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Effect of certain drugs on the rate of excretion of vitamin C

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Effect of certain drugs on the rate of excretion of vitamin C

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Content EFFECT OF CERTAIN DRUGS ON THE RATE OF EXCRETION
OF VITAMIN C
A Thesis
Presented to
the Department of Zoology’
University of Southern California
in Partial Fulfillment
of the Requirements for the Degree
Master of Arts
by
Ellen B. Poyet
June 193s
UMI Number: EP67117
All rights reserved
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Disaeftalfon Pü^MîsMng
UMI EP67117
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This thesis, w ritten by
..............E L L E N . P ^ T ...............
under the direction of A_er_ Faculty Committee,
and approved by a ll its members, has been
presented to and accepted by the Council on
Graduate Study and Research in partial fu lfill
ment of the requirements fo r the degree of
MAbTER OF ARTS
D e a n
Secretary
D a te .fe ne .,....195.8. ....
F aculty C om m ittee
TABLE OF CONTENTS
PAGE
INTRODUCTION........... . . . 1
METHODS ................ 4
RESULTS........................ 10
DISCUSSION . ................ . 2K
SUMMARY................ 26
BIBLIOGRAPHY ............. 28
LIST OF TABLES
TABLE PAGE
I. CHART OF CEVITAMIC EXCRETION OF GROUP I ........... 11
II. CHART OF CEVITAMIC EXCRETION OF GROUP II ..........13
III. VITAMIN C CONTENT OF BLOOD FOLLOWING ADMINISTRATION
OF SALICYLIC ACID.......................... 23
LIST OF FIGURES
FIGURE
1. RAT 1 CEVITAMIC ACID OUTPUT
PAGE
2. RAT 2 CEVITAMIC ACID OUTPUT .................
3.
^
RAT
3
CEVITAMIC ACID OUTPUT
4.
RAT
4
CEVITAMIC ACID OUTPUT.................
5.
RAT
5
CEVITAMIC ACID OUTPUT
6. RAT 6 CEVITAMIC ACID OUTPUT .................
7. RAT 7 CEVITAMIC ACID OUTPUT
8. RAT 8 CEVITAMIC ACID OUTPUT.............. .
9.
AVERAGES OF SUB-GROUP A AND B OF GROUP 2 . . . .
la. APPARATUS FOR COLLECTION OF URINE.........
INTRODUCTION
The problem presented in this paper is based on the effect of
certain drugs on the rate excretion of cevitamic acid. The human body
is able to store only a limited amount of vitamin C. Factors which
might cause an unusual increase in excretion, resulting in depletion,
are therefore important. Various workers have attempted to credit cer
tain infectious diseases with this ability, others suggest various drugs
cause an increase in excretion. Rinehart found that under the combined
influence of vitamin C deficiency and infection, guinea pigs developed
with considerable frequency endocardial, myocardial, and articular
lesions which resembled somewhat those of rheumatic fever. From his
experimental results he advanced the concept that rheumatic fever may
be the result of combined influences of vitamin C deficiency and infec
tion. Rinehart further found that infectious organisms such as Strep
tococcus hemolyticus in the presence of adequate nutrition did not pro
duce rheumatic type lesions.
In more recent work Rinehart attempted to show a relationship
between rheumatoid arthritis and latent scurvy in guinea pigs. The ani
mals were placed on a vitamin C deficient diet over a period of months*
Studies of the joints of these animals revealed an arthropathy and mani
fold similarities to rheumatoid arthritis.
Perry measured the output of cevitamic acid in cases of
rheumatic fever. He used the method described by Harris and Ray, based
on the excretion of ascorbic acid in the urine following admininstration
2
of a test dose of vitamin C. Five active rheumatic fever patients
were used; three showed a marked rise in excretion of ascorbic acid
following the test dose; two cases showed no response. Out of six
quiescent cases three showed a satisfactory rise in excretion follow
ing the test dose, three showed no response.
Rinehart in further work, checked the blood levels of rheu
matoid patients. In acute rheumatic fever reduced ascorbic acid of the
blood plasma was found to be almost uniformly decreased. Quiescent
cases of rheumatic children were found to be in less low but distinct
ly suboptimal ranges. It was not determined whether this was due to
inadequate intake or to what extent this was related to anorexia, di
gestive disorders, or depletion by the disease itself.
