Effect of ethanol on the expression of hepatic glutathione S-transferase: an in vivo/in vitro study.
Ethanol, a human toxicant and a solvent in pharmacological research, is known to interfere with biotransformation of xenobiotics. We compared the in vivo and in vitro long-term effects of ethanol exposure on the expression of glutathione S-transferases (GST, EC 2. 5.1.18) in rat liver. Long-term in vivo ethanol treatment to achieve blood ethanol levels ranging between 10-50 mM was by liquid diet feeding. For in vitro experiments, rat hepatocytes co-cultured with rat liver epithelial cells were exposed to 17 and 68 mM ethanol for up to 10 days. Two weeks of liquid diet ethanol treatment increased total GST activity. Both Mu and Alpha classes and in particular the A1 and A2 subunits and the amount of their corresponding mRNAs were increased. Total GST activity was also increased in co-cultures after exposure to 68 mM ethanol for 10 days. However, the Mu class subunits M1 and M2 and the corresponding mRNAs were increased, rather than the Alpha class subunits. Thus, long-term exposure to ethanol induces hepatic GST both in vivo and in vitro, but different isoenzymes are affected. Consequently, extrapolation of in vitro data on GST expression and regulation to the in vivo situation must be judicious. During xenobiotic metabolism in cell culture, a shift in relative expression and induction of different GST forms may occur, resulting in either an under- or overestimation of effects.
Vanhaecke
T
T
Department of Toxicology, Vrije Universiteit Brussel, B-1090, Brussels, Belgium. tamaravh@vub.vub.ac.be
Lindros
K O
KO
Oinonen
T
T
Coecke
S
S
DeBast
G
G
Phillips
I R
IR
Shephard
E A
EA
Vercruysse
A
A
Rogiers
V
V
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D000431:Ethanol; D005982:Glutathione Transferase