- Email: [email protected]
Fate of intravenously injected iodate and periodate
1930
Short communications
At this time it is impossible to differentiate the mechanism of drug action with the limited data at hand. There are two apparent areas for further investigation. The first deals with the effect of methylphenidate on fixation reactions of COZ involved in cholesterol formation. The second possibility, the differential incorporation of methyl- and carboxyl-labeled acetate into the sterol nucleus, suggests some change in the tricarboxylic acid cycle. Further work is necessary before the mechanism of methylphenidate on brain cholesterol can be elucidated. Acknowledgement-This project was supported in part by Public Health Service Research Grant NB02235 from the National Institute of Neorological Diseases and Blindness and the Michigan Heart Association. JON J. KABARA CAROLA. RIEGEL
Biochemistry Research, Chemistry Department, University of Detroit, Detroit, Mich., U.S.A. REFERENCES
I. J. J. KABARA,J. T. MCLAUGHLINand C. A. RIEGEL, Fed. Proc., 19 (1960). 2. J. J. KABARA,J. T. MCLAUGHLINand C. A. RIEGEL, in Drugs Affecting Lipid Metabolism, pp. 221-23. Elsevier, Amsterdam (1961). 3. J. J. KABARA,Brain Cholesterol VIII: The Effect of Methylphenidate (Ritalin) on the Incorporation of Specifically Labeled Acetate. Proc. Sot. exp. bio/. med., 118, 905 (1965). 4. J. J. KABARA,J. T. MCLAUGHLINand C. A. RIEGEL, Analyt. Chem. 33, 305 (1961). 5. J. J. KABARA, N. SPAFFORD,N. FREEMANand M. MCKENDRY, Proceedings of the Symposia 011 Advances in Tracer Methodology. Plenum Press, New York (1962). 6. J. J. KABARAand G. T. OKITA, Estratto da Biochimica e Biofogia Sperimentale 2, 255 (1963). 7. J. J. KABARA, in Proceedings VIIth Congress on World Federation of Neurology, Rome, Italy (1961). 8. J. J. KABARA,in Progress in Brain Research, vol. 9, p. 155. Elsevier, Amsterdam (1964). 9. J. J. KABARA, Tex. Rep. Biol. Med. 22, 126 (1964). 10. Ibid., p. 134. 11. Ibid., p. 143.
Biochemical
Pharmacology,
1965,
Vol.
14, pp.
1930-1934.
Pergamon
Press
Ltd.,
Printed
in Great
Britain.
Fate of intravenously injected iodate and periodate (Received 14 Jane 1965; accepted 25 August 1965) BECAUSEits relation with thyroid physiology iodide metabolism has been thoroughly studied but littler-3 is known about the distribution and elimination of iodate and periodate after intravenous administration. The rarI-iodate has been prepared by oxidation of ‘“iI-iodine with an excess of sodium chlorate” and the ra11-metaperiodate by oxidation of the i”tI-iodate with chlorine in alkaline solution.5 The radiochemical purity of these labelled compounds was assayed chromatographically. 20 pc of ial-I-labelled iodate (specific activity 5 &mg, or 10 PC of l:~iI-labeled potassium metaperiodate (specific activity lOpc/mg) dissolved in 0.1 ml of distilled water, were injected into adult Wistar rats through the tail vein. Groups of 5 animals (three males and two females) were sacrificed at different intervals and the activity in organs and tissues was determined with a scintillation counter. After this, the organs were homogenized 0.01 N in sodium hydroxide and the supernatant sample analyzed by ascending chromatography on paper Whatman 3 MM and using n-propanol: water: 15 N ammonium hydroxide (30 : 10 : 5). With this solvent the R, values are: Iodate 0.14-0.20, metaperiodate O.oo-O.02 and iodide 0.56-0.62.
