Wormser U, BenZakine S, Nyska A
Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Biochem Int. 1991 Jan;23(2):419-28.
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.
在大鼠和小鼠中研究了速尿对肝脏和肾脏金属硫蛋白的诱导作用。用200和300mg/kg速尿处理小鼠，肝脏金属硫蛋白分别升高117%和366%，而肾脏金属硫蛋白分别诱导升高29%和380%。在大鼠中，该药物的作用较弱，即分别注射300和400mg/kg速尿后，肝脏金属硫蛋白分别增加167%和217%，而肾脏经此处理后无明显变化。通过Sephadex G-75凝胶过滤（Ve/Vo = 2.0）鉴定小鼠肝脏和肾脏金属硫蛋白为含锌硫蛋白。在两个物种中，暴露后24小时观察到最大诱导。然而，额外24小时后小鼠肝脏和肾脏金属硫蛋白含量下降，而大鼠金属蛋白即使在处理72小时后也未降低。提示金属稳态的改变可能是速尿引起肝脏和肾脏金属硫蛋白诱导的原因。
