Dolak J A, Britton R S, Glende E A, Recknagel R O
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106.
J Biochem Toxicol. 1987 Spring;2:57-66. doi: 10.1002/jbt.2570020106.
The effect of chlordecone (CD) on hepatic repair, measured either as recovery of microsomal enzymatic functions or as the induction of cytosolic thymidine kinase (TK) activity, was evaluated in rats given carbon tetrachloride (CCl4). Carbon tetrachloride was administered to CD-potentiated and control animals using doses of this hepatotoxin which produce similar degrees of damage at 24 hours in both groups of animals (6 and 100 microliters CCl4 per 100 g body weight, respectively). Chlordecone had no significant effect on the time course of recovery of microsomal cytochrome P-450 content or glucose-6-phosphatase activity following CCl4 administration. Hepatic TK activity was measured 48 hours after CCl4 administration as a biochemical index of the hepatic regenerative response. Thymidine kinase activity was increased eightfold in CD-treated rats receiving 6 microliters CCl4 per 100 g body weight, whereas in controls a similar induction of TK activity was produced by 100 microliters CCl4 per 100 g body weight. Therefore, the TK response in CD-treated rats receiving CCl4 is appropriate for the amount of damage produced, suggesting that CD does not inhibit the hepatic regenerative response to CCl4-induced injury. The effect of CD on hepatic repair was also examined in rats receiving a two-thirds partial hepatectomy. Pretreatment of animals with CD had no significant effect on the increase in TK activity produced 24 hours after partial hepatectomy. These results offer no support for the idea that CD impairs hepatic repair after either partial hepatectomy or CCl4 administration.
在给大鼠注射四氯化碳（CCl4）的情况下，评估了开蓬（CD）对肝脏修复的影响，评估指标为微粒体酶功能的恢复或胞质胸苷激酶（TK）活性的诱导。分别以能在两组动物中于24小时产生相似损伤程度的该肝毒素剂量（分别为每100克体重6微升和100微升CCl4），给用CD增强的动物和对照动物注射四氯化碳。开蓬对注射CCl4后微粒体细胞色素P - 450含量或葡萄糖 - 6 - 磷酸酶活性的恢复时间进程没有显著影响。在注射CCl4 48小时后测量肝脏TK活性，作为肝脏再生反应的生化指标。在接受每100克体重6微升CCl4的CD处理大鼠中，胸苷激酶活性增加了八倍，而在对照中，每100克体重100微升CCl4产生了类似的TK活性诱导。因此，接受CCl4的CD处理大鼠中的TK反应与所产生的损伤量相符，这表明CD不会抑制肝脏对CCl4诱导损伤的再生反应。还在接受三分之二部分肝切除术的大鼠中研究了CD对肝脏修复的影响。用CD预处理动物对部分肝切除术后24小时产生的TK活性增加没有显著影响。这些结果不支持CD会损害部分肝切除或注射CCl4后肝脏修复的观点。
