Effect of Aminotriazole on Isopropanol- and Acetone-Induced Potentiation of CCl4 Hepatotoxicity

1973 ◽  
Vol 51 (4) ◽  
pp. 291-296 ◽  
Author(s):  
George J. Traiger ◽  
Gabriel L. Plaa
Keyword(s):  
Enzyme System ◽  
Hepatic Triglyceride ◽  
Hydroxylase Activity ◽  
Serum Glutamic Pyruvic Transaminase ◽  
Blood Concentrations ◽  
Drug Metabolizing Enzyme ◽  
Triglyceride Content ◽  
Challenging Dose ◽  
Metabolizing Enzyme

The effect of aminotriazole on (1) isopropanol- and acetone-induced potentiation of CCl4 hepatotoxicity, and (2) the in vivo metabolism of isopropanol and acetone was studied in rats. Aminotriazole plus isopropanol, 18 h prior to a challenging dose of CCl4, reduced the isopropanol-enhanced response of CCl4; serum glutamic–pyruvic transaminase (SGPT) activities were less than those found for isopropanol plus CCl4. Hepatic triglyceride content also reflected reduced hepatotoxicity. Aminotriazole pretreatment did not produce any change in the rate of isopropanol elimination nor was the rise and subsequent decline in the blood concentrations of the derived acetone altered. An 18 h pretreatment with acetone enhanced CCl4 hepatotoxicity. Aminotriazole, 15 min prior to acetone, diminished the enhanced response of CCl4 to acetone (reduced SGPT activities and hepatic triglyceride content). Aminotriazole had no effect on acetone elimination from the blood 1, 4, and 8 h after the oral administration of acetone. Aniline hydroxylase activity was increased 17 h after the administration of isopropanol. The data are consistent with the hypothesis that isopropanol augments CCl4 hepatotoxicity by affecting the microsomal drug-metabolizing enzyme system.

scholarly journals ENZYME-MEMBRANE RELATIONSHIP IN PHENOBARBITAL INDUCTION OF SYNTHESIS OF DRUG-METABOLIZING ENZYME SYSTEM AND PROLIFERATION OF ENDOPLASMIC MEMBRANES

1966 ◽  
Vol 28 (2) ◽  
pp. 181-198 ◽  
Author(s):  
Sten Orrenius ◽  
Jan L. E. Ericsson
Keyword(s):  
Actinomycin D ◽  
Enzyme System ◽  
Drug Metabolizing Enzyme ◽  
Induction Process ◽  
Autophagic Activity ◽  
Metabolizing Enzyme ◽  
Parenchymal Cells ◽  
Phenobarbital Induction ◽  
Stimulation Of

The enzyme-membrane relationship in phenobarbital induction of synthesis of drug-metabolizing enzyme system and proliferation of endoplasmic membranes has been further studied. Ultrastructural observations suggest that newly formed endoplasmic membranes in rat liver parenchymal cells arise through continuous outgrowth and budding off from pre-existing cisternae and tubules of rough-surfaced endoplasmic reticulum. The membranes induced by phenobarbital treatment persist in the cytoplasm of the hepatocyte for up to 15 days after the last of a series of 5 phenobarbital injections; the phase of regression of the induced enzymes lasts for only 5 days. Disappearance of the membranes is gradual and does not seem to be associated with increased autophagic activity in the cell. A second series of injections of phenobarbital to previously induced rats—exhibiting normal drug-hydroxylating activity but an excess of liver endoplasmic membranes—is associated with a stimulation of the rate of Pi32 incorporation into microsomal phospholipid in vivo, similar to that found during the original induction process. Administration of Actinomycin D following a single phenobarbital injection delays the regression of the enhanced drug-hydroxylating activity. Finally, the effects of Actinomycin D and puromycin on the stimulated membrane formation are discussed.

