Chiarpotto E, Biasi F, Comoglio A, Leonarduzzi G, Poli G, Dianzani M U
Department of Experimental Medicine and Oncology of the University, Torino, Italy.
Chem Biol Interact. 1990;74(1-2):195-206. doi: 10.1016/0009-2797(90)90067-w.
A significant increase of the intracellular level of free arachidonic acid was observed in intact rat hepatocytes after poisoning with very low concentrations of CCl4 (0.129-0.172 mM), shown not to exert direct solvent effect. It seems likely that activation of phospholipase A2 (PLA2) is the mechanism mainly responsible for the rise of cytosolic arachidonate, since the latter is prevented by the PLA2 inhibitors indomethacin and mepacrine. The CCl4-induced delay of arachidonic acid incorporation within the cell membrane phospholipids partly contributes to its intracellular accumulation in the early phases of the poisoning. The lack of any significant protection by metabolic inhibitors (SKF 525A, metyrapone), antioxidant compounds (promethazine, diphenylphenylenediamine DPPD) or antioxidant procedures (rat pretreatment with vitamin E) leads to exclude an involvement of CCl4 biotransformation in the increase of intracellular free arachidonate. Finally, the PLA2 inhibitors employed in this study did not afford protection against the enzymic leakage of CCl4-treated hepatocytes.
在用极低浓度的四氯化碳（0.129 - 0.172 mM）中毒后，完整大鼠肝细胞内游离花生四烯酸水平显著升高，且表明其未产生直接溶剂效应。磷脂酶A2（PLA2）的激活似乎是导致胞质花生四烯酸水平升高的主要机制，因为吲哚美辛和米帕林这两种PLA2抑制剂可阻止其升高。四氯化碳诱导的花生四烯酸掺入细胞膜磷脂的延迟在中毒早期部分促成了其在细胞内的积累。代谢抑制剂（SKF 525A、甲吡酮）、抗氧化化合物（异丙嗪、二苯基苯二胺DPPD）或抗氧化措施（用维生素E预处理大鼠）均未提供任何显著保护作用，这表明四氯化碳生物转化与细胞内游离花生四烯酸增加无关。最后，本研究中使用的PLA2抑制剂未能保护四氯化碳处理的肝细胞免受酶泄漏的影响。