Short communications
1931
The examination of the specific activity (count/min per g tissue) found in the various organs after the injection of lalI-labelled iodate (Table 1) shows a maximum during the first hour, with exception of the stomach, which has a rna~rn~ at 6 hr. This peak of stomach activity is a~ompanied by an increase in kidney, intestine, parotid gland, muscle and bone. In the 1sWabelled metaperiodate (Table 2) the maximum of specific activity was found at 6 hr after the injection and only the intestine presented its highest value before (3 hr). The chromatographic analysis performed on the different tissues (Table 3) indicates that a considerable amount of radioactivity has been found in the liver as iodate. The whole body counting (Fig. 1) shows metaperiodate. Fifty per cent of the injected conditions, at 7 hr for the iodate and at 18 hr and 2 as well as in Fig. 1 have been corrected
a similar pattern of elimination for both iodate and radioactivity is etiminated under these experimental for the metaperiodate. All the values given in Tables 1 for the radioactive decay.
a Periodate o Iodate
0
I
5
I 15
7 Time,
days
Fro. 1
DISCUSSION I~~iately after the iodate injection it is distributed throughout the whole body. Later, the liver concentrates the iodate because after 24 hr no iodate was found in stomach and intestine, only 4 per cent appeared in kidney and 98 per cent in liver. According to all these observations the reduction of iodate to iodide occurs in the liver which later eliminates the iodide through the gastric mucose. On the other hand the metaperiodate seems to be reduced to iodate as soon as it is injected and is metabolized as iodate. The correspondence between the maximum activity observed in the stomach and the increase in kidney, parotid gland, muscle and bone could be explained as a temporary increase in the blood activity by a reabsorption of the radioiodide through the intestine. The fact that iodate has not been found in intestine while it was present in the stomach (Table 3 periodate values at 1 hr) could be due to the stomach pH which assures its reduction to iodine according to the following redox reaction: 10; + 6H+ + 5e + l/2 IZ + 3 Hz0
:
: a b
b” a b
:
: a b a b a b a
:: a b
:
a
1.555 f 26% 202 :C 86 0.13 f 0.07 46.50 f 8.16 9.05 155 C 346 0.48 -i- 0.12 975 E 125 6.08 zt 2.30 2070 i 465 1.56 + 0.45 1216 t 320 5.55 z 1.02 2319 i 664 1.67 i 0.62 424 * 195 1150 * 365 0.22 i_ 0.10 1392 zj! 254 0.36 i 0.19 1182 + 228 0.42 1 0.12 11788 E 1022 24.10 + 5.96 958 i 276 0.68 -+-0.21 36890 + 2965 0.24 & 0.08
* = Skin + skeleton + muscles. a = Specific Activity (per g).
Thyroid
Testis
Stomach
Parotid Gland Spleen
Muscle Ovary
LLlng
Liver
Kidney
Intestine
Carcass* Excretat Heart
Bone Brain
1 hr 512 60 0.03 11.82 37.65 733 0.22 441 2.20 806 0.62 734 2.99 1442 0.74 175 623 0.11 528 0.12 670 0.25 23121 41.83 496 0.24 41750 0.27
138 19 0.01 3.25
+ 225 * 0.10 I 160 + 1.25 & 220 + 0.24 & 320 2 0.86 i 362 * 0.18 1 63 E 146 & 0.04 1- 226 + 0.10 i_ 165 * 0.09 + 865 i: 13.61 c 90 = 0.08 T 8036 - 0.16
+ 2 * ‘I
3 hr
RADIOACTIVITY FOUND
376 0.05 574 0.15 503 0.17 25110 37.12 757 0.53 25380 0.16
644 57 0.03 10.10 45.96 669 0.19 605 2.68 851 0.59 578 2.13 821 04; 128 0.09 80 1.01 265 0.19 286 0.50 164 ;;i””
66 12 O-01 4.86
4 58 ‘1 0.02 + 205 i 0.06 i 187 * 0.10 -I_ 2046 $ 8.20 & 62 i 0.15 7_ 2025 + 0.09
+ + & t = 5 5 ~* 2
& + c +
6 hr 12 7 0.03 5.60 31 16 9i3 OX@8 i OQO3 4.25 L 1.86 93.36 15 %8 0.006 ‘- OQO2 36: 18 0.19 z 0.06 20 k 3 0.02 * 0.002 44+ 18 0.19 - O-08 15 i 8 0.01 + OGO8 8--12 12 i 6 0.002 A owl 11 t6 00l3 * 0~001 15 +9 0.006 _C 0.003 67 3 32 0.20 t 0.06 13 + 1 0.01 & OItO6 33760 + 2642 0.33 !: 0.09
5 days
INJECTION OF RADIOIODATE
li, _c 0.56 36 fi 0.02 im36 i 0.16 g 80 :!. 0.08 * 18 f 20 _L 0.01 + 43 C OGO6 1. 60 i 0.02 + 289 + I.60 i: 36 - 0.01 & 3065 = 0.01
-?- 36 4~0.02 c 16
5 + t i
Standard deviation.
