Small human hepatocytes in rotary culture for treatment of alcohol addicts? A pilot study.
BACKGROUND
Current approaches to support alcohol addict and/or benzodiazepine-treated patients with liver failure include culturing human cells to take over basic metabolic functions for a certain time.


METHODS
Small human hepatocytes (SH) were grown in a rotary cell culture system, and their potential to metabolize alcohol and the benzodiazepines oxazepam and diazepam was evaluated. Control experiments were performed with SV40-immortalized HEP cells and cell respective drug-free media.


RESULTS
Our results show that SH in rotary culture are able to metabolize ethanol in reasonable amounts compared with evaporation controls (p<0.01). Moreover, SH are also able to metabolize oxazepam and diazepam which proves their ability to perform conjugation and the presence of functional cytochrome P450 enzymes. Basic metabolic activities such as glucose consumption, albumin and urea production are not significantly influenced by the drugs used, which is a precondition for clinical use of these cells. Significantly increased lactate dehydrogenase release indicates enhanced cell death in cultures of SH incubated with either ethanol (p<0.05) or diazepam (p<0.005), but stable viability at or above 90% suggests that cell proliferation is able to keep up with drug-induced cell death.


CONCLUSIONS
Our preliminary study provides evidence that SH are basically suited to support alcohol-abusing and/or benzodiazepine-treated patients undergoing liver failure.
Pavlic
Marion
M
Institute of Legal Medicine, Innsbruck Medical University, Innsbruck, Austria. marion.pavlic@i-med.ac.at
Libiseller
Kathrin
K
Hermann
Martin
M
Hengster
Paul
P
Margreiter
Raimund
R
Wurm
Martin
M
D000437:Alcoholism / Q000378:metabolism* / Q000628:therapy*; D002452:Cell Count; D018929:Cell Culture Techniques; D002460:Cell Line; D003470:Culture Media; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism* / Q000637:transplantation; D006801:Humans; D006993:Hypnotics and Sedatives / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000096:biosynthesis; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000628:therapy; D019164:Liver, Artificial; D018613:Microscopy, Confocal; D010076:Oxazepam / Q000378:metabolism; D010865:Pilot Projects; D014508:Urea / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
D003470:Culture Media; D006993:Hypnotics and Sedatives; D015262:Xenobiotics; D019344:Lactic Acid; D010076:Oxazepam; D014508:Urea; D003577:Cytochrome P-450 Enzyme System; D007770:L-Lactate Dehydrogenase; D003975:Diazepam