Daniels obtained some unusual results in working on the vita
min C needs of children. One of the children being used in the experi
ment developed a cold; treatment given was 2.5 grains of acetylsalicyl-
ic acid on two successive nights with an increase in liquids. The urin
ary excretion of ascorbic acid was found to be greatly increased.
Daniels repeated this experiment with three children between the ages of
four and six years,, giving orange juice as the source of the vitamin.
At the end of the third day each child received 2.5 grains of the sal
icylate and three days later a similar dose was given. Each time there
was an increase in excretion of ascorbic acid following the administra
tion of the salicylate. She questioned whether the increased vitamin
output was due to conditions producing elevated temperature, to the
salicylate, or to the diuresis produced by the greater fluid intake.
3
Youmans and Corlette, following Daniels* work, studied the
effect of ingested aceylsalicylic acid on four subjects. Three young
adults were on a vitamin C - free diet to which was added 50 mgs. of
ascorbic acid daily in the form of orange juice. Doses of the drug as
high as forty grains had no significant effect on the excretion of as
corbic acid in the urine. The method differed in some aspects from
that of Daniels. Healthy young adults were tested, instead of febrile
children,, the dose of vitamin was less, and the adults were not on a
weighted diet.
METHODS
Two *types of experiments were attempted. The subjects for
one experiment were medical students and dieticians who were given
acetylsalicylic acid or neocincophen while on a diet in which vitamin
C consumption was controlled. The second experiment was with albino
rats, which are capable of producing their own vitamin C. Acetylsali-
cylic acid alone was administered to these animals. Eight full-grown
female albino rats eight months old were used to measure the output of
cevitamic acid in the urine following the administration of acetylsali-
eylic acid. Six male albino rats two and one-half months old were
used to measure the amount of cevitamic acid in the blood plasma on ad
ministration of a dose of the salicylate.
The titration method was used in determining the amount of
cevitamic acid in both urine and blood plasma. The basis of the titra
tion is the action of the cevitamic acid as a reducing agent. Two sub
stances are commonly used to measure this reducing power, namely phos-
photimgstic acid and sodium 2-6 dichloro-benzenoneindophenol. A modi
fication of Harris and Ray’s method with the dye was used in all titra
tions.
The dye solution was prepared by weiring the dry powder on
a chainomatic balance. A small amount of hot, glass-distilled water
was added to twenty^five milligrams of the powder in a mortar. The
mixture was filtered and the filter paper carefully rinsed with more
hot glass-distilled water. The solution was made up to twenty-five
5
cubic centimeters in a volumetric flask. The dye solution maintained
its titre for approximately two weeks.
The dye solution was standardized by the following method.
Grange juice strained through cotton was used as the source of vitamin
G. Ten cubic centimeters of juice was diluted with an equal volume of
10 per cent metaphosphoric acid and titrated with 0.01 N iodine solution.
One cc. of one-hundreth normal iodine solution is equivalent to 0.88
mgs. of cevitamic acid. A ten cc. quantity of juice diluted 1:10 with
distilled water was thoroughly mixed with 10 cc. of 10 per cent meta
phosphoric acid and titrated against the dye. From repeated preparation
of the dye solution the titre was found to be equivalent to five mgs.
of cevitamic acid per cc. of dye.
Human Experiments. - In the case of medical students and
dieticians, twelve hour urine specimens were collected, and preserved
with concentrated glacial acetic acid. The glacial acetic acid was
used instead of metaphosphoric acid due to the difficulty of obstaining
large quantities of the latter. As the titrations were made within two
and one-half hours after the samples were received the glacial acetic
acid was an effective preservative. The volume of each sample was
measured and recorded. A portion of the specimen was filtered and
titrated into 0.1 cc. of dye. In all cases the urine sample was diluted
with an equal volume of 10 per cent glacial acetic acid so that the
amount of dye used required one to two cc. of urine.
The students were started on the diet June 11th. They obtained
6
200 mgs. of vitamin C per day, 100 mgs. from freshly prepared juice,
and 100 mgs. from the diet to be found at the end of the summary.
The first collection, consisting of two twelve hour specimens was
collected June 14th. The other collections were made on June l6th, 20th,
21st, 22nd, 23rd. Collection ceased on the 23rd, due to termination of
school. The drug was given in two ten grain (0.67 gra.) doses, one the
night of the 22nd and the other the morning of the 23rd. Seven students
received acetylsalicylic acid and six students received neocincophen.
