Examination of cytochrome P450 content of primary porcine hepatocyte cultures with various media formulations for use in bioartificial liver devices

2002 ◽  
Vol 5 (1) ◽  
pp. 0037-0043 ◽  
Author(s):  
S. A. Keatch ◽  
L. J. Nelson ◽  
J. I. Mason ◽  
P. C. Hayes ◽  
J. N. Plevris
1996 ◽  
Vol 84 (6) ◽  
pp. 1435-1442 ◽  
Author(s):  
Claudia M. Muller ◽  
Annette Scierka ◽  
Richard L. Stiller ◽  
Yong-Myeong Kim ◽  
Ryan D. Cook ◽  
...  

Background Animals subjected to immunostimulatory conditions (sepsis) exhibit decreased total cytochrome P450 content and decreased P450-dependent drug metabolism. Cytochrome P450 function is of clinical significance because it mediates the metabolism of some opioid and hypnotic drugs. The authors tested the hypothesis that reduced P450 function and decreased drug metabolism in sepsis are mediated by endotoxin-enhanced synthesis of nitric oxide. Methods Hepatic microsomes were prepared from male Sprague-Dawley rats in nontreated rats, rats pretreated with phenobarbital and rats receiving aminoguanidine or NG-L-monomethyl-arginine alone. Nitric oxide synthesis was augmented for 12 h with a single injection of bacterial lipopolysaccharides. Nitric oxide synthase was inhibited with aminoguanidine or N(G)-L-monomethyl-arginine during the 12 h of endotoxemia in some animals. Plasma nitrite and nitrate concentrations were measured in vivo, and total microsomal P450 content, and metabolism of ethylmorphine and midazolam in vitro. Results Administration of endotoxin increased plasma nitrite and nitrate concentrations, decreased total cytochrome P450 content, and decreased metabolism of ethylmorphine and midazolam. Inhibition of nitric oxide formation by aminoguanidine or N(G)-L-monomethyl-arginine partially prevented the endotoxin-induced effects in the nontreated and phenobarbital-treated groups. Aminoguanidine or N(G)-L-monomethyl-arginine alone did not have an effect on either total cytochrome P450 content or P450-dependent drug metabolism. Plasma nitrite and nitrate concentrations correlated significantly negatively with P450 content (nontreated r = -0.88, phenobarbital r = -0.91), concentrations of formed formaldehyde (nontreated r = -0.87, phenobarbital r = -0.95), and concentrations of midazolam metabolites (4-OH midazolam nontreated r = -0.88, phenobarbital r = -0.93, and 1'-OH midazolam nontreated r = -0.88, phenobarbital r = -0.97). Conclusions Altered hepatic microsomal ethylmorphine and midazolam metabolism during sepsis is mediated in large part by nitric oxide.


1996 ◽  
Vol 19 (10) ◽  
pp. 605-609 ◽  
Author(s):  
K. Naruse ◽  
Y. Sakai ◽  
I. Nagashima ◽  
G.X. Jiang ◽  
M. Suzuki ◽  
...  

We previously developed a new bioreactor of the bioartificial liver composed of non-woven fabric. We have also experimented with hepatocyte spheroids, with the aim of improving the efficiency of this NWF bioreactor. In this study, we compared the efficiencies of NWF bioreactors employing hepatocyte spheroids versus single hepatocytes. Hepatocytes were isolated from a whole pig liver by Seglen's method. 1.0 × 1010 single hepatocytes were immobilized in the NWF bioreactor. Another 1.0 × 1010 hepatocytes were allowed to form spheroids by 24 hr suspension culture in a 4-L culture vessel, before being immobilized in the bioreactor. Hepatocyte spheroids were found to be functionally superior, on a per-cell basis, to single hepatocytes in the NWF bioreactor. However, the NWF bioreactor employing hepatocyte spheroids exhibited lower efficiency than that employing single hepatocytes, because the total number of the hepatocytes had decreased during the 24 hr suspension culture.


2018 ◽  
Vol 10 (12) ◽  
pp. 780-790
Author(s):  
Shuo Han ◽  
Shiruo Wei ◽  
Xuan Wang ◽  
Xu Han ◽  
Mingzhi Zhang ◽  
...  

Human hepatic C3A cells have been applied in bioartificial liver development, although these cells display low intrinsic cytochrome P450 3A4 (CYP3A4) enzyme activity.


2002 ◽  
Vol 16 (1) ◽  
pp. 71-79 ◽  
Author(s):  
G.C McKay ◽  
C Henderson ◽  
E Goldie ◽  
G Connel ◽  
C Westmoreland ◽  
...  

2019 ◽  
Vol 26 (4) ◽  
Author(s):  
Yi Li ◽  
Harvey S. Chen ◽  
Mohammed Shaheen ◽  
Dong Jin Joo ◽  
Bruce P. Amiot ◽  
...  

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