Pyridoxine Hydrochloride (Vitamin B6) 및 Essential Fatty Acid의 결핍으로 인한 동맥경화증에 대한 실험적연구

Abstract

[한글]

[영문]

Despite an almost limitless investigations and reports, the exact etiology and

pathogenesis of arteriosclerosis is still unknown. There have been numerous

accumulated evidences, however, to suggest or to incriminate certain factors in the

causation of arteriosclerosis but none of which is universally accepted. One of the

more attractive approaches both clinically and experimentally had been the problems

dealing with dietary factors.

A new way to a re-exploration of the metabolic and structural defects resulting

from sing1e vitamin deficiencies had been opened by Rinehart and Greenberg in 1949,

by adapting the rhesus monkey (Macaca mulatta) to a synthetic diet. During the

course of their long term investigations, they reported occurrence of degenrative

vascular lesions in rhesus monkey subjected to pryidoxine deficiency, and pointed

out that thee degenerative lesions simulated very closely to those of

arteriosclersis in man.

It is the purpose of this investigator to report detailed patholgical findings of

various organs with particular reference to the vascular changes produced by

deficiency of pyridoxine and of Essential Fatty Acids; individually and combined.

MATERIALS AND METHODS

Three groups of healthy rhesus monkeys weighing from 2.5 to 3.0 kg, had been

used. The first group of animals received a synthetic diet deficient in pyridoxine,

the second group was given the diet deficient in essential fatty acids and the

third and the third received the diet dificient in both pyridoxine and essential

fatty acids. The experiments also carried a group of control animals.

The basic diet of the experimental animals was a modification of the M^^-3 diet

of Waisman and associates, and consisted of powdered sucrose 73%, vitamin test

casein(Labco) 18%, Haok & Oset salt mixture 4%, and corn oil 2%. The dry

ingredients were thoroughly blended, granulated, and compressed into 2-g tablets

after the addition of 1 per cent calcium stearate. These tablets were fed ad

libituin. Each monkey received one vitamin tablet daily containing the following ;

thiamine, 0.5mg; riboflavin, 1 mg; nicotinic acid, 5 mg; calcium pantothenate, 3

mg; ascorbic acid, 25 mg; p-aminobenzoic acid, 100 mg; choline dihydrogen citrate

100 mg; inositol, 100 mg, and Biotin, 10 micrograms, plus sufficient powdered

sucrose to make a tablet weighing 1.5 g. Control monkeys also received either 1 mg

pyridoxine hydrochloride daily or 3.5 mg twice a week (on sugar cube). In addition,

each monkey received by mouth 10 drops of a vitamin A and D concentrate(containing

100,000 units of Vitamin A and 10,000 units of vitamin D) and 5 drops of mixed

natural tocopherols (containing 340 mg/g) weekly.

The first group of animals received above mixture of diet except pyridoxine and

the second group was given the diet without corn oil and the third received the

diet dificient both in pyridoxine and corn oil.

The animals were sacrificed after 1.5 to 25 months. Gross features of various

organs were recorded and fixed in 10% neutral formalin. Histologic sections were

mainly stained with Hematoxylin and Eosin. In addition, following histochemical

stains have been carried out to demonstrate specific vascular changes;

aldehyde-fuchsin, colloidal iron, and fat stains.

RESULTS AND SUMMARY

1. Prominent degenerative vascular disease occurs in monkeys when given diets

deficient in pyridoxine hydrochloride, essential fatty acids and both in pyridoxine

and essential fatty acids.

2. The vascular changes are most marked in the group of animals received the diet

deficient in both pyridoxine and essential fatty acids, less marked in pyrioxine

deficient group, and the least degree of changes in the group deficient in

essential fatty acids alone.

3. Prominent fatty metamorphosis of liver was observed in the first and the third

group, however, this was not observed in the second group. The third group showed

cirrhotic changes of liver in some animals.

4. The gross and microscopic features of the degenerative vascular diseases

produced in these experiments simulate very closely to those of human

arteriosclerosis.

5. In view of above experiments, attention is called to the essentiality of

vitamin B^^6 in metabolism, particularly of proteins and its possible relation to

pathogenesis of human arteriosclerosis. Importance of essential fatty acids can not

also be discarded, and the deficiency in combination of these two factors appear to

be certainly related to the enhancement of arteriosclerosis.