Rat Experiments. The diet of the rats was as follows: 22 1/2
pounds yellow com meal, 14 pounds wholewheat flour, 9 pounds powdered
skimmed milk, 2 pounds alfalfa meal, 2 pounds cod liver oil, 1 pound
brewers yeast, 117 gr^s calcium carbonate, 117 grams sodium chloride.
Their usual supply of lettuce was omitted for the duration of the experi
ment. They were given Rubin-Krick solution to drink, which contains
CaClg .329 per cent, McCl2 .015 per cent, NaClg .70 per cent, KCl .035
per cent, and distilled H2O 99.22 per cent.
The urinary excretion of the female rats was titrated for
thirty-five consecutive days. From the results of the first twelve
titrations the rats were divided into two groups, A and B, both groups
averaging as closely as possible in output of cevitamic acid. Group A
consisted of rats 2, 3, 5, 7, and group B of rats 1, 4> 6, 8. On the
thirteenth and fourteenth days rats in group A were given a dose of 15
mgs. of acetysalicylic acid per 100 grams of body weight by means of
stomach tube. Each rat of group B received 3 cc. of water by stomach
7
tube. Both groups were given three cc. of water per rat daily until
the nineteenth day. On the nineteenth day and twentieth day group B
received 30 mgs. of the drug per 100 grams of body weight and group A
served as the control. The daily intake of 3 cc. of water per rat was
continued for both groups until the 27th day. On the 27th day and 28th
day a dose of 45 mgs* per 100 grams of body weight was given to group A.
Daily titrations were continued through the 35th day.
For the collection of urine the rats were placed in a cylin
drical cage about ten inches in diameter containing food and water. The
cage was placed over a glass funnel with a slightly greater diameter.
A smaller funnel was fitted on to the larger one by means of adhesive
tape, paper clips, and rubber bonds. (See figure la) This funnel
2 1 /2 inches in diameter contained crushed metaphosphoric acid in a
filter paper. The smaller funnel emptied into a fifty cc. graduate
cylinder containing 2 cc. of a 10 per cent solution of metaphosphoric
acid and a few crystals of the solid acid. A layer of paraffin oil was
used to prevent oxidation. The urine was collected at 24 hour intervals
on consecutive days. The amount of urine was recorded, and diluted with
distilled water up to the 45 or 50 cc. mark. The oil film was removed.
The urine was filtered, a sample was poured into a 25 cc. burrette, and
the aiaount of urine required to decolorize 0.1 cc. of dye was recorded.
A shell vial resting bn a white background was used for the titration.
Knowing the value of the dye and the total output of urine it is
possible to determine the amount of cevitamic acid excreted per day.
8
Group 3 consisted of six male albino rats* The urine was
collected and titrated as in the female rats* The amount of cevitamic
acid present in the blood stream was determined six hours and ten hours
following the administration of 45 mgs* of acetylsalicylate per 100
grams of body weight* 0.2 cc* of blood was collected from the rat’s
tail and immediately added to 1 cc. of tungstic acid reagent. The
mixture was centrifuged for ten minutes. 0.5 cc. of the supernatant
fluid was added to 0.13 cc. of 10 per cent metaphosphoric acid and
titrated with diluted dye. The dye was added to the sample from a
microburrette graduated to 0.001 of a cc. The results were interpreted
for 100 cc. of blood. The output of urine was also measured giving the
relationship between excretion and the amount in the blood stream.
In the case of the rats a check was made to determine
whether or not there was any loss in cevitamic acid during the interval
between excretion of the urine and contact with metaphosphoric acid in
the funnel. The control consisted of 20 cc. of a solution of cevitamic
acid which was added directly to crystals of metaphosphoric acid. Test
1 was 20 cc. of the same solution poured over the cage set up at the
rate of 1 cc. every five munutes. Test 2 consisted of 20 cc. of the
same solution poured over the cage set up at the rate of 2 cc. every ten
minutes and allowed to stand 14 hours before titration. Each tube was
made up to 31 cc. with distilled water before titrating. The control
and Test 1 were titrated immediately, the control requiring 0.33 cc.
of urine for 0.1 cc. of dye and Test 1 required 0.4 cc. for 0.1 cc. of
9
dye. The results when converted into mgs. of cevitamic acid were:
control 2 .4 8 mgs.. Test 1 - 2.05 mgs., and Test 2 - 1.53 mgs. This
test was repeated with similar results. There is evident loss in the
method of collection, this however would be the same for each rat. The
loss might be remedied by more frequent collection, however this would
be impractical as the 24 hour output is very small and too many collec
tions might lead to error due to loss in handling.
