Induction of metallothionein synthesis by glutathione depletion after trans- and cis-stilbene oxide administration in rats.
To investigate the relationship between glutathione (GSH) depletion and metallothionein (MT) synthesis, the effects of substrates and an inhibitor of GSH S-transferases on concentrations of hepatic GSH, zinc (Zn) and MT were studied in rats. Trans-stilbene oxide (TSO) is an inducer of drug metabolizing enzymes and also a substrate of GSH S-transferase, whereby it covalently reacts with and depletes GSH. The hepatic GSH level was decreased to 25% of the control 2 h after injection of TSO, and returned to the control level by 24 h. TSO significantly increased hepatic concentrations of Zn and MT in a dose-dependent manner. Two isoforms of MT (MT-I and MT-II) were increased by TSO; MT-II was the dominant form. Pretreatment with buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, enhanced MT synthesis itself as well as that induced by TSO and cis-stilbene oxide (CSO). On the contrary, infection into rats of perfluorodecanoic acid (PFDA), an inhibitor of GSH S-transferase, resulted in a decrease in basal levels of Zn, and prevented the increase in MT synthesis by TSO and CSO. These results suggest that the decrease of GSH concentration in the liver which causes oxidative stress conditions may be related to MT induction.
Sato
M
M
Department of Biomolecular Sciences, Fukushima Medical College, Japan.
Sasaki
M
M
Oguro
T
T
Kuroiwa
Y
Y
Yoshida
T
T
D000818:Animals; D019328:Buthionine Sulfoximine; D003652:Decanoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005466:Fluorocarbons / Q000494:pharmacology; D005978:Glutathione / Q000502:physiology*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000235:genetics; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism
D003652:Decanoic Acids; D004791:Enzyme Inhibitors; D005466:Fluorocarbons; D012333:RNA, Messenger; D013267:Stilbenes; D008717:Methionine Sulfoximine; C036567:perfluorodecanoic acid; D019328:Buthionine Sulfoximine; D008668:Metallothionein; D005982:Glutathione Transferase; D005978:Glutathione; D015032:Zinc; C025906:stilbene oxide