The effect of thyrocalcitonin (TCT) injections on the metabolism of water and electrolytes in free-moving and immobilized chinchilla hares is described. Calcium excretion from immobilized animals was elevated, but normalized in those also receiving TCT injections. TCT also normalized water content and excretion rates

Dmitriyev, B. S.

Krotov, B. P.

Shashkov, V. S.

Volozhin, A. N.

Yegorov, B. B.

English

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NASA TECHNICAL .MEMORANDUM NASA J;M-;[5938i 
EXPERI~ffiNTAL INVESTIGATION OF THE ROLE OF THYROCALCITONIN 

IN THE PROPHYL4XIS OF DISTURBANCES ~N THE WATER-SALT AND 

MINERAL METABOLISM DURING A 30-DAY HYPOKINESIA 

V. S. Shashkov, B B. Yegorev,. B. S. Dmitriyev, 
A.N. Volozhin, B.P; Krotov 
Translation of "Eksperimental'noye issledovaniye xoli 
tirokal'tsitonina v profilaktike narusheny vodno-solevogo
i mineral'nogo obmena pri 30-sutochnoy gipokinesii,"
Fiziologichesky Zhurnal SSSR im. I.M. Sechenova, 
Vol. 60, No.2, 1974, pp. 290-294 
NATIONAL AERONAUTICS AND SPACE ADMINISTRATION 
WASHINGTON, D.C. 20546 . NOVEMBER 1979 
https://ntrs.nasa.gov/search.jsp?R=19800010428 2020-03-21T20:05:53+00:00Z
STANDARD TtTLE PAGE 
1. Report No. i 2. Govenment Accss,on No. 3 RIcp.unt's-CataJ, No.NASA TM-75938
 
4. Title and Subt~tle 5. Roport Dote 
EBPER-IMENTAL INVESTIGATION OF THE ROLE November 1979
 
OF THYROCALCITONIN IN THE PROPHYLAXIS 6. Prrfomnb Orgonization Code
 
OF DISTURBANCES OF THE WATER-SALT .....
 
. 8. Peortm,ng Otganizat,ion Report No. 
V. Shashkov., B%,B-. Yegorov, B Ditriyv, 
A. Volozhin, -B-ZP:.-Krotov 10. Work Unit No 
-= 11. Contract or Giant No. 
Q. Performing Organizotion Name and Address NASW-3199 
Leo Kanner Associates 13. Type of Report and Per,od Coeed 
Redwood City, California 94063 
" Translation
 
12. Sponsoring Agency N rmeand Address
 
National Aeronautics and Space Adminis- 14. Sponswin Ag.nc, Code
 
tration, Washington, D.C. 20546
 
i5. Supplementary Notes 
Translation of "Eksperimental'noye issledovaniye roli 
tirokal'tsitonina v profilaktike narusheny vodno-solevogo 
i mineral'nogo obmena ori 30-sutochnoy gipokinesii," 
Fiziologichesky Zhurnal SSSR im. P.M. Sechenova, Vol. 60, 
No. 2, 1974, pp. 290-294 (A74-26557) 
16. Abstract 
The effect-of thyrocalcitonin (TCT) injections on the
 
-- tdb wer and eeCtrol6yes in ree-moving and
 
immobilized chinchilla hares is described. Calcium excre­
tion from immobilized animals was elevated, but normalized
 
1n those also receiving TCT injections. TCT also normal­
ized water content and excretion rates.
 
17. Key Words (Selected by Author(s)) 18. Distribution Statement 
UNCLASSIFIED Unlimited
 
19. Security Clossif.A(of this reprt) 20. Security Clossif. (of this page) 21- No. of Pages 22. Price
 
Unclassified Unclassified 10
 
NASA-1, 
EXPERIMENTAL INVESTIGATION OF THE ROLE OF THYROCALCITONIN
 
IN THE PROPHYLAXIS OF DISTURBANCES IN THE WATER-SALT AND 
MINERAL METABOLISM DURING A 30-DAY HYPOKINESIA 
V.S. Shashkov, B.B. Thborav,, B.S. Dmitt±_ev, 
A.N. Volozhin, B.P. Krotov
 
Moscow
 
Studies were conducted on the influence of thyrocalcitonin (TCT)/290*
 
on the metabolism of water, calcium, magnesium, potassium, and sodium,
 
as well as its influence on the condition of skeletal bones of hares
 
under conditions of their free-ranging captivity and during a 30-day
 
restriction of movement. The research was carried out on 98 male
 
chinchilla hares. TCT (bovine, 300 units MRC per mg) was injected
 
subcutaneously two times a day, 50 units per injection, over the period
 
of the experiment.
 