Comparison of in vivo and in vitro methods for assessing the effects of phenobarbital on the hepatic drug-metabolizing enzyme system

1985 ◽  
Vol 29 (2-3) ◽  
pp. 95-105 ◽  
Author(s):  
Robert W. Chadwick ◽  
M. Frank Copeland ◽  
Gary P. Carlson ◽  
Bruce A. Trela ◽  
Bernard M. Most
Keyword(s):  
Enzyme System ◽  
Hepatic Drug ◽  
In Vitro Methods ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme

Comparison of in vivo and in vitro methods for assessing the effects of carbon tetrachloride on the hepatic drug-metabolizing enzyme system

1988 ◽  
Vol 42 (3) ◽  
pp. 309-316 ◽  
Author(s):  
Robert W. Chadwick ◽  
M.Frank Copeland ◽  
Gary P. Carlson ◽  
Bruce A. Trela ◽  
Bernard M. Mos
Keyword(s):  
Carbon Tetrachloride ◽  
Enzyme System ◽  
Hepatic Drug ◽  
In Vitro Methods ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme

scholarly journals Generation of tetracycline-controllable CYP3A4-expressing Caco-2 cells by the piggyBac transposon system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Moe Ichikawa ◽  
Hiroki Akamine ◽  
Michika Murata ◽  
Sumito Ito ◽  
Kazuo Takayama ◽  
...  
Keyword(s):  
Small Intestine ◽  
Drug Absorption ◽  
Cell Model ◽  
Negative Effects ◽  
Piggybac Transposon ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Cyp3a4 Expression

AbstractCaco-2 cells are widely used as an in vitro intestinal epithelial cell model because they can form a monolayer and predict drug absorption with high accuracy. However, Caco-2 cells hardly express cytochrome P450 (CYP), a drug-metabolizing enzyme. It is known that CYP3A4 is the dominant drug-metabolizing enzyme in human small intestine. In this study, we generated CYP3A4-expressing Caco-2 (CYP3A4-Caco-2) cells and attempted to establish a model that can simultaneously evaluate drug absorption and metabolism. CYP3A4-Caco-2 cells were generated by piggyBac transposon vectors. A tetracycline-controllable CYP3A4 expression cassette (tet-on system) was stably transduced into Caco-2 cells, thus regulating the levels of CYP3A4 expression depending on the doxycycline concentration. The CYP3A4 expression levels in CYP3A4-Caco-2 cells cultured in the presence of doxycycline were similar to or higher than those of adult small intestine. The CYP3A4-Caco-2 cells had enough ability to metabolize midazolam, a substrate of CYP3A4. CYP3A4 overexpression had no negative effects on cell proliferation, barrier function, and P-glycoprotein activity in Caco-2 cells. Thus, we succeeded in establishing Caco-2 cells with CYP3A4 metabolizing activity comparable to in vivo human intestinal tissue. This cell line would be useful in pharmaceutical studies as a model that can simultaneously evaluate drug absorption and metabolism.

scholarly journals Studies on Metabolism and Disposition of Sizofiran (SPG), an Anti-tumor Polysaccharide. II. Effects on Hepatic Drug-Metabolizing Enzyme System in Rats

1990 ◽  
Vol 110 (2) ◽  
pp. 159-162
Author(s):  
Shohji TANJI ◽  
Kazuo AKIMA ◽  
Minoru YOSHIOKA ◽  
Kazuo NOMURA ◽  
Masahiro HORIBA ◽  
...  
Keyword(s):  
Enzyme System ◽  
Hepatic Drug ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme

Dose-dependent effects of medroxyprogesterone acetate on the hepatic drug-metabolizing enzyme system in rats

1980 ◽  
Vol 29 (8) ◽  
pp. 1155-1159 ◽  
Author(s):  
Hannu Saarni ◽  
Jorma T. Ahokas ◽  
Niilo T. Karki ◽  
Olavi Pelkonen ◽  
Eero A. Sotaniem
Keyword(s):  
Medroxyprogesterone Acetate ◽  
Enzyme System ◽  
Hepatic Drug ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Dose Dependent
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