Sundari P N, Wilfred G, Ramakrishna B
Department of Biochemistry, Christian Medical College & Hospital, Vellore, Tamilnadu, India.
Biochim Biophys Acta. 1997 Dec 31;1362(2-3):169-76. doi: 10.1016/s0925-4439(97)00065-3.
Free radicals have been implicated in the pathogenesis of alcohol-induced liver injury in humans and carbon tetrachloride (CCl4)-induced liver injury in rats. The most extensively studied aspect of free radical induced liver injury is lipid peroxidation. Recently it has been found that free radicals can cause oxidative damage to cellular proteins and alter cellular function. One such susceptible protein is the enzyme glutamine synthase (GS). The chemical effects of CCl4 on cell proteins and their biological consequences are not known. Hence, in our study, the effect of CCl4 on liver protein oxidation and GS activity were investigated and compared with lipid peroxidation. A significant increase in liver protein carbonyl content (2-3 fold) and a significant decrease in hepatic GS activity (44-57%) were observed. Damage to proteins was rapid in onset and increased with time. Acute exposure of rats to CCl4 resulted in an increase in hepatic protein carbonyl content and a decrease in hepatic GS within 1 h. In cirrhosis of the liver induced by CCl4, the decrease in hepatic GS activity was accompanied by a significant increase in plasma ammonia levels. We conclude that protein oxidation may play a role in the pathogenesis of CCl4 induced liver injury and that the accumulation of oxidised proteins may be an early indication of CCl4 induced liver damage.
自由基与人类酒精性肝损伤以及大鼠四氯化碳（CCl4）诱导的肝损伤发病机制有关。自由基诱导肝损伤研究最广泛的方面是脂质过氧化。最近发现，自由基可对细胞蛋白质造成氧化损伤并改变细胞功能。谷氨酰胺合成酶（GS）就是这样一种易受影响的蛋白质。四氯化碳对细胞蛋白质的化学作用及其生物学后果尚不清楚。因此，在我们的研究中，研究了四氯化碳对肝脏蛋白质氧化和GS活性的影响，并与脂质过氧化进行了比较。观察到肝脏蛋白质羰基含量显著增加（2至3倍），肝脏GS活性显著降低（44%至57%）。蛋白质损伤起病迅速且随时间增加。大鼠急性暴露于四氯化碳后1小时内，肝脏蛋白质羰基含量增加，肝脏GS降低。在四氯化碳诱导的肝硬化中，肝脏GS活性降低伴随着血浆氨水平显著升高。我们得出结论，蛋白质氧化可能在四氯化碳诱导的肝损伤发病机制中起作用，氧化蛋白质的积累可能是四氯化碳诱导肝损伤的早期迹象。