A check was also made on the rate of oxidation to determine
whether or not the results obtained were from cevitamic acid. To 10 cc,
of urine collected from group II on the 25th day was added 4 cc. of 10
per cent NaOH (until the urine was decidedly alkaline) and 2 cc. of
supraoxal. Ten cc. of the same urine was kept as a control. To 5 cc.
of a solution of cevitamic acid was added 2 cc. of HpO, 3 cc. of 10 per
cent NaOH, 5 cc. of 10 per cent metaphosphoric acid and 2 cc. of
supraoxal. The cevitamic acid control consisted of 5 cc. of cevitamic
acid solution, 5 cc. of water, and 5 cc. of metaphosphoric acid. These
were set up at 6 and titrated at 8 P.M. 3 days later. The results
were as follows:
Treated Urine Urine Control Value of Urine
3rd day 3rd day as Made Up
neg. 1.2 cc. for .1 cc. dye .55 cc. for .1 cc.
neg. .95 cc. for .1 cc. dye .45 cc. for .1 cc.
neg. 1.1 cc. for .1 cc. dye .5 cc. for .1 cc.
Treated Cevitamic Acid Cevitamic Acid Control
neg* .75 cc. for .1 cc. dye
RESULTS
The effect of salicylate and neocincophen on a group of
medical students and dieticians is found in Table I. There were ten
men and three women taking part in this experiment. The first record
of each day on the chart is the day specimen, the second is the night
specimen and the third is the twenty-four hour output. Six men and one
woman took acetysalicylic acid, the remainder of the group received
neocincophen. The drug was given the night of the twenty-second day
of June and the morning of the twenty-third* The two rows at the bottom
of the chart are the averages for the effects of each drug for the en
tire day. In fifty-seven out of sixtyrfive cases the greatest output
of cevitamic acid was from the twelve hour period from eight in the
morning until eight at night. The orange juice was taken at breakfast
time. Neither aspirin nor cincophen produced uniform rise in the
excretion of cevitamic acid. On the other hand the averages did show
a slight rise with both drugs.
Table II gives a record of the daily output of group 2 for
thirty-five days. The encircled figures indicate the effect of admin
istration of acetysalicylic acid on the urinary excretion of cevitamic
acid. Figures 1-8 inclusive indicate graphically the results for each
individual rat. The dotted lines indicate the reaction to the drug.
It is significant that all rats showed a decided rise on the administra
tion of the drug. In some instances a less marked rise occurred at
times other than the administration of the drug. No satisfactory
TABLE I
ASPIRIN
A Cu
Tu
Ba
Lee
K1
Wal
A1
CHART OF CEVITAMIC EXCRETION OF GROUP I
f
6/15/37
6/17/37 6/21/37
6/22/37 6/23/37 6/24/37
185.0 (day) 78.79
67.3 (night) 115.13
252.8 (24 hrs) 193.9
113.08
^1.4
164.48
36.19
57.28
94.47
4 2 .4
3 1 .5
73.9
143.28
-45.16
188.44
85.47
. 60.8
49.88
14.44
6.2
20.68
59.08
32.5
107.53
neg.
neg.
46.18
146.27
64.33 26.88
91.58
107.53 46.18
76.27
88.40
60.39
21.08
105.2
88.3
-
78.7
58.0
136.7
155.1
64 .7
219.8
164.67
81.47
193.5
88.4
15.0
103.4
80.95
17.47
98.42
95.49
17.38
112.87
—
93.28
265_.3_7
358.65
134.42
-35.67
170.09
93.062
166.307
82.445
-Î5.5QO
79.08
^&3.6
81.27
46.53,
117.46
_33.44
70.7
117.945 102.34 127.80
150.90
29.349
25.80
-
104.90
23.78
, 29 . 5
50.14
5.99
93.87
23.78
55.149
128.63
56.14
117.65
58.69
71.96
130.65
130.12
-22..J5.