2;9’, 0.11 113 0.49 151 0.17 44 108 0.03 95 0.02 99 0.04 3492 4.13 100 0.05 12130 0.08
139 94 0.06 Il.05 76.45 136 0.05 45
1 day
IN THE DIFFERENT TISSUES AFTERTHE
f : Urine + Faeces (cumulative values). c : b = Per cent of injected dose.
TABLE 1. VALUES OFTHE
0.002 c 0.001 411 0.002 t oXtO 31-2 0.002 1 O+Ol 52 5 36 0.001 IO.001 4 ‘I oGO3 ‘~ 0.001 61900 = 5874 0.55 -’ 0.06
4~2
27 8 1 * 0.2 0.001 + 0+301 0.93 z 0.31 98.21 6,2 0,002 ‘- 0~001 31 Cl2 o+IO3 z O+IOl 15 X2 0.002 + 0~001 4 -f 2 o+IO2 * ONtl 11 56 0.001 - oXtO 4 & I
15 days
;
$
“b a b a b a b
; a
121 009 72
6.003 13.45
87 i 16 0.11 4 o-04 4805g 2 :855$
33:; 2 l&z 044 -Ir 0.13
o-oz I+ 8090 + 7.65 308 rt 0*15 + 348 *
* = Skin + skeleton + muscles. a = Specific Activity (cpm/g).
Thyroid
Testis
Stomach
CEzd Spleen
Muscle Ovary
Lung
Liver
Kidney
Intestine
; a b a b a b
bb b
carcass*
Eztat
a a
Bone Brain
1lW
f 208 -f- 0.10 z 265
+ 15.40
__ f 0.01
.
+-
+- 167 j, 0.08 f 89 _c 0.09 4: 349 * 0.19 rt: 3946 2 3$8
966 0.18 816 0.24 1143 0.35 8147 6;;; 0.41 rt OS22 42920 & 8324 0,53 i 0.10
& 164 & 126 rfr o-13 & 196 * 1.12 $473 2 ;21
4.33 633 068 678 364 945 0288
0.10 & O-01 48.96 _c 12.23 3356 854 j; 126 0;; 2 $8.
6 hr 2.51 f 72 48 -+ 6 0.04 j, 0*006 19.34 & 8.75 66.56
1 day
t = Urine + Faeces (cumulative values). b = Per cent of injected dose. c = Standard deviation.
.
217 z 112 0.28 f 0.09 8% f ;77624
516 537 I: tf;. 2.15 201 0.56 :!z 0.20
o-03 62.15 2068 510 0.24 703
_-
3hr
13 0.008 18 0.09 11 0@04 317:
&4 & O@OZ & 3 rir 0.01 It2 f O+xll ; ;b”6”
0.03 4 0*003
91140 . 811z2 0.006 rfr:O+Ol 50 f 46 07; $ F34
32 i 8 3fl 01@99 f x’$O3
7 days
YOl 0*0001 6721 Q-72
“‘S z PO05 o%l6 i @OOl 512
lrtl
oGO3 f 0.001 14 + 3
15 days
“‘“I: 2 O-005 f 92074 & 3.72 f
TABLE 2. VALUESOF THE RADXOACWWYFOUNDIN THE DIFFERENT TISSUES AFTERTHEENJECTION OF RADIOPERIODATE
1934
Short communications TABLE 3. CHR~MATOGRAPHIC
ANALYSIS-VALUES OF THE FOUND ACTIVITY IN THE HOMOGENIZED ORGANS*
Supernatant As Radioiodide As Radioiodate
After iodate injection
Liver Stomach Intestine Urine Feces After periodate
(%)
(%)
94.8 1.9 96.8 94.9 81.7 99.0
3.9 92.1 -
(activity remaining in pellet (%)
A:; 3.2 5.1
12.3 -
1.0
94.2t I ,9 72.67
1.q I.0 9.31
88.2 19.07
4.3 4.6t 2.3 3.9 4.3
injection
Kidney
4.07
97.0 1;:;t
Liver Stomach
76.31 97.7 96,lt 95.7 100.0 99.0
Intestine Intestine Urine
-
I.0
* As a percentage of the total activity t = Values 1 hr after the injection, the other values correspond to I day after the injection. In our experiment the intestine which according to Postat? excretes the iodide does not eliminate the iodate. Also, a part of the radioactivity is excreted through the urine in both chemical forms, as iodide and as iodate but through the feces only as iodide. The delay observed in the elimination of metaperiodate may be related with general inflammation in the vicinity of the site of injection. For a correct evaluation of the radioactivity balance Regoeczi’s observations that approximately 25 per cent of the animal’s iodide pool is localized in the skin must be considered. The importance of the liver in the deiodination of ‘alI-labeled organic molecules has been previously studied by Chaikoff,7 Straubs and the author s, 10 but, in this case the de-iodination occurred by splitting off the radioiodine. SUMMARY The distribution in various organs and tissues of the rat at different times of intravenously injected l:“l-labelled iodate and metaperiodate has been studied. This study showed that the liver concentrates and reduces the iodate to iodide which is eliminated through the gastro-intestinal tract. In the first day half of the injected radioactivity was excreted. The chromatographic analysis of the excretas showed that in urine both iodide and iodate were present but in feces only iodide. Comisidn National Buenos Aires, Argentina.
