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Abstract

PART Ⅰ

THE EFFECTS OF VITAMINS C ON THE CHANGES OF THE ENDOCRINE GLANDS IN ALBINO RATS

PRODUCED BY ORAL ADMINISTRATION OF TOXIC DOSES OF VITAMIN A.

In Rodabl'e investigation, the toxic effect of polar bear lives was found to be

due to its very high content of vitamin A, causing hypervitaminosis A in

experimental animals which ingested it in large quantities.

This condition was first described by Mouriquand, and Coliazo, Rodahl, Drigalaki,

Bomakov, Domagk, Uolita and other workers have done extensive work on experimental

hypervitaminosis A. The studies on various organs in hypervitaminosis A have not

been so studied.

A voluminous literature has accumulated concerning the effects of vitamin C on

every function of the body. Ascorbic acid is closely related with acrbohydrate

metabolism as is evidenced by the fact that scorbutic animals produce

hyperglycernia, reduced glucese tolerance, low hepatic glucogen content. Also it is

a well-known fact that ascorbic acid occurs in high concentration in the cortex of

the adrenal gland.

In the experiments on rats by Rodahl, in all cases daily doses of ever 50 to 100

I.U. vitamin A/gram of body weight result in appreciable toxic manifestations in

rats. Doses of between 47 and 185 I.U. vitamin A/gram of body weight produced only

slight toxic symptoms. Doses of between 200 and 500 I.U. vitamin A/gram of body

weight caused pronounced clinical symptoms and pathological changes of typical

hypervitaminosis A.

These facts lad to the approach of the problem from a new angle.

All the male rats were kept separated in special cages for each group and all

experimental animals lived under indentical condition.

All the male rats were diveded into groups as follows:

Control group : Six normal healthy rats were fed a noromal laboratory diet.

Group 1. This group consisted of 6 rats which were fed on a normal laboratory

diet and in addition to this, received orally 500 I.U. of vitamin A per gram of

body weight daily for 90 days.

Group 2. This group was placed on the same regimen as group 1 and, in addition to

this, received subcutaneousy 10 mgm of vitamin C daily for 30 days.

Group 3. This group was placed for 30 days on the same regimen as group 1,

following aseptic castration. (castration was done 10 days before the

administration of vitamin A).

Group 4. This group was placed on the same regimen as group 2, following aseptic

castration. At the end of each experiment, the rats were killed by injecting air

into the heart and then subjected to study.

1) The endocrine glands of rats that received toxic doses of vitamin A showed a

moderate to high degree of degeneration with exhaustion. The changes were most

marked in the anterior pituitary, thyroid and adrenal cortex. The changes in the

endocrine glands of rats that in addition received vitamin C subcutaneously were

definitely lessened.

2) The endocrine glands of castrated rats that received toxic doses of vitamin A

showed a degree of degeneration that was moderated but less prominent than in the

case of non-castrated rats.

RART Ⅱ

THE EFFECTS OF VITAMIN C ON THE CHANGES OF THE ENDOCRINE GLANDS IN ALBINO RATS

PRODUCED BY ORAL ADMINISTRATION OF TOXIC DOSES OF VITAMIN D.

The administration of toxic doses of vitamin D daily over a period of time

produces a marked disorder of calcium metabolism known as hypervitaminosis D. This

condition was first described by Hess and has since been studied by many workers.

Experimentally, the studies on various organs with administration of toxic doses

of vitamin D were carried out by many workers, but the study of changes on the

endocrine glands in hypervitaminosis D have not been so.

The mechanism of vitamin D intoxication is not entirely clear. Albright believes

that excessive vitamin D produces a hypervitaminosis which causes an exaggeration

of one or both of its known actions. There are increased absorption of calcium from

the gastrointestinal tract and increased urinary excretion of phosphorus simulating

hyperparathyroidism. Both actions predispose to the development of hypercalcemis,

subsequent calcification in certain tissue of the body may occur with cellular

injury and impairment of function. It has been suggested by others that vitamin D

in excessive amounts is a tissue toxin capable of producing cellular injury. The

damaged cells may subsequently become calcified.

The effects of massive dose of vitamin D must be judged on the basis of the dose

per unit body weight and not on the absolute size of the dose. When considered in

this light the order of increasing susceptibility appears to run as follows: rat,

dog, human, rabbit, with little difference between the dog and human, while the rat

is very much more resistant, and the rabbit, much less so. In the experiments on

dogs by Steck and his associates, with daily doses of between 20 and 50 I.U.

vitamin D per gram of body weight the average survival period was 39 days and with

20 I.U. or less 68 days. On the other band, Lim has shown that the change of

endocrine glands with administration of excessive dose(rabbit, 10 I.U./g/d) of

vitamin D daily over a period was significantly reduced or improved by

administration of vitamin C parenterally during vitamin D administration.

The author has studied experimentally the effects of vitamin C on the change of

the endocrine glands with oral administration of toxic doses(rat, 60 I.U./g/d) of

vitamin D daily over a proionged period.

The rats were all male and were kept separated in special cages for each group,

all experimental animals lived under identical conditions.

All the rats were divided in grops as follows:

Control group: Six normal healthy rats were fed a noraml laboratory diet.

Group 1. This group consisted of 6 rats which were fed on a normal laboratory

diet and in addition to this, received orally 60 I.U. of vitamin D per gram of body

weight daily for 30 days.

Group 2. This group was placed on the same regimen as was group 1 and, in

addition to this, received subcutaneously 10 mgm of vitamin G daily for 30 days.

Group 3. This group was placed for 30 days on the same regimen as was group 1,

following aseptic castration(castration was done 10 days before the administration

of vitamin D).

Group 4. This group was placed on the same regimen as was group 2, following

aseptic castration.

At the end of each experiment, the rats were killed by injecting air in to the

heart and then subjected to study.

1) The endocrine glands of rats that received toxic doses of vitamin D showed a

moderate to high degree of degeneration with exhaustion. The changes were most

marked in the anterior pituitary, thyroid and adrenal cortex. The changes on the

endocrine glands of rats that in addition received vitamin C subcutaneously were

definitely lessened.

2) The endocrine glands of castrated rats that received toxic doses of vitamin D

showed a degree of degeneration that moderate but less prominent than in the case

of non-castrated rats.