Human Liver Slices to Investigate Injury and Repair

2018 ◽  
Vol 4 (3) ◽  
pp. 280-287 ◽  
Author(s):  
Alison E.M. Vickers ◽  
Robyn L. Fisher
2018 ◽  
Vol 19 (12) ◽  
pp. 4130
Author(s):  
Alison E.M. Vickers ◽  
Anatoly V. Ulyanov ◽  
Robyn L. Fisher

Human liver slice function was stressed by daily dosing of acetaminophen (APAP) or diclofenac (DCF) to investigate injury and repair. Initially, untreated human liver and kidney slices were evaluated with the global human U133A array to assess the extended culture conditions. Then, drug induced injury and signals of repair in human liver slices exposed to APAP or DCF (1 mM) were evaluated via specific gene expression arrays. In culture, the untreated human liver and kidney slices remained differentiated and gene expression indicated that repair pathways were activated in both tissues. Morphologically the human liver slices exhibited evidence of repair and regeneration, while kidney slices did not. APAP and DCF exposure caused a direct multi-factorial response. APAP and DCF induced gene expression changes in transporters, oxidative stress and mitochondria energy. DCF caused a greater effect on heat shock and endoplasmic reticulum (ER) stress gene expression. Concerning wound repair, APAP caused a mild repression of gene expression; DCF suppressed the expression of matrix collagen genes, the remodeling metalloproteases, cell adhesion integrins, indicating a greater hinderance to wound repair than APAP. Thus, human liver slices are a relevant model to investigate the mechanisms of drug-induced injury and repair.


Cryobiology ◽  
1991 ◽  
Vol 28 (2) ◽  
pp. 131-142 ◽  
Author(s):  
Robyn Fisher ◽  
Charles W. Putnam ◽  
Lawrence J. Koep ◽  
I.Glenn Sipes ◽  
A.Jay Gandolfi ◽  
...  

1960 ◽  
Vol 38 (1) ◽  
pp. 739-756
Author(s):  
Thomas Sandor ◽  
Wojciech J. Nowaczynski ◽  
Jacques Genest

Surviving dog liver slices were incubated with d,l-aldosterone-21-monoacetate, d,l-aldosterone, d-aldosterone, and d-aldosterone-21-C14. Human liver slices were incubated with d,l-aldosterone-21-monoacetate and d-aldosterone. The incubations were performed in a Krebs–Ringer–phosphate medium (pH 7.4), with 200 mg glucose added per 100 ml of medium, at a temperature of 37 °C. After incubation, the medium was extracted with chloroform and the crude extract extensively fractionated on column and paper chromatographic systems. In addition to free aldosterone, four metabolic products were isolated, two ring A reduced α-ketolic and two ultraviolet absorbing, non-reducing substances. The partial chemical characterization of these metabolites was attempted. The search for aldosterone metabolites in human urine resulted in the isolation of a substance in acetate form from the urine of a patient suffering from primary aldosteronism which may be identical with one of the ring A reduced metabolites obtained in the in vitro experiments.


Hepatology ◽  
2012 ◽  
Vol 56 (3) ◽  
pp. 861-872 ◽  
Author(s):  
Sylvie Lagaye ◽  
Hong Shen ◽  
Bertrand Saunier ◽  
Michelina Nascimbeni ◽  
Jesintha Gaston ◽  
...  

1998 ◽  
Vol 95 ◽  
pp. 99
Author(s):  
C. Lerche-Langrand ◽  
V. Moronvalle-Halley ◽  
D. Chevalier ◽  
D. Hoët ◽  
D. Leroy ◽  
...  

Xenobiotica ◽  
1997 ◽  
Vol 27 (11) ◽  
pp. 1165-1173 ◽  
Author(s):  
B. G. LAKE ◽  
S. E. BALL ◽  
A. B. RENWICK ◽  
J. M. TREDGER ◽  
J. KAO ◽  
...  

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