de Energia Atdmica,
LEOPOLDO J. ANGHILERI*
* Present address:
lnstitut du Radium, Paris, France REFERENCES 1. N. S. BRICKER and C. J. HLAD, J. Clin. Ino. 34, 1057 (1955). 2. 1. PASTAN, Endocrinology 61(l), 93 (1957). 3. Y. TAKEDA and E. B. REEVE, J. Lab. clin. Med. 60 (6), 944 (1962). 4. H. H. WILLARD, Inorganic Syntheses, Vol. I, p. 168. H. S. Booth Ed. McGraw-Hill (1939). 5. H. H. WILLARD, Inorganic Syntheses, Vol. I, p. 171. H. S. Booth Ed. McGraw-Hill (1939). 6. E. REGOECZI, Proc. Sot. exp. biol. Med. 112, 547 (1963). 7. 1. L. CHAIKOFF and A. TAUROG, J. biol. Chem. 207, 57 (1954). 8. W. H. STRAUB,D. F. FLANAGAN,R.AARON~~~J. C. ROSE, Proc.soc.expt.biol. Med. 116,i 119
(1964). 9. L. J. ANGHILERI, Nucl.-Med., 3, 368 (1963). 10. L. J. ANGHILERI, J. nucl. Med. 6, 69 (1965).
Short communications
At this time it is impossible to differentiate the mechanism of drug action with the limited data at hand. There are two apparent areas for further investigation. The first deals with the effect of methylphenidate on fixation reactions of COZ involved in cholesterol formation. The second possibility, the differential incorporation of methyl- and carboxyl-labeled acetate into the sterol nucleus, suggests some change in the tricarboxylic acid cycle. Further work is necessary before the mechanism of methylphenidate on brain cholesterol can be elucidated. Acknowledgement-This project was supported in part by Public Health Service Research Grant NB02235 from the National Institute of Neorological Diseases and Blindness and the Michigan Heart Association. JON J. KABARA CAROLA. RIEGEL
Biochemistry Research, Chemistry Department, University of Detroit, Detroit, Mich., U.S.A. REFERENCES
I. J. J. KABARA,J. T. MCLAUGHLINand C. A. RIEGEL, Fed. Proc., 19 (1960). 2. J. J. KABARA,J. T. MCLAUGHLINand C. A. RIEGEL, in Drugs Affecting Lipid Metabolism, pp. 221-23. Elsevier, Amsterdam (1961). 3. J. J. KABARA,Brain Cholesterol VIII: The Effect of Methylphenidate (Ritalin) on the Incorporation of Specifically Labeled Acetate. Proc. Sot. exp. bio/. med., 118, 905 (1965). 4. J. J. KABARA,J. T. MCLAUGHLINand C. A. RIEGEL, Analyt. Chem. 33, 305 (1961). 5. J. J. KABARA, N. SPAFFORD,N. FREEMANand M. MCKENDRY, Proceedings of the Symposia 011 Advances in Tracer Methodology. Plenum Press, New York (1962). 6. J. J. KABARAand G. T. OKITA, Estratto da Biochimica e Biofogia Sperimentale 2, 255 (1963). 7. J. J. KABARA, in Proceedings VIIth Congress on World Federation of Neurology, Rome, Italy (1961). 8. J. J. KABARA,in Progress in Brain Research, vol. 9, p. 155. Elsevier, Amsterdam (1964). 9. J. J. KABARA, Tex. Rep. Biol. Med. 22, 126 (1964). 10. Ibid., p. 134. 11. Ibid., p. 143.
