Jacobs J M, Rutkowski J V, Roebuck B D, Smith R P
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03756.
Toxicol Lett. 1987 Oct;38(3):257-64. doi: 10.1016/0378-4274(87)90006-3.
The hepatotoxic effects of allyl alcohol with particular reference to mitochondrial morphology and function were compared in male CD1 mice and male CD rats 24 h after 0.05 ml/kg i.p. in corn oil. As already noted by others, allyl alcohol-treated rats usually showed histologic evidence of tissue necrosis when hematoxylin-eosin-stained tissue sections were examined whereas mouse tissue sections did not. The serum glutamic pyruvic transaminase (SGPT) activities were significantly elevated in both mice and rats but to a much greater extent in the latter. Pentobarbital sleeping time was significantly increased over that of corn oil control groups in rats but decreased in mice. In rats electron microscopy showed mitochondria which contained flocculent densities. State 4 respiration was not altered by allyl alcohol in rats, but state 3 respiration was significantly depressed indicating an absence of respiratory control and an inability to perform energy coupling. In allyl alcohol-treated mice the isolated mitochondria were found to be primarily in a condensed form. Except for the effect on pentobarbital sleeping time and SGPT, no other findings were different from those in control groups given only corn oil. When the dose of allyl alcohol in mice was increased to 0.15 ml/kg in an attempt to elicit more severe signs of hepatotoxicity, there was a high mortality in the first 24 h period without histologic evidence of liver necrosis. Thus, we confirm that at equivalent doses, male rats are more sensitive to the hepatotoxic effects of allyl alcohol than are male mice, and extend the generalization to the liver mitochondria of the 2 species.
在雄性CD1小鼠和雄性CD大鼠腹腔注射0.05 ml/kg玉米油溶液24小时后,比较烯丙醇对肝脏的毒性作用,特别关注线粒体的形态和功能。正如其他人已经指出的,当检查苏木精-伊红染色的组织切片时,烯丙醇处理的大鼠通常显示出组织坏死的组织学证据,而小鼠组织切片则没有。小鼠和大鼠的血清谷丙转氨酶(SGPT)活性均显著升高,但后者升高幅度更大。大鼠的戊巴比妥睡眠时间比玉米油对照组显著延长,而小鼠则缩短。电子显微镜检查显示,大鼠的线粒体含有絮状密度物质。烯丙醇对大鼠的状态4呼吸没有影响,但状态3呼吸显著受抑制,表明缺乏呼吸控制且无法进行能量偶联。在烯丙醇处理的小鼠中,分离出的线粒体主要呈浓缩形式。除了对戊巴比妥睡眠时间和SGPT的影响外,没有其他发现与仅给予玉米油的对照组不同。当小鼠的烯丙醇剂量增加到0.15 ml/kg以试图引发更严重的肝毒性迹象时,在最初的24小时内死亡率很高,但没有肝脏坏死的组织学证据。因此,我们证实,在等效剂量下,雄性大鼠比雄性小鼠对烯丙醇的肝毒性作用更敏感,并将这一普遍现象扩展到这两个物种的肝脏线粒体。