94.94
82.65
81.68
49.78
13 4.9
_59.4
113.74
40.1
189.97
177.59 131.46
194.3 158.84
NEOCINCOPHEN
Walk
Pa
Bra
116.47
38.03
154.503
78.642
55.512
134.154
83.268
28.896
112.164
112.90
36.19 124.08
81.69
..^.0 21.8
26.46
20.68
167.9
57.99
150.54 102.37
58.17 59.61
80.75 35.1
14.26
40.84 34.74
72.43 100.45
115.49
128.3
176.2 177.8 130.2
26.21
-35.-3
_48.^ 68.7
154.0$
211.5 226.6
198.9
TABLE I
CHART OF CEVITAMIC EXCRETION OF GROUP I
NEOCINCOPHEN
6/15/37 6/17/37 6/21/37 6/22/37 6/23/37 6/24/37
Go
—
15.97 71.08 43.78 53.56
JZi:.65
. _54±20
14.68
27.55
91.62 125.98 58.46 81.11
Wi 292.98 131.07 201.6 242.47 305.85 234.35
49.65 -84,29- .
86.1 93.0 46 .86 41.0
342.63 216.36 287.7 335.473 352.71
375.35
Re
—
93.0
191.29 107.2 126.25
48.4
-28^18
81.16
44.4
141.4 189.87 188.36 170.65
Average:
Asp. 169.6
124.1 115.2
111.3 154 149
181.3 185.6
Neo. 150.3 112.164 152.0 171.6
TABLE II
CHART OF CEVITAMIC EXCRETION OF GROUP II
Daily record of excretion of cevitamic acid for a 35 day period,
(1) (2) (3) (4) (5) (6) (7) (8) (9)
1, .93 1.44 1.44 .75 1 .3 2 1.60 2 .3 2 2.12 1.6 5
2. • 86 .85 1.02 1.10 1.3 6 1.26 1.17 1.01
1.33
3.
1.38 1.18 1.06 1.06 ♦90 1.09 .98 1.03 .94
4* .93
.32 .65
.5 1
.77 .91 .65 .53 .29
5.
1.21 1.40 1.27 .70 1.17 1.31 1.3 5 1.1 4
.50
6* 1.0 1.36 1 .1 9 1.3
1.18 1.18
1.54
1.21 1.12
7. 1.39 1.30 1.24 1 .4 1.32 1.03 1.01 1.09 .92
8. 2.0 1.65 1.77 1.7 1.52 1 .5 8 1.79 2.02
1—4*"
6-8 1.21 1.32 1.26 1.06 1.0 9 1 .3
1.5 2
1.41
1.27
2-3-
5-7 1.21 1.18
1.1 5
1.06
1.1 9 1.17 1.13 1.07 .9 6
(10) (11) (12) ( 13) ( 14) ( 15) (16) (17) (18)
1. 1.79
1.57 1.01 3.8
/Drug
2.87
/Drug
1.4 9
2.6 2.8 2.39
2. .71 .71 .75
2.16 1.58 2.07 .9 .73
.98
3. .75 .59 1.23 1.87 3.37 3*32 2.81
1 .9 1
.98
4. .63 .42 .75
1.58 1.68 1.66 %.29
2.06
2.03
5.
.78 .95 .94 1.6 5 3.11
3.02 .1.9
1.61
1 .7 4
6.
1.04
.78 .91
2.10 2.0
1.93
1.6 1.5 2 2.06
7. 1.47 .74
.82 1.77 2.88
2 .7 9 1.59
1. 2 6. 1.21
8. .78 1.11 1 .3 4 2.4 7 1.6 1.72 1.38 2.17 1.97
1—4—
6-8 1.06 .97 .98
2.5 2.0 1.7 1.71 2.1 2.1
2—3—
5-7 .93 .75 .94
1.86 3.12 3 .0 4
1.8 1 .3 6 1.5
Drug: 15mg/l00gms. of body wt.
TABLE II CONTINUED
CHART OF CEVITAMIC EXCRETION OF GROUP II
Daily record of excretion of cevitamic acid for a 35 day period
(19)
(20) (21) (22) (23) (24) (25)
(26) (27)
1.
/Drug
4.25
/Drug
3.59 2.44 1.85 1.79
1.90 3.36
/Drug
2.79
2. 1.56 1.81 1.73
1.61 1.61 1.11
.95
1.11
3 .3 1
3.
1.06
1.75 1.64 1.49
.6
1.31 .92 1.85 3.86
4. 3.73 3.34 1.85 1.85 1.45
1.61 1.96 2.8 3.38
5. 2.41
1.81 2.58 2.39 2.91 2.4 1 .7 4 2.5 5.4
6.
