Summer K H, Klein D, de Ruiter N, Abel J
Institute of Toxicology, Gesellschaft für Strahlen- und Umweltforschung München, Neuherberg, FRG.
Biol Trace Elem Res. 1989 Jul-Sep;21:165-9. doi: 10.1007/BF02917248.
In the present study we report on the effects of commonly used nonsteroidal antiinflammatory drugs on metallothionein (MT) and MT-I mRNA levels. A single dose of chloroquine (100 mg/kg), diclofenac (100 mg/kg), indomethacin (10 mg/kg), or piroxicam (100 mg/kg) was administered ip to C57B1 mice. After 18 h, MT levels were determined with a Cd-saturation radioassay. MT-I mRNA levels were measured by Northern Blot analyses using a probe containing the mouse MT-I gene. All drugs tested caused an increase in the MT content of the liver but not of the kidneys and lung. The lowest and highest effects were observed with chloroquine (8 times the control value) and diclofenac (18 times), respectively. In accordance with the stimulation of MT synthesis, increased accumulation of hepatic MT-I mRNA could be demonstrated. These results indicate that elevated MT levels may contribute to the effectiveness of nonsteroidal antiinflammatory drugs in the treatment of rheumatoid arthritis (RA).
在本研究中，我们报告了常用非甾体抗炎药对金属硫蛋白（MT）和MT-I mRNA水平的影响。给C57B1小鼠腹腔注射单剂量的氯喹（100毫克/千克）、双氯芬酸（100毫克/千克）、吲哚美辛（10毫克/千克）或吡罗昔康（100毫克/千克）。18小时后，用镉饱和放射分析法测定MT水平。使用含有小鼠MT-I基因的探针，通过Northern印迹分析测量MT-I mRNA水平。所有测试药物均导致肝脏中MT含量增加，但肾脏和肺中的MT含量未增加。氯喹（为对照值的8倍）和双氯芬酸（为对照值的18倍）分别观察到最低和最高效应。与MT合成的刺激一致，可以证明肝脏MT-I mRNA的积累增加。这些结果表明，MT水平升高可能有助于非甾体抗炎药治疗类风湿性关节炎（RA）的有效性。