During hypokinesia there was no change in body excretion of
 
magnesium, potassium, and stdium, but that of calcium progressively
 
increased. Injectionof5TCT into the motion-restricted animals led to
 
a reduction in calcium excretion, which, however, remained at a higher
 
level than that of the control hares. In addition, TOT had a prophyl­
actic effect on the status of calcium metabolism in the mineralized
 
tissues.
 
Thyrocalcitonin (TCT), a thyroid iron hormone, is used for prevention
 
of osteoporosis in Itsenko-Cushing's disease, hyperparathyroidism,
 
Paget's disease, etc. (4,5,7). Data are also available on the normal­
ization of calcium metabolism in the bone tissues of rats during
 
prolonged hypokinesia (1). How TCT affects various aspects of water­
salt and mineral metabolism during movement-restriction of other types
 
of animals is unknown. The need for carrying out such research is
 
substantiated by data in the literature dealing with the versatility
 
of TCT effects on water and electrolyte metabolism.
 
The aim of our work was the study of the influence of TOT on
 
water, calcium, magnesoim, potassium, and s6dium metabolism, as well as
 
*Numbers in the margin indicate pagination in the foreign text.
 
-1­
its effects on the condition of skeletal bones of hares in free-ranging
 
captivity and during a 30-day restriction of movement (hypokinesia).
 
Methodology
 
Four analogous series of experiments were carried out on 98 male
 
chinchilla hares with initial weights of 2500 + 200 g. The animals
 
were divided into 4 equal groups: the first was the control group,
 
the second was hypokinetic, the third was the TCT group, and the
 
fourth was hypokinetic + TCT. The 30-day hypokinesia was created by
 
using cramped cages having walls variable in three dimensions (2).
 
TCT (bovine, 300 units MRC/mg (3) ) was injected subcutaneously, twice
 
a day at 50 units per injection, into the hares of the third and
 
fourth groups over the entire period of the experiment. The hares were
 
maintained on an adequate standard pelleted ration with the addition
 
of hay and vegetables. Water intake was not limited. On the 2nd, 8th,
 
15th, 22nd, and 30th days during the expetiment, concentrations of
 
sodium and potassium were measured using flame photometry; the concen­
tration of magnesium was measured by atomic absorptiometry, and that
 
of calcium by photoelectrocolorimetric titration; the hares had empty
 
stomachs when tested. Daily measurements of the same electrolyted in
 
the urine and feces were made using atomic absorptiometry. Data on
 
excretion were expressed in milliequivalents per kg weight of the hares.
 
Overall body water was determined by using tritium oxides. For the
 
study of calcium metabolism, Ca4 5 was used, being injected 24 hours /291
 
before sacrifice (series 1), as well as 24 hours before the beginning
 
of experiments (series II), 30 days before (series IIl), and 60 days
 
before (series IV). After sacrifice, the skeletal bones were removed
 
and processed using the generally accepted method. For morphometric
 
study, identical roehtgenograms of the tubular bones were obtained; the
 
thickness of the dense layer and width of the medullary canal in the
 
middle of the diaphysis was determined using an MBS-2 microscope.
 
Results
 
In the control hares the concentration of plasma electrolytes
 
during the experiment fluctuated within the following limits: for calcium
 
-2­
-- from 6.2-9 to 8.06 mEq/liter, magnesium-- from 1.13 to 1.78 mEq/liter, 
potassium-- from 4.13 to 4.85 mEq/liter, and sodium-- from 141 to
 
150 mEq/liter. For the hares of all the experimental groups (2nd,
 
3rd, and 4th), the concentration 6f potassium and sodium did not
 
differ during the course of the Expeiment from that found in the
 
control group. The concentration of plasma magnesium during hypo­
kinesia (2nd group) did not change, but that of calcium decreased on
 
the 8th and 15 days (by 6 and 14%, respectively, relative to the
 
control group). Inject iono6f MT tintotheheanesodftnhe33rdPgroup 
led to hypocalcemia on the 8th day (84%, relative to controls, p<0.001),
 
but the concentration ofmagneium increased on the 8th, 15th,;i and
 
22nd days (118--123% relative to controls). In the motion-restricted
 
animals (4th group) TCT lowered the concentration of calcium on the
 
8th and 15th days by 6 and '8%(p <0.05) and increased the concentration
 
of magnesium by 11 and 34% (p>0.05).
 
As can be seen from the illustration, the excretion of calcium
 
from the body (total in urine and feces) during hypokinesia progress­
ively increased: after 7 days--by 10%, 14 days--by 32%, 21 days--by
 
74%, and 28 days--by 111%, relative to the controls (reliably-- on
 
the 21st and 28th days). Excretion of magnesium, potassium, and
 
sodium did not change. TCT caused reduced excretion of calcium and
 
magnesium in the animals of the 3rd group on the 7th day (81 and 75%)
 
and on the 28th day (88 and 71%, relative to controls). Sodium excre­
tion.remained unchanged, but that of potassium increased (164%, relative
 
to controls). With injection of TOT into the motion-restricted animals,
 
excretion of calcium from the body increased, after 14 days--by 27%,
 
21 days--by 47%, and 28 days--by 24% relative to controls.
 
