|Abstract or Summary
- The inhibition of the enolase enzyme system by fluoride has
been established for many years in in vitro experiments; however,
this inhibitory action has never been demonstrated in an intact mammal.
The present work was designed to examine the effect of fluoride
administered by intravenous infusion in rats, under the assumption
that enolase inhibition would be reflected in depressed glucose
Companion experiments were also carried out using ¹⁸F
as a tracer to examine the time course of fluoride
in rats, thereby providing a better understanding of the over-all toxic
action of fluoride.
Radiorespirometric studies were carried out using ¹⁴C-labeled glucose to investigate the effect of fluoride upon glucose
catabolism in intact rats.
The results demonstrate that, when the
concentration of administered fluoride builds up to 2x10⁻⁴ M on
the basis of even distribution of fluoride in body fluid, significant inhibition of glucose catabolism occurs.
Use was also made of
as a radiotracer of stable fluoride
in the tissues of rats intravenously infused with various concentrations of fluoride. When fluoride was infused at a concentration
0.126 M (2 mg fluoride per hour) the amount of fluoride accumulated
in soft tissue was proportional to the cumulative amount of fluoride
The concentration of fluoride in soft tissue ranged from 10⁻⁴ to 10⁻³ M at a time which corresponded to the maximum
fluoride inhibition of glucose catabolism seen in the radiorespirometric studies.
The concentration of fluoride causing significant inhibitory
effect on enolase in
as reported in the literature, is on the
order of 10⁻³ M. Two independent methods in the present study
show that, when administered fluoride reaches a concentration of 10⁻⁴ to 10⁻³ M in blood and soft tissues, severe inhibition of glucose
catabolism occurs in intact rats.
Therefore, there is every reason
to believe that one of the major toxic actions of
fluoride in rats is
due to the inhibition of the enolase system, a key step of glucose
Data obtained in ¹⁸F experiments in which 0.126 M fluoride
was administered indicate that the
fluoride in blood and soft tissues
was promptly deposited in bone.
Upon termination of fluoride administration, the major route of depletion of fluoride from blood andsoft tissues was by way of renal excretion, while
fluoride incorporated into the bone remained at the same level
without noticeable depletion over the period of these experiments.
was administered to rats at
concentrations lower than 0.126 M,
fluoride build-up in blood and soft tissues appeared to
follow a similar pattern as that observed in 0.126 M fluoride
experiments it was also noted that, as the cumulative dose
of fluoride administered by way of continuous infusion
there existed a defined ceiling in the capacity for fluoride
by bone deposition or renal excretion.
This resulted in excessive
accumulation of fluoride in blood and soft tissues.
It is is believed that the findings in the present
much to the current understanding of fluoride
toxicology in intact
It is also noteworthy that a detailed description
preparation of ¹⁸F is presented in the present work, including several important revisions of previously published