Biochemical
Pharmacology,
1965,
Vol.
14, pp.
1930-1934.
Pergamon
Press
Ltd.,
Printed
in Great
Britain.
Fate of intravenously injected iodate and periodate (Received 14 Jane 1965; accepted 25 August 1965) BECAUSEits relation with thyroid physiology iodide metabolism has been thoroughly studied but littler-3 is known about the distribution and elimination of iodate and periodate after intravenous administration. The rarI-iodate has been prepared by oxidation of ‘“iI-iodine with an excess of sodium chlorate” and the ra11-metaperiodate by oxidation of the i”tI-iodate with chlorine in alkaline solution.5 The radiochemical purity of these labelled compounds was assayed chromatographically. 20 pc of ial-I-labelled iodate (specific activity 5 &mg, or 10 PC of l:~iI-labeled potassium metaperiodate (specific activity lOpc/mg) dissolved in 0.1 ml of distilled water, were injected into adult Wistar rats through the tail vein. Groups of 5 animals (three males and two females) were sacrificed at different intervals and the activity in organs and tissues was determined with a scintillation counter. After this, the organs were homogenized 0.01 N in sodium hydroxide and the supernatant sample analyzed by ascending chromatography on paper Whatman 3 MM and using n-propanol: water: 15 N ammonium hydroxide (30 : 10 : 5). With this solvent the R, values are: Iodate 0.14-0.20, metaperiodate O.oo-O.02 and iodide 0.56-0.62.
Short communications
1931
The examination of the specific activity (count/min per g tissue) found in the various organs after the injection of lalI-labelled iodate (Table 1) shows a maximum during the first hour, with exception of the stomach, which has a rna~rn~ at 6 hr. This peak of stomach activity is a~ompanied by an increase in kidney, intestine, parotid gland, muscle and bone. In the 1sWabelled metaperiodate (Table 2) the maximum of specific activity was found at 6 hr after the injection and only the intestine presented its highest value before (3 hr). The chromatographic analysis performed on the different tissues (Table 3) indicates that a considerable amount of radioactivity has been found in the liver as iodate. The whole body counting (Fig. 1) shows metaperiodate. Fifty per cent of the injected conditions, at 7 hr for the iodate and at 18 hr and 2 as well as in Fig. 1 have been corrected
a similar pattern of elimination for both iodate and radioactivity is etiminated under these experimental for the metaperiodate. All the values given in Tables 1 for the radioactive decay.
a Periodate o Iodate
0
I
5
I 15
7 Time,
days
Fro. 1
DISCUSSION I~~iately after the iodate injection it is distributed throughout the whole body. Later, the liver concentrates the iodate because after 24 hr no iodate was found in stomach and intestine, only 4 per cent appeared in kidney and 98 per cent in liver. According to all these observations the reduction of iodate to iodide occurs in the liver which later eliminates the iodide through the gastric mucose. On the other hand the metaperiodate seems to be reduced to iodate as soon as it is injected and is metabolized as iodate. The correspondence between the maximum activity observed in the stomach and the increase in kidney, parotid gland, muscle and bone could be explained as a temporary increase in the blood activity by a reabsorption of the radioiodide through the intestine. The fact that iodate has not been found in intestine while it was present in the stomach (Table 3 periodate values at 1 hr) could be due to the stomach pH which assures its reduction to iodine according to the following redox reaction: 10; + 6H+ + 5e + l/2 IZ + 3 Hz0
:
: a b
b” a b
:
: a b a b a b a
:: a b
:
a
1.555 f 26% 202 :C 86 0.13 f 0.07 46.50 f 8.16 9.05 155 C 346 0.48 -i- 0.12 975 E 125 6.08 zt 2.30 2070 i 465 1.56 + 0.45 1216 t 320 5.55 z 1.02 2319 i 664 1.67 i 0.62 424 * 195 1150 * 365 0.22 i_ 0.10 1392 zj! 254 0.36 i 0.19 1182 + 228 0.42 1 0.12 11788 E 1022 24.10 + 5.96 958 i 276 0.68 -+-0.21 36890 + 2965 0.24 & 0.08
* = Skin + skeleton + muscles. a = Specific Activity (per g).
