Iproniazid 및 Lithium이 가토 혈중주정농도에 미치는 영향에 관한 실험적 연구 = EFFECTS OF IPRONIAZID AND LITHIUM ON BLOOD ALCOHOL LEVEL IN RABBITS

다국어 초록 (Multilingual Abstract)

In recent years, it has been known that lithium has marked psychotropic effects in controlling manic excitement, various other psychotic excitements and the recurrence of both manic and depressive symptoms.
Iproniazid is the very first antidepressant which first introduced in medicine as a antituberculous agent in 1951. Thereafter many investigators established that iproniazid was of particular value in treating patients with depression and that it was an inhibitor of monoamine oxidase. Its usage, however, had been discontinued around 1960 due to svere hepatotoxicity.
It has lately been reported that lithium and several other psychotrophic drugs elevated the blood alcohol level in rabbits.
In view of these reports the author conducted an animal experiment to investigate the effects of iproniazid, alone or in combination with lithium ion, on blood alcohol level in rabbits.
Materials and Method
1. The experimental work was done with mature rabbits of both sexes, weighting between 2.0㎏ and 3.0㎏
2. The experimental animals were divided into 2 groups : control and experimental. The control group was given alcohol alone and the experimental group was divided into 3 subgroup: alcohol+iproniazid group, alcohol+lithium group and alcohol+iproniazid +lithium group.
3. Iproniazid was given orally in a capsule form, 30㎎/㎏ of body weight, in 3 divided doses, a day for 5 days. The last dose of iproniazid was given 1.5 hours before alcohol administration.
4. Lithium chloride solution, 6.3%, was given in a dose of 3.0 mEq/㎏ of body weight a day for 4 days by intravenous route. The last dose was given 1 hour before alcohol administration.
5. In all groups, 20 Vol. % ethanol solution was given in a dose of 5.0 ㎖/㎏ of body weight in 5 minutes by intravenous route.
6. All of the blood specimens were obtained by cardiac puncture at 10 and 30 minutes respectively after alcohol administration, but additional blood specimens were obtained from the alcohol+iproniazid group at 20 minutes after alcohol administration.
7. The blood alcohol level was determined by Cavett's method.
8. In order to observe histopathological changes of the liver cell, the experimental animals were divided into 2 groups, control and experimental. To control group, normal saline was given in a dose of 5.0 ㎖/㎏ of body weight for 5 days by intravenous route. Experimental group, was divided into 3 subgroups. To the first subgroup, iproniazid was given for 10 days, to the second subgroup, lithium was given for 9 days and to the third subgroup, iproniazid combined with lithium were given. All animals were sacrlfied by intravenous injection of air.
9. For the light microscopic examinations, histoathological alteration of the liver cells was bserved by the routine hematoxilin-eosin staining chique.
10. For the electron microscopic examinations, e liver tissue was fixed in 1% osmium tetroxide (OsO₄), dehydrated with graded alcohol and embeded with Epon 812. The sections were cut with a ass knife in 400-500 Å thickness and stained with ranyl acetate and lead hydroxide. The pictures were taken with the Hitachi model Hu 11E-1 type electron microscope.
Results
1. Alcohol+iproniazid group:
Iproniazid significantly elevated the blood alcohol level at 10, 20 and 30 minutes after alcohol administration(P<0.05).
2.Alcohol+lithium group:
Lithium elevated the blood alcohol level significantly at both 10 (P<0.01) and 30 minutes (P<0.05) after alcohol administration.
3. Alcohol+iproniazid+lithium group:
Iproniazid combined with lithium elevated significantly the blood alcohol level at both 10 and 30 minutes after alcohol administration (P<0.01). The blood alcohol levels of these groups were significantly higher than those of alcohol+iproniazid group and alcohol +lithium group (P<0.05).
4. Electron microscopic findings:
Iproniazid group revealed mild swelling of mitochondria, loss of cristae and dense body in cytoplasm. Lithium group revealed enlarged nucleus and nucleous and scattered glycogen in cytoplasm. Ipronizid+lithium group reveled separated nucleolus in enlarged nucleus with irregular nuclear membrane and dilatated rough endopiasmic reticulum and several vacuoles in cytoplasm.
Conclusions
1. The orally administered iproniazid in a dose of 30 ㎎/㎏ a day for 5 days elevated significantly the blood alcohol level in rabbits at 10, 20 and 30 minutes after alcohol administration.
2. The intravenous injection of lithium chloride in a dose of 3.0mEq/㎏ a day for 4 days elevated significantly the blood alcohol level in rabbits at both 10 and 20 minutes after alcohol administration.
3. The iproniazid combined with lithium chloride elevated significantly the blood alcohol level in rabbits at both 10 and 30 minutes after alcohol administration.
4. On electron microscopy, iproniazid group, in which iproniazid was given orally in a dose of 30 ㎎/㎏ body weight a day for 10 days revealed mild swelling of mitochondria, loss of cristae and dense body in cytoplasm, lithium group, in which lithium chloride solution, 6.36% was given intravenously in a dose of 3.0 mEq/㎏ of body weight a day for 9 days revealed enlarged nucleus and nucleolus and scattered glycogen in cytoplasm and iproniazid combined lithium group, in which iproniazid was given for 10 days and lithium was given for 9 days revealed sparated nucleolus in enlarged nucleus with irregular nuclear membrane and dilatated rough endoplasmic reticulum and vacuoles in cytoplasm.