scholarly journals The acylation of proteins by xenobiotic amphipathic carboxylic acids in cultured rat hepatocytes

1988 ◽  
Vol 254 (1) ◽  
pp. 39-44 ◽  
Author(s):  
R Hertz ◽  
J Bar−Tana
Keyword(s):  
Protein Synthesis ◽  
Carboxylic Acids ◽  
Mode Of Action ◽  
Biological Effects ◽  
Rat Hepatocytes ◽  
Protein Adducts ◽  
Cultured Rat Hepatocytes ◽  
Acylated Proteins ◽  
Dose Dependent ◽  
Protein Acylation

Three xenobiotic amphipathic carboxylates, namely MEDICA 16, nafenopin and bezafibrate, which differ remarkably in their hydrophobic backbones, were found to acylate membrane and cytosolic liver proteins in cultured rat hepatocytes. The acylation patterns observed were time- and dose-dependent, and the acylated residue consisted of the original xenobiotic. The acylation patterns generated by the three xenobiotic carboxylates included common proteins which were acylated by the three xenobiotics (e.g. proteins of 32, 52, 56 and 72 kDa) as well as unique proteins which were specifically acylated by the respective xenobiotics. The acylation of liver proteins by either MEDICA 16 or nafenopin remained unaffected under conditions where protein synthesis was completely inhibited by cycloheximide. Protein acylation thus offers a common mode of action of xenobiotic amphipathic carboxylates, which may, however, result in diverse xenobiotyl-protein adducts. The xenobiotyl-acylated proteins might be involved in triggering some of the biological effects exerted by xenobiotic amphipathic carboxylates employed as hypolipidaemic effectors, peroxisomal proliferators or preadipocyte convertors.

scholarly journals Although it is rapidly metabolized in cultured rat hepatocytes, lauric acid is used for protein acylation

2003 ◽  
Vol 43 (5) ◽  
pp. 419-430 ◽  
Author(s):  
Vincent Rioux ◽  
Stéphanie Daval ◽  
Hervé Guillou ◽  
Sophie Jan ◽  
Philippe Legrand
Keyword(s):  
Lauric Acid ◽  
Rat Hepatocytes ◽  
Cultured Rat Hepatocytes ◽  
Protein Acylation

Involvement of Reactive Metabolites of Diclofenac in Cytotoxicity in Sandwich-Cultured Rat Hepatocytes

2017 ◽  
Vol 36 (3) ◽  
pp. 260-267 ◽  
Author(s):  
Atsushi Kawase ◽  
Ryota Hashimoto ◽  
Mai Shibata ◽  
Hiroaki Shimada ◽  
Masahiro Iwaki
Keyword(s):  
Lactate Dehydrogenase ◽  
Rat Hepatocytes ◽  
Protein Adducts ◽  
Reactive Metabolites ◽  
Uridine Diphosphate ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Protein Adduct ◽  
Acute Cytotoxicity ◽  
Cultured Rat Hepatocytes

Background and Objectives: Diclofenac (DIC) is metabolized to reactive metabolites such as diclofenac acyl-β-d-glucuronide (DIC-AG). It is possible that such reactive metabolites could cause tissue damage by formation of covalent protein adducts and other modification of cellular proteins or by induction of immune responses against its covalent protein adducts. However, the detailed mechanisms of idiosyncratic drug-induced liver injury (DILI) have been unclear. The objective is to clarify the involvement of DIC-AG and 4′hydroxydiclofenac (4′OH-DIC) in acute DILI. Methods: We examined the effects of inhibiting DIC-AG and 4′OH-DIC production on covalent protein adduct formation and lactate dehydrogenase leakage using sandwich-cultured rat hepatocytes (SCRHs). Results: After pretreatment of SCRH with (−)-borneol (BOR, a uridine diphosphate (UDP)-glucuronosyltransferase inhibitor) or sulfaphenazole (SUL, a cytochrome P450 2C9 inhibitor) for 30 minutes, intracellular concentrations of DIC, DIC-AG, and 4′OH-DIC were determined after further treating cells with 300 μM DIC for 3 hours. The decreased levels of reactive metabolites caused by BOR or SUL pretreatment resulted in decreased lactate dehydrogenase leakage from SCRH, although the formation of covalent protein adducts was not affected. Conclusion: These results suggested that both DIC-AG and 4′OH-DIC may be involved in acute cytotoxicity by DIC.

