Protective effect of sulfhydryl compounds on acute toxicity of morphinone |
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Authors: | Kunisuke Nagamatsu Yasumasa Kido Tadao Terao Takashi Ishida Satoshi Toki |
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Institution: | 1. National Institute of Hygienic Sciences, Setagaya-ku, Tokyo, 158, Japan;2. Faculty of Pharmaceutical Sciences, Fukuoka University Nishi-ku, Fukuoka, 814-01 Japan |
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Abstract: | The ability of sulfhydryl compounds to provide protection against the acute toxicity of morphinone was investigated in mice. Subcutaneous administration of morphinone produced a reduction of hepatic non-protein sulfhydryl concentration. Pretreatments of mice with glutathione or cysteine significantly increased the survival rate of mice given a lethal dose of morphinone, whereas morphinone lethality was markedly potentiated by diethyl maleate. On the other hand, the administration of morphine produced a dose dependent reduction of hepatic non-protein sulfhydryl contents. However, neither glutathione nor cysteine protected mice from the acute toxicity of morphine. A possible explanation for these observations was proposed as follows: morphine is oxidized by morphine 6-dehydrogenase to morphinone, and the morphinone thus produced decreases the sulfhydryl contents in the liver. This mechanism is supported by the fact that morphinone reacts easily with glutathione and cysteine . |
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