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KMID : 0365819650050010015
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Journal of Pusan Medical College
1965 Volume.5 No. 1 p.15 ~ p.40
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Effects of Isonicotinie Acid Iiydrazide on the Biochemical Changes of Rabbits
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Abstract
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The most effective antitubercular drug isonicotinic acid hydrazide (INH) is one of the pyridoxine analogs and acting as Bs antivitamins, It combines with pyridoxal and pyridoxal phosphate to form isonicotinyl hydrazone and thereby causes competitive inhibiton of transaminases (aminopherase), amino acid decarboxylases, tryptophanase, and other pyridoxal enzymes in living cells. The manifestations of acute and chronic intoxication with INH in man and animals (convulsive fits, cutaneous lesions and neuritis etc) are similar to those of pyridoxine deficiency. Drugging with INH induces the excretion of pyridoxal (partly as the nicotinyl hydrazone) in the urine and efficiently lowers the vitamin Be content and rates of some pyridoxal phosphate dependent reactions in the animal tissues.
There are various experimental reports concerning INH intoxication used susceptible animals and pyidoxine deficient diets. However there are few studies regarding brain acetyltcholine esterase and transaninase activity of pyridoxine deficient rabbits induced with INH administration. The present experiments are undertaken to clarify the relationship between transaminase and acetylcholine esterase activity and to investigate other biochemical changes induced with INH administration,
Rabbits were used as experimental animals for this study by reason of the similarity of metabolic pattern to INH and susceptibility to Be deficiency between human body and this animal.
Animals were divided into following groups. Each subgroup consists of 8 animals weighing 1, 0-1, 8Kg.
1. Normal group: 8 animals. Rabbits fed unsusual diet,
2. `A group: Consists of 4 subgroups. A- I , A- II , A- Ill and A IV ; all 32 animals. Rabbits received normal diet plus 20 mg INH per kg body weight.
3. B group: Consists of 4 subgroups. B- I , B- II , B III and B IV ; all 32 animals. Rabbits received
normal diet plus 20 mg INH per kg body weight and 10 mg pyridoxine hcl/kg,
4. C group: Consists of 3 subgroups. C- I , C- Il and C-III ; all 24 animals. Rabbits given normal
diet plus 20 mg INH/kg and injection of 10mg/kg royal jelly.
5, D group: Consists of 3 subgroups: D- I , D- II an d D-III; all 24 animals. Rabbits were given nor
mal diet contained pyridoxine 10 mg/kg only.
Body weight, brain water content, serum total protein, total cholesterol and cholesterol ester concentration, acetylcholine esterase and G.O.T. activity of the brain cortex, and other hepatic enzyme activity (cholinesterase, G. 0. T. , G. P. T. , cysteine desulfhydrase and catalase activity) were determined weekly according to each subgroup.
The following results were obtained.
l. Growth retardation was recognized in the A group remarkably, but in the other groups growth rate were almost normal.
Brain water content was not changed due to INH administration. No variable changes occurred in each group.
2. Serum total protein content was not influenced by INH, and no significant differences occurred in each group.
Serum total cholesterol and cholesterol ester concentration remained normal limit in the A, B, D group but in the C group significant hypocholesterolemic action of royal jelly Was observed.
3. Acetylcholine esterase activity of the brain cortex was markedly decreased temporally by INH administration and plateued by 2 week, and increased gradually thereafter, recovered almost normal range at the end of the experimental period. Acetylcholine esterase activity of B and D group rised considerably but returned to normal range in the 5th week. Choline esterase activity of the liver was markedly decreased and recovery to normal value was delayed by acetylcholine esterase of the brain cortex.
4. G, 0. T. activity of the brain cortex and liver tissue were significantly decreased due to INH administration but recovered to normal range at the end of 5 weeks. Elevation of G.O,T activity ware observed in the B and D group.
G. P. T. activity of the liver showed steep decline by INH and recovery has not occurred in the observation period. Elevation of G.P.T. were observed in the B and D group.
5. Cysteine desulfhydrase activity of the liver was decreased slightly due to INH administration and
remarkable elevation of activity was not seen in the B and D group. Catalase activity of the liver was not affected with INH,
6. The correlation between G. 0. T. and acetylcholine esterase activity of the brain was significant but weak correlation were observed between hepatic transaminase and choline esterase activity.
7. Severe BB deficient manifestations and longstanding biochemical changes have not occurred to the rabbits except growth retardation and declination of G. P. T. activity due to INH administration. It seemed that some adaptation reactions or defencing mechanisms, accentuation of detotoxication, acetylation, excretion and other processes proceeded continuously in the living cells of rabbits to minimize the hazard of INH intoxication.
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