- Tissue distribution studies of calcium and lead in brain tissue
of rats were increased subsequent to a single intravenous injection
of lead, 10 mg/kg, in the form of lead acetate. Time-course
studies demonstrated that brain concentrations of calcium and lead
(in terms of wet tissue weight) were found to be increased at days
1, 3 and 7 post treatment. At 24 hours brain levels of calcium and
lead were elevated 70 and 350% respectively. Over the subsequent
48 hours, brain levels of calcium reached maximal values and brain
lead decreased slightly from day 1 values. At the end of 7 days,
brain concentrations of calcium and lead were still elevated significantly
above controls. The effect of lead on calcium in liver, heart,
kidney, skeletal muscle, smooth muscle, hair, bone and serum of
lead-exposed rats were not significantly altered.
Studies were undertaken to determine if the effect was mediated
by the thyroid-parathyroid complex. Calcium concentrations in the
brain of lead-treated thyroparathyroidectomized (TX-PTX) rats
were 30, 47 and 70% lower at days 1, 3 and 7, respectively, when
compared to levels of intact lead-injected rats at 10 mg/kg. Brain
levels of lead in lead-treated TX-PTX rats were comparable to
levels in treated intact animals. This implies that the thyroparathyroid
system was necessary for complete expression of
increased levels of brain calcium, but not essential for lead distribution
in brain tissue of rats.
Concentrations of brain lead were dose related, but the effect
of lead on brain calcium was not. At 5 mg/kg of lead, brain calcium
was increased maximally after 24 hours when compared to the effects
produced by other doses of lead, e.g. , 10, 25 and 50 mg/kg. At 72
hours, brain calcium was elevated about two-fold in lead-treated
rats regardless of the dose of lead administered; these levels of
calcium were found unchanged or slightly lower at 7 days. Doses of
lead at 25 and 50 mg/kg were not associated with altered calcium
levels in the other tissues. In comparison, levels of brain lead
associated with the various doses of lead changed little over the same
time-course except for the 50 mg/kg dose of lead; at this dose brain
lead continued to increase over 7 days.
Employment of dry tissue weight established that increased
hydration of brain tissue was another effect of lead on brain tissue in lead-treated rats. This additional effect of lead was associated only
with the 25 and 50 mg/kg doses and was prominent at days 3 and 7.
Elevated brain concentrations of calcium and lead with increased
brain water suggested that lead's actions were on the permeability
of brain tissue.
Alterations of biological parameters were determined in male
rats chronically exposed to dietary lead, 300 parts per million for
8 weeks in the form of lead acetate. Equal concentrations of lead
in water and in food differed in influencing various biological parameters.
Whole-blood concentrations of lead were significantly
elevated in all animals exposed to dietary lead. Lead-food and the
combined effect of lead-water and lead-food significantly increased
whole-blood levels of lead (10.5 and 17.9 μg/ 100 ml), respectively,
above the levels in the lead-water group. Muscle concentrations of
lead in the tibialis anterior of lead-food groups were increased
significantly above the muscle levels in control, reconstituted food
and lead-water groups. Absorption and distribution of lead depended
on whether lead was administered in food or water.
Calcium concentrations in brain, blood and muscle (tibialis
anterior) and lead levels in brain tissues of rats fed lead in their
chow were increased, although not statistically significant. These
elevated levels were associated with altered neuromuscular parameters
that were determined in situ. The ratio of muscle twitch
amplitude/tetanus amplitude of the tibialis anterior was reduced
significantly in the lead-food groups. Prolongation of the active
state of contraction in tetanus due to increased intracellular calcium
and/or lead's influence on the duration of the active state of muscle
contraction mediated by the motor axons were suggested to account
for the results. The tibialis anterior of lead-food groups tetanized
at significantly lower frequencies than the other groups. Increased
neuromuscular transmission and/or responsiveness at the junctional
sites were suggested to explain these observations. It was not
ascertained if elevated levels of calcium in blood, brain and muscle
and/or the body burden of lead produced the alterations of the
examined neuromuscular system.
Infusion of calcium (120 mg/kg/hr) to intact and conscious
rabbits caused progressive increases in the serum concentration of
thyrocalcitonin as determined by radioimmunologic methods. The
hormone was detected in the blood of six normal rabbits at a mean
concentration of 0. 80 ng/ml ± S. E. 0. 25; an increased level of
thyrocalcitonin was detected within 15 minutes after infusion of calcium,
and peak concentrations were found during maximal hypercalcemia.
Peak levels of thyrocalcitonin declined to pre-infusion levels
within 30 minutes after cessation of calcium infusion in the normal
rabbit. Also, the infusion of lead, 6 mg/kg/hr, tended to increase
concomitantly serum calcium and thyrocalcitonin levels in rabbits,
although the elevations were not statistically significant.