Dietz F K, Traiger G J
Toxicology. 1979 Nov;14(3):209-15. doi: 10.1016/0300-483x(79)90003-9.
The role of ketaone metabolism in 2-butanone-induced potentiaion of carbon tetrachloride (CCl4) hepatotoxicity was studied in rats. The blood concentrations of 2-butanol, 3-hydroxy-2-butanone and 2,3-butanediol detected 4 h after dosing were 3.2 mg/100 ml, 2.4 mg/100 ml and 8.6 mg/100 ml, respectively. Eighteen hours after 2-butanone, the concentration of 2,3-butanediol rose to 25.6 mg/100 ml, while the concentrations of 2-butanol and 3-hydroxy-2-butanone declined to 0.6 mg/100 ml and 1.4 mg/100 ml, respectively. A 16-h pretreatment with either 2-butanone (2.1 ml/kg, p.o.) or 2,3-butanediol (2.12 ml/kg, p.o.) markedly enhanced the hepatotoxic response to CCl4 (0.1 ml/kg, i.p.), as measured by serum glutamic pyruvic transaminase activity and hepatic triglyceride content. In vivo, limited formation of 3-hydroxy-2-butanone occurred after this dose of 2,3-butanediol. These data suggest that the production of 3-hydroxy-2-butanone and 2,3-butanediol via 2-butanone metabolism may participate in the augmented necrogenic effect of CCl4 seen after pretreatment with 2-butanone.
在大鼠中研究了酮代谢在2-丁酮诱导的四氯化碳（CCl4）肝毒性增强中的作用。给药4小时后检测到的2-丁醇、3-羟基-2-丁酮和2,3-丁二醇的血药浓度分别为3.2毫克/100毫升、2.4毫克/100毫升和8.6毫克/100毫升。2-丁酮给药18小时后，2,3-丁二醇的浓度升至25.6毫克/100毫升，而2-丁醇和3-羟基-2-丁酮的浓度分别降至0.6毫克/100毫升和1.4毫克/100毫升。用2-丁酮（2.1毫升/千克，口服）或2,3-丁二醇（2.12毫升/千克，口服）进行16小时预处理，显著增强了对CCl4（0.1毫升/千克，腹腔注射）的肝毒性反应，通过血清谷丙转氨酶活性和肝脏甘油三酯含量来衡量。在体内，给予该剂量的2,3-丁二醇后，3-羟基-2-丁酮的生成有限。这些数据表明，通过2-丁酮代谢产生的3-羟基-2-丁酮和2,3-丁二醇可能参与了用2-丁酮预处理后所见的CCl4增强的致坏死作用。