scholarly journals The Effect of Laurel Leaf Extract Against Toxicity Induced by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin in Cultured Rat Hepatocytes

2011 ◽  
Vol 62 (4) ◽  
pp. 309-315 ◽  
Author(s):  
Hasan Turkez ◽  
Fatime Geyikoglu
Keyword(s):  
Dna Damage ◽  
Cell Viability ◽  
Leaf Extract ◽  
Antioxidant Properties ◽  
Rat Hepatocytes ◽  
Toxic Effects ◽  
Dependent Manner ◽  
Cultured Rat Hepatocytes ◽  
Tetrachlorodibenzo P Dioxin ◽  
Dose Dependent

The Effect of Laurel Leaf Extract Against Toxicity Induced by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin in Cultured Rat Hepatocytes2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a very toxic environmental pollutant that raises great public concern about its impact on human health. Recent studies indicate that laurel leaf extract exhibits antioxidant properties that can counter the toxic effects of certain compounds in the liver. The aim of this study was to assess how effective LE is against the toxicity of TCDD in a primary culture of rat hepatocytes. The extract (50 mg L-1, 100 mg L-1, and 200 mg L-1) was added to cultures alone or with TCDD (1.61 mg L-1 and 3.22 mg L-1) for 48 hours. Cell viability was measured using the [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and the lactate dehydrogenase (LDH) cytotoxicity assay, while oxidative damage was assessed by measuring total antioxidant capacity (TAC) and total oxidative stress (TOS). DNA damage was also analysed using the micronucleus (MN) assay of the cultured hepatocytes. TCDD alone lowered, and laurel extract had no effect on cell viability. TCDD also increased TOS and significantly decreased TAC. It significantly increased the frequency of micronucleated hepatocytes in a dose-dependent manner. In cultures exposed to LE alone, TOS did not change and TAC significantly increased in a dose-dependent manner. Added to TCDD, laurel countered its toxic effects and showed protective effects against TCDD-mediated DNA damage. This points to the therapeutic potential of laurel against TCDD toxicity in the liver.

Amiloride blocks cell-free protein synthesis at levels attained inside cultured rat hepatocytes

1982 ◽  
Vol 108 (2) ◽  
pp. 738-745 ◽  
Author(s):  
H.L. Leffert ◽  
K.S. Koch ◽  
M. Fehlmann ◽  
W. Heiser ◽  
P.J. Lad ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Rat Hepatocytes ◽  
Free Protein ◽  
Cultured Rat Hepatocytes ◽  
Cell Free Protein Synthesis

scholarly journals Evidence that ligand formation is a mechanism underlying the maintenance of cytochrome P-450 in rat liver cell culture. Potent maintenance by metyrapone

1980 ◽  
Vol 188 (3) ◽  
pp. 937-939 ◽  
Author(s):  
A J Paine ◽  
P Villa ◽  
L J Hockin
Keyword(s):  
Cell Culture ◽  
Protein Synthesis ◽  
Rat Liver ◽  
Liver Cell ◽  
Rat Hepatocytes ◽  
Liver Cell Culture ◽  
Substituted Pyridines ◽  
Cultured Rat Hepatocytes ◽  
Highly Correlated ◽  
Cytochrome P 450

The loss of cytochrome P-450 in cultured rat hepatocytes can be prevented by substituted pyridines, especially isonicotinamide, 3-hydroxypyridine and metyrapone. The effect of these compounds is independent of protein synthesis, suggesting that they maintain pre-existing cytochrome P-450. The efficiency of pyridines at maintaining cytochrome P-450 in hepatocyte culture is highly correlated with their ability to bind to this cytochrome, suggesting that ligand formation with cytochrome P-450 prevents its accelerated turnover in liver cell culture.

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