5.3 4.95 2.51 2.23
1.61 2.06
1.53 3.7 3.1
7. 1.16 1.48 1.59 1.23 .95
1.8
1.4 2 .4
3.86
8. 3.03 3.17 2.42 1.74
1.52
2.33 2.3 3.07 2.8
1—4"“
6-8 4.08 3.76 2.05 1.92 1.59 2.0 1.92 3.23
3.0
2—3—
5-7 1.55
1.71 1.63 1.7 1.40 1.05 1.25
1.96 4.36
Drug: 30mg/l00gms.
Drug: 45mg/l00gais.
(28) (29)
of body
of body
(30)
wt. (19)
wt. (27)
(31)
1 (20)
1
(32) (33) (34) (35)
(36)
1.
/Drug
2.49 2.6 2.6 3.10 2.6 2.06 2.52 5.36
/Drug
2.94
2.
—
1.07 1.24 1.03
.98 1.10 1.28
1.25
1.28
3. 3.51 3.1 2.5 1.34 1.29 2.32 1.4 4 1.25
1.08
4. 2.5 2.63 2.5 2.3 2.79
2.01 2.36 1.39 2.89
5. 4.13
2.78 2.89
2.68 2.06
1.44
1.8 1.9 6
1.34
6.
2.5 2.42 2.0 2.0
2.74 1.7 2.0 1.86 2.58
7. 2.21 2.5 1.95 1.65 1.75 1.41 1.34 1 .4 4
1.28
8. 2.21 2.68 2.2 1.96 — 1.8 2.2 1.28 2.58
1—4—
6-8 2.6 2.58 2.3 2.3 2.03 1.6 4 2.27 1.72
2.75
2—3—
5-7 3.3
2.36
2.14 1.7 1.52 1.3 1
1.4 6 1.25 1.25
Drug: 45mg/l00gm8. of body wt. (28)
Drug: 45mg/l00gms. of body wt. (36)
TABLE II CONTINUED
CHART OF CEVITAMIC EXCRETION OF GROUP II
Daily record of excretion of cevitamic acid for a 35 day period,
WEIGHTS
12 day 18 day 27 day
1. 232 gms. 226 gms. 224 gms,
2. 198 gms. 176 gms. 174 gms
3.
222 gms. 220 gms. 222 gms.
4.
212 gms. 212 gms. 210 gms.
5.
222 gms. 220 gms. 222 gms.
6. 220 gms. 222 gms. 222 gms.
7. 258 gms. 254 gms. 250 gms.
8. 210 gms. 205 gms. 204 gms.
25
ILO
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N O . 6 1 0 1 , U N IV E R S IT Y B O O K S T O R E , L O S A N G E L E S
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N O . 6 1 0 1 , U N IV E R S IT Y B O O K S T O R E . L O S A N G E L E S
20
explanation for this effect was found. It does not in any way discredit
the results.
Figure 9 consists of composite curves of the sub-groups A and
B of group 2. The amount of salicylate administered was 15 mgs., 30 mgs.,
and IS mgs. per 100 grams of body weight consecutively. It is apparent
that an increase in dosage results in a definite rise in excretion of
cevitamic acid in the urine. The drug in all three instances was given
for two consecutive days. In observing the graph it can be seen that
with the increasing dose the output is proportionately decreased and
second day of drug administration. The mean for the cevitamic acid
excretion during the control periods was 1.657 mgs. I. 027. The mean
for the urines on the days following drug administration equaled 3*626
mgs. I .117. The difference is 1.97 I .12.
Group three consisted of male albino rats. These were run to
determine whether or not there was a change in the amount of vitamin G
in the blood following the administration of salicylic acid. The
results for this group are shown in Table III.^
^According to the results shovm in Table III, two out of three
male rats responded to the drug. The effects on the blood stream corres
ponded with the excretion in the urine. Thus rat 1 did not show an
increase in urinary excretion following the drug, nor did the blood show
any change. Rats 2 and 3 however showed a change in blood content and
urine content. At the time of heaviest urinary excretion the blood
level was lowest. Apparently this low level in the circulation return
ed to normal level within ten hours after drug administration. The
control rats 4 - , 5> 6, showed none or slight change in both blood and urine.
X D3 .
