Toxicity studies in isolated hepatocytes from selenium-deficient rats and vitamin E-deficient rats.
Toxicity studies in isolated hepatocytes from selenium-deficient rats and vitamin E-deficient rats.
复制标题
对缺硒大鼠和维生素 E 缺乏大鼠的分离肝细胞进行毒性研究。
DOI：
10.1016/0041-008x(84)90246-1
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发表时间：
1984
影响因子：
3.8
通讯作者：
Burk,RF
中科院分区：
文献类型：
--
作者：
Hill,KE;Burk,RF
用氢过氧化异丙苯 (CuOOH)、佛尔酮（二异丙烯丙酮）、对乙酰氨基酚和敌草快处理来自缺硒、维生素 E 缺乏和对照大鼠的分离肝细胞。这些化学物质对细胞活力、谷胱甘肽合成和释放以及通过硫代巴比妥酸 (TBA) 反应物质测量的脂质过氧化的影响是在 37°C、95% O2:5% CO2 的完全培养基中孵育 4 小时期间确定的。 CuOOH 处理（0.5 mm）的缺硒和维生素 E 肝细胞比对照肝细胞更快失去活力。因此，肝细胞中硒或维生素 E 的损失导致细胞更容易受到 CuOOH 的损害。佛尔酮处理 (1.65 mm) 导致所有三组细胞内谷胱甘肽的消耗量约为未处理肝细胞的 20%。处理和未处理的肝细胞中的细胞活力和TBA反应物质是相同的。因此，细胞内谷胱甘肽的降低不会导致细胞活力自发丧失或缺硒或维生素 E 缺乏的肝细胞中脂质过氧化增加。对乙酰氨基酚对缺硒肝细胞的毒性似乎比对对照的毒性要小。这一发现与之前报道的整体动物研究一致，表明缺硒可以保护大鼠免受对乙酰氨基酚的肝毒性。这一结果的一个可能的解释是缺硒会刺激谷胱甘肽的合成。 12.5 和 25.0 mm 对乙酰氨基酚显然具有抗氧化特性，可保护严重缺乏维生素 E 的肝细胞免于细胞死亡，而 50.0 mm 对乙酰氨基酚对肝细胞有毒。在所有使用浓度下，对乙酰氨基酚都能减少肝细胞悬浮液中存在的 TBA 反应物质。与对照肝细胞相比，敌草快 (0.1 mm) 在缺硒肝细胞中引起更快的细胞死亡和更高水平的 TBA 反应物质。然而，敌草快对缺硒的离体肝细胞的毒性并不像对缺硒的整个动物的毒性那么严重。
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% CO2at 37°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 acetaminophe, 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.