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Decrease in hepatic drug-metabolizing enzyme activities after removal of rats from pine bedding

机译:从松床上褥中取出大鼠后,肝脏药物代谢酶活性的降低

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Wood is often used as a contact bedding material for laboratory animals. It has been established that wood, particularly softwood, has the potential to induce hepatic drug-metabolizing enzymes. However, to the authors' knowledge, changes in enzyme activity after removal of animals from bedding have not been characterized. The purpose of the study reported here was to determine how hepatic ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylation activities alter over time after removal of rats from pine bedding. Male rats, three to four months old, raised in cages containing pine bedding, were transferred to wire-bottomed cages. At various times thereafter (up to 84 days), groups of rats were euthanized and the liver was processed to obtain microsomes. The microsomal protein and total cytochrome P450 (CYP) content and enzyme activities were determined. Significant differences in total microsomal protein or total CYP values were not observed over the 84 days, but a decrease in ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylation activities was detected. For p-nitrophenol hydroxylation, the decrease was exponential, with a half-life of approximately nine days, whereas for ethoxyresorufin-O-deethylation, a rapid decrease in activity in the first week was followed by a reduced rate of decrease thereafter. Enzyme activities did not stabilize for at least six weeks. Researchers using laboratory animals should, therefore, be aware that it takes several weeks for enzyme activities to stabilize once animals are removed from the bedding.
机译:木材通常用作实验动物的接触垫料。已经确定的是,木材,特别是针叶木材,具有诱导肝药物代谢酶的潜力。然而,据作者所知,动物从被褥中移出后酶活性的变化尚未得到表征。此处报道的研究目的是确定从松床上褥中取出大鼠后,肝乙氧基间苯二酚-O-脱乙基和对硝基苯酚羟基化活性如何随时间变化。将三至四个月大的雄性大鼠饲养在装有松木被褥的笼子中,将其转移到金属丝网笼中。此后的不同时间(最多84天),对各组大鼠实施安乐死,并对肝脏进行处理以获得微粒体。测定了微粒体蛋白和总细胞色素P450(CYP)含量以及酶活性。在84天中未观察到总微粒体蛋白或总CYP值的显着差异,但检测到乙氧基异佛手菌素-O-脱乙基化和对硝基苯酚羟基化活性降低。对硝基苯酚羟基化反应呈指数下降,半衰期约为9天,而乙氧基间苯二酚-O-脱乙基化反应在第一周活性迅速下降,随后下降速率下降。酶活性至少六周未稳定下来。因此,使用实验动物的研究人员应该意识到,一旦将动物从被褥中取出,酶的活性就需要数周才能稳定下来。

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