Pyridoxine Hydrochloride (Vitamin B6) 및 Essential Fatty Acid의 결핍으로 인한 동맥경화증에 대한 실험적연구
Experimental production of arteriosclerosis in rhesus monkeys by deficiency of pyridoxine hydrochloride (Vitamin B6) and essential fatty acids
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
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.