptor/acceptor capacity rather than a hard ceiling. Co-ingested solubilizers (ascorbate; methionine/cysteine/cystine) increased absorption by maintaining lead in an absorbable state at neutral pH, whereas equimolar Fe, Zn, and Ca reduced absorption without altering solubility, consistent with competition for shared mucosal transport pathways. Physiologic status mattered: iron deficiency and rapid growth increased absorption; prolonged starvation and iron loading decreased it; total body lead burden did not down-regulate uptake, indicating no effective feedback limiter at the gut interface.

After intravenous dosing, lead cleared rapidly from plasma and associated predominantly with erythrocytes (transit pool), then redistributed to kidneys and liver early, with bone becoming the long-term reservoir. Excretion was biphasic, substantial early urinary and fecal loss (with bile an important fecal route) followed by slow elimination (∼months half-time), explaining cumulative skeletal storage despite active excretory pathways. Mechanistically, these data position the small-intestinal mucosa, bile, erythrocyte shuttling, and renal–hepatic handling as the principal determinants of whole-body kinetics.

Key implications

Lead absorption and excretion in the rat are dominated by duodenal uptake modulated by bile chemistry and by competitive interactions with essential cations. Iron deficiency emerges as a high-risk state for exaggerated uptake, supporting iron repletion as a protective strategy. Because body burden fails to curb further absorption, exposure reduction remains paramount. Biliary excretion returns lead to the intestinal lumen, so enterohepatic cycling may prolong gut exposure even after systemic dosing. The erythrocyte-centric transport and the kidney–liver early handling, with bone as a long-term sink, align with biomonitoring patterns and underscore why chelation must consider both rapidly exchangeable pools and slowly mobilized skeletal stores.