Segmental and intracellular distribution of lead in rat kidney and salivary glands

The segmental and intracellular distribution of lead (Pb) was studied in the kidney and salivary gland of Sprague-Dawley rats. Lead acetate was administered i.v. in a single dose (10 or 65 mg/kg body wt) or multiple biweekly doses (subchronic: 7 X 10 mg/kg over 3 months; chronic: 13 X 10 mg/kg over 6 months). Segments of cortical nephrons and salivary glands were separated following tissue slicing, incubation with collagenase and centrifugation on a Percoll density gradient medium. Subcellular fractions were obtained by differential centrifugation of renal and salivary tissue homogenates. Lead was predominantly localized in the renal proximal tubules, which contained at least twice as much of the metal as the distal tubules. Segment populations prepared from salivary tissues contained far less Pb than the renal fractions and showed no clear differences among themselves in their affinity for the metal. Intracellular Pb distribution was as follows: kidney nuclei (Nu) greater than mitochondria (Mt) greater than cytosol (Cy) greater than microsomes (Mc); salivary gland Cy greater than Mc greater than Mt greater than Nu. In most cases, 45Ca followed the same intracellular distribution as lead. Our data suggest that the proximal tubular segment may be the most likely renal target of chronic lead toxicity. The results point also to a much greater retention of Pb by the kidney than by salivary glands. The ability of the kidney to accumulate a great deal of lead to be released into tubular fluid over long periods, makes urinary lead a poor indicator of duration and frequency of exposure. On the other hand, the inability of salivary glands to retain this metal makes saliva lead concentration a potential indicator of current exposure.