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苯巴比妥对兔肾混合功能氧化酶的诱导作用:近端小管的细胞特异性超微结构变化

Induction of rabbit renal mixed-function oxidases by phenobarbital: cell specific ultrastructural changes in the proximal tubule.

作者信息

Rush G F, Maita K, Sleight S D, Hook J B

出版信息

Proc Soc Exp Biol Med. 1983 Apr;172(4):430-9. doi: 10.3181/00379727-172-41583.

DOI:10.3181/00379727-172-41583
PMID:6844353
Abstract

Administration of phenobarbital (60 mg/kg) daily for 4 days to male rabbits resulted in induction of renal cytochrome P-450 (3.5-fold) and a corresponding increase in ethoxycoumarin-O-deethylase and benzphetamine-N-demethylase activity (17- and 4-fold, respectively). Kidney weight to body weight ratio and renal ethoxyresorufin-O-deethylase were not affected by phenobarbital pretreatment. Numerous focal areas of proliferation of smooth endoplasmic reticulum (SER) were evident in proximal tubule cells from phenobarbital treated rabbits while proximal tubular cells from control rabbits had only small and sparcely located aggregates of SER. Phenobarbital-induced SER proliferation was specifically localized to the S3 segment of the proximal tubule. Proliferation was not observed in S2 cells of the proximal tubule, cells of Henle's loop, distal tubules, or collecting tubules in rabbits pretreated with phenobarbital. These data demonstrate the biochemical heterogeneity of cell types within the proximal tubules of rabbits. Furthermore, induction of mixed-function oxidases specifically in S3 cells of the proximal tubule may be of toxicological significance in the metabolic activation of certain nephrotoxicants.

摘要

对雄性兔子每日给予苯巴比妥(60毫克/千克),持续4天,可诱导肾脏细胞色素P - 450(增至3.5倍),并相应增加乙氧香豆素 - O - 脱乙基酶和苄非他明 - N - 脱甲基酶活性(分别增至17倍和4倍)。苯巴比妥预处理对肾脏重量与体重之比以及肾脏乙氧试卤灵 - O - 脱乙基酶没有影响。在经苯巴比妥处理的兔子的近端小管细胞中,可见许多光滑内质网(SER)增殖的局灶性区域,而对照兔子的近端小管细胞仅有少量且分布稀疏的SER聚集体。苯巴比妥诱导的SER增殖特异性地定位于近端小管的S3段。在用苯巴比妥预处理的兔子中,未在近端小管的S2细胞、髓袢细胞、远端小管或集合小管中观察到增殖。这些数据证明了兔子近端小管内细胞类型的生化异质性。此外,在近端小管的S3细胞中特异性诱导混合功能氧化酶可能对某些肾毒物的代谢活化具有毒理学意义。

相似文献

1
Induction of rabbit renal mixed-function oxidases by phenobarbital: cell specific ultrastructural changes in the proximal tubule.苯巴比妥对兔肾混合功能氧化酶的诱导作用:近端小管的细胞特异性超微结构变化
Proc Soc Exp Biol Med. 1983 Apr;172(4):430-9. doi: 10.3181/00379727-172-41583.
2
Induction of renal mixed function oxidases in the rat and mouse: correlation with ultrastructural changes in the proximal tubule.大鼠和小鼠肾混合功能氧化酶的诱导:与近端小管超微结构变化的相关性。
Fundam Appl Toxicol. 1986 Feb;6(2):307-16. doi: 10.1016/0272-0590(86)90245-9.
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Renal cortical accumulation of phenobarbital in rats and rabbits: lack of correlation with induction of renal microsomal monooxygenases.苯巴比妥在大鼠和兔子肾皮质中的蓄积:与肾微粒体单加氧酶诱导缺乏相关性。
J Pharmacol Exp Ther. 1982 Mar;220(3):547-51.
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Induction of renal and hepatic mixed function oxidases in the hamster and guinea pig.
Toxicology. 1986 Feb;38(2):209-18. doi: 10.1016/0300-483x(86)90122-8.
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Distribution and some characteristics of cytochrome P-450 in the kidney.细胞色素P-450在肾脏中的分布及一些特性
J Toxicol Sci. 1983 Aug;8(3):165-76. doi: 10.2131/jts.8.165.
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Biological and induction effects of phenobarbital and 3-methylcholanthrene in mink (Mustela vison).苯巴比妥和3-甲基胆蒽对水貂(鼬属)的生物学及诱导效应
Drug Metab Dispos. 1983 Sep-Oct;11(5):441-5.
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Effects of lipid ingestion on the induction of drug metabolizing enzymes of nuclear envelope and microsomes by phenobarbital.脂质摄入对苯巴比妥诱导核膜和微粒体药物代谢酶的影响。
J Environ Pathol Toxicol. 1980 Aug;4(1):219-35.
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Species differences in stimulation of intestinal and hepatic microsomal mixed-function oxidase enzymes.肠道和肝脏微粒体混合功能氧化酶的刺激作用中的物种差异。
Biochem Pharmacol. 1980 Apr 15;29(8):1161-5. doi: 10.1016/0006-2952(80)90412-8.
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[Effect of age on the activity of hepatic mixed function oxidases in female rats after phenobarbital induction].[苯巴比妥诱导后年龄对雌性大鼠肝脏混合功能氧化酶活性的影响]
Med Pr. 1988;39(6):381-90.
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Pulmonary cytochromes P-450 from rabbits treated with phenobarbital.用苯巴比妥处理的家兔的肺细胞色素P-450
Pharmacology. 1985;31(1):40-9. doi: 10.1159/000138096.

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