Thyroid
Testis
Stomach
Parotid Gland Spleen
Muscle Ovary
LLlng
Liver
Kidney
Intestine
Carcass* Excretat Heart
Bone Brain
1 hr 512 60 0.03 11.82 37.65 733 0.22 441 2.20 806 0.62 734 2.99 1442 0.74 175 623 0.11 528 0.12 670 0.25 23121 41.83 496 0.24 41750 0.27
138 19 0.01 3.25
+ 225 * 0.10 I 160 + 1.25 & 220 + 0.24 & 320 2 0.86 i 362 * 0.18 1 63 E 146 & 0.04 1- 226 + 0.10 i_ 165 * 0.09 + 865 i: 13.61 c 90 = 0.08 T 8036 - 0.16
+ 2 * ‘I
3 hr
RADIOACTIVITY FOUND
376 0.05 574 0.15 503 0.17 25110 37.12 757 0.53 25380 0.16
644 57 0.03 10.10 45.96 669 0.19 605 2.68 851 0.59 578 2.13 821 04; 128 0.09 80 1.01 265 0.19 286 0.50 164 ;;i””
66 12 O-01 4.86
4 58 ‘1 0.02 + 205 i 0.06 i 187 * 0.10 -I_ 2046 $ 8.20 & 62 i 0.15 7_ 2025 + 0.09
+ + & t = 5 5 ~* 2
& + c +
6 hr 12 7 0.03 5.60 31 16 9i3 OX@8 i OQO3 4.25 L 1.86 93.36 15 %8 0.006 ‘- OQO2 36: 18 0.19 z 0.06 20 k 3 0.02 * 0.002 44+ 18 0.19 - O-08 15 i 8 0.01 + OGO8 8--12 12 i 6 0.002 A owl 11 t6 00l3 * 0~001 15 +9 0.006 _C 0.003 67 3 32 0.20 t 0.06 13 + 1 0.01 & OItO6 33760 + 2642 0.33 !: 0.09
5 days
INJECTION OF RADIOIODATE
li, _c 0.56 36 fi 0.02 im36 i 0.16 g 80 :!. 0.08 * 18 f 20 _L 0.01 + 43 C OGO6 1. 60 i 0.02 + 289 + I.60 i: 36 - 0.01 & 3065 = 0.01
-?- 36 4~0.02 c 16
5 + t i
Standard deviation.
2;9’, 0.11 113 0.49 151 0.17 44 108 0.03 95 0.02 99 0.04 3492 4.13 100 0.05 12130 0.08
139 94 0.06 Il.05 76.45 136 0.05 45
1 day
IN THE DIFFERENT TISSUES AFTERTHE
f : Urine + Faeces (cumulative values). c : b = Per cent of injected dose.
TABLE 1. VALUES OFTHE
0.002 c 0.001 411 0.002 t oXtO 31-2 0.002 1 O+Ol 52 5 36 0.001 IO.001 4 ‘I oGO3 ‘~ 0.001 61900 = 5874 0.55 -’ 0.06
4~2
27 8 1 * 0.2 0.001 + 0+301 0.93 z 0.31 98.21 6,2 0,002 ‘- 0~001 31 Cl2 o+IO3 z O+IOl 15 X2 0.002 + 0~001 4 -f 2 o+IO2 * ONtl 11 56 0.001 - oXtO 4 & I
15 days
;
$
“b a b a b a b
; a
121 009 72
6.003 13.45
87 i 16 0.11 4 o-04 4805g 2 :855$
33:; 2 l&z 044 -Ir 0.13
o-oz I+ 8090 + 7.65 308 rt 0*15 + 348 *
* = Skin + skeleton + muscles. a = Specific Activity (cpm/g).
Thyroid
Testis
Stomach
CEzd Spleen
Muscle Ovary
Lung
Liver
Kidney
Intestine
; a b a b a b
bb b
carcass*
Eztat
a a
Bone Brain
1lW
f 208 -f- 0.10 z 265
+ 15.40
__ f 0.01
.
+-
+- 167 j, 0.08 f 89 _c 0.09 4: 349 * 0.19 rt: 3946 2 3$8
966 0.18 816 0.24 1143 0.35 8147 6;;; 0.41 rt OS22 42920 & 8324 0,53 i 0.10
& 164 & 126 rfr o-13 & 196 * 1.12 $473 2 ;21
4.33 633 068 678 364 945 0288
0.10 & O-01 48.96 _c 12.23 3356 854 j; 126 0;; 2 $8.