■ e —
N O . 6 1 0 1 . U N IV E R S IT Y B O O K S T O R E , L O S A N G E L E S
—— wiT9 Sc
F,^u.)re tcL ppOL'ra.’ ttA.s Jjor Coflecti'orx O/j u-irir»e
TABLE III
VITAMIN G CONTENT OF BLOOD FOLLOWING
ADMINISTRATION OF SALICYLIC ACID
MGS. OF ACID IN URINE MGS. PER 100 cc. OF BLOOD
Day 1 2 3
6 hrs. after drug 12 hrs. after (
Rat
1 .982 .62 .82 .72 .72
2
.93 .79 1.34 .48 .72
3 .77 .41
1.08
.54 .72
U .57 .66 .87 .72 .84
5 1.28 .72 .77 .72 .72
6 .72 .72 .77 .72 .72
DISCUSSION
In working with students it was found that although
the averages for vitamin C excretion in the urine following
adequate doses of acetylsalicylic acid and neocincophen were
greater than normal, there was such a wide range in the re
sults that their value was questionable. The difficulties which
present themselves in working with a group of active human sub
jects should be recognized. These students were under a heavy
class schedule with final examinations to detract their attention,
making cooperation a problem.
Experiments run on rats were controlled in every possible
way. The consistently high increase in cevitamic excretion follow
ing test doses of salicylate agrees with the work of Daniels on
children. The results seemed to indicate that the increase in
excretion was directly dependent on the increase in dosage. A low
blood plasma level following drug administration in contrast to
a high renal excretion indicates a possible increase in renal
permeability which Daniels suggested as an explanation of the mech
anics of salicylates on vitamin C excretion.
SUMMARY
1. Acetyl salicylic acid and neocincophen seemed to
produce a slight rise in cevitamic acid excretion in a group of
medical students.
2. In a group of rats, acetyl salicylic acid produced
a measurable increase in cevitamic acid excretion.
3. The loss in vitamin C in the group or rats was
directly in proportion to an increase in dosage of salicylate.
4. Parallel with a high renal excretion, the blood
plasma level was found to be low.
BIBLIOCmAPHÏ
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Ahmad, Bashir, “Observations on excretion of vitamin C in human urine.”
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Archer, H.E., and George Graham, "Some observations on the excretion of
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Daniels, A.L., and G.J. Everson, "Influence of Acetylsalicylic acid
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Dry, T.J., “Avitaminosis in natives of Rhodesia.” Arch. Int. Med..
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Everson, G.J., A.L. Daniels, "Vitamin C studies with children of pre
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Guho, B.C., and A.R. Ghosh, “Biological synthesis of ascorbic acid."
Nature. 135:871-872, May 25, 1935.
Harde, E., I.A. Rothstein, and H.D. Ratish, “Urinary excretion of vitamin
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Lancet 1:71, Jan., 1935.
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dependence on the dietary intake." Biochem. J. 27:2011-2015, 1933.
29
Hawley, Estelle, D.J. Stephens, and George Anderson, "Excretion of
vitamin C in normal individuals following a comparable quantitative
administration in the form of orange juice, cevitamic acid by mouth
and cevitamic acid intravenously." J. Nutrition 11:135-145, 1936.
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of ascorbic acid." Proc. Soc. Exp. Biol, and Med.. 34:854-858, 1936.
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McHenry, E.W., and Graham Murray, "Observations on the estimation of
ascorbic acid by titration." Biochem. J. 29:2013, 1935*
Medes, Grace, "Determination of ascorbic acid in urine with phospho; -
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of vitamin G." _J. Biol. Ghem., 116:409-413, Nov. 1936.
Perry, G. Bruce, "Rheumatic heart disease and vitamin C." Lancet 2:426-
427, Aug. 1935.
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deficiency in rheumactic fever." J. Lab. and Glin. Med.. 21:597-
608, Mar. 1936.
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rheumatoid arthritisj experimental, clinical, and general con
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, L.D. Gruenbei*g, and A.Ü. Ghristie, "Reduced ascorbic acid
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30
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Asset Metadata

Creator Poyet, E. B. (author)

Core Title Effect of certain drugs on the rate of excretion of vitamin C

Degree Master of Arts

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag Biological Sciences,OAI-PMH Harvest

Format application/pdf (imt)

Language English

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Permanent Link (DOI) https://doi.org/10.25549/usctheses-c39-255425

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Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the au...

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