Proliferative response and renewal of hepatic function following cocaine administration in mice.
Proliferative response and renewal of hepatic function following cocaine administration in mice.
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小鼠给予可卡因后的增殖反应和肝功能更新。
DOI：
10.1111/j.1365-2184.1984.tb00577.x
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Rosen,GM
中科院分区：
文献类型：
--
作者：
Padilla,GM;Kloss,MW;Rauckman,EJ;Rosen,GM
进行实验，以调查单次注射可卡因（一种已知的肝毒素）后事件的肝脏、时间和空间序列。注射后（PI）24小时，在雄性小鼠（DBA/2 Ha）中诱导小叶中心坏死。通过测定微粒体细胞色素P450含量、微粒体含FAD-单加氧酶（FAD-M）的活性和测定血清谷丙转氨酶（SGPT）水平来监测肝损伤的时间过程。通过肝薄切片的放射自显影和3 H-甲基胸苷掺入高氯酸沉淀物质来确定DNA合成开始的动力学。在PI的前24小时，标记指数（LI）和胸苷（TdR）掺入没有增加。LI上升至14.6%，TdR掺入显示比对照值增加5倍（48小时PI）。这两个指数在PI 72小时略有下降，并在PI 96小时恢复到对照值。相比之下，细胞色素P450含量下降69%，FAD-M活性下降40%，SGPT水平在PI 24 h时增加18倍，与坏死的细胞学体征一致。虽然这些选定的酶之间的恢复模式不同，正常值达到96小时PI。这些结果表明，细胞损伤和肝功能障碍先于DNA合成和随后的增殖的开始。
Experiments were undertaken to investigate the hepatic, temporal and spatial sequence of events following a single injection of cocaine, a known hepatotoxin. Centrilobular necrosis was induced in male mice (DBA/2Ha) 24 hr post‐injection (PI). the time course of hepatic damage was monitored by assaying microsomal cytochrome P450content, the activity of microsomal FAD‐containing monooxygenase (FAD‐M) and by determining the levels of serum glutamic pyruvic transaminase (SGPT). Kinetics of the onset of DNA synthesis were determined by autoradiography of thin liver sections and the incorporation of3H‐methyl thymidine into perchloric‐acid‐precipitable material. There was no increase in the labelling index (LI) and thymidine (TdR) incorporation in the first 24 hr PI. the LI rose to 14.6% and TdR incorporation showed a 5‐fold increase over control values 48 hr PI. Both indices declined slightly at 72 hr PI and returned to control values by 96 hr PI. In contrast, the cytochrome P450content declined by 69%, the FAD‐M activity dropped by 40% and the SGPT levels showed an 18‐fold increase at 24 hr PI, coincident with cytological signs of necrosis. Although the patterns of recovery differed between these selected enzymes, normal values were attained by 96 hr PI. These results demonstrate that cell damage and hepatic dysfunction precede the onset of DNA synthesis and subsequent proliferation.