Hill K E, Burk R F
Toxicol Appl Pharmacol. 1984 Jan;72(1):32-9. doi: 10.1016/0041-008x(84)90246-1.
Isolated hepatocytes from selenium-deficient, vitamin E-deficient, and control rats were treated with cumene hydroperoxide (CuOOH), phorone (diisopropylene acetone), acetaminophen, and diquat. The effect of these chemicals on cell viability, glutathione synthesis and release, and lipid peroxidation as measured by thiobarbituric acid (TBA)-reactive substances was determined during a 4-hr incubation in a complete medium under 95% O2:5% CO2 at 37 degrees C. CuOOH-treated (0.5 mM) selenium-deficient and vitamin E-deficient hepatocytes lost viability sooner than control hepatocytes. Thus, loss of selenium or vitamin E from the hepatocyte resulted in a cell more susceptible to damage by CuOOH. Phorone treatment (1.65 mM) resulted in depletion of intracellular glutathione in all three groups to approximately 20% of that in untreated hepatocytes. Cell viability and TBA-reactive substances were the same in treated and untreated hepatocytes. Thus, lowering of intracellular glutathione did not result in the spontaneous loss of cell viability or increased lipid peroxidation in selenium-deficient or in vitamin E-deficient hepatocytes. Acetaminophen appeared to be less toxic to selenium-deficient hepatocytes than to controls. This finding is in agreement with whole animal studies reported previously showing that selenium deficiency protects rats against acetaminophen hepatotoxicity. A potential explanation of this result is stimulation of glutathione synthesis by selenium deficiency. Severely vitamin E-deficient hepatocytes were protected from cell death by 12.5 and 25.0 mM acetaminophen, apparently by its antioxidant properties, while 50.0 mM acetaminophen was toxic to them. At all concentrations used, acetaminophen decreased the TBA-reactive substances present in the hepatocyte suspensions. Diquat (0.1 mM) caused more rapid cell death and higher levels of TBA-reactive substances in selenium-deficient hepatocytes than in control hepatocytes. Diquat toxicity in selenium-deficient isolated hepatocytes was not as severe as its toxicity in selenium-deficient whole animals, however.
用氢过氧化异丙苯（CuOOH）、佛尔酮（二异丙基丙酮）、对乙酰氨基酚和百草枯处理来自缺硒、缺维生素E大鼠以及对照大鼠的分离肝细胞。在37℃、95%O₂:5%CO₂条件下，于完全培养基中孵育4小时期间，测定这些化学物质对细胞活力、谷胱甘肽合成与释放以及通过硫代巴比妥酸（TBA）反应性物质测量的脂质过氧化的影响。经CuOOH处理（0.5 mM）的缺硒和缺维生素E的肝细胞比对照肝细胞更快丧失活力。因此，肝细胞中硒或维生素E的缺失导致细胞对CuOOH损伤更敏感。佛尔酮处理（1.65 mM）使所有三组细胞内谷胱甘肽耗竭至未处理肝细胞中谷胱甘肽含量的约20%。处理组和未处理组肝细胞的细胞活力和TBA反应性物质相同。因此，缺硒或缺维生素E的肝细胞中细胞内谷胱甘肽的降低并未导致细胞活力的自发丧失或脂质过氧化增加。对乙酰氨基酚对缺硒肝细胞的毒性似乎比对对照组小。这一发现与先前报道的全动物研究一致，表明缺硒可保护大鼠免受对乙酰氨基酚肝毒性。这一结果的一个可能解释是缺硒刺激了谷胱甘肽的合成。严重缺维生素E的肝细胞受到12.5 mM和25.0 mM对乙酰氨基酚的保护而免于细胞死亡，显然是由于其抗氧化特性，而50.0 mM对乙酰氨基酚对它们有毒性。在所使用的所有浓度下，对乙酰氨基酚均降低了肝细胞悬液中存在的TBA反应性物质。百草枯（0.1 mM）在缺硒肝细胞中比在对照肝细胞中导致更快的细胞死亡和更高水平的TBA反应性物质。然而，百草枯在缺硒分离肝细胞中的毒性不如其在缺硒全动物中的毒性严重。
