| THE EFFECT OF TOXIC DOSES OF FAT SOLUBLE VITAMINS ON THE CHANGES OF ENDOCRINE GLANDS
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KOOK HOON KO |
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Department of Pediatrics Yonsei University College of Medicine Seoul, Korea |
| 中毒量 脂落性 비타민이 內分秘系器官에 미치는 影響 |
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高克勳 |
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延世大學校 醫科大學 小兒科學敎室 |
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| Abstract |
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THE EFFECTS OF VITAMIN C ON THE CHANGES OF THE ENDOCRINE GLANDS IN ALBINO RATS PRODUCED BY ORAL ADMINISTRATION OF TOXIC DOSES OF VITAMIN A. In Rodahrs investigation, the toxic effect of polar bear liver 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 Collazo, Rodahl, Drigalski, Bomskov, Domagk, Uolita and other workers have done extensiva work on experimental hypervitaminosis A. The studies on various organs in hypervitaminosis A have been carried out by many
workers, but the endocrine glands 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 carbohydrate metabolism as is evidenced by the fact that scorbutic animals prodace hyperglycemia, reduced glucose tolerance, low hepatic glycogen 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 over 50 to 100 I. U. vitamin A gram of body weight result in appreciable toxic manifestations in rats. Doses of between 47 and 135 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 typical of hypervitaminosis A. These facts led 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 identical conditions. All the male rats were divided into groups as follows Control group: Six normal healthy rats were fed a normal 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 30 days. Group 2. This group was placed on the same regimen as group 1 and, in addition to this,
received subcutaneously 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 dministration of vitamin A).Group 4. This group was placed on th© 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 G subcutaneously were de兵nitely lessened. 2)The endocrine glands of castrated rats that received toxic do3es of vitamin A showed a degree of degeneration that was moderated but less prominent than in the case of non-castrated
rats. PART II THE EFFECTS OF VITAMIN G 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 hypervitanainosis 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 th© study of changes on the endocrine glands in hyper vitaminosis 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 caussa an exaggeration of one or both of its known actions. There are increased absorption of calcium from tha gastrointestinal tract and increased urinary excretion of phosphorus simulating hyperparathyroidism. Both actions predispose to the development of hypercalcamia, subsquent 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. Tha damaged cells may subsequently become calcified. The effects of massive dose of vitamin D must ba judged on the basis of the dosa par unit body weight and not on tha absolute siza of the doss. 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 hand, Lim has shown that the change of endocrine glands with administration of excessive dose (rabbit, 10 l.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 G on the change of the endocrine glands with oral administration of toxic doses (rat, 60 l.U./g/d) of vitamin D daily over a prolonged period. The rats were all male and were kept separated in special cages for each group, ail experimental animals lived under identical conditions. All the rats were divided in groups as follows: Control group： Six normal healthy rats were fed a normal 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 C daily for 30 days. Croup 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 into 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 gland3 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 was moderate but 1033 prominent than in the case of non castrated rats.
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