Hepatic and renal metallothionein induction in the rat and mouse after treatment with furosemide.
Induction of hepatic and and renal metallothionein by furosemide was studied in the rat and mouse. Treatment of mice with 200 and 300 mg/kg furosemide elevated hepatic metallothionein by 117% and 366%, while renal metallothionein was induced by 29% and 380%, respectively. In the rat the drug was less potent i.e. liver metallothionein was increased by 167% and 217% following injection of 300 and 400 mg/kg furosemide, respectively, whereas kidney was not significantly changed by this treatment. The mouse hepatic and renal metallothionein was identified as zinc-containing thionein by Sephadex G-75 gel filtration (Ve/Vo = 2.0). In both species maximal induction was observed 24 hours post exposure. However, the mouse hepatic and renal metallothionein content declined after additional 24 hours whereas the rat metalloprotein was not reduced even after 72 hours of treatment. It is suggested that alterations in metal homeostasis may be responsible for hepatic and renal metallothionein induction caused by furosemide.
Wormser
U
U
Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
BenZakine
S
S
Nyska
A
A
D000818:Animals; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000378:metabolism
D005665:Furosemide; D008668:Metallothionein; D015032:Zinc