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标题：Comparative Studies on the Inducing Effects of Cobalt Chloride and Co-Protoporphyrin on Hepatic Ornithine Decarboxylase and Heme Oxygenase in Rats
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作者：Satoshi NUMAZAWA ; Takiko OGURO ; Takemi YOSHIDA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1989
卷号：12
期号：1
页码：50-59
DOI：10.1248/bpb1978.12.50
出版社：The Pharmaceutical Society of Japan
摘要：Co-protoporphyrin, like Co²⁺, produced a significant and persistent induction of hepatic ornithine decarboxylase (ODC) as well as its known inducing effect on heme oxygenase and the decreasing effects on drug-metabolizing enzymes. The induction of ODC and heme oxygenase by Co-protoporphyrin occurred dose-dependently with the lowest effective dose of 6.25 μmol/kg. Although Co-protoporphyrin produced similar effects on ODC and heme oxygenase to Co²⁺, there were differences in the mode of ODC induction. In particular, pretreatment with diethyl maleate failed to augment the induction of ODC by Co-protoporphyrin. Moreover, multiple administrations of Co²⁺, but not Co-protoporphyrin, caused super-addtive induction of ODC to about 1000-fold over the controls. This super-additive induction of ODC by Co²⁺ was dependent on the doses and time intervals between two administrations. In parallel with a large induction of ODC evoked by two administrations of Co²⁺, hepatic putrescine content was increased markedly, while spermine content was decreased as compared to the control levels. Pretreatment with Co²⁺ led to super-additive induction of ODC by subsequent administration of the metal ion itself or diethyl maleate, but not by other ODC inducers, such as Co-protoporphyrin and thioacetamide, and not by subsequent partial hepatectomy. Under these experimental conditions, the magnitudes of heme oxygenase induction were similar. ODC induced by two doses of Co²⁺ was insensitive to exogenous putrescine, but sensitive to α-difluoromethylornithine and 1, 3-diaminopropane. These findings add new insight into the effects of Co²⁺ and Coprotoporphyrin on hepatic polyamine metabolism ; and the results suggest that the metal ion could cause extensive derangement of the ODC regulatory system in a manner different from the metalloporphyrin.
关键词：polyamine