Hence, increased calcium excretion began later and-was less
 
pronounced than in the animals with "pure"' hypokinesia, particularly
 
on the 28th day, when calcium excretion in the 4th group was 41%
 
lower, relative to data from the 2nd group. Under the influence of
 
hypokinesia and TCT, the total excretion of magnesium did not change,
 
that of sodium decreased on the 21st day (72%), while potassium ex­
cretion increased on the 28th day (138% relative to controls), i.e.,
 
-3­
analogously with data from the 3rd group.
 
The status of water metabolism was judged by urine excretion,
 
overall body water content, and the rate of average daily water loss
 
and replenishment. Urine excretion changed in the same direction
 
for all groups of hares: it decreased on the 2nd day (70--82%) and
 
increased thereafter (119--132% relative to controls). It is possible
 
that the decrease in urine excretion observed at the beginning of the
 
experiment was conditioned by stress and an increased secretion of
 
antidiuretic hormone (6).
 
Body water content (determined using tritium oxide) in the control
 
animals changed from 634 + 8.8 ml/kg body weight at the beginning of
 
the experiment to 646 + 9.9 ml/kg at the termination. With TCT injec­
tion, the quantity of water decreased by 3% relative to initial figures
 
(p<0.05). Restriction of movement led to a 7 and 10% increase in
 
water quantity on the 15th and 30th days (p<0.001). 
 With injection
 
of TCT into the motion-restricted animals (4th group), the combined
 
effects of the two influences werecbbserv defor,30,'dgys. This ampunted
 
to a somewhat smaller increase in water content-- 7% relative to
 
initial. The half-replenishment rate of water in the control animals
 
was 4.6 t 0.2 days, and increased with injection of TCT to 4.1 + 0.2
 
days (p> 0 .05), and even more as a result of hypokinesia-- to
 
3.8 + 0.1 days (p< 0.01). With injection of TCT into the motion­
restricted animals, the half-excretion period did not differ from
 
that of the controls-- 4.9 + 0.2 days. Overall water loss in the /292
 
control hares totaled 100 + 6.1 
ml/kg/day, but during hypokinesia it
 
grew 26% (p<0.01) by day 30. Injection of TOT had no effect on
 
water loss in the free-moving animals (3rd group), but promoted normal
 
water loss in the motion-restricted hares-- 95.5 + 5.7 ml/kg/day.
 
Radiometric studies confirmed a sharp decrease in Ca45 
assimilation
 
(series I) in the calcaneal, femoral, tibial, and parietal bones of
 
the hypokinetic hares (36,775, 61, and 65%, respectively, relative to
 
controls, p 
0.05), which evidenced the general alteration in calcium
 
metabolism. Injection of TCT into the free-moving hares resulted in /293
 
-4­
____ 
-
. -- r1 
m8/g 0.-LDV - - -T I i'! 
NaK, T
miEqlkg 5.0 -Ml - 7BI_ 
Ca, 2.0 
-t-I Kiqkg__ _ .1l
 
_a T _TmEq/kg 4.6­
.,~~ ~lotI!!l 
1.0- T onfdneitra 
Mg, I Confidence intervalI 
Control I Il1! 1111I I 1111! .12­7 14 21 
I 
98,-Vays 
Excretion of electrolytes in urine and feces
 
during hypokinesia T nd ihjecti6n of thyrocalcitonin
 
(by body weight in kg)
 
I--Thyrocalcitonin, II-Hypokinesia, III--hypokinesia+TCT
 
a--total excretion of electrolytes
 
b--excretion of electrolytes in fees.
 
-5­
increased inclusionodfZa 4 5 into mineralized tissues, particularly
 
the tibiae (155%, p <0.05). During hypokinesia, injection of TCT
 
caused a significant increase in isotope inclusion in the bones:
 
in the calcanei--by 88%, in the femurs--by 39%, in the tibiae--by222%,
 
and in the parietals=-by 78%,compared with data from the 2nd group
 
(p<0.05). Because of the restriction of movement, Ca45 resorption
 
in the rapidly-metabolized fractions (series II) of the calcaneal,
 
femoral, and parietal bones was accelerated (isotope content totaled
 
65, 59, and 75%, respectively, relative tocontrols, p <0.05). Injec­
tion of TOT into the hares of the 3rd group raised radiocalcium resorp­
tion in the mineralized tissues an average of.10--30%, while the
 
resorption rate decreased in the hypokinetics (4th group). Thus, there
 
was normalization of Ca45 removal from the rapidly-metabolized fraction.
 
