STUDIES ON NITROSAMINE FORMATION BY THE INTERACTION BETWEEN DRUGS AND NITRITE. II. : Hepatotoxicity by the simultaneous administration of several drugs and nitrite.

元データ 1981-11-25 日本トキシコロジー学会

概要

The alterations of biochemical parameters, namely, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in serum, hepatic microsomal drug oxidation systems, glucose-6-phosphate dehydrogenase and lysozomal enzymes in hepatic soluble fraction were investigated for the purpose of semiquantitatively estimating the hepatotoxicity caused by the interaction of several drugs and sodium nitrite in rats. The simultaneous administration of aminopyrine and sodium nitrite induced the alterations of these parameters. However, these alterations were not induced by the administration of antipyrine and sodium nitrite. Therefore the alterations were thought to be mainly due to N-nitrosodimethylamine formed. The administration of 0.4 mmole/kg of aminopyrine and 1.0 mmole/kg of sodium nitrite was thought to induce the alterations to almost the same extent as induced by 0.15 mmole/kg of N-nitrosodimethylamine. The simultaneous administrations of sodium nitrite and several other drugs with tertiary amino groups, namely, oxytetracycline, diphenhydramine, oleandomycin, erythromycin and minocycline induced small alterations of these parameters. However, these alterations were not thought to relate to the hepatic injury induced by N-nitrosodimethylamine. Therefore the amount of N-nitrosodimethylamine formed from these drugs in rats was thought to be rather small. We also investigated the effect of several antioxidants on the alterations of biochemical parameters induced by aminopyrine and sodium nitrite. Ascorbic acid, sodium erythorbate and propyl gallate inhibited these alterations. On the other hand, sorbic acid did not.

著者

Ohno Yasuo National Institute of Health Sciences
Ohno Yasuo Div. Of Pharmacology Biological Safty Research Center National Institute Of Hygienic Sciences
Kawanishi Toru Div. Of Drugs National Inst. Of Health Sci. Jpn
Kawanishi T 大妻女子大学 食物学科
Kawanishi T Division Of Drugs National Institute Of Health Science
Kawanishi Toru National Institute Of Health Sciences
TAKAHASHI Atsushi National Institute of Hygienic Sciences
OMORI Yoshihito National Institute of Hygienic Sciences
Takahashi Atsushi Division Of Pharmacology National Institute Of Hygienic Sciences
KASUYA YUTAKA Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo
KOBAYASI TADASHI Kobe Pharmaceutical University
Kasuya Y Hoshi Univ. Tokyo Jpn
Kawanishi Toru Division Of Drugs National Institute Of Health Science
Kawanishi Toru 国立医薬品食品衛生研究所
TAKANAKA Akira The Organization for Pharmaceutical Safety and Research
Kasuya Yutaka Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokyo
Onoda Kin-ichi National Institute Of Hygienic Sciences Biological Safety Research Center Division Of Pharmacology
Takanaka Akira Division Of Pharmacology Bsrc National Institute Of Hygienic Sciences
Takanaka A National Inst. Hygienic Sciences Tokyo Jpn
Takahashi Atsushi National Institute Of Health Sciences
Sunouchi Momoko Div. Pharmacol. Natl. Inst. Health Sci.
Kawanishi Toru Division Of Pharmacology National Institute Of Hygienic Sciences
SUNOUCHI Momoko National Institute of hygienic sciences, Biological Safety Research Center Division of Pharmacology
Sunouchi Momoko Division Of Pharmacology National Institute Of Hygienic Sciences
Ohno Yasuo National Inst. Of Health Sci. Tokyo Jpn
Takahashi A Division Of Pharmacology Bsrc National Institute Of Hygienic Sciences
Takahashi Atsushi National Institute Of Advanced Industrial Science And Technology
Sunouchi Momoko National Institute Of Hygienic Sciences Biological Safety Research Center Division Of Pharmacology

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