Journal of The Showa Medical Association
Online ISSN : 2185-0976
Print ISSN : 0037-4342
ISSN-L : 0037-4342
HISTOPATHOLOGICAL STUDIES ON THE SINGLE AND COMBINED ADMINISTRATION OF INAH AND TIBIONE
Naohiko Megawa
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1957 Volume 17 Issue 1 Pages 92-110

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Abstract
Remarkable advances and developments of the chemotherapeutic preparations were made in recent years. Simultaneously, reports on their side reactions are also beingg published quite frequently.
In the present paper, the author investigated histopathologically the influences of the single or combined administrations of INAH and Tibione on the kidney of mice.
In the cases of single administrations of INAH, an oral dosis of 10 mg/kg, subcutaneous doses of 10 mg/kg, 60 mg/kg and 100 mg/kg were given. In the cases of the single administration of Tibione, both oral and subcutaneous doses of 0.5 mg/kg, 1.0 mg/kg, 2.5 mg/kg and 5.0 mg/kg were given. In the cases of combined subcutaneous administrations, all combinations were given, and in the cases of combined oral administrations, only combinations, of 10 mg/kg of INAH and varying doses of Tibione were given. Administrations of drugs were conducted daily for 30 days, and the animals were observed for 1 week thereafter without administration before they were sacrificed.
In the cases of single subcutaneous injections of 10 mg/kg, 60 mg/kg and 100 mg/kg of INAH, granular degeneration, vacuolar degeneration, desquamation, defects, dissociation and necrosis of the epithelial cells of the urinal tubuli of mice were observed. The degree of these pathological changes became greater in parallel with the increment in the dosis. The degree of the granular degeneration, vacuolar degeneration etc. of the epithelial cells of the urinal tubuli observed in the cases of Tibione, was not found to be proportional to the doses when administered orally. However, when administered subcutaneously, the degree of these changes formed a curve indicating gradual increase with the highest point at 5.0 mg/kg dose.
In the cases of combined INAH-Tibione subcutaneous administrations, the regressive changes in the epithelial cells of the urinal tubuli were found roughly in proportion to the doses of Tibione combined. The granular degeneration in the epithelial cells of the urinal tubuli was considered to be based on the tissue intoxication mechanism, consequently was considered to correspond to the secondary direct type.
The vacuola degeneration was also considered to be originated from the tissue intoxication, and further to the development tc the edema formation mechanism, consequently was considered to be related to the edematous changes of the interstitium. In view of the above, this was considered to be corresponding to the secondary indirect type. Consequently, the author considered that the changes in the kidney of secondary direct and secondary indirect types were co-existing side by side in the present experiments.
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