Toxicity of ethanol and acetaldehyde in hepatocytes treated with ursodeoxycholic or tauroursodeoxycholic acid.
In hepatocytes ethanol (EtOH) is metabolized to acetaldehyde and to acetate. Ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) are said to protect the liver against alcohol. We investigated the influence of ethanol and acetaldehyde on alcohol dehydrogenase (ADH)-containing human hepatoma cells (SK-Hep-1) and the protective effects of UDCA and TUDCA (0.01 and 0.1 mM). Cells were incubated with 100 and 200 mM ethanol, concentrations in a heavy drinker, or acetaldehyde. Treatment with acetaldehyde or ethanol resulted in a decrease of metabolic activity and viability of hepatocytes and an increase of cell membrane permeability. During simultaneous incubation with bile acids, the metabolic activity was better preserved by UDCA than by TUDCA. Due to its more polar character, acetaldehyde mostly damaged the superficial, more polar domain of the membrane. TUDCA reduced this effect, UDCA was less effective. Damage caused by ethanol was smaller and predominantly at the more apolar site of the cell membrane. In contrast, preincubation with TUDCA or UDCA strongly decreased metabolic activity and cell viability and led to an appreciable increase of membrane permeability. TUDCA and UDCA only in rather high concentrations reduce ethanol and acetaldehyde-induced toxicity in a different way, when incubated simultaneously with hepatocytes. In contrast, preincubation with bile acids intensified cell damage. Therefore, the protective effect of UDCA or TUDCA in alcohol- or acetaldehyde-treated SK-Hep-1 cells remains dubious.
Henzel
Karin
K
Medical Clinic II, Department of Gastroenterology, Center of Internal Medicine, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfort on the Main, Germany. henzel@em.uni-frankfurt.de
Thorborg
Christian
C
Hofmann
Michael
M
Zimmer
Guido
G
Leuschner
Ulrich
U
D000079:Acetaldehyde / Q000633:toxicity*; D000426:Alcohol Dehydrogenase / Q000032:analysis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D000431:Ethanol / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D013655:Taurochenodeoxycholic Acid / Q000378:metabolism* / Q000494:pharmacology; D014580:Ursodeoxycholic Acid / Q000378:metabolism* / Q000494:pharmacology
D000431:Ethanol; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D014580:Ursodeoxycholic Acid; D000426:Alcohol Dehydrogenase; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D000079:Acetaldehyde