6 hr 2.51 f 72 48 -+ 6 0.04 j, 0*006 19.34 & 8.75 66.56
1 day
t = Urine + Faeces (cumulative values). b = Per cent of injected dose. c = Standard deviation.
.
217 z 112 0.28 f 0.09 8% f ;77624
516 537 I: tf;. 2.15 201 0.56 :!z 0.20
o-03 62.15 2068 510 0.24 703
_-
3hr
13 0.008 18 0.09 11 0@04 317:
&4 & O@OZ & 3 rir 0.01 It2 f O+xll ; ;b”6”
0.03 4 0*003
91140 . 811z2 0.006 rfr:O+Ol 50 f 46 07; $ F34
32 i 8 3fl 01@99 f x’$O3
7 days
YOl 0*0001 6721 Q-72
“‘S z PO05 o%l6 i @OOl 512
lrtl
oGO3 f 0.001 14 + 3
15 days
“‘“I: 2 O-005 f 92074 & 3.72 f
TABLE 2. VALUESOF THE RADXOACWWYFOUNDIN THE DIFFERENT TISSUES AFTERTHEENJECTION OF RADIOPERIODATE
1934
Short communications TABLE 3. CHR~MATOGRAPHIC
ANALYSIS-VALUES OF THE FOUND ACTIVITY IN THE HOMOGENIZED ORGANS*
Supernatant As Radioiodide As Radioiodate
After iodate injection
Liver Stomach Intestine Urine Feces After periodate
(%)
(%)
94.8 1.9 96.8 94.9 81.7 99.0
3.9 92.1 -
(activity remaining in pellet (%)
A:; 3.2 5.1
12.3 -
1.0
94.2t I ,9 72.67
1.q I.0 9.31
88.2 19.07
4.3 4.6t 2.3 3.9 4.3
injection
Kidney
4.07
97.0 1;:;t
Liver Stomach
76.31 97.7 96,lt 95.7 100.0 99.0
Intestine Intestine Urine
-
I.0
* As a percentage of the total activity t = Values 1 hr after the injection, the other values correspond to I day after the injection. In our experiment the intestine which according to Postat? excretes the iodide does not eliminate the iodate. Also, a part of the radioactivity is excreted through the urine in both chemical forms, as iodide and as iodate but through the feces only as iodide. The delay observed in the elimination of metaperiodate may be related with general inflammation in the vicinity of the site of injection. For a correct evaluation of the radioactivity balance Regoeczi’s observations that approximately 25 per cent of the animal’s iodide pool is localized in the skin must be considered. The importance of the liver in the deiodination of ‘alI-labeled organic molecules has been previously studied by Chaikoff,7 Straubs and the author s, 10 but, in this case the de-iodination occurred by splitting off the radioiodine. SUMMARY The distribution in various organs and tissues of the rat at different times of intravenously injected l:“l-labelled iodate and metaperiodate has been studied. This study showed that the liver concentrates and reduces the iodate to iodide which is eliminated through the gastro-intestinal tract. In the first day half of the injected radioactivity was excreted. The chromatographic analysis of the excretas showed that in urine both iodide and iodate were present but in feces only iodide. Comisidn National Buenos Aires, Argentina.
de Energia Atdmica,
LEOPOLDO J. ANGHILERI*
* Present address:
lnstitut du Radium, Paris, France REFERENCES 1. N. S. BRICKER and C. J. HLAD, J. Clin. Ino. 34, 1057 (1955). 2. 1. PASTAN, Endocrinology 61(l), 93 (1957). 3. Y. TAKEDA and E. B. REEVE, J. Lab. clin. Med. 60 (6), 944 (1962). 4. H. H. WILLARD, Inorganic Syntheses, Vol. I, p. 168. H. S. Booth Ed. McGraw-Hill (1939). 5. H. H. WILLARD, Inorganic Syntheses, Vol. I, p. 171. H. S. Booth Ed. McGraw-Hill (1939). 6. E. REGOECZI, Proc. Sot. exp. biol. Med. 112, 547 (1963). 7. 1. L. CHAIKOFF and A. TAUROG, J. biol. Chem. 207, 57 (1954). 8. W. H. STRAUB,D. F. FLANAGAN,R.AARON~~~J. C. ROSE, Proc.soc.expt.biol. Med. 116,i 119
(1964). 9. L. J. ANGHILERI, Nucl.-Med., 3, 368 (1963). 10. L. J. ANGHILERI, J. nucl. Med. 6, 69 (1965).