Heilmaier H E, Jiang J L, Greim H, Schramel P, Summer K H
Toxicology. 1986 Dec 1;42(1):23-31. doi: 10.1016/0300-483x(86)90089-2.
Intraperitoneal injection of D-Penicillamine (D-PA) at a dose range of 20-500 mg/kg increased rat hepatic but not renal and pancreatic metallothionein (MT). Elevated MT predominantly contained Zn. Maximal induction was obtained 18 h after a single injection of 200 mg D-PA/kg resulting in 148 +/- 18 micrograms MT/g liver which was 16.4-times the control level of 9 +/- 2 micrograms MT/g. At 48 h after injection, MT declined to 18 +/- 9 micrograms MT/g liver. At maximal MT increase the content of total hepatic Zn but not of Cu was elevated. Increased amounts of Zn in liver homogenate, cytosol and MT could be detected approximately 4 h after injection of 200 mg D-PA/kg. Concomitantly there was a decrease in Zn bound to cytosolic non-MT ligands. All Zn changes reversed at 18 h. These data show that already single doses of D-PA cause induction of Zn-thionein in rat liver and lead to synchronous redistribution of Zn from endogenous sources to newly synthesized MT.
腹腔注射剂量范围为20 - 500毫克/千克的D-青霉胺（D-PA）可增加大鼠肝脏中的金属硫蛋白（MT），但不会增加肾脏和胰腺中的MT。升高的MT主要含有锌。单次注射200毫克D-PA/千克后18小时可获得最大诱导效果，导致肝脏中MT含量达到148±18微克/克，是对照组9±2微克/克水平的16.4倍。注射后48小时，MT降至18±9微克/克肝脏。在MT增加到最大值时，肝脏中总锌含量升高，但铜含量未升高。注射200毫克D-PA/千克后约4小时，可检测到肝脏匀浆、细胞溶质和MT中的锌含量增加。与此同时，与细胞溶质中非MT配体结合的锌减少。所有锌的变化在18小时时逆转。这些数据表明，单剂量的D-PA就可诱导大鼠肝脏中锌硫蛋白的产生，并导致锌从内源性来源同步重新分布到新合成的MT中。