As a result of hypokinesia, the resorption rate in the slowly-metabol­
ized fraction of the bones (settesTIIT)ddecreasdd. Injection of TCT
 
into the animals of the 3rd group led to accelerated Ca4 5 resorption
 
in the mineralized tissues; an analogous effect was observed in the
 
hares of the 4th group. The table shows that resorption of Ca4 5 injec­
ted 60 days before the experiment (series IV) increased in the bones
 
of the hypokinetic hares. Resorption of radiocalcium also increased
 
under the influence of TCT (3rd group). Injectio4 of TCT into the
 
motion-restricted animals brought about normalization of Ca45 content
 
in the mineralized tissues.
 
Ca45 
Table 1. content in the bones of
 
hafg,-,n-gypokinesia and injection of
 
hyrbbiaidin (data from series IV).
 
Results are given in percents of injected isotope dose.
 
Femur Calcaneus
 
Groups Statistical indices
 %vs%vs 
M ± m P cfltl M ± U p cntrlControl
 
Hypokinesia .
 
TtT - ioSoW o.18,o0.010 - -00
OT0.75 > . o.145>00J84 > 0.05 80.5Hypokinesia+TCT 	 o.2..... <.12A, 3.1 <005 73.2
 
U I' Ai~+.,I > .J (L187 70.0t5s > 0.1 404.3
 
-6­
The thickness of the dense layer of the humeral, femoral, and
 
tibial bones' diaphyses amounted too 1.94 + 0.032, 2.31 ± 0.044,
 
2.82 + 0.110 mm, while the width of the medullary canals were :t! : 
4.54 + 0..086, 6.10 + 0.097, and 4.74 ± 0.118 mm, respectively. During
 
hypokinesia the dense layer of the diaphyses decreased by 10% in the
 
humeral(p<0.02), by 14.2% in the femoral (p<0.01) and by 18.2%
 
in the tibial bones (p<0.02). Injection of TCT into the free-moving
 
hares resulted in thickening of the diaphyseal walls of the humeral,
 
femoral, and tibial bones (106.3, 109.9, and 111.7% of control values,
 
p 0.05). In the animals kept hypokinetic and also receiving TCT,
 
diaphyseal wall thicknesses were normalized in the humeral and tihial
 
bones (96.7 and 94.3% of control values, p)0.1) and remained almost
 
the same as with "pure" hypokinesia in the femurs (88.7% of control
 
values, p(O.02). Medullary canal widths for animals of all these
 
experimental groups did not actually change.
 
Thus, we have established that regular changes in water, electro­
lyte, and mineral metabolism result from 30-day hypokinesia. Injection
 
of TCT has a prophylactic effect primarily on the status of calcium
 
metabolism in mineralized tissues,, and also on some water-salt meta­
bolism indices.
 
-7­
REFERENCES
 
1. 	Volzhin, A.I., P.V. Vasil'yev, N.N. Uglova, V.E. Potkin,
 
Kosmicheskaya biolog., 3, '(1922).
 
2. Savel'yeva, T.P., V.P. Krotov, Certification No. 278291 (1970).
 
3. 	Stekol'nikov, L.I., S.B. Katkovsky, O.M. Tepelina, V.M. Kono­
patskaya, A. Abdukarimov, T.V. Egorova, Vopr. Med. Khimii, 3,
276, (1969).
 
4. Band, C.L., et al., Schweiz. med. Wschr., 199, 657, (1969).
 
5. 	Bijvoet, O.L.M., Sluys Veer, V. d. S, De Vries, H.R., Kopper,
 
V.A.T., Engl. J. Med., 284, 13, 681, (1971).
 
6. Fujita, T.H.O., Ohata, M., Endo6rino1. Japon, 15, 8, (1968).
 
7. Gilbert, G.Z., Glaser, G.H., Arch. Neurol., 2, 179, (1961).
 
8. Fujita, T.H.O., Ohata, M., et al., Endocrinol. Japon., 15, 8, (1968).
 
9. 	Keeler, R., Kopp, D.H., McIntoch, H.W., Walker, V., Proc. Can.
 
Fed. Biol. Soc., 13, 78, (1970).
 
10. Keeler, R., Walker, V., Copp, D.H., Can. J. Physiol. and Pharmacol.,
 
48, 838, (1970).
 
8 


Experimental investigation of the role of thyrocalcitonin in the prophylaxis of disturbances in the water-salt and mineral metabolism during a 30-day hypokinesia

Experimental investigation of the role of thyrocalcitonin in the prophylaxis of disturbances in the water-salt and mineral metabolism during a 30-day hypokinesia

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