Shen E S, Garry V F, Anders M W
Biochem Pharmacol. 1982 Dec 1;31(23):3787-93. doi: 10.1016/0006-2952(82)90294-5.
The effect of hypoxia on carbon tetrachloride-induced hepatotoxicity was studied. Male rats were exposed to carbon tetrachloride for 2 hr in the presence of differing oxygen concentrations. Serum glutamate-pyruvate transaminase (SGPT) activities were measured 24 hr after the end of the exposure. Exposure of rats to 5000 ppm carbon tetrachloride in the presence of 100, 21, 12, or 6% oxygen resulted in SGPT activities of 489, 420, 3768, and 1788 I.U./l respectively. Exposure of rats to air and 0, 1250, 2500, 5000, or 7500 ppm carbon tetrachloride gave SGPT activities of 35, 32, 69, 420, and 2188 I.U./l respectively; when 12% oxygen was used, the corresponding SGPT activities were 32, 665, 691, 3768, and 4200 I.U./l respectively. Exposure of rats to hypoxia produced histopathologically detectable condensation of hepatic cytoplasmic material, and exposure to 5000 ppm carbon tetrachloride in the presence of air produced mild centrilobular necrosis, which was much more severe when rats were exposed to 5000 pm carbon tetrachloride in the presence of 12% oxygen. Hepatic microsomal conjugated diene concentrations were increased by hypoxia and by exposure to carbon tetrachloride, but no synergistic interaction was observed. Hepatic microsomal cytochrome P-450 concentrations were decreased after exposure to carbon tetrachloride, but were the same after exposure to carbon tetrachloride and 12 or 21% oxygen. Hepatic carbon tetrachloride concentrations were the same in rats exposed to carbon tetrachloride in the presence of 12 or 21% oxygen; hepatic chloroform concentrations were higher in rats exposed to carbon tetrachloride in the presence of air than in the presence of 12% oxygen. The covalent binding of [14C]carbon tetrachloride metabolites to hepatic microsomal lipids and proteins was increased markedly by hypoxia as compared with normoxia. The covalent binding of metabolites of carbon tetrachloride to cellular macromolecules may play a role in the potentiation of carbon tetrachloride toxicity by hypoxia.
研究了缺氧对四氯化碳诱导的肝毒性的影响。雄性大鼠在不同氧浓度条件下接触四氯化碳2小时。接触结束后24小时测量血清谷丙转氨酶（SGPT）活性。大鼠在100%、21%、12%或6%氧气存在下接触5000 ppm四氯化碳后，SGPT活性分别为489、420、3768和1788国际单位/升。大鼠在空气中接触0、1250、2500、5000或7500 ppm四氯化碳时，SGPT活性分别为35、32、69、420和2188国际单位/升；当使用12%氧气时，相应的SGPT活性分别为32、665、691、3768和4200国际单位/升。大鼠暴露于缺氧环境会产生组织病理学上可检测到的肝细胞质物质浓缩，而在空气中接触5000 ppm四氯化碳会产生轻度的小叶中心坏死，当大鼠在12%氧气存在下接触5000 ppm四氯化碳时，这种坏死会严重得多。缺氧和接触四氯化碳都会增加肝微粒体共轭二烯浓度，但未观察到协同相互作用。接触四氯化碳后肝微粒体细胞色素P - 450浓度降低，但在接触四氯化碳以及12%或21%氧气后浓度相同。在12%或21%氧气存在下接触四氯化碳的大鼠肝脏中四氯化碳浓度相同；在空气中接触四氯化碳的大鼠肝脏中氯仿浓度高于在12%氧气存在下的浓度。与常氧相比，缺氧显著增加了[14C]四氯化碳代谢产物与肝微粒体脂质和蛋白质的共价结合。四氯化碳代谢产物与细胞大分子的共价结合可能在缺氧增强四氯化碳毒性中起作用。
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