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在氧气供应受限情况下,离体灌注大鼠肝脏中的还原性药物代谢。

Reductive drug metabolism in isolated perfused rat liver under restricted oxygen supply.

作者信息

Jonen-Kern R, Jonen H G, Schupp R R, Minck K, Kahl G F, Netter K J

出版信息

Xenobiotica. 1978 May;8(5):271-80. doi: 10.3109/00498257809060950.

DOI:10.3109/00498257809060950
PMID:664749
Abstract
  1. Hepatic azo and nitro reductase activities were studied in the perfused rat liver under normal and restricted oxygen supply. 2. Formation of sulphanilamide or p-aminobenzoic acid from neoprontosil or p-nitrobenzoic acid under aerobic conditions of liver perfusion was negligible, even at a reduced oxygen saturation of a pO2 of 300 mm Hg in the haemoglobinfree perfusion system. At a pO2 of 200 mm Hg reductase activities were almost maximal. 3. Conjugation of sulphanilamide (0-08 mM) was similar under aerobic and anaerobic conditions. Hepatic elimination of p-aminobenzoic acid (0-08 mM) showed an oxygen-dependent increase for 15 min after addition of substrate. 4. p-Nitroanisole demethylation was inhibited 80% under hypoxic perfusion at 200 mm Hg pO2 and was completely inhibited after gassing with anoxic mixtures. 5. Restitution of aerobic conditions after 30 min anaerobic perfusion restored hepatic respiration, lactate pyruvate ratio, and pH value to levels found under aerobic conditions, but bile flow remained 50% reduced.
摘要
  1. 在正常和受限氧气供应条件下,对灌注大鼠肝脏中的肝偶氮还原酶和硝基还原酶活性进行了研究。2. 在肝脏灌注的有氧条件下,即使在无血红蛋白灌注系统中氧饱和度降至pO2为300 mmHg时,新诺明或对硝基苯甲酸形成磺胺或对氨基苯甲酸的量也可忽略不计。在pO2为200 mmHg时,还原酶活性几乎达到最大值。3. 在有氧和无氧条件下,磺胺(0.08 mM)的结合情况相似。添加底物后,肝脏对对氨基苯甲酸(0.08 mM)的清除在15分钟内呈现出氧依赖性增加。4. 在pO2为200 mmHg的低氧灌注条件下,对硝基苯甲醚脱甲基作用受到80%的抑制,在用缺氧混合物通气后则被完全抑制。5. 厌氧灌注30分钟后恢复有氧条件,可使肝脏呼吸、乳酸/丙酮酸比值和pH值恢复到有氧条件下的水平,但胆汁流量仍减少50%。

相似文献

1
Reductive drug metabolism in isolated perfused rat liver under restricted oxygen supply.在氧气供应受限情况下,离体灌注大鼠肝脏中的还原性药物代谢。
Xenobiotica. 1978 May;8(5):271-80. doi: 10.3109/00498257809060950.
2
Enhancement of reductive metabolism of p-nitrobenzoate and nitrazepam in isolated perfused rat liver by ethanol.乙醇对离体灌注大鼠肝脏中对硝基苯甲酸和硝西泮还原代谢的增强作用。
Drug Metab Dispos. 1979 May-Jun;7(3):176-80.
3
The continuous kinetic determination of p-nitroanisole O-demethylation in hemoglobin-free perfused rat liver.在无血红蛋白灌注大鼠肝脏中对4-硝基苯甲醚O-去甲基化进行连续动力学测定。
J Pharmacol Exp Ther. 1977 May;201(2):498-506.
4
Role of reducing equivalents from fatty acid oxidation in mixed-function oxidation: studies with 2-bromooctanoate in the perfused rat liver.脂肪酸氧化产生的还原当量在混合功能氧化中的作用:用2-溴辛酸酯对灌注大鼠肝脏进行的研究。
J Pharmacol Exp Ther. 1981 Nov;219(2):383-8.
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Stimulation of p-nitroanisole O-demethylation by ethanol in perfused livers from fasted rats.禁食大鼠灌流肝脏中乙醇对对硝基苯甲醚O-去甲基化的刺激作用。
J Pharmacol Exp Ther. 1979 Oct;211(1):133-9.
6
Enhancement of nitro reduction in rat liver microsomes by haemin and haemoproteins.血红素和血红蛋白对大鼠肝微粒体中硝基还原的增强作用。
Xenobiotica. 1978 May;8(5):281-8. doi: 10.3109/00498257809060951.
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[Dinitroorthocresol dissociation of oxidative phosphorylation in the rat liver perfused in situ].[二硝基邻甲酚对原位灌注大鼠肝脏氧化磷酸化的解离作用]
Ukr Biokhim Zh. 1976 Mar-Apr;48(2):200-5.
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p-Nitroanisole O-demethylation in perfused hamster liver. High rates of pentose cycle-independent mixed-function oxidation.灌注仓鼠肝脏中的对硝基苯甲醚O-去甲基化。戊糖循环非依赖性混合功能氧化的高发生率。
Biochem Pharmacol. 1984 Apr 15;33(8):1315-21. doi: 10.1016/0006-2952(84)90186-2.
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Unique role of oxygen in regulation of hepatic monooxygenation and glucuronidation.
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Oxygen dependence of omeprazole clearance and sulfone and sulfide metabolite formation in the isolated perfused rat liver.奥美拉唑清除率及砜和硫化物代谢产物形成在离体灌注大鼠肝脏中的氧依赖性
J Pharmacol Exp Ther. 1989 Sep;250(3):1043-7.

引用本文的文献

1
Reductive and oxidative metabolism of nitrofurantoin in rat liver.呋喃妥因在大鼠肝脏中的还原代谢和氧化代谢。
Naunyn Schmiedebergs Arch Pharmacol. 1980;315(2):167-75. doi: 10.1007/BF00499260.
2
Relationship between alveolar PO2 and the rate of p-nitroanisole O-demethylation by the cytochrome P-450 pathway in isolated rabbit lungs.离体兔肺中细胞色素P-450途径介导的对硝基苯甲醚O-去甲基化速率与肺泡氧分压之间的关系。
J Clin Invest. 1979 Sep;64(3):770-4. doi: 10.1172/JCI109522.